Kanker

S U P P L E M E N T
Volume 8 Supplement 3
JNCCN
Journal of the National Comprehensive Cancer Network
The Abu Dhabi Declaration: Adapted

Application of NCCN Clinical Practice
Guidelines in Oncology in the Middle East
and North Africa Region
The Process of NCCN Guidelines Adaptation to the Middle East
Abdul-Rahman Jazieh, Hamdy A. Azim, Joan McClure,
and Mohammad Jahanzeb
Also Featuring
Modification and Implementation of NCCN Guidelines
in the Middle East and North Africa Region on:
Breast Cancer
Omalkhair Abulkhair, Nagi Saghir, Lobna Sedky, et al.
NonSmall Cell Lung Cancer

Abdul-Rahman Jazieh, Hanaa Bamefleh, Ahmet Demirkazik, et al.
Colon Cancer
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NCCN content is produced completely
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therapeutic modality. The distribution of
this task force report is supported by an
educational grant from Roche.
Fikri li, Hakan Akbulut, Shouki Bazarbashi, et al.
Prostate Cancer
Waleed A. Hassen, Farrok A. Karsan, Farhat Abbas, et al.
Lymphomas
Ali Bazarbachi, Hamdy A. Azim, Hussain Alizadeh, et al.
Hepatobiliary Cancers
Muhammed Aasim Yusuf, Vinay Kumar Kapoor,
Refaat Refaat Kamel, et al.
Palliative Care
Omar Shamieh and Abdul-Rahman Jazieh
NCCN.org
JNCCN
Volume 8 Supplement 3 Journal of the National Comprehensive Cancer Network

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JNCCN
The Abu Dhabi Declaration: Adapted Application of NCCN Clinical Practice Guidelines in Oncology
in the Middle East and North Africa Region
Featured Articles
S-1 Welcome
S-2 Editorial: The Abu Dhabi Declaration: Why the Hustle?

Hamdy A. Azim, MD, PhD; Abdul-Rahman Jazieh, MD, MPH; and Mohammad Jahanzeb, MD
S-5 The Process of NCCN Guidelines Adaptation to the Middle East and North Africa Region
Abdul-Rahman Jazieh, MD, MPH; Hamdy A. Azim, MD, PhD; Joan McClure, MS; and Mohammad Jahanzeb, MD
NCCN Guidelines set the standard of cancer care in the United States. Because of wide acceptance of, need for, and interest in
standardized treatment practices across the world, NCCN launched initiatives to help international groups adapt these guidelines.
This article describes the initiative in the Middle East and North Africa region.
S-8 Modification and Implementation of NCCN Guidelines on Breast Cancer in the Middle East
Omalkhair Abulkhair, MD; Nagi Saghir, MD; Lobna Sedky, MD; Ahmed Saadedin, MD; Heba Elzahwary, MD;
Neelam Siddiqui, MD; Mervat Al Saleh, MD; Fady Geara, MD; Nuha Birido, MD; Nadia Al-Eissa, MD;
Sana Al Sukhun, MD; Huda Abdulkareem, MD; Menar Mohamed Ayoub, MD; Fawaz Deirawan, MD;
Salah Fayaz, MD; Alaa Kandil, MD; Sami Khatib, MD; Mufid El-Mistiri, MD; Dorria Salem, MD;
El Siah Hassan Sayd, MD; Mohammed Jaloudi, MD; Mohammad Jahanzeb, MD; and William I. Gradishar, MD
Published data from the Middle East and North Africa (MENA) region indicate suboptimal quality of cancer care, while the World
Health Organization predicts an increase in cancer cases in developing countries. Major advances in breast cancer management
mandate the development of guidelines to improve the quality and efficacy of oncology practice in the MENA region.
S-16 Modification and Implementation of NCCN Guidelines on NonSmall Cell Lung Cancer in the
Middle East and North Africa Region
Abdul-Rahman Jazieh, MD, MPH; Hanaa Bamefleh, MBchB, FRCPC; Ahmet Demirkazik, MD;
Rabab Mohamed Gaafar, MD; Fady B. Geara, MD, PhD; Mansur Javaid, MD, FCCP, FRCP; Jamal Khader, MD;
Kian Khodadad, MD; Walid Omar, MD; Ahmed Saadeddin, MD; Hassan Al Sabe, MD;
Mohammad Behgam Shadmehr, MD; Amgad El Sherif, MD, FCCP; Najam Uddin, FRCR; Mohammad Jahanzeb, MD;
and David Ettinger, MD
A lung cancer committee from the Middle East and North Africa region was established to modify the NCCN Guidelines on Lung
Cancer, to create a platform for standard care in the region.
S-22 Modification and Implementation of NCCN Guidelines on Colon Cancer in the Middle East
Fikri li, MD; Hakan Akbulut, MD; Shouki Bazarbashi, MD; Mehmet Ayhan Kuzu, MD; Mohandas K. Mallath, MD;
Kakil Ibrahim Rasul, FRCP Edin; Scott Strong, MD; Aamir Ali Syed, FRCS; Faruk Zorlu, MD; and Paul F. Engstrom, MD
Colorectal cancer is less common in the Middle East and South Asia than in western countries, with the rectum the most common
primary site, unlike in the United States. Major differences also exist in treatment preferences, as discussed in this article.
S-26 Modification and Implementation of NCCN Guidelines on Prostate Cancer in the Middle East
Waleed A. Hassen, MD; Farrok A. Karsan, MD; Farhat Abbas, MD; Yasar Beduk, MD; Ahmed El-Khodary, MD;
Marwan Ghosn, MD, MBA; Jamal Khader, MD; Raja Khauli, MD; Danny M. Rabah, MD; Ali Shamseddine, MD;
and Sandy Srinivas, MD
The treatment of prostate cancer in the Middle East and North Africa region has numerous challenges. The hope is that
this effort to modify the NCCN Guidelines on Prostate Cancer for practical use in the MENA region will improve regional
awareness and patient care.
JNCCN
Featured Articles
S-29 Modification and Implementation of NCCN Guidelines on Lymphomas in the Middle East
Ali Bazarbachi, MD, PhD; Hamdy A. Azim, MD, PhD; Hussain Alizadeh, MD, PhD; Mahmoud Aljurf, MD;
Ibrahim Barista, MD; Naeem A. Chaudhri, MD; Zahira Fahed, MD; Omar A. Fahmy, MD;
Ardeshir Ghavamzadeh, MD; Mohamed H. Khalaf, MD; Sami Khatib, MD; Aghiad Kutoubi, MD; Semra Paydas, MD;
Hanadi Rafii Elayoubi, MD; Ghazi Zaatari, MD; Hamdy M. Zawam, MD; and Andrew D. Zelenetz, MD, PhD
In the Middle East and North Africa (MENA) region, cancer has many epidemiologic and clinical features that are different
from those in the rest of the world. A critical need exists for regional guidelines for cancer care, including those for lymphoid
malignancies. This article presents the consensus recommendations from lymphoma experts from the MENA region on the NCCN
Guidelines on Non-Hodgkins Lymphoma.
S-36 Modification and Implementation of NCCN Guidelines on Hepatobiliary Cancer in the

Muhammed Aasim Yusuf, FRCP Edin; Vinay Kumar Kapoor, MS, FRCS; Refaat Refaat Kamel, FRCS;
Ather Kazmi, MRCP, FRCR; Najam Uddin, FRCR; Nehal Masood, MD; and
Abdulmajeed Al-Abdulkareem, MD, FRCSC, FACS
Hepatocellular cancer incidence is higher in the Middle East and North Africa region than in the West, and hepatitis B and C
infections are particularly important. Regional problems discussed in this article include delay in diagnosis, shortage of trained
staff, and insufficient liver transplant facilities, and treatment cost is an ongoing concern.
S-41 Modification and Implementation of NCCN Guidelines on Palliative Care in the Middle East
Omar Shamieh, MD, and Abdul-Rahman Jazieh, MD, MPH

Advancing palliative care in the developing countries is essential to improving patient care. Palliative care is in its early stage of
evolution in the Middle East and North Africa region, and its practice encounters many challenges and barriers. Adaptation of
guidelines must consider the situation and conditions in the targeted region.
S-1

The National Comprehensive Cancer Network (NCCN) and our 21 member
institutions are dedicated to improving the care available to patients around the world.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the
attendant scientific, evaluative process has become the model for the development
and communication of clinical recommendations based on evidence review integrated
with expert judgment.
The NCCN is pleased to extend our scientific, clinical collaboration to thought
leaders in the Middle East and North Africa (MENA). The NCCNMENA
Guidelines Congress held in Abu Dhabi, running from April 23 to 26, 2009, brought
together leading clinicians to review the NCCN Guidelines and supporting data
and to discuss the applicability of the NCCN Guidelines to patients in this part of
our world. As always, the clinical discussion highlighted areas for improvement and
clarification in the NCCN Guidelines. As Drs. Azim, Jazieh, and Jahanzeb point out
in the accompanying introduction, the work has begun and the initial thinking is
published is this Abu Dhabi Declaration. Much work remains as experts identify
issues for study in trials or through other research methods, issues that relate to possible
differences in genetic makeup and its expression, differences in the availability of
technology across the 16 countries, and other factors.
The NCCN thanks our colleagues in the Middle East and North Africa for their
willingness to share their knowledge, expertise, and experience as we work to improve
cancer care for patients whom we serve.
Welcome

William T. McGivney, PhD, is Chief
Executive Officer of the NCCN,
responsible for the development
of strategies and programs to
improve the quality of care
available to cancer patients.
Such programs include the
NCCN Clinical Practice Guidelines
in Oncology, NCCN Oncology
Outcomes Database, NCCN
Oncology Research Program,
and NCCN Drugs & Biologics
Compendium. Strategically, Dr.
McGivney is responsible for the
growth of NCCNs influence in
the oncology community and
for assuring the development of
partnerships with managed care
companies and employers, the
development of NCCNs health
information capabilities, and the
expansion of centralized research
programs.
Before joining NCCN, Dr.
McGivney was Director of
the Division of Health Care
Technology at the American
Medical Association and then
Vice President for Clinical
and Coverage Policy at Aetna
Health Plans. While at Aetna, he
helped establish the first formal
independent outside review
process.
Dr. McGivney, a recognized
expert in coverage policy and
in drug and device regulatory
policy, was awarded the FDA
Commissioners Medal of
Appreciation in 1989. He has
served on numerous national
boards and committees including
as President of the Board of the
Patient Advocate Foundation
and National Patient Advocate
Foundation and as a member of
the UNOS Board of Directors and
the Medicare Coverage Advisory
Committee.
The ideas and viewpoints

expressed in this editorial are
those of the author and do not
necessarily represent any policy,
position, or program of the NCCN.
Journal of the National Comprehensive Cancer Network | Volume 8 Supplement 3 | July 2010
S-2
Editorial
The Abu Dhabi Declaration: Why the Hustle?
Hamdy A. Azim, MD, PhD

Dr. Azim is Professor of Clinical
Oncology at Cairo University
in Egypt. His interests lie in
lymphoma, breast cancer, bone
metastases, and translational
research, and has published
more than 50 papers and 100
abstracts. Dr. Azim is a member
of numerous societies, including
ASCO and ASH. He sits on
several scientific committees
and has been an invited speaker
to more than 100 regional
and international conferences
in the Middle East, Europe,
United States, and Asia, and has
published more than 50 papers
and 100 abstracts.
Abdul-Rahman Jazieh, MD,

MPH
Dr. Abdul-Rahman Jazieh,
MD, MPH, is Chairman of the
Department of Oncology at the
King Abdulaziz Medical City
in Riyadh, Kingdom of Saudi
Arabia. He is also a Professor
at the King Saud bin Abdulaziz
University for Health Sciences
and a volunteer professor at the
University of Cincinnati in Ohio.
He is board certified in internal
medicine, hematology, and
medical oncology.
Over the past decade, the NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines) have emerged as a very useful tool for supporting and improving the
quality of decision-making for oncologists worldwide. Considering that approximately
12 million cancer patients were registered by the WHO during 2008 and that the
NCCN Web site (www.NCCN.org) attracts more than 150,000 visitors per month,
one can conclude that the NCCN Guidelines program has potentially influenced the
management of approximately 15% of all cancer patients worldwide. Although this
example shows its far-reaching benefit, it also shows that there is plenty of room for
expanding its application. A real need exists within the oncology community to have
a reliable evidence-based tool to translate the rapidly accumulating scientific research
into practical medical decisions that may offer a better and more consistent treatment
outcome for patients.
The NCCN recently launched the NCCNMiddle East and North Africa
(NCCNMENA) Guidelines Congress in an attempt to provide versions of the
original NCCN Guidelines tailored for cancer management in this region. However,
one may ask whether it is really important to have a revised set of Guidelines
specifically dedicated to a certain geographical region, when the original NCCN
guidelines are satisfactory and comprehensive. We believe the answer is YES for 3
main reasons: differences in race, genetic, and environmental factors; differences in
presenting features and stage; and differences in access to technology and drugs.
Differences in Racial, Genetic, and Environmental Factors

The NCCN Guidelines have been generated based on high-level evidence provided by
large trials conducted mainly in the United States and Europe (hence predominantly
enrolling a Western population) with a limited contribution from the rest of the
world, including the Middle East.
Racial and genetic factors are known to play a vital role in the development
of cancer. For example, in Europe, the United States, and Australia, people have
a higher risk of developing skin cancer because they have fair skin, a characteristic
that is uncommonly witnessed in other regions. Although guidelines for prevention
and early detection of skin cancer are needed in these countries, they are of lesser
importance in the Middle East.1
Racial and genetic factors are not only relevant in cancer epidemiology but also
can have significant influence on treatment strategies because of varying sensitivities
to, and metabolism of, different drugs, resulting in a different prioritization of these
approaches. For example, studies recently showed that Asian patients with advanced
nonsmall cell lung cancer have a higher incidence of epidermal growth factor receptor
(EGFR) mutations, and therefore experienced a greater benefit from treatment with
EGFR inhibitors such as gefitinib and erlotinib.2,3 As a result of these findings, these
agents were established as first-line therapies for these patients, before platinum-based
chemotherapy, unlike in patients with nonsmall cell lung cancer in Europe and the
United States.4 This raises an important question: can the results from large studies
conducted mainly in Caucasian patient populations be accurately applied to the nonCaucasian majority in the rest of the world?
Of course, the pharmacogenomic preferential benefit of EGFR inhibitors reported
in the above-mentioned studies does not necessarily exist in the same magnitude
in other races or with other types of anticancer drugs. However, one may assume
S-3
Editorial
The Abu Dhabi Declaration
that certain differences are likely to emerge from the integrated efforts of experts
in the region. The same concept may also be applied to the differences in some
environmental factors that may also play a role in the process of carcinogenesis and
response to treatment. For example, in contrast to the West, where hepatocellular
carcinoma (HCC) is less common and mainly secondary to alcoholic hepatitis and
hepatitis B virus,7 in many Middle East countries, HCC is one of the most common
cancers and usually secondary to hepatitis C virus (HCV).8 In a subgroup analysis
of a pivotal sorafenib study, a greater benefit of this drug was seen among patients
with HCV-associated HCC. Another example is bladder cancer, which is usually
of transitional cell histology in Europe and the United States, but is commonly of
squamous cell histology in several countries in the Middle East where schistosomiasis
is rampant.9 These differences may limit the applicability of West-centric guidelines
in the clinical practice of oncology in other regions of the world.
These issues presented significant challenges for our diverse team while setting the
objectives of the NCCNMENA project, because the geography of our loosely defined
region stretches from the west of Morocco to the eastern part of India. Therefore, the
so-called MENA cancer patients according to this geographic definition are in fact a
large population of racially and environmentally heterogeneous people among whom
one might elicit differences rather than similarities. Still, in the current project of
NCCNMENA, we made a thorough review of the available literature generated from
cancer patients in our region, seeking any convincing evidence that may suggest a
unique therapeutic feature attributable to racial, genetic, or environmental factors.
Differences in Presenting Features and Stage

In the Middle East and in other developing regions of the world, cancer is often
diagnosed at a younger age and tends to be of more advanced-stage compared with
cases reported among the Western populations.5 For example, in the Middle East, the
median age of breast cancer diagnosis is younger 50 years (with 25% of patients < 40
years) compared with older than 60 years in the West. The lack of early detection
programs in the Middle East has resulted in most breast cancer and other solid tumors
presenting at stages III/IV compared with in Western countries. Taken together, the
screening policy adopted in the West would certainly miss early detection of breast
cancer in many young women, who represent a good proportion of cases in the region.
Mohammad Jahanzeb, MD,

FACP
Dr. Jahanzeb is an international
lecturer on issues related to
breast and lung cancers. He
is currently National Director
for Quality Improvement in
the Aptium Oncology network
and a Professor of Medicine
at University of Tennessee. He
has served as a member of the
National Comprehensive Cancer
Network (NCCN) Board of
Directors, the NCCN Guidelines
Steering and Investigators
Steering Committees, and the
Breast Cancer and Non-Small
Cell Lung Cancer Panels. He is
currently the Medical Advisor on
Global Initiatives. Dr. Jahanzeb
is board certified in Internal
Medicine with subspecialties
in Hematology and Medical
Oncology.
Differences in Access to Technology and Drugs

The Middle East is composed mostly of developing nations with restricted access to
advanced technology and novel agents incorporated in current oncology practice.
Costbenefit analysis studies conducted in the West are difficult to apply to this region
because of the differences in health systems among the developing and developed
nations. Guidelines taking into account these limitations would help optimize the
application of novel strategies to best use the limited resources available. Current
NCCN Guidelines are cost-blind and do not address these issues, and therefore fall
short in a resource-restricted setting.
Despite these limitations, we believe that this project will provide better
guidance for oncologists in the MENA region. These regionally targeted projects
are likely to stimulate oncologists in the region to not only practice more evidencebased medicine but also conduct local epidemiologic studies and clinical trials to
better define the magnitude of the problem and customize solutions for their part of
the world. We believe that the MENA region would benefit greatly if they invested
in the area of predictive and prognostic biomarkers.10 Expensive and sophisticated
The ideas and viewpoints

expressed in this commentary are
those of the author and do not
necessarily represent any policy,
position, or program of the NCCN.
Editorial
S-4
The Abu Dhabi Declaration
technologies can then be channelled to the subsets of

patients who are really likely to benefit from them.
Finally, we would like to invite all oncologists in the
MENA region to provide feedback on the applicability
and usefulness of the first edition of NCCNMENA
Guidelines. It is vital to ensure that this project achieves
its primary objective: facilitating the decision-making
process in the clinic.
Our hope is that this serves as an NCCN pilot project,
and that similar initiatives are launched in other regions
of the world, such as Central and South Africa, Latin
America, and beyond, which are underrepresented in
clinical trials on which most NCCN Guidelines are based.
References
1. Wheless L, Ruczinski I, Alani RM, et al. The association between
skin characteristics and skin cancer prevention behaviors. Cancer
Epidemiol Biomarkers Prev 2009;18:26132619.
2. Shigematsu H, Lin L, Takahashi T, et al. Clinical and biological
features associated with epidermal growth factor receptor gene
mutations in lung cancers. J Natl Cancer Inst 2005;97:339346.
3. Lynch TJ, Bell DW, Sordella R, et al. Activating mutations in the
epidermal growth factor receptor underlying responsiveness of non-
small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129

2139.
4. Mok TS, Wu YL, Thongprasert S, et al. Gefitinib or carboplatinpaclitaxel in pulmonary adenocarcinoma. N Engl J Med
2009;361:947957.
5. Salim EI, Moore MA, Al-Lawati JA, et al. Cancer epidemiology
and control in the Arab worldpast, present and future. Asian Pac
J Cancer Prev 2009;10:316.
6. El Saghir NS, Khalil MK, Eid T, et al. Trends in epidemiology
and management of breast cancer in developing Arab countries: a
literature and registry analysis. Int J Surg 2007;5:225233.
7. Fasani P, Sangiovanni A, De Fazio C, et al. High prevalence of
multinodular hepatocellular carcinoma in patients with cirrhosis
attributable to multiple risk factors. Hepatology 1999;29:1704
1707.
8. Lehman EM, Wilson ML. Epidemiology of hepatitis viruses among
hepatocellular carcinoma cases and healthy people in Egypt: a
systematic review and meta-analysis. Int J Cancer 2009;124:690
697.
9. Zaghloul MS, Nouh A, Moneer M, et al. Time-trend in
epidemiological and pathological features of schistosoma-associated
bladder cancer. J Egypt Natl Canc Inst 2008;20:168174.
10. Azim HA, Azim HA Jr. Review article optimizing the use of
her-2/neu targeting agents in breast cancer: a developing nation
perspective. J Egypt Natl Canc Inst 2007;19:225230.
Journal of the National Comprehensive Cancer Network | Volume 7 Supplement 1 | February 2010
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The Process of NCCN Guidelines

Adaptation to the Middle East and
North Africa Region
Abdul-Rahman Jazieh, MD, MPH;a Hamdy A. Azim, MD;b Joan McClure, MS;c and Mohamad Jahanzeb, MD;d
Riyadh, Kingdom of Saudi Arabia; Cairo, Egypt; Fort Washington, Pennsylvania; and Memphis, Tennessee
Key Words
NCCN Clinical Practice Guidelines in Oncology, NCCN Guidelines,
Middle East and North Africa region, MENA region
Abstract
The NCCN developed clinical practice guidelines for oncology
that set the standard of cancer care in the United States. Because of wide acceptance of, need for, and interest in standardized treatment practices across the world, NCCN launched initiatives to help international groups adapt these guidelines. This
article describes the initiative in the Middle East and North Africa
(MENA) region. A group of oncology experts and key opinion
leaders were assembled into 7 specific committees to develop
treatment guidelines for breast cancer, lung cancer, colon cancer,
prostate cancer, hepatobiliary cancer, lymphoma, and palliative
care. The committees reviewed the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) to identify any modifications
required for them to be more applicable to the MENA region
based on available evidence and regional experience. These modifications were discussed with NCCN experts and summarized for
each specific area. The development of these guidelines generated a strong interest in the region to develop more evidencebased practice and create further networking and collaboration.
(JNCCN 2010;8[Suppl 3]:S5S7)
From the aDepartment of Oncology, King Saud bin Abdulaziz

University for Health Sciences, Riyadh, Kingdom of Saudi Arabia;
b
Department of Oncology, Cairo University, Cairo, Egypt; cNational
Comprehensive Cancer Network, Fort Washington, Pennsylvania;
and dAptium Oncology, Lynn Cancer Institute, Boca Raton, Florida,
and University of Tennessee, Memphis, Tennessee.
Drs. Jazieh and Azim and Ms. McClure had disclosed that they
have no financial interests, arrangements, or affiliations with the
manufacturers of any products discussed in the article or their
competitors. Dr. Jahanzeb has disclosed that he is on the speakers
bureau for and an advisor for Genentech, Inc. and sanofi-aventis.
Correspondence: Abdul-Rahman Jazieh, MD, MPH, Department of
Oncology, Mail Code 1777, P.O. Box 22490, Riyadh 11426, Kingdom
of Saudi Arabia. E-mail: jazieha@ngha.med.sa
The National Comprehensive Cancer Network

(NCCN), an alliance of 21 of the leading cancer centers in the United States, has emerged as a leader in
setting the standard of care and impacting the practice
of oncology in the United States.13 NCCN has established more than 45 multidisciplinary, disease-specific
committees and panels and developed more than 100
guidelines that are updated annually and well publicized on the NCCN Web site (www.NCCN.org), in
JNCCNThe Journal of the National Comprehensive Cancer Network, and at various national and international
events.4 The process of developing these guidelines is
elaborate and well described, using the expertise of physicians from these leading institutions.
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) became a global phenomenon,
with various groups and regions around the world expressing interest in adapting these guidelines. In response,
NCCN launched outreach programs to share their extensive experience and resources with interested entities.
These efforts were translated into regional guidelines in
Korea, Japan, and China, and recently the Middle East
and North Africa (MENA) region,5 including countries
extending from Morocco to India (WestEast) and Turkey to Yemen (NorthSouth). The region spans a wide
geographic area, has diverse social and economic profiles,
and has significant heterogeneity in health care delivery and infrastructure. This diversity is not only across
countries but also among regions within the same country. Therefore, the current standard of oncology care also
varies greatly within the region.
Developing uniform guidelines that will be widely
accepted by practicing oncologists in the region may help
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Jazieh et al.
close the gap in the region, or at least will help delineate these variations so that a systemic approach to
remedy them can be established.
Readers should note that the guidelines referenced during this initiative and discussed throughout
this document were the 2009 versions. The most recent versions of the NCCN Guidelines are available
on the NCCN Web site at www.NCCN.org.
Methods
Committee Formations
Seven disease committees were formed for breast cancer, lung cancer, colon cancer, prostate cancer, hepatocellular carcinoma, lymphoma, and palliative care.
These committees included multidisciplinary expertise from different countries in the MENA region.
Each committee comprised a chair and individual members with expertise in that area of oncology care, in addition to a United Statesbased
NCCN expert from the applicable NCCN panel.
The NCCN panel member helped explain the process and thoughts behind certain NCCN guideline
recommendations and served as an external advisor
with whom to discuss certain issues raised by committee members. The panel of committee chairs was
led by a regional chair who coordinated the efforts of
the whole group centrally. NCCN staff and leadership provided support and advice to the committees
based on the NCCN experience.
A launch meeting was held at which the objectives and details of the initiative were presented to
the committee members. Thereafter, the committees held meetings separately at convenient times
and locations, and members corresponded frequently
via e-mail. A large regional symposium was held at
the conclusion of the first year activities to provide
education for the oncologists in the region regarding
NCCN guidelines, review the status of care in the
MENA region, and finalize the recommendations in
person among the committee members, experts in
the United States, and NCCN staff.
Adaption Process
The committee members reviewed the 2009 versions

of the NCCN guidelines specific to their area of expertise to determine what areas required modification for use in the MENA region. Recommendations
to modify an item were requested to be evidencebased and derived from experience and publications
relevant to the region, to avoid having substandard
guidelines because of the stark variations in health
care delivery among these countries.
All modifications and suggestions were listed according to the NCCN guidelines flow. The justification and references were put forth using a set format
(Table 1). Committee members discussed these suggestions in group meetings and then with the NCCN
experts. A final version of the recommendations were
compiled and submitted as a manuscript for publication. During the process, committee members were
asked to compile a list of potential research projects
that they believed important to the region to help fill
the gap in knowledge and address vital issues related
to cancer care.
Results
Each committee developed lists of suggested modifications with justification and references. The status
of care of the particular disease in the region was presented in a general meeting, and then the suggestions
were discussed with the respective NCCN expert to
address any ambiguous or controversial issues. A final version was then drafted and 7 manuscripts were
written and submitted for publication. The committee members also identified various research projects
required to address certain gaps in knowledge regarding the management of the diseases.
Discussion
The NCCNMENA initiative was an enriching experience and a good learning opportunity that had a
positive impact on involved parties and participants.
This initiative was the first in the MENA region
Table 1 Template Form for NCCN Guidelines Modification for the Middle East and North Africa
Page
Setting
Suggested Modifications
Justification
Reference
List page number in

NCCN Guidelines
Write specific clinical

setting in that page
Suggest modification
concisely and clearly
Explain the reason for

recommending the
modifications
List references
especially relevant to
the region
Supplement
Process of NCCN Guidelines Adaptation to MENA Region
with the goal of creating guidelines for standardizing cancer care across the countries. Although local
guidelines for certain diseases are available, collaboration across countries had not previously occurred
in the region.6
The credibility and experience of NCCN helped
move the process forward, in addition to strong interest from practicing oncologists in the region for
improving the standard of care and the realization
of the need for a collaborative approach. Having
NCCN experience and guidance coupled with the
diverse backgrounds and a high level of expertise
from the committee members was very complementary and productive. The interaction facilitated the
exchange of thoughts and ideas on how to approach
certain issues, and the experience was both educational and professionally stimulating.
Participants learned first-hand about the process
of guidelines adaptation and gained better insight
into the process of guideline development. During
the process, participants realized that regional evidence is lacking for many of the recommendations,
highlighting the need for future studies to address
the issue. Therefore, identifying top priority research
projects is a step in the right direction. The initiative generated obvious interest and enthusiasm, and
the hope is that further actions will materialize in
future meetings.
However, this initiative encountered challenges
related to the diversity of the participants backgrounds. Countries in the region have diverse socioeconomic and health care infrastructures, and span a
wide geographic area, presenting a logistic challenge
in getting members connected for group discussion.
This problem was minimized by using electronic
communication more frequently and giving each
committee chair the flexibility to select the timing
and venue of their committee meeting. The entire
group, including all the committees, convened in
person only once. The diversity in health care practices, resources, and infrastructures (e.g., access to
care and medications) also presented challenges to
implementation of standardized guidelines.
To maintain NCCN standards, the best available

evidence was adopted irrespective of cost-effectiveness or availability of resources. This approach was
adopted so that standards were not lowered to meet
the situation in deprived areas; the group avoided
making convenience guidelines. To improve the
standard of care, the group decided to include an
ideal target and allow each country or even each institution to decide what practice is suitable for them.
This initiative was not intended to develop guidelines for countries with limited resources, as had others.7 Notably, many countries in the region are not
among those with limited resources.
Conclusions
This initiative is still in its infancy. However, as with
any large-scale pioneer projects that face many challenges, the positive impact that it will have on the
thousands of cancer patients will serve as motivation
to the participants who already demonstrated enthusiasm and commitment.
References
1. McGivney WT. The National Comprehensive Cancer
Network: present and future directions. Cancer 1998;82(10
Suppl):20572060.
2. Winn RJ, Botnick W, Dozier N. The NCCN Guidelines
Development Program. Oncology (Williston Park) 1996;10(11
Suppl):2328.
3. Winn RJ, Botnick WZ. The NCCN Guideline Program: a
conceptual framework. Oncology (Williston Park) 1997;11:2532.
4. Winn RJ. National Comprehensive Cancer Network. Oncology
(Williston Park) 2000;14:26262630.
5. Jiang ZF, Wang T. An interpretation of the China edition of
National Comprehensive Cancer Network (NCCN) clinical
practice guideline for breast cancer. Zhonghua Wai Ke Za Zhi
2009;47:485487 [in Chinese].
6. Jazieh A. The process of guideline development. Ann Thorac Med
2008;3:6061.
7. Anderson BO, Yip CH, Smith RA, et al. Guideline implementation
for breast healthcare in low-income and middle- income countries:
overview of the Breast Health Global Initiative Global Summit
2007. Cancer 2008;113(8 Suppl):22212243.
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Modification and Implementation of NCCN

GuidelinesTM on Breast Cancer in the
Omalkhair Abulkhair, MD;a Nagi Saghir, MD;b Lobna Sedky, MD;c Ahmed Saadedin, MD;d Heba Elzahwary, MD;e
Neelam Siddiqui, MD;f Mervat Al Saleh, MD;g Fady Geara, MD;h Nuha Birido, MD;i Nadia Al-Eissa, MD;j
Sana Al Sukhun, MD;k Huda Abdulkareem, MD;l Menar Mohamed Ayoub, MD;m Fawaz Deirawan, MD;n
Salah Fayaz, MD;o Alaa Kandil, MD;p Sami Khatib, MD;q Mufid El-Mistiri, MD;r Dorria Salem, MD;s
El Siah Hassan Sayd, MD;t Mohammed Jaloudi, MD;u Mohammad Jahanzeb, MD;u and William I. Gradishar, MD;v
Riyadh, Kingdom of Saudi Arabia; Beirut, Lebanon; Giza, Egypt; Cairo, Egypt; Lahore, Pakistan; Kuwait, Kuwait;
Khartoum, Sudan; Damman, Kingdom of Saudi Arabia; Amman, Jordan; Damascus, Syria; Alexandria, Egypt;
Benghazi, Libya; Al Ain, United Arab Emirates; Memphis, Tennessee; and Chicago, Illinois
Key Words
Middle East and North Africa, breast cancer
Abstract
Published data from the Middle East and North Africa (MENA) region indicate suboptimal quality of cancer care, while the World
Health Organization predicts an increase in cancer cases in developing countries. Major advances in breast cancer management
mandate the development of guidelines to improve the quality
and efficacy of oncology practice in the MENA region. A Breast
Cancer Regional Guidelines Committee was organized and activated, comprising experts from various regional cancer institutions. The multidisciplinary team included 12 medical oncologists,
3 radiation oncologists, 2 radiologists, 2 surgeons, and 1 pathologist. The committee members agreed on adapting the current
NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines)
From the aDepartment of Oncology, King Saud bin Abdulaziz University
for Health Sciences, Riyadh, Kingdom of Saudi Arabia; bDepartment
of Internal Medicine, American University of Beirut, Beirut, Lebanon;
c
Clinical Oncology Department, Faculty of Medicine, Cairo University,
Giza, Egypt; dDepartment of Oncology, Armed Forces Hospital, Riyadh,
Kingdom of Saudi Arabia; eDepartment of Oncology, National Cancer
Institute, Cairo, Egypt; fDepartment of Oncology, Shaukat Khanum
Memorial Cancer Hospital and Research Center, Lahore, Pakistan;
g
Department of Surgery, Kuwait University, Kuwait, Kuwait; hDepartment
of Radiation Oncology, American University of Beirut, Beirut, Lebanon;
i
Department of Surgery, Khartoum Breast Care Center, Khartoum, Sudan;
j
Department of Radiology, King Fahad Specialist Hospital, Dammam,
Kingdom of Saudi Arabia; kDepartment of Oncology/Hematology,
University of Jordan, Amman, Jordan; lHematology/Oncology Unit,
King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia;
m
Department of Pathology, Cairo University, Cairo, Egypt; nNuclear
Medicine Center, National Cancer Institute, Damascus, Syria; oBreast Unit,
Kuwait Cancer Center, Kuwait, Kuwait; pDepartment of Clinical Oncology
& Nuclear Medicine, Alexandria School of Medicine, Alexandria, Egypt;
q
Medical Oncology, King Hussein Institute for Biotechnology and
on Breast Cancer for use in the MENA region to achieve common

practice standards for treating patients. The members suggested
several modifications to the guidelines, especially those related to
risk factor profiles. United Statesbased NCCN experts reviewed
these recommendations before final approval. The MENANCCN
Breast Cancer Guidelines modification process was the first initiative in the development of common practice guidelines in the region. This project may serve as a foundation for the development
of evidence-based practice standards, and improve collaborative
projects and initiatives. (JNCCN 2010;8[Suppl 3]:S8S15)
Breast cancer is the most common malignant disease

in women, with an increasing incidence worldwide,
especially in developing countries such as the Middle
East and North Africa (MENA) region.13 However, the
mortality rate has declined dramatically in developed
Cancer, Amman, Jordan; rFaculty of Medicine, Garyounis University,
Benghazi, Libya; sDepartment of Radiology, Cairo University, Cairo,
Egypt; tDepartment of Oncology, Tawam Hospital, Al Ain, United Arab
Emirates; uDepartment of Medical Oncology, Tawam Hospital, Al Ain,
United Arab Emirates; vUniversity of Tennessee, Memphis, Tennessee; and
w
Northwestern University, Chicago, Illinois.
Drs. Abulkhair, Saghir, Sedky, Saadedin, Elzahwary, Siddiqui, Al Saleh,
Geara, Birido, Al-Eissa, Al Sukhun, Abdulkareem, Ayoub, Deirawan,
Fayaz, Kandil, Khatib, El-Mistiri, Salem, Sayd, Jaloudi, and Gradishar
have disclosed that they have no financial interests, arrangements, or
affiliations with the manufacturers of any products discussed in the
article or their competitors. Dr. Jahanzeb has disclosed that he is on the
speakers bureau and an advisor for GlaxoSmithKline, Genentech, Inc.,
and sanofi-aventis.
Correspondence: Omalkhair Abulkhair, MD, Division of Adult Medical
Oncology, Department of Oncology, King Abdulaziz Medical City, King
Saud bin Abdulaziz University for Health Sciences, Riyadh, Kingdom of
Saudi Arabia. E-mail: abulkhairo@ngha.med.sa
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Breast Cancer
countries, including the United States, Canada,

Australia, and Europe. This reduction could be attributed to the efficacy of mammography in detecting early-stage breast cancer,4,5 and to the introduction of adjuvant systemic therapy.6
All published clinical epidemiologic data on
breast cancer in the MENA region are based on
hospital-based registries. Nonetheless, most of the
regional and national registries are published as an
annual report in a booklet format.3,7
Breast cancer represents 14% to 42% of all cancers in Arab women. Age-adjusted standardized incidence rates (ASR) were reported to vary from 9.5
to 50 cases per 100,000 women per year. Median age
at presentation is 48 to 52 years, with 50% of cases
in women younger than 50 years compared with 25%
in developed countries, and 50% of the cases are in
women older than 63 years.4,5 Therefore, women in
Arab countries seem to present with breast cancer
almost 10 years earlier than in the United States and
Europe.
The ASR for breast cancer has increased in
many countries in the region, such as Lebanon (20
in 1996, 46.7 in 1998, and 69 in 2003), Jordan (from
7.6/100,000 women in 1982 to 32.8/100,000 in
1997), Palestine (increased by 93%), and Egypt (up
to 49.6). Reports from the Gulf Center for Cancer
Registration (GCCR) presented data from 6 Gulf
countries: Kingdom of Saudi Arabia (KSA), United
Arab Emirates (UAE), Kingdom of Bahrain, Sultanate of Oman, State of Qatar, and State of Kuwait.
The GCCR data showed that breast cancer was

the most common cancer in the GCCR states from
January 1998 to December 2005, with 8349 breast
cancers registered from all GCCR states, accounting for 11.6% of all malignancies and 23.2% of all
female cancers. The overall breast cancer ASR for
all GCCR states was 18.2 per 100,000 population.
Although Bahrain reported the highest incidence
of breast cancer, it was the pioneer in establishing
a National Screening Program for detecting breast
cancer at a very early stage. The ASR per 100,000
women was 53.4 for Bahrain, followed by Qatar
(48.2), Kuwait (46.6), UAE (22.8), Oman (17.5),
and KSA (14.8;8 Figure 1).
Although these rates are low compared with
those in developed countries, they are rising and expected to reach levels similar to those in Western
countries. Many factors can attribute to this rise,
including improvement in health care with subsequent prolonged life expectancy, delayed age of marriage and first pregnancy, and decline in breast feeding. Recent socioeconomic changes have resulted
in a sedentary modified lifestyle, such as increased
prevalence of tobacco use, decreased physical activity, and unhealthy diet consisting of fatty fast food.
Advanced disease is commonly seen at diagnosis,
whereas ductal carcinoma in situ (DCIS) represents
fewer than 5% of the cases.3,7,8 (Figure 2). Factors
contributing to late presentations include decreased
awareness, lack of knowledge, and social factors such
as shyness, fear of divorce stigma, and low index of
60
ASR per 100,000
50
40
30
20
10
0
KSA
Oman
UAE
Kuwait
Qatar
Bahrain
GCC
Figure 1 Age standardized incidence rate (ASR) of female breast cancer in the Gulf Cooperation Council States, 19982005.
Abbreviations: GCC, Gulf Cooperation Council; KSA, Kingdom of Saudi Arabia; UAE, United Arab Emirates.
From Al-Madouj AN, Al-Zahrani AS. Eight-year cancer incidence among nationals of the GCC states: 19982005. Gulf Center for
Cancer Registration, 2005. Available at: http://www.sgh.org.sa/PDF/cancer%201998-2005.pdf. Accessed June 8, 2010.
Journal of the National Comprehensive Cancer Network | Volume 8 Supplement 3 | Juy 2010
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Abulkhair et al.
suspicion by primary physicians.9

Two publications from Saudi Arabia and
Lebanon reported that young age at presentation
(> 3539 years) was associated with poor prognosis10,11 (Figure 3).
Health care standards vary among different areas
within the region, and the quality of care depends
on many factors, including where the patient lives
and how long it takes for the patient to reach the
cancer center and undergo treatment. Although a
wide range of breast cancer treatment approaches are
available in the MENA region, primary prevention is
still rarely practiced and secondary prevention (i.e.,
screening and early detection) is applied sporadically in many countries that lack regular inspection
strategies, quality control, and licensing for screening centers. A few national screening programs were
initiated in the past 2 to 3 years in Bahrain, Egypt,
KSA, and Kuwait. However, efforts should be made
to study detection rates, screen-initiated testing, biopsies results, and outcomes.10,11
One small retrospective single-institution study
in Qasseem, KSA showed that the quality of care
provided to breast cancer patients did not meet international standards, possibly because of nonavailability of some resources, the absence of local guidelines, and small sample size.12
Radiation therapy centers in the region are scarce
and mostly available in major cities, and many young
women do not undergo breast-conserving surgery
11.4
20.9
20.7
47.0
Localized
Distant
Regional NOS
Unknown
Figure 2 Stage distribution of breast cancer, 19982005.

From Al-Madouj AN, Al-Zahrani AS. Eight-year cancer
incidence among nationals of the GCC states: 19982005.
Gulf Center for Cancer Registration, 2005. Available at: http://
www.sgh.org.sa/PDF/cancer%201998-2005.pdf. Accessed June
8, 2010.
because of lack of access to radiotherapy facilities

(Table 1). Furthermore, a multidisciplinary approach
is applied only in major cancer centers. In general,
there is a marked deficiency in supportive care systems, trained social workers, health educators, and
plastic surgeons to perform breast reconstruction.
Based on international studies, adjuvant therapy
includes chemotherapy, targeted therapy with trastuzumab, and hormonal therapy.1315 In countries with
limited resources, anthracyclines and taxanes are the
1.00
1.0
0.8
0.75
0.6
DFS
Cumulative Survival
Breast Cancer
0.5
Age > 40
Age 40
3549
above 50
below 35
3549-censored
above 50-censored
below 35-censored
0.2
0.50
0.25
P = .035
0.0
0.00
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
0.0
2.5
5.0
Follow Up Time (Years)
7.5
10.0
12.5
15.0
Years
Figure 3 Relation of young age to worse prognosis in breast cancer.

Abbreviation: DFS, disease-free survival.
From El Saghir NS, Seoud M, Khalil MK, et al. Effects of young age at presentation on survival in breast cancer. BMC Cancer
2006;6:194; and Elkum N, Dermime S, Ajarim D, et al. Being 40 or younger is an independent risk factor for relapse in operable
breast cancer patients: the Saudi Arabia experience. BMC Cancer 2007;7:222.
17.5
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Breast Cancer
Table 1 Radiation Therapy Centers in the Arab Countries Compared With United States (Equivalent

in Population Numbers)
Countries
Population
Radiation Treatment Centers
Radiation Oncologists
Radiation Technologists
Arab
301,227,000
87*
325
490
United States
298,213,000
1875
3068
5155
*Source: International Atomic Energy Agency IAEA 2007 (www.iaea.org)

Adapted and updated from El Saghir NS, Khalil MK, Eid T, et al. Trends in epidemiology and mangament of breast cancer in
developing Arab countries: a literature and registry analysis. Int J Surg 2007;5:225233.
most commonly used drugs, either in combination or

sequentially, according to the recommendations of
the Breast Health Global Initiative (BHGI).16
However, locally advanced breast cancer is treated with neoadjuvant chemotherapy, mainly an anthracycline/taxane-based regimen, to improve breast
conservation rates and increase complete pathologic
remission.17,18 In HER2-positive tumors, chemotherapy with targeted trastuzumab yields higher rates of
clinical and pathologic remissions.19 Evidence shows
that patients with less residual disease or who experience complete pathologic response tend to have
better survival.20 However, preoperative therapy in
early-stage breast cancer requires availability of adequate radiologic and pathologic evaluation is limited
in some MENA region countries.21
With many major advances in breast cancer
therapy and the WHO expectation of an increase in
cancer cases in developing countries, a pressing need
exists for the MENA region to develop guidelines for
breast cancer management. This explains the interest in participating in NCCN Guidelines development to improve the quality of oncology practice in
the region.
Material and Methods

The global need for comprehensive and evidencebased guidelines has encouraged the NCCN administration to expand their experience to include other regions such as China, Japan, and, recently, the
MENA region.
In November 2008, the MENA Breast Cancer
Regional Guidelines Committee (BCRGC) was organized and activated. The members are prominent experts representing various regional cancer institutions,
and included 12 medical oncologists, 3 radiation oncologists, 2 radiologists, 2 surgeons, and 1 pathologist.
The committee members reviewed the 2009
NCCN Clinical Practice Guidelines in Oncology

(NCCN Guidelines) on Breast Cancer and suggested modifications suitable to the region. These modifications were discussed among the group members
and with a United Statesbased NCCN expert to
establish the final version.
Results
After a series of meetings, members of the BCRGC
reached agreement on a few modifications to the
guidelines based on the state of breast cancer care in
the region. These suggestions, which were presented
during the second NCCNMENA conference held
in Abu Dhabi from April 23 to 26, 2009, emphasized
5 major modifications:
Diagnosis at age younger than 40 years should
be considered an independent risk factor of
poor prognosis.
Staging workup for stage IIB breast cancer should
include bone scan and CT of the chest and abdomen as the standard of care, not optional.
For DCIS, lumpectomy without radiation is not
considered acceptable because of risk for recurrence.
Adjuvant radiotherapy for locoregional stages I and
IIA should be given after systemic chemotherapy.
Several clinical research plans were suggested to
prioritize a database bank for breast malignancies in the MENA region.
Specific Recommended Modifications

The committee recommended several modifications
to the 2009 NCCN Guidelines on Breast Cancer for
use in the MENA region.
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Abulkhair et al.
DCIS
Invasive Breast Cancer
Radiation Therapy
Workup
Recommendations: Delete lumpectomy without radiation.

Justification: Patients who undergo lumpectomy
without radiation have been shown to have a high
risk for relapse.2224
Margin Status
Recommendations: Hospitals should have guidelines for the assessment of margins. Surgeons should
ink specimen margins to enable pathologists to provide better assessment.
Justification: Most hospitals in the MENA region do
not have written policies for handling of specimen
and inking of margins. Inking allows evaluation of
negativity and distance between tumor and margins.
Primary Status
Recommendations: Sentinel lymph node biopsy is

recommended for large DCIS (> 3 cm) and highgrade and extensive in situ disease.
Justification: Large and high-grade DCIS may harbor invasive disease.
The recommendation for performing sentinel
lymph node biopsy is based on the tumor size and
pathologic characteristics rather than type of surgery.
The type of surgery chosen (mastectomy vs. lumpectomy) may be based on tumor size but not always
(e.g., may be patient choice based on risk factors).
Genetic Counseling for High-Risk Women
Recommendations: Setup for infrastructure, genetic

counselors, and nurses is encouraged and should be
prepared along with laws to protect women and families with positive hereditary factors from discrimination at jobs and regarding insurance, particularly
health insurance policies.
Justification: These important elements for genetic
counseling are not currently available in the region,
but are very crucial components of a proper genetic
counseling process.
Adjuvant Tamoxifen (Surveillance/Follow-up)
Recommendations: Treatment with adjuvant

tamoxifen during surveillance and follow-up should
be considered a category 1 recommendation.
Justification: In contrast to the findings reported by
NSABP B-24, other studies have shown no benefit
associated with adjuvant tamoxifen in patients with
DCIS.25,26
Recommendations: Staging workup should be standard for stage IIA or IIB disease and not optional.
Justification: In clinical practice, physicians in the
MENA region encounter many patients with metastasis and node-negative stage IIA/IIB disease.
Adjuvant Therapy: Locoregional Treatment of
Clinical Stage I, IIA, or IIB Disease or T3, N1, M0
Recommendations: Recommendation should read

postchemotherapy radiation rather than consider
postchemotherapy radiation.
Justification: Postchemotherapy radiation is indicated because of risk for recurrence.27
Systemic Adjuvant Treatment: Hormone
ReceptorPositive/HER2-Positive Disease
Recommendations: Patient age younger than 40

years should be considered a risk factor.
Justification: Young age (< 40 years) has been shown
to be an independent factor for poor prognosis.10,11,28
ReceptorPositive/HER2-Negative Disease
Recommendations: Adjuvant chemotherapy should

be recommended for patients younger than 40 years.
Furthermore, adjuvant chemotherapy is recommended for moderately/poorly differentiated tumors,
and particularly in young patients with poorly differentiated tumors. Trastuzumab is given for HERpositive tumors.
Justification: Young age carries worse prognosis by itself,
especially if 21-gene reverse transcription-polymerase
chain reaction (RT-PCR) assay is not performed.10,11,28
For patients with poorly differentiated tumors,
young age was added as a criterion to emphasize the
need for aggressive therapy. According to 2 studies in
MENA region, young age was a contributing factor
for poor prognosis in patients with breast cancer.10,11
Referral to Adjuvant Hormonal Therapy and
Chemotherapy
Recommendations: Guidelines should specify that

patients should undergo adjuvant chemotherapy followed by adjuvant hormonal therapy.29
Justification: The recommendation becomes clearer
when it states that chemotherapy should be followed
by hormonal therapy. These therapies are not given
concurrently because hormonal therapy decreases
the effects of chemotherapy.29
Supplement
Breast Cancer
21-Gene RT-PCR
Recommendations: When recommending 21-gene

RT-PCR assay, specify when available.
Justification: Specifying when available is important because this procedure is listed as a category 2B
recommendation. The specimen must be shipped
overseas and the process is very costly. It may be more
important to have pathologists become more familiar and reliable in reporting readily available proliferation indices, such as mitotic counts and Ki67.30
Tumor Size Less Than 1 cm
Recommendations: Guidelines should be modified to recommend that young women with ERpositive breast cancer should always be given adjuvant tamoxifen hormonal therapy.
Justification: The committee suggested adding adjuvant hormonal therapy, specifying that young patients should always be given tamoxifen. Young age
is a poor prognostic factor and a large percentage of
patients in the MENA region are young (< 50 years)
and very young (< 35 years).
T1a
Recommendations: The committee suggested not

recommending adjuvant therapy except in the
footnote.
Justification: The committee suggested adding adjuvant hormonal therapy, specifying that young patients should always be given tamoxifen. Young age
is a poor prognostic factor and large percentage of
patients in MENA region are young (< 50 years) and
very young (< 35 years).7
Estrogren ReceptorPositive/HER2-Negative
Disease
Justification: Young age alone is an independent

factor associated with a worse prognosis.10,11,28 Up to
50% of patients with breast cancer in the MENA
countries are younger than 50 years.
Systemic Adjuvant Treatment: Favorable
Histopathologies
Recommendations: Adjuvant endocrine therapy

should be given for tumors less than 1 to 2.9 cm. Tumors 1 cm or smaller should be given no adjuvant
therapy, and tumors 1 cm or greater should be treated
with endocrine therapy.
Justification: No evidence exists for not giving adjuvant endocrine therapy to patients with tumors
1 to 2.9 cm. Therefore, hormonal therapy is recommended for all women with hormone receptor
positive tumors.
Preoperative Chemotherapy Guideline: Workup
Recommendations: Complete staging should be performed (chest/abdominal CT, bone scan) for stage
IIA/IIB disease even if laboratory tests are normal or
patients are asymptomatic.
Justification: In the committee members clinical experience, metastatic disease is discovered not
commonly in these patients.
Locally Advanced Invasive Breast Cancer:
Noninflammatory
Recommendations: Full staging should be performed

(chest/abdominal CT, bone scan), even in the absence
of symptoms or the presence of normal laboratory tests.
Justification: In the committee members clinical experience, metastatic disease is discovered frequently
in these patients.
Recommendations: Adjuvant hormonal therapy

should be given alone with tamoxifen plus leuteinizing hormonereleasing hormone (LHRA)
with zoledronic acid, at least in patients with
node-negative disease.
Justification: Results of the ABCSG-12 study
showed 94% survival in patients treated with hormonal therapy alone.31
Surveillance/Follow-Up

ReceptorNegative/HER2-Negative Disease
Recommendations: The committee members suggest adding consider checking 25-hydroxy vitamin
D levels.
Justification: Insufficient and deficient vitamin D levels have been associated with poorer outcome among
women with breast cancer in Canada.32 Aromatase inhibitors can cause secondary osteopenia and osteopo-
Recommendations: Adjuvant chemotherapy should

be recommended for patients younger than 40 years,
including those with stage IIB disease. Furthermore,
chemotherapy should be recommended for patients
with T1b, especially young women.
Recommendations: A history and physical examination should be performed every 3 months for the first
2 years, then every 4 to 6 months for 3 years, and
then annually.
Justification: Patients have a high recurrence rate in
the first 2 years.
Surveillance
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Abulkhair et al.
rosis in postmenopausal women. Because of traditional dress codes, a large number of women in the MENA
region do not get enough exposure to sunlight, and
studies have shown that despite living in sunny countries, women may have vitamin D deficiency because
of poor exposure to sunlight. Vitamin D levels should
be checked and may need to be corrected.32,33
Phyllodes Tumor
Phyllodes Tumor Recurrence: Treatment
Recommendations: Mastectomy is recommended

rather than re-excision.
Justification: Whole organ resection is the best option in case of recurrence.
Recurrent or Initial Workup for Stage IV
Recommendations: Rebiopsy at recurrence is

recommended.
Justification: This recommendation is made to confirm the diagnosis and tumor pathologic profile (estrogen receptor, progesterone receptor, and HER2
status).
Systemic Treatment of Recurrent or Stage IV
Disease
Recommendations: The committee recommends

administering adjuvant radiation therapy to supraclavicular lymph nodes. The committee also prefers
the term visceral disease over visceral crisis and would
rather classify treatment for asymptomatic visceral
disease based on either presence of minimal visceral
disease with a long disease-free interval or presence
of visceral disease, young age, multiple disease sites,
and a short disease-free interval. Therefore, the
treatment nodes would appear as:
Conclusions
The process of reviewing the NCCN Breast Cancer
Guidelines and discussing their applicability in the
MENA region was a unique and productive experience. As a result, the key opinion leaders in the breast
cancer field in the MENA region were able to provide their input and clinical recommendations that
might be more practical in daily use. Furthermore,
the committee members highlighted the deficiencies
in the standards of oncology practice and the urgent
need for a common database, and provided potential
research ideas. This experience is evidence of the
interest in and possibility of establishing a multidisciplinary working group, comprising representatives
from different countries, to improve cancer care in
the MENA region.
References
Asymptomatic
visceral
disease
Long disease-free
interval, minimal
visceral disease
(endocrine therapy if
not refractory)
Visceral, young
age, multiple site,
short diseasefree interval
(chemotherapy)
Justification: Radiation volumes for recurrence

should include all regional lymphatic basins. The
modified terminology was preferred because visceral
disease is understood as disease involving visceral
organs such as liver and lungs. The treatment classification was proposed because the presence of visceral disease with young age, multiple sites of disease, and short disease-free intervals is an indication
for chemotherapy.
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2007. CA

Cancer J Clin 57:4366.
2. Kamangar F, Dores GM, Anderson WF. Patterns of cancer
incidence, mortality and prevalence across five continents defining
priorities to reduce cancer disparities in different geographic
regions of the world. J Clin Oncol 2005;24:21372150.
3. Kingdom of Saudi Arabia Ministry of Health National Cancer
Registry. Cancer incidence report Saudi Arabia. Available at:
http://www.scr.org.sa. Accessed March 31, 2010.
4. Ries LA, Melbert D, Krapcho M, et al, eds. SEER Cancer Statistics
Review, 1975-2004, National Cancer Institute. Bethesda, MD.
Available at: http//seer.cancer.govt/cst/1975-2004, based on
November 2006 SEER data submission, posted to the SEER Web
site, 2007.
5. Jemal A, Ward E, Thun MJ. Recent trends in breast cancer
incidence rates by age and tumor characteristics among US women.
Breast Cancer Res 2007;9:R28.
6. Early Breast Cancer Trialists Collaborative Group (EBCTCG).
Effects of chemotherapy and hormonal therapy for early breast
cancer on recurrence and 15-year survival: an overview of the
randomized trials. Lancet 2005;365:16841717.
7. El Saghir NS, Khalil MK, Eid T, et al. Trends in epidemiology
and management of breast cancer in developing Arab countries: a
literature and registry analysis. Int J Surg 2007;5:225233.
Supplement
Breast Cancer
8. Gulf Center for Cancer Registration, 2005. Gulf Center for Cancer
Registration, 2005. Available at: http://www.sgh.org.sa/PDF/
cancer%201998-2005.pdf. Accessed March 31, 2010.
9. Lamyian M, Hydarnia A, Ahmadi F, et al. Barriers to and factors
facilitating breast cancer screening among Iranian women: a
qualitative study. East Mediterr Health J 2007;13:11601169.
0. Elkum N, Dermime S, Ajarim D, et al. Being 40 or younger is
1
an independent risk factor for relapse in operable breast cancer
patients: the Saudi Arabia experience. BMC Cancer 2007;7:222.
1
1. El Saghir NS, Seoud M, Khalil MK, et al. Effects of young age at
presentation on survival in breast cancer. BMC Cancer 2006;6:194.
1
2. Akhtar SS, Nadrah HM. Assessment of the quality of breast cancer
care: a single institutional study from Saudi Arabia. Int J Qual
Health Care 2005;17:301305.
1
3. Goldhirsch A, Wood WC, Gelber RD, et al. Progress and promise:
highlights of the international expert consensus on the primary
therapy of early breast cancer 2007. Ann Oncol 2007;18:1133
1144. Erratum in: Ann Oncol 2007;18:1917.
1
4. El Saghir NS, Hatoum H, Shamseddeen W, Shamseddine AI.
Prediction of prognosis and survival in early stage breast cancer
using the lymph node ratio of involved lymph nodes to the
total number of removed lymph nodes from the axilla [abstract].
Presented at 2007 Breast Cancer Symposium; September 78,
2007; San Francisco, California. Abstract 70.
1
5. Carlson RW, Allred DC, Anderson BO, et al. NCCN clinical
practice guidelines in oncology: breast cancer. Version 1, 2009.
The most recent version is available at: www.NCCN.org. Accessed
September 20, 2008.
1
6. Anderson BO, Yip CH, Smith RA, et al. Guideline implementation
for breast healthcare in low and middle income countries: overview
of the breast health global initiative summit 2007. Cancer
2008;113(8 Suppl):22212242.
1
7. Mauri D, Pavlidis N, Ionnidis JP. Neoadjuvant versus adjuvant
systemic treatment in breast cancer: a meta-analysis. J Natl Cancer
Inst 2005;97:188194.
1
8. Wolmark N. Preoperative chemotherapy, NSABP protocols
B-18 and B-27: an update. Available at: http://ctep.cancer.gov/
highlights/docs/wolmark.pdf. Accessed March 31, 2010.
1
9. Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher
pathological complete remission rate after neoadjuvant therapy
with trastuzumab, paclitaxel, and epirubicin chemotherapy: results
of a randomized trial in human epidermal growth factor receptor
2-positive operable breast cancer. J Clin Oncol 2005;23:3676
3685.
20. Escobar PF, Patrick R, Rybicki L, et al. Clinical predictors with
residual breast disease after primary induction chemotherapy
[abstract]. J Clin Oncol 2004;22(Suppl 1):Abstract 688.
21. El Saghir NS, Eniu A, Carlson RW, et al. Locally advanced breast
cancer: treatment guidelines with particular attention to low- and
middle-income countries. Cancer 2008;113(8 Suppl):23152324.
2
2. Wong JS, Kaelin CM, Troyan SL, et al. Prospective study of wide
excision alone for ductal carcinoma in situ of the breast. J Clin
Oncol 2006;24:10311036.
23. Kerlikowske K, Molinaro A, Cha I, et al. Characteristics associated

with recurrence among women with ductal carcinoma in situ
treated by lumpectomy. J Natl Cancer Inst 2003;95:16921702.
24. Wagner LI, Wang M, Miller K, et al. Health-related quality of life
among patients with metastatic breast cancer receiving paclitaxel
versus paclitaxel plus bevacizumab: results from the Eastern
Cooperative Oncology Group (ECOG) study E2100 [abstract].
Breast Cancer Res Treat 2006;100(Suppl 1):Abstract 5078.
25. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment
of intraductal breast cancer: National Surgical Adjuvant Breast
and Bowel Project B-24 randomised controlled trial. Lancet
1999;353:19932000.
26. Houghton J, George WD, Cuzick J, et al. Radiotherapy and
tamoxifen in women with completely excised ductal carcinoma
in situ of the breast in the UK, Australia and New Zealand:
randomized controlled trial. Lancet 2003;362:95102.
27. Guarneri V, Piacentini F, Frassoldati A, et al. A prognostic model
based on nodal status and Ki-67 predicts the risk of recurrence
and death in breast cancer patients with residual disease after
preoperative chemotherapy. Presented at the 31st Annual San
Antonio Breast Cancer Symposium; December 1014, 2008; San
Antonio, Texas.
28. Peppercorn J, Partridge AH. Breast cancer in young women: a new
color or a different shade of pink? J Clin Oncol 2008;26:3303
3305.
29. Albain K, Barlow W, Shak S, et al. Prognostic and predictive value
of the 21-gene recurrence score assay in postmenopausal, nodepositive, ER-positive breast cancer (S8814, INT0100). Presented
at 30th Annual San Antonio Breast Cancer Symposium; December
1316, 2007; San Antonio, Texas.
30. Ellis MJ, Luo J, Tao Y, et al. Tumor Ki67 proliferation index within
4 weeks of initiating neoadjuvant endocrine therapy for early
identification of non-responders. Presented at 32nd Annual San
Antonio Breast Cancer Symposium; December 912, 2009; San
Antonio, Texas.
31. Gnant M, Mlineritsch B, Schippinger W, et al. Endocrine therapy
plus zoledronic acid in postmenopausal breast cancer. N Engl J Med
2009;360:2367.
32. Goodwin P. Toronto researcher reveals vitamin D deficiency
associated with breast cancer [media release]. Toronto: The Samuel
Lunenfeld Research Institute of Mount Sinai Hospital, May 15,
2008.
33. El-Rassi R, Baliki G, El-Hajj Fulheihan G. Vitamin D status in
Middle East and Africa. [International Osteoporosis Foundation
Web site]. Available at: http://www.iofbonehealth.org/download/
osteofound/filemanager/health_professionals/pdf/Vitamin-Dreports/Vitamin_D-MEast_Africa.pdf. Accessed March 31, 2010.
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Guidelines on NonSmall Cell Lung
Cancer in the Middle East and North
Africa Region
Abdul-Rahman Jazieh, MD, MPH;a Hanaa Bamefleh, MBchB, FRCPC;b Ahmet Demirkazik, MD;c
Rabab Mohamed Gaafar, MD;d Fady B. Geara, MD, PhD;e Mansur Javaid, MD, FCCP, FRCP;f Jamal Khader, MD;g
Kian Khodadad, MD;h Walid Omar, MD;i Ahmed Saadeddin, MD;j Hassan Al Sabe, MD;k
Mohammad Behgam Shadmehr, MD;l Amgad El Sherif, MD, FCCP;m Najam Uddin, FRCR;n
Mohammad Jahanzeb, MD;o and David Ettinger, MD;p Riyadh, Kingdom of Saudi Arabia; Ankara, Turkey;
Cairo, Egypt; Beirut, Lebanon; Lahore, Pakistan; Amman, Jordan; Tehran, Iran; Damascus, Syria;
Al Ain, United Arab Emirates; Memphis, Tennessee; and Baltimore, Maryland
Key Words
Middle East and North Africa, lung cancer
Abstract
A lung cancer committee from the Middle East and North Africa
(MENA) region was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on NonSmall Cell
Lung Cancer to create a platform for standard care in the region.
The committee comprised different experts in thoracic oncology
from the region, including the disciplines of medical and clinical
oncology, radiation oncology, thoracic surgery, pulmonary medicine, radiology, and pathology. The committee reviewed version 2
of the 2009 NCCN Guidelines on NonSmall Cell Lung Cancer and
identified recommendations requiring modification for the region
using published evidence and relevant experience. These sug-
From the aDepartment of Oncology and bPathology, King Saud bin

Abdulaziz University for Health Sciences, Riyadh, Kingdom of Saudi Arabia;
c
Section of Medical Oncology, Ankara University, Cebeci Hastaneleri,
Ankara, Turkey; dDepartment of Medical Oncology, National Cancer
Institute, Cairo, Egypt; eRadiation Oncology, American University of Beirut
Medical Center, Beirut, Lebanon; fPulmonary & Critical Care, Shaukat
Khanum Memorial Cancer Hospital, Lahore, Pakistan; gRadiation Oncology,
King Hussein Cancer Center, Amman, Jordan; hThoracic Oncology Section,
National Institute of Tuberculosis and Lung Disease, Tehran, Iran; iNuclear
Medicine Unit, National Cancer Institute, Faculty of Medicine, Cairo, Egypt;
j
Department of Oncology, Riyadh Military Hospital, Riyadh, Kingdom of
Saudi Arabia; kAl Bieruni Cancer Hospital, Damascus, Syria; lDepartment of
Surgery, National Institute of Tuberculosis and Lung Disease, Tehran, Iran;
m
Cardiothoracic Surgery, Tawam Hospital, Al Ain, United Arab Emirates;
n
Department of Radiology, Shaukat Khanum Memorial Cancer Hospital
gested modifications were discussed among the group and with a

United Statesbased NCCN expert for approval. The recommended
modifications, with justification and references, were categorized
based on the NCCN Guidelines flow. This article describes these recommended modifications. The process of adapting the first NCCNbased guidelines in the region is a step toward helping to improve
lung cancer care in the region and encouraging networking and
collaboration. (JNCCN 2010;8[Suppl 3]:S16S21)
Lung cancer is the leading cancer worldwide; not only
in incidence but also in cancer-related death, with approximately 1.2 million cases diagnosed worldwide and
18% of cancer deaths related to lung cancer.1,2 In the
United States, lung cancer kills more people than the 3
most common cancers, namely breast, prostate, and co& Research Center, Lahore, Pakistan; oUniversity of Tennessee, Memphis,
Tennessee; and nThe Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins, Baltimore, Maryland.
Drs. Jazieh, Bamefleh, Demirkazik, Gaafar, Geara, Javaid, Khader,
Khodadad, Omar, Saadeddin, Al Sabe, Shadmeht, El Sherif, and Uddin
have disclosed that they have no financial interests, arrangements, or
affiliations with the manufacturers of any products discussed in the
article or their competitors. Dr. Jahanzeb has disclosed that he is an
advisory board member, member of the speakers bureau, or consultant
for Genentech, Inc.; sanofi-aventis; and GlaxoSmithKline. Dr. Ettinger has
disclosed that he is a consultant for Eli Lilly and Company; Genentech,
Inc.; and Pfizer Inc.
Correspondence: Abdul Rahman Jazieh, MD, MPH, Department of
Oncology (Mail Code 1777), P.O. Box 22490, Riyadh 11426, Kingdom of
Saudi Arabia. E-mail: jazieha@ngha.med.sa
Supplement
lon. However, the lung cancer epidemic is not limited to developed countries. Developing countries are
also seeing an increased lung cancer burden because
of the increased prevalence of the main risk factor:
tobacco use.3,4
Lung cancer varies in incidence and mortality
among countries, but in Western Asian countries it
is ranked number 1, and was number 3 in North African countries.5 It is number 1 in cancer incidence
in 7 of 13 Arab countries.6
Furthermore, available data indicate that lung
cancer is on the rise in many countries and that
its health toll will mirror, and even may exceed,
that of Western countries if tobacco control is not
properly addressed.
For example, in the Kingdom of Saudi Arabia,
lung cancer is the third most common cancer in men
and twelfth in women, with an age standardized rate
of 6.1 per 100,000 and 1.9 per 100,000, respectively.
Its incidence increased by 57% between 2001 and
2005,7 and was approximately 40% in Jordan around
the same period. In Egypt, lung cancer is the fourth
most common cancer in men and ninth in women.
According to the Gharbia Cancer registry, it represents 7.4% of all male and 2.7% of female malignancies. The Egyptian National Cancer Institute data
shows that the frequency of lung cancer was not different between 2001 and 2006.8
Current Status of Lung Cancer Care in

the Middle East and North Africa Region
The Middle East and North Africa (MENA) region is
diverse in many aspects, especially in economic background and health care infrastructure. Even within
the same country, disparities may be present in health
care resources and services. Therefore, no absolute
universal statement can be made about health care in
the region, although some common findings are descriptive of the status of lung cancer care in general.
The cancer care issues can be categorized into 5
areas that are related to the principles of oncology
care:9 cancer diagnosis, proper staging, offering curative treatment whenever possible, offering palliative
and supportive care when cure is not attainable, and
participation in clinical research.
Confirming Diagnosis
Bronchoscopy and CT scanguided biopsies are

available only in tertiary centers in major cities,
making tissue specimens difficult to obtain, although

they are possible in most countries.
The laboratories in the regions are equipped
for straightforward procedures, such as classic immunohistochemical staining, but generally are not
ready for more sophisticated tests, such as molecular
studies for customization of therapy (e.g., epidermal
growth factor receptor [EGFR] mutation analysis).
Staging
Proper staging of lung cancer is essential for management and prognosis, which may require invasive
procedures or imaging studies.
In the MENA region, mediastinoscopy is not
used as frequently as indicated because of lack of expertise, interest, or agreement on its value. CT scanning is generally available, more so than MRI. However, PET scans are scarce because many countries
do not have any machines, some have only one, and
few have more than one. Therefore, PET scanning is
not widely accessible.
Offering Curative Treatment
Providing curative treatment often requires a multimodality approach. However, multidisciplinary

teams and tumor boards are not widely used and
there is shortage of properly trained thoracic surgeons in the region.
Regarding treatment, adjuvant chemotherapy is
not standard practice across the region, and many
logistical challenges make concurrent chemotherapy
and radiotherapy difficult to offer in some settings,
including the fact that a shortage exists of adequate
radiotherapy machines and expertise.
Palliative Treatment
Systemic Therapy: The MENA region has issues related to access to care, in that tertiary centers may
not accept patients with metastatic cancer, instead
directing resources toward curable cancers. Furthermore, access to routine chemotherapy is limited
in many countries and is even more so for biologic agents. Some tertiary centers do not have new
biologic and targeted therapies for economic and
financial reasons.
Symptom Management: The MENA region has a
clear shortage of trained palliative care physicians
and support staff, in addition to lack of proper facilities. Access to pain medications such as morphine is
also challenging.
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Jazieh et al.
Participation in Research
Like other developing countries, participation in research in the region is limited to major centers in
some countries and plagued with many challenges,
such as lack of research culture, infrastructure, expertise, and funding.10
The Importance of Lung Cancer Guidelines
Although the described limitations and variations

may represent challenges to creating uniform guidelines, they are actually strong reasons to attempt to
establish these guidelines in effort to close the oncology practice gap in the region. Identifying these
limitations and variables is the first step toward addressing them.
Methodology
As a part of the initiative to adapt the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on NonSmall Cell Lung Cancer11 to the
MENA region, a lung cancer guidelines committee
was formed.
The committee comprises various experts in thoracic oncology, including medical and clinical oncology, radiation oncology, pulmonology medicine, thoracic surgery, radiology, and pathology. The committee
convened twice and corresponded frequently electronically. They reviewed the second version of the
2009 NCCN Guidelines thoroughly, identified items
requiring modification for the region, and considered
justification and references. Adherence to NCCN
Guidelines principles and structure was required, with
emphasis on the same categories of evidence and consensus as justification for adopting a modification.
A summary of the suggested modifications was
then discussed thoroughly with the NCCN experts
to reach an agreement on the recommendations and
understand the mechanism and rationale of some
of the United States guidelines recommendations.
Furthermore, the committee members were asked to
identify a priority list of research projects for the region. This article summarizes these recommendations.
Recommended Modifications
The committee recommended the following modifications to the second version of the 2009 NCCN
Guidelines on NonSmall Cell Lung Cancer for the
MENA region.
Initial Evaluation: Chemistry Profile
Recommendations: The committee suggested specifying the tests constituting the chemistry profile,
including at least calcium, albumin, alkaline phosphatase, lactate dehydrogenase, renal function, and
liver function tests such as total bilirubin, alanine
aminotransferase, and aspartate aminotransferase.
Justifications: To prevent requesting unnecessary
laboratory tests and to emphasize obtaining valuable
laboratory tests that may have an impact on prognosis, may reflect the presence of distant metastases, or
might impact treatment choice.
Clinical Stage IIIB, T4 (Pleural or Pericardial
Effusion)
Recommendations: The term malignant should be

placed before pleural or pericardial effusion for stage
IIIB, T4.
Justifications: All pleural/pericardial effusions are
not necessarily malignant, and only malignant fluids
meet the criteria for T4, although this stage will be
reclassified as stage IV in the seventh edition of the
TNM staging system.12
Pretreatment Evaluation: Stage I (Peripheral T2,
N0 and Central T12, N0) and Stage II (T12, N1)
Recommendations: Add endoscopic and endobronchial ultrasound procedures to the list of workup
procedures.
Justifications: These techniques can be alternative procedures for evaluation of mediastinal lymph
nodes, in addition to other mentioned procedures
and/or imaging.1318
Adjuvant Treatment, Stage IB, T2, N0, Margin
Negative (R0)
Recommendations: For the treatment option of chemotherapy, adding especially for tumor size T 4
cm is recommended.
Justifications: Based on updated results of CALGB
9633, patients with tumors 4 cm or larger will benefit
from chemotherapy,19 although many of these cases
will be reclassified as stage II in the seventh version
of the TNM staging system.
Adjuvant Treatment, Stage IIIA, T12, N2, Margin
Negative (R0)
Recommendations: The committee suggested changing the recommendation for Chemotherapy + mediastinal RT to chemotherapy +/ mediastinal RT as a
category 2B recommendation.
Justification: The committee questioned whether ad-
Supplement
juvant mediastinal radiotherapy (RT) is necessary for

all patients at this stage after mediastinal lymph node
dissection (not sampling), and suggested that perhaps
only high-risk groups should be considered for adjuvant
mediastinal RT for multilevel involvement of mediastinal lymph nodes or extracapsular spread, or for inadequate lymph node dissection.
Adjuvant RT
Recommendations: Do not include recommendation of chemoradiation for N1 disease with adverse

factors (category 3)
Justification: Studies have shown that postoperative
RT is detrimental in N1 disease.20
All Stages of Positive Margins (R1, R2)
Recommendations: For all stages of positive margins, the committee suggested adding If resection is
not possible after recommendation for chemoradiotherapy. For stage IA, committee suggested adding
if chemoradiotherapy is not feasible after RT, followed by chemotherapy.
Justification: All residual disease that is not resectable should be practically treated like unresectable
stage III, with concurrent chemoradiotherapy as the
preferred modality.
Initial Treatment: Superior Sulcus Tumor T34,
N01
Recommendations: The committee suggested adding surgery alone as an initial modality (category 3
recommendation).
Justification: This NCCN recommendation is based
on a phase II study that did not compare chemoradiation followed by surgery with surgery alone and
does not eliminate surgery as a valid initial treatment
option for resectable disease.21
Initial Treatment: Chest Wall, Proximal Airway, or
Mediastinum, T34, N01
Recommendations: The committee suggested adding

an option for unresectable tumors, with initial treatment
as concurrent chemoradiotherapy + chemotherapy.
Justification: In some cases in this stage, the initial
workup determines that the tumor is not completely
resectable. In these cases, the preferred treatment
could be a multimodality option of chemoRT followed by chemotherapy and preclude an unnecessary operation. According to the current NCCN
algorithm all of these patients must undergo surgery.
Initial Treatment: T1-2, N2 Nodes Positive,

Negative for M1 Disease
Recommendations: The committed suggested adding especially responders after surgery for patients with no progression.
Justification: Patients responding to treatment are
more likely to benefit from surgery more than those
with stable disease.
Performance Status 3 and 4
Recommendations: The committee suggests separating recommendations for performance stage (PS) 3
and 4, with erlotinib or single-agent chemotherapy
(category 2B) recommended for PS 3 and palliative
care for PS 4.
Justification: Because erlotinib has activity in previously treated patients with PS 3, it probably will
have some benefits as first-line treatment. Committee
members had encouraging experience with singleagent erlotinib in these patients.22
Therapy for Recurrence and Metastases: Cycle 1
Recommendations: The committee suggested deleting tumor response evaluation after cycle 1, and
adding a footnote after cycle 2 stating if symptoms
suggestive of disease progression, evaluation can be
done after 1 cycle.
Justification: No strong evidence exists for performing response evaluation after one cycle; however,
this will save patients with symptoms suggesting disease progression from undergoing further treatment
that will prove futile.
Therapy for Recurrence and Metastases:
46 Cycles (Total)
Recommendations: The committee suggested deleting or until disease progression (category 2B),
changing the recommendation to 4 cycles for stable
disease and up to 6 cycles for responders, and adding (category 2B) or docetaxel for all histology after
squamous histology.
Justification: No evidence shows benefit of therapy
beyond 4 to 6 cycles of the same chemotherapy,23 and
new evidence shows maintenance with premetrexed
(for nonsquamous carcinoma) and docetaxel.24,25
Performance Status 02 and 34
Recommendations: The committee recommended that

erlotinib be considered in patients with PS 0 through 3
after first progression. They also suggested separating
PS 3 from PS 4, with the recommendation to give erlotinib to patients with PS 3 if not given previously, and
S-19
S-20
Supplement
Jazieh et al.
offering palliative care to patients with PS 4.

Justification: The BR21 study,22 which showed a survival benefit associated with erolotinib, included some
patients with PS 3, and the committee members reported similar results based on personal experience.
Principles of Surgical Resection
Recommendations: The committee suggested adding a bullet stating that Chemotherapy and radiation therapy are recommended to start between
46 weeks postoperatively, if patient recovered
from surgery.
Justification: This recommendation was made to assure full recovery from surgery and avoid unnecessary
delays.
Principles of Radiation Therapy
Recommendations: The committee recommends

adding Gross tumor volume can be reduced to postchemotherapy volume if there was reexpansion of
the lung after the first sentence of the bullet beginning In patients who receive induction chemotherapy, attempts should be made to obtain a baseline
planning CT prior to induction chemotherapy.
Justification: This modification was recommended
to decrease irradiation to expanded normal lung tissue and minimize lung toxicity.
Recommendations: The committee suggested modifying the radiation doses as follows:
Extracapsular nodal extension or microscopic
positive margins: 50 Gy
Gross residual tumor: 66 Gy
Definitive RT: 70 Gy
Definitive RT with concurrent chemotherapy:
6066 Gy
Justification: Data do not favor high doses for postoperative RT; they do not show a doseresponse relationship for RT in lung cancer except for hyperfractionation (which is uncommonly used currently).
However, RT with concurrent chemotherapy using
66 Gy has shown very good median survival.
Systemic Therapy for Advanced or Metastatic
Disease
First-Line Therapy: Recommendations: The committee suggested changing the statement that systemic
chemotherapy is not indicated in patients with PS 3
or 4 to patients with PS 3 may benefit from singleagent erlotinib. Single-agent chemotherapy can be
used in selected cases.
Second-Line Therapy: Recommendations: The com-
mittee recommended adding a new bullet stating

Gefinitib was shown to be noninferior to docetaxel
in second-line therapy.26
Future Research Ideas for MENA Region

During the discussion among committee members,
many information gaps were identified that can be
addressed through future research projects.
The following is a short list of projects the committee members indentified as important:
Epidemiology data collection on incidence, subtypes, and treatment patterns (registry)
Early detection/screening studies to address what
is the best recommendation
PET scan studies to determine best use of this
technology relevant to the region
Radiotherapy:
!! Stereotactic radio-surgery in lung cancer
management such as inoperable disease
!! Role of radiotherapy in N1 disease
!! Role of prophylactic cranial irradiation in
certain setting of stage III nonsmall cell
lung cancer
Molecular studies, such as ERCC1, RRM1,
EGFR, and Kras, in terms of their prevalence
and use in clinical research and practice (pharmacogenomic studies)
Validate phase III data from Western countries
in MENA population, in simple multisite studies to assure the capabilities to do research as a
group/network
Conclusions
MENANCCN Lung Cancer Guidelines development was a very enriching experience to participants
through providing in-depth exposure to the extensive NCCN experience. Furthermore, it helped develop the first regional guidelines and encouraged
networking. It also helped highlight the major gaps
in practice evidence in the region, allowing the committee to propose future research ideas. Future refinement of these guidelines to incorporate emerging
evidences and regional experiences is being planned.
Supplement
References
1. Parkin DM, Bray F, Ferlay J, Pisani P. Global cancer statistics, 2002.
CA Cancer J Clin 2005;55:74108.
2. Alberg AJ, Samet JM. Epidemiology of lung cancer. Chest
2003:123;21S49S.
3. Proctor RN. Tobacco and the global lung cancer epidemic. Nat
Rev Cancer 2001;1:8286.
4. Cooley ME, Kaiser LR, Abrahm JL, Giarelli E. The silent epidemic:
tobacco and the evolution of lung cancer and its treatment. Cancer
Invest 2001:19:739751.
5. International Agency for Research on Cancer. The GLOBOCAN
2002 Database. Available at: http://www-dep.iarc.fr/globocan/
database.htm. Accessed March 31, 2010.
6. Salim EI, Moore MA, Al-Lawati JA, et.al. Cancer epidemiology
and control in the Arab worldpast, present and future. Asian Pac
J Cancer Prev 2009;10:316.
7. National Cancer Registry, Saudi Arabia. Available at: http://
bportal.kfshrc.edu.sa. Accessed March 31, 2010.
8. National Cancer Institute: Egypt. Cairo Registry, 2006. Available
at: www.nci.edu.eg.
9. Jazieh AR. The principles of oncology care: back to basics. Am J
Clin Oncol 2009;32:330331.
10. Sumathipala A, Siribaddana S, Patel V. Under-representation
of developing countries in the research literature: ethical issues
arising from a survey of five leading medical journals. BMC Med
Ethics 2004;5:E5.
16. Herth FJ, Rabe KF, Gasparini S. Transbronchial and

transoesophageal (ultrasound-guided) needle aspirations for the
analysis of mediastinal lesions. Eur Respir J 2006;28:12641275.
17. El-Bayoumi E, Silvestri GA. Bronchoscopy for the diagnosis and
staging of lung cancer. Semin Respir Crit Care Med 2008;29:261
270.
18. Alberts WM; American College of Chest Physicians. Diagnosis
and management of lung cancer executive summary: ACCP
evidence-based clinical practice guidelines (2nd edition). Chest
2007;132:1S19S.
19. Strauss GM, Herndon JE II, Maddaus MA, et al. Adjuvant
paclitaxel plus carboplatin compared with observation in stage
IB non-small-cell lung cancer: CALGB 9633 with the Cancer
and Leukemia Group B, Radiation Therapy Oncology Group, and
North Central Cancer Treatment Group Study Groups. J Clin
Oncol 2008;26:50435051.
20. Dautzenberg B, Arriagada R, Chammard AB, et al. A controlled
study of postoperative radiotherapy for patients with completely
resected nonsmall cell lung carcinoma. Group dEtude et de
Traitement des Cancers Bronchiques. Cancer 1999;86:195196.
21. Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation
and surgical resection for non-small cell lung carcinomas of the
superior sulcus: initial results of the Southwest Oncology Group
trial 9416 (Intergroup trial 0160). J Thorac Cardiovasc Surg
2001;121:472483.
22. Shepherd FA, Rodrigues Pereira J, et al. Erlotinib in previously
treated non-small cell cancer. N Engl J Med 2005;353:123132.
11. Ettinger DS, Akerley W, Bepler G, et al. NCCN clinical practice

guidelines in oncology: non-small cell lung cancer. Version 2, 2009.
The most recent version is available at: www.NCCN.org. Accessed
September 20, 2008.
23. Socinski MA, Schell MJ, Peterman A, et al. Phase III trial
comparing a defined duration of therapy versus continuous therapy
followed by second-line therapy in advanced-stage IIIB/IV nonsmall-cell-lung cancer. J Clin Oncol 2002;20:13351343.
12. Rami-Porta R, Crowley JJ, Goldstraw P. The revised TNM staging

system for lung cancer. Ann Thorac Cardiovasc Surg 2009;15:49.
24. Ciuleanu T, Brodowicz T, Belani C, et al. Maintenance pemetrexed

plus best supportive care versus placebo plus best supportive care: a
randomised, double-blind, phase III study. Lancet 2009:374:1432
1440.
13. Herth F, Becker HD, Ernst A. Conventional vs endobronchial

ultrasound-guided transbronchial needle aspiration: a randomized
trial. Chest 2004;125:322325.
14. Herth FJ, Eberhardt R, Vilmann P. Real-time endobronchial
ultrasound guided transbronchial needle aspiration for sampling
mediastinal lymph nodes. Thorax 2006;61:795798.
25. Fidias PM, Dakhil SR, Lyss AP, et al. Phase III study of immediate
compared with delayed docetaxel after front-line therapy with
gemcitabine plus carboplatin in advanced non-small-cell lung
cancer. J Clin Oncol 2009;27;591598.
15. Herth FJ, Ernst A, Eberhardt R. Endobronchial ultrasoundguided transbronchial needle aspiration of lymph nodes in the
radiologically normal mediastinum. Eur Respir J 2006;28:910914.
26. Maruyama R, Nishiwaki Y, Tamura T, et al. Phase III study, V-15-32,

of gefitinib versus docetaxel in previously treated Japanese patients
with non-small-cell lung cancer. J Clin Oncol 2008;26:42444252.
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Supplement

Guidelines on Colon Cancer in the
Fikri li, MD;a Hakan Akbulut, MD;a Shouki Bazarbashi, MD;b Mehmet Ayhan Kuzu, MD;c
Mohandas K. Mallath, MD;d Kakil Ibrahim Rasul, FRCP Edin;e Scott Strong, MD;f Aamir Ali Syed, FRCS;g
Faruk Zorlu, MD;h and Paul F. Engstrom, MD;i Ankara, Turkey; Riyadh, Kingdom of Saudi Arabia;
Mumbai, India; Doha, Qatar; Abu Dhabi, United Arab Emirates; Lahore, Pakistan; and Philadelphia, Pennsylvania
Key Words
NCCN Clinical Practice Guidelines in Oncology NCCN Guidelines,
Middle East and North Africa, colorectal cancer, colon cancer
Abstract
Colorectal cancer is less common in the Middle East and South Asia
than in western countries, with the rectum the most common primary site, unlike in the United States. A project was planned to address various local issues regarding the management of common
cancers, including colorectal cancer, and to adapt the NCCN Clinical
Practice Guidelines in Oncology (NCCN Guidelines) to the Middle
East and North Africa (MENA) region. A survey of oncologists in
this geographic area showed that the management practices and
issues regarding colorectal cancer are similar to those presented
in the NCCN Colorectal Cancer Guidelines. However, 2 major differences exist: most oncologists in the MENA region prefer chest
radiograph over CT in pretreatment workup, and almost 50% of
From aAnkara University Medical School, Ankara, Turkey;

b
Section of Medical Oncology, King Faisal Specialist and Research
Centre, Riyadh, Kingdom of Saudi Arabia; CUniversity of Ankara,
Department of Surgery, Ankara, Turkey; dTata Memorial Center,
Mumbai, India; eHamad Medical Corporation, Al-Amal Hospital,
Doha, Qatar; fSheikh Khalifa Medical City, Abu Dhabi, United
Arab Emirates; gShaukat Khanum Memorial Cancer Hospital and
Research Centre, Lahore, Pakistan; hHacettepe University Medical
School, Ankara, Turkey; and iFox Chase Cancer Center, Philadelphia,
Pennsylvania.
Drs. li, Akbulut, Bazarbashi, Kuzu, Rasul, Strong, Syed, and Zorlu
have disclosed that they have no financial interests, arrangements,
or affiliations with the manufacturers of any products discussed
in this article or their competitors. Dr. Mallath has disclosed that
he has received research funding from GlaxoSmithKline, Amgen
Inc., Merck & Co., Inc., and Pfizer Inc. Dr. Engstrom has disclosed
that he is an advisory board member for Novartis Pharmaceuticals
Corporation.
Correspondence: Fikri li, MD, Department of Medical Oncology,
Ankara University School of Medicine, Cebeci Hastanesi, Dikimevi,
Ankara 06590, Turkey. E-mail: Fikri.icli@medicine.ankara.edu.tr
them prefer to use cetuximab in the first-line treatment of patients with the wild-type KRAS gene. The committee, comprising
9 oncologists from different countries, proposed 4 modifications
to the 2009 version of the NCCN Colorectal Cancer Guidelines for
use in the MENA region, relating to 1) short-course preoperative
radiotherapy, 2) dose of capecitabine, 3) stereotactic radiotherapy
for liver metastasis, and 4) qualification of surgeons performing
colorectal surgery. The modification of NCCN Colorectal Cancer
Guidelines for use in the MENA region represents a step toward
creating a uniform practice in the region based on evidence and
local experience. (JNCCN 2010;8[Suppl 3]:S22S25)
Colorectal cancer is less common in the Middle East and
South Asia region than in the United States (Table 1).

However, it is among the 10 most common cancer types
in all the countries.1 The age-standardized incidence rate
is below 10 per 100,000 in most countries in this region,
and ranges between 10 to 40 per 100,000 in a few countries such as Turkey, Qatar, Kuwait, and Israel.1
In a study from Turkey, one third of patients were
younger than 50 years, and the rectum was the most common site of occurrence (42.5%), followed by the sigmoid
colon (23.2%).2 The epidemiologic features are similar in
India.3 However, in a study from Qatar, the descending
and sigmoid colon were the most common sites.4
Although the management of colorectal cancer
should ideally be based on evidence-based medicine, standardized practices do not exist in other parts of the world.
The social, cultural, and economic differences among the
countries may be responsible for this lack of standard management. The paucity of local randomized trials from the
Supplement
Colon Cancer
Table 1 Colorectal Cancer Age Standardized

Rate per 100,000 Population
Country
Men
Women
Egypt
6.3
4.3
Lebanon
5.5
4.2
Syria
8.0
5.1
Qatar
31.7
7.7
Kuwait
15.0
14.5
United Arab Emirates
5.8
6.3
Kingdom of Saudi Arabia
8.3
6.3
Pakistan
7.8
5.2
India
4.7
3.2
Israel
40.6
32.7
Turkey
19.7
11.9
Data from Borchana et al.5
region adds to the difficulty in following new developments and innovations. However, the need for guidelines that are compatible with evidence-based medicine and social, cultural, and economic realities of the
MENA region cannot be denied. The NCCNMENA
project was established to address this need.
Methods and Results

The colorectal cancer committee comprised 9 members from 6 different countries who collected the data
and participated in the deliberations. A survey with 11
questions related to the management of colorectal cancer was prepared and sent to all members to determine
the patterns of care and compatibility with the 2009
version of the NCCN Clinical Practice Guidelines in
Oncology: Colorectal Cancer (to view the most recent
version of these guidelines, visit the NCCN Web site
at www.NCCN.org). The survey was distributed to
24 well-known gastrointestinal oncologists in Turkey,
and personal opinions were obtained from members in
Qatar, United Arab Emirates, and India; Table 2 summarizes the results. Answers from most oncologists in
Turkey and committee members from other countries
were generally in accordance with the NCCN Guidelines, except those related to questions number 1 and
10. According to the results, 69% did not perform
routine chest CT before surgery for all patients with
colon cancer. With regard to first-line chemotherapy
for metastatic colorectal cancer, 47% of those surveyed
preferred to use cetuximab in addition to chemother-
apy as first-line treatment in patients with wild-type

KRAS tumors.
Committee members met on March 8, 2009, in
Istanbul to discuss the survey results and other issues,
including proposals for adapting the NCCN guidelines
to the MENA region. The proposals accepted by the
majority were prepared for presentation at a congress
in the United Arab Emirates.
Proposed Modifications
Proposal 1
Short-course preoperative radiotherapy (SCRT)

may be an alternative for long-course preoperative
radiotherapy (LCRT) or chemoradiotherapy in operable rectal cancer with smaller tumors (< T4).
Rationale
Preoperative SCRT was found to reduce the local

recurrence in rectal cancer when compared with surgery alone.5 In a large randomized trial, the Dutch
Colorectal Cancer Group showed a significant reduction of local recurrence risk with SCRT followed
by total mesorectal excision (TME) compared with
TME alone.6 Significant improvement was observed
for rectal lesions 5 cm or smaller and those larger
than 5 cm.
Another small randomized study from Bulgaria
suggests that although SCRT is less effective than
conventional radiotherapy in reducing local tumor
recurrences in the lower third of the rectum and for
advanced rectal cancer (T4 and N2), it is equally as effective in treating other occurrences.7 A Polish study
comparing preoperative SCRT with chemoradiation
showed similar survival, local control, and late toxicity for both treatments at 4 years.8 Another review of
the 2 randomized trials on 396 patients showed that
SCRT may be as effective as conventional radiotherapy/chemoradiation.9 A recent retrospective analysis
of clinical outcome in 520 Danish patients with rectal cancer also confirmed the efficacy of SCRT.10 Furthermore, a survival benefit was observed for SCRT
in the Swedish Rectal Cancer Trial.11
In conclusion, the evidence favors preoperative SCRT as an alternative to conventional preoperative radiotherapy/chemoradiation in operable
rectal cancer.
Proposal 2
Dose of capecitabine may be lower than 1000 mg/m2
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Supplement
li et al.
Table 2 Questionnaire Related to the Management of Colorectal Cancer and the Results
Questions
Most Relevant Answers
1. Do you recommend routine chest CT before surgery in patients with

resectable colorectal cancer?
No: 69%
2. What is your choice for adjuvant chemotherapy of patients with

T3N0M0 colon cancer (no high-risk factors)?
Observation: 53 %
Mayo regimen: 23.5%
3. What do you prefer for adjuvant chemotherapy in patients with

T3N0M0 rectal cancer?
Mayo regimen: 57%
4. What do you prefer for adjuvant chemotherapy of patients with

T14/N12/M0 rectal cancer?
FOLFOX: 72%
5. Do you recommend routine PET scan in the surveillance of patients

with stage T3/4N0M0 colon cancer?
No: 100%
6. What is your choice for neoadjuvant treatment of patients with

synchronous resectable liver only or lung-only metastases?
FOLFIRI or FOLFOX or CapeOX: 41%

Chemotherapy + bevacizumab: 47%
7. What is your choice for adjuvant treatment of patients with

synchronous resectable liver only or lung-only metastases after surgery?
FOLFIRI or FOLFOX or CapeOX: 39%

8. Do you add bevacizumab to the active chemotherapy (FOLFIRI/

FOLFOX/CapeOx) in patients with unresectable liver only or lung-only
metastases?
Yes: 86%
9. What is your choice of first-line treatment in patients with

unresectable metastatic colorectal cancer who are not candidates for
any future surgical treatment?
FOLFIRI or FOLFOX or CapeOX + bevacizumab:

75%

unresectable metastatic colorectal cancer with wild-type KRAS gene?

Chemotherapy + cetuximab: 47%

metastases who cannot tolerate intensive treatment?
Continuous-infusion 5-FU or capecitabine: 26%

Continuous-infusion 5-FU or capecitabine +
bevacizumab: 36%
Continuous-infusion 5-FU or capecitabine +
cetuximab if wild-type KRAS gene: 26%
Abbreviations: 5-FU, fluorouracil; CapeOX, capecitabine and oxaliplatin; FOLFIRI, leucovorin, fluorouracil, and irinotecan;
FOLFOX, leucovorin, fluorouracil, and oxaliplatin; Mayo regimen, fluorouracil and leucovorin.
twice daily.
Rationale
Many patients in this region are unable to tolerate recommended higher dosages because of severe
handfoot syndrome or diarrhea (based on personal
experience of the committee). This could be related
to high folate intake in the diet or issues related to
food hygiene. The committee proposed a prospective
trial be conducted to find the optimal dose for the
patients in the region.
Proposal 3
Stereotactic radiation for liver metastasis could be

an alternative.
Rationale
Resection is the standard of care for treating liver

metastasis in colorectal cancer. However, more than
80% of patients have unresectable disease. Several
studies have shown the efficacy of stereotactic body
radiation therapy as an alternative to radiofrequency

ablation in treating this condition.1215 A phase I/
II study showed that it is also safe and effective for
treating grade 1 to 3 metastasis.16
Proposal 4
Operations should be performed by surgeons experienced in colorectal surgery and TME, and the surgeries should occur at centers conducting more than 50
surgeries per year.
Rationale
The surgeon is an independent factor for outcome in

colorectal surgery. The outcome was also related to
surgical caseload and training/teaching activities.17
Because of the lower incidence of colorectal cancer,
a dilution of cases between centers occurs in some
countries. Some patients managed by general surgeons are found to lack TME for rectal cancer or adequate lymph node dissection. Although no specific
Supplement
Colon Cancer
caseload number has been established for surgeons,

the committee recommended that colorectal surgery
should be performed at centers performing at least 50
operations per year.
Conclusions
This multinational project is the first in the region
with the goal of establishing standard management
of colorectal cancer. The recommendations are
based on evidence in the literature and personal experiences that must be tested in prospective randomized studies. Continuation of this scientific cooperation between NCCN and the MENA countries may
improve quality of care for patients with colorectal
cancer in the region.
6. Kapteijn E, Marijnen CA, Nagtegaal ID, et al. Preoperative

radiotherapy combined with total mesorectal excision for resectable
rectal cancer. N Engl J Med 2001;345:638646.
7. Klenova A, Georgiev R, Kurtev P, Kurteva G. Short versus
conventional preoperative radiotherapy of rectal cancer:
indications. J BUON 2007;12:227232.
8. Bujko K, Nowacki MP, Nasierowska-Guttmejer A, et al. Longterm results of a randomized trial comparing preoperative shortcourse radiotherapy with preoperative conventionally fractionated
chemoradiation for rectal cancer. Br J Surg 2006;93:12151223.
9. Sajid MS, Siddiqui MR, Kianifard B, Baig MK. Short-course versus
long-course neoadjuvant radiotherapy for lower rectal cancer: a
systematic review. Ir J Med Sci 2010; in press.
10. Jensen LH, Altaf R, Harling H, et al. Clinical outcome in 520
consecutive Danish rectal cancer patients treated with short course
preoperative radiotherapy. Eur J Surg Oncol 2009;36:237243.
11. Siegel R, Burock S, Wernecke KD, et al. Preoperative shortcourse radiotherapy versus combined radiochemotherapy in locally
advanced rectal cancer: a multi-centre prospectively randomised
study of the Berlin Cancer Society. BMC Cancer 2009;9:50.
12. Mendez Romero A, Wunderink W, Hussain SM, et al. Stereotactic
body radiation therapy for primary and metastatic liver tumors: a
single institution phase I-II study. Acta Oncol 2006;45:831837.
References
1. Barchana M, Ibrahim AS, Mikhail N, et al. MOS Epidemiology
Group Special report: cancer incidence in Mediterranean
populations. Mediterranean Oncology Society Web site. Available
at: http://www.mosepi.org. Accessed March 31, 2010.
2. Eser SY. Cancer incidence in Turkey. In: Tuncer M, ed. Cancer
Control in Turkey. Ankara, Turkey: The Ministry of Health of
Turkey; 2007:1744.
3. Mohandas KM, Desai DC. Epidemiology of digestive tract cancers
in India. Indian J Gastroenterol 1999:18:118121.
4. Rasul KI, Awidi AS, Mubarak AA, Al-Homsi UM. Study of
colorectal cancer in Qatar. Saudi Med J 2001;22:705707.
5. Goldberg PA, Nicholls RJ, Porter NH, et al. Long-term results of
a randomised trial of short-course low-dose adjuvant pre-operative
radiotherapy for rectal cancer: reduction in local treatment failure.
Eur J Cancer 1994:30A:16021606.
13. Kim MS, Kang JK, Cho CK, et al. Three-fraction stereotactic
body radiation therapy for isolated liver recurrence from colorectal
cancer. Tumori 2009;95:449454.
14. Dawood O, Mahadevan A, Goodman KA. Stereotactic body
radiation therapy for liver metastases. Eur J Cancer 2009;45:2947
2959.
15. Fuss M, Thomas CR Jr. Stereotactic body radiation therapy: an
ablative treatment option for primary and secondary liver tumors.
Ann Surg Oncol 2004;11:130138.
16. Rusthoven KE, Kavanagh BD, Cardenes H, et al. Multiinstitutional phase I/II trial of stereotactic body radiation therapy
for liver metastases. J Clin Oncol 2009;27:15721578.
17. Renzulli P, Laffer UT. Learning curve: the surgeon as a prognostic
factor in colorectal cancer surgery. Recent Results Cancer Res
2005;165:86104.
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Supplement

GuidelinesTM on Prostate Cancer in the
Waleed A. Hassen, MD;a,b Farrok A. Karsan, MD;c Farhat Abbas, MD;d Yasar Beduk, MD;e
Ahmed El-Khodary, MD;f Marwan Ghosn, MD, MBA;g Jamal Khader, MD;h Raja Khauli, MD;i
Danny M. Rabah, MD;j Ali Shamseddine, MD;k Sandy Srinivas, MD;l Bethesda, Maryland;
Al Ain, United Arab Emirates; Karachi, Pakistan; Ankara Turkey; Kuwait City, Kuwait; Beirut, Lebanon;
Amman, Jordan; Riyadh, Kingdom of Saudi Arabia; and Stanford, California
Key Words
Middle East and North Africa, prostate cancer
Abstract
A prostate cancer committee was established to modify the NCCN
Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Prostate Cancer for adaptation and implementation in the Middle East
and North Africa (MENA) region. The objective was to enhance the
multidisciplinary approach to the treatment of prostate cancer. The
committee, comprising regional experts in the fields of urologic,
medical, and radiation oncology, reviewed the 2009 version of the
NCCN Guidelines on Prostate Cancer and suggested modifications
based on the unique needs of the regions determined through
published evidence and local expertise. The committee identified
several areas in the NCCN Guidelines that they believed required
modification, which are presented in this article. The treatment of
From the aDepartment of Urology, Johns Hopkins Medical

Institutions, Bethesda, Maryland; bDepartment of Urology, Tawam
Hospital, Al Ain, United Arab Emirates; cDepartment of Radiation
Oncology, Aga Khan University Hospital, Karachi, Pakistan;
d
Department of Urology, Aga Khan University Hospital, Karachi,
Pakistan; eDepartment of Urology, Ankara University, Ankara,
Turkey; fDepartment of Oncology, Kuwait Cancer Control Center,
Kuwait City, Kuwait; gDepartment of Urology, Hotel Dieu Hospital,
Beirut, Lebanon; hDepartment of Radiation Oncology, King Hussein
Cancer Center, Amman, Jordan; iDepartment of Urology, American
University of Beirut, Beirut, Lebanon; jDivision of Urology,
Department of Surgery, College of Medicine, King Saud University,
Riyadh, Kingdom of Saudi Arabia; kDepartment of HematologyOncology, American University of Beirut, Beirut, Lebanon; and
l
Stanford University School of Medicine, Stanford, California.
The authors have disclosed that they have no financial interests,
arrangements, or affiliations with the manufacturers of any
products discussed in the article or their competitors.
Correspondence: Waleed A. Hassen, MD, Department of Urology,
Tawam Hospital, P.O. Box 15258, Al Ain, United Arab Emirates.
E-mail: whassen@tawamhospital.ae
prostate cancer in the MENA region has numerous challenges. The

hope is that this effort to modify the NCCN Guidelines on Prostate
Cancer for practical use in the MENA region will improve regional
awareness and patient care. (JNCCN 2010;8[Suppl 3]:S26S28)
Prostate cancer is a significant source of morbidity and
mortality in the West, and remains the second leading cause of death from a solid malignancy in men in
the United States.1 However, its effect on populations
in the Middle East and North Africa (MENA) region
is not completely known. A prostate cancer committee was established to modify the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on
Prostate Cancer for adaptation and implementation in
the MENA region. The objective was to enhance the
multidisciplinary approach to the treatment of prostate
cancer. The committee, comprising regional experts in
the fields of urologic, medical, and radiation oncology,
reviewed the 2009 version of the NCCN Guidelines
on Prostate Cancer and suggested modifications based
on the unique needs of the region determined through
published evidence and local expertise. The committee
identified several areas in the NCCN Guidelines that
they believed required modification, which are presented in this article. The treatment of prostate cancer in
the MENA region has numerous challenges. The hope
is that this effort to modify the NCCN Guidelines on
Prostate Cancer for practical use in the MENA region
will improve regional awareness and patient care.
Supplement
Prostate Cancer
The Region
Diagnosis and Staging
For the purposes of this section, the MENA region

refers to Afghanistan, Algeria, Armenia, Egypt,
Ethiopia, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya,
Oman, Pakistan, Qatar, Kingdom of Saudi Arabia
(KSA), Somalia, Sudan, Syria, Tunis, Turkey, United
Arab Emirates (UAE), and Yemen. This collection
of countries is obviously extremely heterogeneous
in terms of economic resources and health care infrastructure. Although generalizations are difficult,
some pertinent issues and challenges are broadly applicable to this region.
Because PSA screening is not routine in the MENA

region, patients tend to present with more advanced
disease. A general lack of primary care exists in
the health systems of the region, which represents
a challenge to timely diagnosis. Transrectal sonography is not routinely available except in regional
centers, and experience with transrectal sonographic
biopsy of the prostate also seems to be limited to regional centers. Similarly, experience with the pathologic diagnosis of prostate cancer (including the nuances of grading) is also limited to referral centers.
Although CT and nuclear bone scans are generally
available, MRI has more limited availability.
Incidence
Although the exact incidence of prostate cancer in
the MENA region is unknown, the reported incidence is approximately 5.8 cases per 100,000, with
a mortality rate of 4.9 cases per 100,000.2 The accuracy of these data is not clear, however, because they
are derived from unweighted averages from other
regions. In general, prostate-specific antigen (PSA)
screening is not routine, and therefore whether the
lower incidence rate is secondary to the absence of
screening or from a truly lower prevalence in the
population is unknown. Smaller regional cancer
databases, however, suggest that the true impact of
this disease may be more significant than generally
perceived. Young3 reported on regional cancer databases from 8 countries in the MENA region (Jordan, Egypt, Bahrain, KSA, Kuwait, Qatar, Oman,
and UAE), and found that prostate cancer ranked
among the top 4 malignancies in terms of frequency
in 5 countries.3 Shamseddine et al.4 reported that
prostate cancer represented the most frequently reported malignancy in Lebanese men.
In general it is the committees perception that
most patients present with late-stage disease because
of the lack of PSA screening. It is also important to
consider that the MENA region population is approximately 750 million.5
Because 65% of the population is currently
younger than 30 years, even if the incidence of prostate cancer is lower than that of the West, the scope
of the problem will only become more significant
over the next 20 years as the population ages and
presumably has access to improved medical care.
Treatment
The definitive and palliative treatment of prostate
cancer has multiple regional challenges. Definitive
treatment typically involves either surgery or radiotherapy, and experience in the management of this
disease is generally lacking. A brief poll of urologists,
for example, found that awareness of the existence
of NCCN Guidelines on Prostate Cancer varied between 5% and 86%.
Adequate experience in the surgical management of prostate cancer has been shown to improve
outcomes.6 A lack of surgical experience in the localized management of prostate cancer generally exists,
even in referral centers, and radiation therapy has
similar issues. According to the International Atomic Energy Agency (IAEA), only 93 machines are capable of delivering greater than 10 mV of energy in
a region of 730 million people.7 More importantly,
70 machines are clustered in 3 countries (Turkey,
Egypt, and KSA), leaving 23 machines to service the
needs of 19 countries. Only 30 of 93 machines are
capable of delivering CT dosimetry and planning.
Furthermore, the costs of neoadjuvant hormonal
therapy in combination with radiation therapy are
also challenging, and experience with brachytherapy
is limited.
Similar issues arise when addressing the management of advanced disease. Although the cost of hormonal ablation is prohibitive, bilateral orchiectomy
is a viable option and available. Access to systemic
chemotherapy is limited, palliative care specialists
are few, and the availability of narcotics tends to
be limited.
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S-28
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Hassen et al.
Recommendations
Based on these challenges, the committee recommended the following modifications to the NCCN
Guidelines on Prostate Cancer.
Staging Workup
tion, the committee suggests the daily use of diethylstilbestrol in low doses (13 mg) in combination with
warfarin as an affordable second-line alternative.
Diethylstilbestrol has been shown to result in PSA
declines in up to 42% of patients with rising PSA.8
Staging with CT/MRI seems restrictive for stage 1

to 2, which limits these imaging modalities to those
patients with a 20% or more probability of lymph
node involvement. Given that expertise in treatment is limited, a diagnosis of metastatic disease
would potentially avoid needless definitive intervention. Therefore, the committee believed that a cutoff
of 10% would be more appropriate.
Principles of Radiation Therapy
Expected Patient Survival
The treatment of prostate cancer in the MENA region is a challenge and numerous obstacles hinder
the delivery of what would be deemed appropriate
care in the West. Although the incidence of prostate
cancer seems to be less than in the West, the true
incidence probably is at least partially understated.
Physician awareness of appropriate treatment guidelines may not be sufficient; the hope is that this initial effort in tailoring guidelines to the region will
lead to improved patient care.
Life expectancy estimates from data obtained in the

developed world may not be representative of the
MENA region. Morbidity and mortality from the
same illness may be more severe because of genetic
factors, access to health care facilities, and availability of technology, socioeconomics, and education.
Barring the availability of country-specific life expectancy tables, the committee recommends a combination of factors, including performance status,
comorbid conditions, disease stage, and physician
judgment based on local experience.
Initial Therapy
Although data show that a certain percentage of patients with locally advanced disease (T3bT4) may
be treated with surgery, the availability of surgical
expertise for treating this patient population is extremely limited. Surgery is not recommended as an
option, except in the rare institutions with a high
level of surgical expertise.
Primary Salvage Therapy
Because experience with cryotherapy or brachytherapy is extremely limited, the management of postradiation recurrence with either of these modalities
should be restricted to a research setting.
Systemic Salvage Therapy
As stated in the NCCN guidelines, the clinical benefit of antiandrogens in hormone-refractory disease
is limited. Given that the cost of these medications
is prohibitive for a significant segment of the popula-
Although the NCCN guidelines do not mention

highdose-rate brachytherapy in the principles of radiation therapy, the committee believes that guidelines for the use of this technology should be incorporated.
Summary
References
1. Jemal A, Siegel R, Ward E, et al. Cancer statistics, 2009. CA
Cancer J Clin 2009;59:225249.
2. Parkin DM, Bray F, Ferlay J, Pisani P. Global Cancer Statistics,
2002. CA Cancer J Clin 2005;55:74108.
3. Young JL. Cancer incidence in the Middle East and Gulf
Cooperation Council countries. Presented at the Middle East
Cancer Consortium Steering Committee Meeting; January 20,
2003; Lyon, France.
4. Shamseddine A, Sibai AM, Gehchan N, et al. Cancer incidence in
postwar Lebanon: findings from the first national population-based
registry, 1998. Ann Epidemiol 2004;14:663668.
5. Unicef Regional Statistics, 2009.
6. Bianco FJ Jr, Riedel ER, Begg CB, et al. Variations among high
volume surgeons in the rate of complications after radical
prostatectomy: further evidence that technique matters. J Urol
2005;173:20992103.
7. International Atomic Energy Agency. Directory of Radiotherapy
Centres. Available at: http://www-naweb.iaea.org/nahu/dirac/
default.asp. Accessed March 31, 2010.
8. Smith DC, Redman BG, Flaherty LE, et al. A phase II trial of oral
diethylstilbesterol as a second-line hormonal agent in advanced
prostate cancer. Urology 1998;52:257260.
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GuidelinesTM on Lymphomas in the Middle
East and North Africa Region
Ali Bazarbachi, MD, PhD;a Hamdy A. Azim, MD, PhD;b Hussain Alizadeh, MD, PhD;c Mahmoud Aljurf, MD;d
Ibrahim Barista, MD;e Naeem A. Chaudhri, MD;d Zahira Fahed, MD;g Omar A. Fahmy, MD;b
Ardeshir Ghavamzadeh, MD;g Mohamed H. Khalaf, MD;h Sami Khatib, MD;i Aghiad Kutoubi, MD;j
Semra Paydas, MD;k Hanadi Rafii Elayoubi, MD;l Ghazi Zaatari, MD;m Hamdy M. Zawam, MD;b and
Andrew D. Zelenetz, MD, PhD;n Beirut, Lebanon; Cairo, Egypt; Al Ain, United Arab Emirates;
Riyadh, Kingdom of Saudi Arabia; Ankara, Turkey; Damascus, Syria; Tehran, Iran; Amman, Jordan;
Adana, Turkey; Doha, Qatar; and New York, New York
Key Words
Middle East and North Africa, lymphoma, non-Hodgkins lymphoma, Hodgkin lymphoma
Abstract
In the Middle East and North Africa (MENA) region, cancer has
many epidemiologic and clinical features that are different from
those in the rest of the world. Additionally, the region has a relatively young population and large disparities in the availability of
resources at diagnostic and treatment levels. A critical need exists
for regional guidelines on cancer care, including those for lymphoid malignancies. A panel of lymphoma experts from MENA reviewed the 2009 version of the NCCN Clinical Practice Guidelines
in Oncology (NCCN Guidelines) on Non-Hodgkins Lymphoma and
Hodgkin Lymphoma and suggested modifications for the region
that were discussed with the United States NCCN Lymphoma Panels. This article presents the consensus recommendations. (JNCCN
2010;8[Suppl 3]:S29S35)
From the aDepartment of Internal Medicine, American University of

Beirut Medical Center, Beirut, Lebanon; bCairo University, Cairo, Egypt;
c
Tawam Hospital/Johns Hopkins, Al Ain, UAE; dSection of Hematology/
Hematopoietic Stem Cell Transplant, King Faisal Specialist Hospital and
Research Center, Riyadh, Kingdom of Saudi Arabia; eDepartment of
Medical Oncology, Hacettepe University Faculty of Medicine, Ankara,
Turkey; fHematology and Medical Oncology, Al Bairouni University
Hospital for Cancer, Damascus, Syria; gTehran University of Medical
Sciences, Tehran, Iran; hDepartment of Hematology and Bone Marrow
Transplantation, Maadi Armed Forces Medical Compound, Cairo, Egypt;
i
King Hussein Institute for Biotechnology and Cancer, Amman, Jordan;
j
Department of Diagnostic Radiology, American University of Beirut
Medical Center, Beirut, Lebanon; kDepartment of Oncology, Faculty of
Medicine, Cukurova University, Adana, Turkey; lAl Amal Hospital, Doha,
Qatar; mDepartment of Pathology and Laboratory Medicine, American
University of Beirut Medical Center, Beirut, Lebanon; and nDivision
Overview
In the Middle East and North Africa (MENA) region,
cancer has many epidemiologic and clinical features that

are different from those in the rest of the world. Additionally, the region has a relatively young population
and large disparities in the availability of resources at diagnostic and treatment levels. A critical need exists for
regional guidelines on cancer care, including those for
lymphoid malignancies. A panel of lymphoma experts
from MENA reviewed the 2009 version of the NCCN
Clinical Practice Guidelines in Oncology (NCCN
Guidelines) on Non-Hodgkins Lymphoma and the 2008
version of the NCCN Clinical Practice Guidelines in
Oncology (NCCN Guidelines) on Hodgkin Lymphoma
(to view the most recent version of these guidelines, visit
the NCCN Web site at www.NCCN.org) and suggested
of Hematology/Oncology, Department of Medicine, Memorial SloanKettering Cancer Center, New York, New York.
Drs. Bazarbachi, Azim, Alizadeh, Aljurf, Barista, Chaudhri, Fahed,
Fahmy, Ghavamzadeh, Khalaf, Khatib, Kutoubi, Paydas, Elayoubi,
Zaatari and Zawam have disclosed that they have no financial interests,
arrangements, or affiliations with the manufacturers of any products
discussed in the article or their competitors. Dr. Zelenetz has disclosed
that he receives research support from Abbott Laboratories; Cephalon,
Inc.; GlaxoSmithKline; Allos Pharmaceuticals; Glouster Pharmaceuticals;
Roche; and Seattle Genetics. He is an advisory board member for
Bristol-Myers Squibb Company; Cephalon, Inc.; Eli Lilly and Company;
Genentech, Inc.; GlaxoSmithKline; and Allos Pharmaceuticals. He is also
a consultant for Genentech, Inc.; GlaxoSmithKline; Cancer Genetics; and
sanofi-aventis U.S.
Correspondence: Ali Bazarbachi, MD, PhD, Department of Internal
Medicine, American University of Beirut Medical Center, P.O. Box 1136044, Beirut, Lebanon. E-mail: bazarbac@aub.edu.lb
S-30
Supplement
Bazarbachi et al.
modifications for the region that were discussed with

the United States NCCN Non-Hodgkins Lymphoma Panel. This article presents the consensus recommendations.
For Hodgkin lymphoma, if PET-CT scan is not
available, Gallium scan or biopsy is recommended to
evaluate for residual disease. In mantle cell lymphoma,
rituximab and a high-dose cytarabinecontaining regimen such as DHAP (dexamethasone, cisplatin, cytarabine) were added to the first-line options. In diffuse large
B-cell lymphoma, the dose-dense, dense-intense RACVBP (rituximab, doxorubicin, cyclophosphamide,
vindesine, bleomycin, prednisone) regimen was added
as an acceptable alternative to R-CHOP (rituximab,
cyclophosphamide, doxorubicin, vincristine, prednisone) in patients younger than 60 years. In Burkitts
lymphoma, the LMB (B-cell non-Hodgkins lymphoma
and B-cell acute lymphoblastic leukemia) protocol was
added as an acceptable alternative and rituximab use
was recommended for all CD20-positive tumors. In cutaneous lymphomas, human T-cell lymphotropic virus
type 1 (HTLV-1) serology was recommended, particularly for patients from endemic areas. Finally, the panel
formulated new recommendations for the diagnosis,
workup, and management of HTLV-1associated adult
T-cell leukemia/lymphoma (ATL). In the acute, chronic, and smoldering forms of ATL, antiviral therapy using
the combination of zidovudine and interferon (IFN)-
is recommended. Allogeneic hematopoietic stem cell
transplantation (HSCT) is recommended in patients
with acute ATL who do not experience a complete remission. In ATL lymphoma, first-line chemotherapy followed by allogeneic HSCT is recommended.
In the MENA region, these suggested modifications should encourage the use of the NCCN guidelines for treating patients with lymphoma. At the
global level, they represent an important addition
to the NCCN guidelines by providing recommendations for the management of patients with ATL.
Background
Malignant lymphomas constitute a sizeable percentage of human cancers, and recent epidemiologic data
suggest a worldwide increase in incidence (approximately 30% in the past 5 years),1,2 which may be
caused by environmental factors, including increased
pesticide use, and the emergence of infectious diseases, such as hepatitis C virus infections. These malig-
nant lymphomas represent a heterogeneous group of

lymphoproliferative malignancies with differing patterns of behavior and responses to treatment. Most
non-Hodgkin lymphoma (NHL) cases are of B-cell
origin; however, histologic subtypes may vary in different parts of the world.
Prognosis depends on histologic type, stage, age,
and treatment. In addition, tumor environment
(e.g., immune and stromal infiltration), presence of
infectious agents associated with lymphomagenesis,
and molecular events involved in cell proliferation,
differentiation, and apoptosis are emerging as new
prognostic factors that eventually may be used for
targeted therapies. Hodgkin lymphoma is characterized by a very good prognosis and a significant cure
rate with ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-type chemotherapy.3 However,
targeted therapy either alone or in combination with
chemotherapy has significantly improved the prognosis of NHL of B-cell origin, particularly with the use
of rituximab, an anti-CD20 monoclonal antibody.4,5
Diffuse large B-cell lymphoma (DLBCL) is a
distinct histologic type within B-cell NHL characterized by large tumor cells and aggressive clinical
behavior. This subtype accounts for approximately
30% to 40% of adult NHL.6
Regional specificities in the incidence of lymphomas have been reported with a significantly
lower incidence of follicular lymphoma and chronic
lymphocytic leukemia, and a significantly higher
incidence of T-cell lymphomas in Asian countries
compared with Europe and North America.79 A
high incidence of Epstein-Barr virusassociated
lymphomas has been reported in some Middle East
countries.10,11 In addition, HTLV-1associated ATL
is endemic in some Middle East regions.12,13
Finally, management of malignant lymphomas
in developing countries is variable and largely depends on the availability of diagnostic and therapeutic resources, such as immunohistochemistry and
molecular techniques, PET-CT scan, and expensive
targeted therapies.
Methods
The NCCNMENA project was launched during
a preparatory meeting held in Abu Dhabi, United
Arab Emirates on November 9, 2008, involving
NCCN members and chairpersons of the different
Supplement
Lymphoma
guidelines panels. The goal was to adapt the NCCN

guidelines to the region. The chair of the NCCN
Lymphoma Panel, in consultation with the chairman of the NCCNMENA project and chairpersons
of other groups, nominated lymphoma experts from
multiple specialties, including hematology, medical
oncology, radiation oncology, pathology, and diagnostic radiology, join the NCCNMENA guideline
committee. These individuals were contacted by email and agreed to participate. All members were emailed the 2008 version of the NCCN Guidelines on
Non-Hodgkins Lymphomas and the 2009 version of
the NCCN Guidelines on Hodgkin Lymphoma and
asked to communicate their suggested modifications.
Several members sent their suggested modifications
to the whole group.
The regional lymphoma group met in Beirut,
Lebanon on February 21, 2009, to discuss the suggested modifications. Consensus recommendations
were made, including specific modifications to the
existing NCCN recommendations and new recommendations for ATL management because none were
present in the 2009 version of the NCCN Guidelines
on Non-Hodgkins Lymphomas. The chair compiled
these modifications and forwarded them to the chair
of the NCCN Non-Hodgkins Lymphomas Panel in
the United States, and then the comments of the
NCCN panel were e-mailed to the MENA lymphoma committee. Subsequently suggested MENA modifications were presented at the Abu Dhabi meeting
in April 2009; consensus recommendations were
then established at a special lymphoma committee
meeting attended by several MENA lymphoma committee members and the chair of the NCCN panel.
These recommendations were then discussed and finalized by the NCCN panel in June 2009.
Hodgkin Lymphoma
Background
The current NCCN treatment algorithm for Hodgkin lymphoma is based on PET-CT findings. However, this modality is not available or accessible
everywhere. A small survey of the groups practices
showed that Gallium scan is more widely available
and accessible in the MENA region. Imaging with
Gallium requires several days, but there is no need
to wait after the end of treatment. A baseline scan is
also required.
Some studies14 indicate no statistical difference

between the imaging methods. However, most studies indicate that PET is superior to Gallium scan in
terms of sensitivity for activity and site detection,
and also has a slightly higher specificity.
Suggested Modification
If PET-CT is not available, Gallium scan is

recommended.
If Gallium scan is not available, a biopsy of the
residual disease is recommended.
If Gallium scan is positive, a biopsy is
recommended.
If Gallium scan is negative, the group recommends following the NCCN guidelines for negative PET-CT scan.
Mantle Cell Lymphoma

Background
Several reports show that high-dose cytarabine is

an effective chemotherapeutic agent in mantle cell
lymphoma. For example, the protocol involving RDHAP (dexamethasone, cisplatin, high-dose cytarabine, rituximab) followed by autologous stem cell
transplant (ASCT)15 for previously untreated younger patients (< 65 years) is a very affordable and rather
effective regimen, with 3-year overall and event-free
survival rates of 75% and 76%, respectively, based on
an intent-to-treat analysis.
The group recommended that suggested first-line

treatment regimens include a rituximab and highdose cytarabinecontaining regimen, such as DHAP,
with a corresponding footnote indicating that highdose chemotherapy and ASCT should be given after
high-dose cytarabine.
DLBCL
Background
Multiple studies have shown that advances in treatment can improve the outcome of patients with
DLBCL, and that the standard CHOP regimen is
not sufficient as first-line chemotherapy to cure
many patients. The first improvement was reported
in 2 randomized studies, which showed the superiority of a dose-dense and -intense regimen, ACVBP
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Bazarbachi et al.
(doxorubicin, cyclophosphamide, vindesine, bleomycin, prednisone), over CHOP.16,17 This regimen is

now widely used in several countries in Europe and
the MENA region. The second improvement was
the increased survival achieved with the addition of
rituximab to combination chemotherapy.18,19
The group recommended adding R-ACVBP as an

acceptable alternative to R-CHOP.
Burkitts Lymphoma
Background
Excellent results are reported in young adults treated

with the pediatric LMB protocol.20,21 The second
improvement was the increased survival achieved
with the addition of rituximab to combination chemotherapy.18,19 Furthermore, rituximab significantly
improves outcome in patients with CD20-positive
Burkitts lymphoma.
The group suggested that the LMB protocol be added

as an acceptable alternative to the current NCCN
Guidelines for Burkitts Lymphoma (CODOX-M or
HyperCVAD), and that rituximab use be considered
for all tumors that are CD20-positive.
T-Cell Lymphomas
ATL
Background: ATL is an aggressive malignancy of

mature activated CD4-positive CD25-positive T
cells associated with a retrovirus-designated HTLVI.22 Endemic areas include Japan, the Caribbean, intertropical Africa, Brazil, Eastern Europe (Romania),
and the Middle East (particularly Iran).23,24 The diversity in clinical features and prognosis of patients
with this disease has led to its subclassification into
4 categories: acute, lymphoma, chronic, and smoldering types (Table 1).25 The chronic and smoldering subtypes are considered indolent, but eventually
have poor long-term survival.
Patients with aggressive ATL (acute and lymphoma types) generally have a very poor prognosis
because of multidrug resistance of malignant cells, a
large tumor burden with multiorgan failure, hypercalcemia, or frequent infectious complications from
a profound T-cell immunodeficiency.22,26,27 Numerous small phase II studies using zidovudine (AZT)
and IFN- have shown responses in patients with
ATL.2831 High doses of both agents were used: 6 to
9 million units of IFN- in combination with daily
divided AZT doses of 800 to 1000 mg/d. However,
only patients with wild-type p53 and low IFN regulatory factor 4 expression seem to exhibit long-term
responses to AZT/IFN therapy.32,33 The results of a
recent worldwide meta-analysis on the use of AZT/
IFN for treating ATL indicate a significant survival
advantage in acute, chronic, and smoldering-type
ATL, but not in lymphoma ATL.34 The recently published proposal from the International Consensus
Meeting recommended a strategy for treating ATL.35
Suggested Modification:
Diagnosis: In all patients with leukemic manifestations, ATL is usually diagnosed based on the presence of 5% or more abnormal T lymphocytes in
peripheral blood according to morphology and flow
cytometry. In those without leukemic manifestations, it is diagnosed based on a finding of T-cell
lymphoma on biopsy of involved organs. Additionally, HTLV-1 seropositivity is mandatory for ATL
diagnosis. Clonal integration of HTLV-1 provirus
should be performed in most cases and is mandatory in atypical cases.
Workup: The group recommended that workup for
ATL include the following:
CBC and blood smear: lymphocytosis (absolute
lymphocyte count > 4000) in acute and chronic
subtypes. Typical ATL cells (flower cells) have
markedly polylobated nuclei with homogeneous
and condensed chromatin, small or absent nucleoli, and agranular and basophilic cytoplasm,
but multiple morphologic variations can be encountered.
Flow cytometry on peripheral blood: mature Tcell phenotype. Minimum panel: CD3, CD4,
CD7, CD8, and CD25. Usually CD4-positive
cells with expression of CD2, CD5, CD25,
CD45RO, CD29, T-cell receptor, and HLADR. Most cases are CD7-negative and CD26negative with low CD3 expression. Rare cases
are CD8-positive or CD4/CD8-double positive
or CD4/CD8-double negative.
HTLV-I serology: positive (enzyme-linked immunosorbent assay and Western blot).
Molecular analysis: monoclonal integration of
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Supplement
Lymphoma
Table 1 Adult T-Cell Leukemia/Lymphoma Subtype According to Shimoyama Classification

Healthy Carrier
Smoldering ATL
Chronic ATL
Acute ATL
ATL Lymphoma
HTLV-I serology
Clonal integration of provirus
(blood)
+
(blood)
+
(blood)
+
(blood)
+
(lymph nodes)
Lymphocyte count
Normal
Normal
Elevated
Elevated
Normal
Abnormal cells
< 5%
> 5%
> 5%
> 5%
< 1%
Hypercalcemia
LDH level
Normal
< 1.5 N
<2N
>2N
>2N
Skin or lung involvement
Bone marrow or spleen involvement
Bone, gastrointestinal, or central

nervous system involvement
Abbreviations: ATL, adult T-cell leukemia/lymphoma; HTLV-1, human T-cell lymphotropic virus type 1; LDH, lactate dehydrogenase.
HTLV-I provirus (Southern blot or inverted

polymerase chain reaction).
Bone marrow aspirate and biopsy: generally not
required to make the diagnosis. However, bone
marrow involvement is an independent poor
prognostic factor.
Radiologic imaging: CT scans of neck, thorax, abdomen, and pelvis. Skeletal survey in
symptomatic patients.
Gastrointestinal evaluation: upper gastrointestinal endoscopy (frequent gastrointestinal
involvement).
Central nervous system evaluation: CT scan,
MRI, and/or lumbar puncture in all patients
with acute or lymphoma subtypes or in those
with neurologic manifestations.
Biopsy of lymph nodes (excisional), skin biopsy,
gastrointestinal tract biopsy, or bone marrow biopsy is required if the diagnosis is not established
based on molecular assay of peripheral blood
(for histology and molecular analyses of HTLV-I
provirus integration), or to rule out an underlying infection (e.g., tuberculosis, histoplasmosis,
toxoplasmosis).
Chemistry: electrolyte, blood urea nitrogen, creatinine, serum calcium, and serum lactate dehydrogenase (LDH) levels.
Stool examination for parasites.
Treatment of Chronic/Smoldering ATL: The group
recommends treatment for all patients with chronic/smoldering ATL. Recent results from a Japanese
study show poor outcome for patients treated with a
watch and wait strategy or chemotherapy.36
The group recommended that treatment include

the following:
Initial therapy outside clinical trials: AZT (1 g/d
orally) and IFN- (610 million units per day).
A recent worldwide meta-analysis showed this
regimen resulted in 100% long-term survival.34
Response evaluation: complete remission is
defined by normalization of lymphocytosis (if
present) and LDH level (if elevated), with disappearance of all clinical manifestations (particularly skin involvement and lymphadenopathy).
However, persistence of fewer than 5% flower
cells on peripheral smear is allowed.
Almost all patients with chronic or smoldering
ATL should experience response to AZT/IFN.
Outside clinical trials, treatment should never be
interrupted in these patients. Response is usually
obtained within 1 to 2 months. If no response is
seen at 2 months, treatment should be discontinued. In patients who experience progression
with life-threatening manifestations, treatment
can be discontinued before 2 months.
Very few patients with chronic/smoldering ATL
will not experience response or will experience
progression after AZT/IFN. For these patients,
chemotherapy is recommended (CHOP is the
most used regimen, although one randomized
study showed that Japanese LSG15 [vincristine,
cyclophosphamide, doxorubicin, and prednisone (VCAP); doxorubicin, ranimustine, and
prednisone (AMP); and vindesine, etoposide,
carboplatin, and prednisone (VECP)] is superior
to CHOP).37
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Bazarbachi et al.
Treatment of Acute ATL:

Recommended initial therapy outside clinical
trials: AZT (1g/d orally) and IFN- (610 million units per day). This strategy is associated
with an improved survival rate compared with
first-line chemotherapy in worldwide meta-analysis. High doses of both agents are needed for at
least 1 month. Dose reduction for hematotoxicity is allowed starting from month 2.
Response evaluation: complete remission is defined by normalization of lymphocytosis (if present) and the LDH level (if elevated), with disappearance of all clinical manifestations and tumor
sites. However, persistence of less than 5% flower
cells on peripheral smear is allowed.
Outside clinical trials, treatment should never
be interrupted in patients experiencing response.
Response is obtained within 1 to 2 months. If
no response is achieved at 2 months, AZT/IFN
should be discontinued. In patients experiencing
progression with life-threatening manifestations,
treatment can be discontinued before 2 months.
Alternative first-line option and for patients who
do not experience respond or will experience
progression after AZT/IFN: inclusion in clinical
trials or chemotherapy (CHOP is the most used
regimen, although one randomized study showed
that Japanese LSG15 [VCAP, AMP, and VECP]
is superior to CHOP).37 Data are weak for monoclonal antibodies (anti-CD52 or -CD25).
Young patients with a human leukocyte antigen
(HLA)identical donor should be referred for
allogeneic HSCT (myeloablative or reducedintensity conditioning) except those who experience complete response on AZT/IFN (80%
long-term survival is expected).
Antimicrobial prophylaxis: trimethoprim-sulfamethoxazole (Bactrim) and strongyloidosis prophylaxis is recommended.
Central nervous system prophylaxis: intrathecal
chemotherapy is recommended (methotrexate,
cytarabine, and corticosteroids).
Treatment of ATL Lymphoma:
AZT/IFN is not effective in these patients (inferior outcome compared with chemotherapy).
Chemotherapy is more effective in ATL lymphoma than in acute ATL.
Recommended first-line therapy: inclusion in
clinical trials or chemotherapy (CHOP is the
most used regimen, although one randomized

study showed that Japanese LSG15 [VCAP,
AMP, and VECP] is superior to CHOP).37 Data
are weak for monoclonal antibodies (anti-CD52
or -CD25).
Young patients with an HLAidentical donor
should be referred for allogeneic HSCT (myeloablative or reduced-intensity conditioning).
Antimicrobial prophylaxis: trimethoprim-sulfamethoxazole (Bactrim) and strongyloidosis prophylaxis is recommended.
Central nervous system prophylaxis: intrathecal
chemotherapy is recommended (methotrexate,
cytarabine, and corticosteroids).
Cutaneous T-Cell Lymphomas

Background
Many patients with smoldering ATL can be misdiagnosed with mycosis fungoides or Szary syndrome if
HTLV-I serology is not requested.
Suggested modification
The group recommends including HTLV-I serology as part of the workup, particularly if the patient is from an endemic area.
Conclusions
In the MENA region, these suggested modifications
should encourage the use of the NCCN guidelines
for treating patients with lymphoma. At the global
level, they represent an important addition to the
NCCN guidelines by providing recommendations
for managing patients with ATL.
References
1. Eltom MA, Jemal A, Mbulaiteye SM, et al. Trends in Kaposis sarcoma
and non-Hodgkins lymphoma incidence in the United States from
1973 through 1998. J Natl Cancer Inst 2002;94:12041210.
2. Grulich AE, Vajdic CM. The epidemiology of non-Hodgkin
lymphoma. Pathology 2005;37:409419.
3. Evens AM, Hutchings M, Diehl V. Treatment of Hodgkin
lymphoma: the past, present, and future. Nat Clin Pract Oncol
2008;5:543556.
4. Sonet A, Bosly A. Rituximab and chemotherapy in diffuse large
B-cell lymphoma. Expert Rev Anticancer Ther 2009;9:719726.
5. Leonard JP, Martin P, Barrientos J, Elstrom R. Targeted treatment
and new agents in diffuse large B-cell lymphoma. Semin Hematol
2008;45(3 Suppl 2):S1116.
Supplement
Lymphoma
6. Armitage JO, Weisenburger DD. New approach to classifying nonHodgkins lymphomas: clinical features of the major histologic
subtypes. Non-Hodgkins Lymphoma Classification Project. J Clin
Oncol 1998;16:27802795.
7. Gross SA, Zhu X, Bao L, et al. A prospective study of 728 cases
of non-Hodgkin lymphoma from a single laboratory in Shanghai,
China. Int J Hematol 2008;88:165173.
8. Shih LY, Liang DC. Non-Hodgkins lymphomas in Asia. Hematol
Oncol Clin North Am 1991;5:9831001.
9. Intragumtornchai T, Wannakrairoj P, Chaimongkol B, et al. NonHodgkins lymphomas in Thailand. A retrospective pathologic and
clinical analysis of 1391 cases. Cancer 1996;78:18131819.
10. Vasef MA, Ubaidat MA, Khalidi HS, et al. Association between
Epstein-Barr virus and classic Hodgkin lymphoma in Jordan: a
comparative study with Epstein-Barr virus-associated Hodgkin
lymphoma in North America. South Med J 2004;97:273277.
11. Al-Salam S, John A, Daoud S, et al. Expression of Epstein-Barr
virus in Hodgkin lymphoma in a population of United Arab
Emirates nationals. Leuk Lymphoma 2008;49:17691777.
12. Sidi Y, Meytes D, Shohat B, et al. Adult T-cell lymphoma in Israeli
patients of Iranian origin. Cancer 1990;65:590593.
13. Kchour G, Tarhini M, Sharifi N, et al. Increased microvessel density
in involved organs from patients with HTLV-I associated adult T
cell leukemia lymphoma. Leuk Lymphoma 2008;49:265270.
14. Fruchart C, Reman O, Le Stang N, et al. Prognostic value of
early 18 fluorodeoxyglucose positron emission tomography and
gallium-67 scintigraphy in aggressive lymphoma: a prospective
comparative study. Leuk Lymphoma 2006;47:25472557.
15. de Guibert S, Jaccard A, Bernard M, et al. Rituximab and
DHAP followed by intensive therapy with autologous stem-cell
transplantation as first-line therapy for mantle cell lymphoma.
Haematologica 2006;91:425426.
16. Reyes F, Lepage E, Ganem G, et al. ACVBP versus CHOP plus
radiotherapy for localized aggressive lymphoma. N Engl J Med
2005;352:11971205.
17. Tilly H, Lepage E, Coiffier B, et al. Intensive conventional
chemotherapy (ACVBP regimen) compared with standard CHOP
for poor-prognosis aggressive non-Hodgkin lymphoma. Blood
2003;102:42844289.
18. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus
rituximab compared with CHOP alone in elderly patients with
diffuse large-B-cell lymphoma. N Engl J Med 2002;346:235242.
19. Gisselbrecht C, Fitoussi O, Belhadj K, et al. Survival impact of
rituximab combined to ACVBP (R-ACVBP) in 209 poor risk
diffuse large B-cell lymphoma (DLBCL) patients treated with
upfront high-dose consolidative autotransplantation (HDC): a
GELA phase II study [abstract]. Blood 2008;112:286. Abstract 771.
20. Patte C, Philip T, Rodary C, et al. High survival rate in advancedstage B-cell lymphomas and leukemias without CNS involvement
with a short intensive polychemotherapy: results from the French
Pediatric Oncology Society of a randomized trial of 216 children. J
Clin Oncol 1991;9:123132.
21. Divin M, Casassus P, Koscielny S, et al. Burkitt lymphoma in adults:
a prospective study of 72 patients treated with an adapted pediatric
LMB protocol. Ann Oncol 2005;16:19281935.
22. Bazarbachi A, Ghez D, Lepelletier Y, et al. New therapeutic

approaches for adult T-cell leukaemia. Lancet Oncol 2004;5:664
672.
23. Kaplan J, Khabbaz R. The epidemiology of human T-lymphotropic
virus type I and II. Medical Virol 1993;3:137148.
24. Gessain A. Epidemiology of HTLV-1 and associated diseases.
Human T-cell lymphotropic virus type 1. In: Hllsberg P, Hafler
DA, eds. Human T-Cell Lymphotropic Virus Type I. Chichester,
UK: John Willey & Sons Ltd; 1996:3364.
25. Shimoyama M. Diagnostic criteria and classification of clinical
subtypes of adult T-cell leukaemia-lymphoma. A report from the
Lymphoma Study Group (1984-87). Br J Haematol 1991;79:428
437.
26. Shimoyama M. Treatment of patients with adult T-cell leukemialymphoma: an overview. In: Takatsuki K, Hinuma Y, Yoshida M,
eds. Advances in Adult T-Cell Leukemia and HTLV-I Research.
Tokyo: Japan Scientific Societies Press; 1992:4356.
27. Hermine O, Wattel E, Gessain A, Bazarbachi A. Adult T-cell
leukaemia: a review of established and new treatments. BioDrugs
1998;10:447462.
28. Gill PS, Harrington W Jr, Kaplan MH, et al. Treatment of adult
T-cell leukemia-lymphoma with a combination of interferon alfa
and zidovudine. N Engl J Med 1995;332:17441748.
29. Hermine O, Bouscary D, Gessain A, et al. Brief report: treatment
of adult T-cell leukemia-lymphoma with zidovudine and interferon
alfa. N Engl J Med 1995;332:17491751.
30. Bazarbachi A, Hermine O. Treatment with a combination of
zidovudine and alpha-interferon in naive and pretreated adult
T-cell leukemia/lymphoma patients. J Acquir Immune Defic Syndr
Hum Retrovirol 1996;13(Suppl 1):S186S190.
31. Kchour G, Tarhini M, Kooshyar MM, et al. Phase 2 study of
the efficacy and safety of the combination of arsenic trioxide,
interferon alpha, and zidovudine in newly diagnosed chronic adult
T-cell leukemia/lymphoma (ATL). Blood 2009;113:65286532.
32. Datta A, Bellon M, Sinha-Datta U, et al. Persistent inhibition
of telomerase reprograms adult T-cell leukemia to p53-dependent
senescence. Blood 2006;108:10211029.
33. Ramos JC, Ruiz P Jr, Ratner L, et al. IRF-4 and c-Rel expression
in antiviral-resistant adult T-cell leukemia/lymphoma. Blood
2007;109:30603068.
34. Bazarbachi A, Plumelle Y, Ramos JC, et al. A worldwide metaanalysis on the use of zidovudine and interferon-alpha in adult
T-cell leukemia/lymphoma: improved survival in the leukemic
subtypes. J Clin Oncol 2010; in press.
35. Tsukasaki K, Hermine O, Bazarbachi A, et al. Definition, prognostic
factors, treatment, and response criteria of adult T-cell leukemialymphoma: a proposal from an international consensus meeting. J
Clin Oncol 2009;27:453459.
36. Takasaki Y, Iwanaga M, Imaizumi Y, et al. Long-term study of
indolent adult T-cell leukemia-lymphoma (ATL). Blood 2010; in
press.
37. Tsukasaki K, Utsunomiya A, Fukuda H, et al. VCAP-AMPVECP compared with biweekly CHOP for adult T-cell leukemialymphoma: Japan Clinical Oncology Group Study JCOG9801. J
Clin Oncol 2007;25:54585464.
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Guidelines on Hepatobiliary Cancers in
the Middle East and North Africa Region
Muhammed Aasim Yusuf, FRCP Edin;a Vinay Kumar Kapoor, MS, FRCS;b Refaat Refaat Kamel, FRCS;c
Ather Kazmi, MRCP, FRCR;d Najam Uddin, FRCR;e Nehal Masood, MD;f and
Abdulmajeed Al-Abdulkareem, MD, FRCSC, FACS;g Lahore, Pakistan; Lucknow, India; Cairo, Egypt;
Karachi, Pakistan; and Riyadh, Kingdom of Saudi Arabia
Key Words
Middle East and North Africa region, MENA region, hepatobiliary
cancer, cancer
Abstract
The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) on Hepatobiliary Cancers address hepatocellular cancer,
cancer of the gallbladder, extrahepatic cholangiocarcinoma, and
intrahepatic cholangiocarcinoma. Hepatocellular cancer incidence
is higher in the Middle East and North Africa (MENA) region than
in the West, and hepatitis B and C infections are particularly important; the incidence of gallbladder cancer is among the highest
in the world. Regional problems include delay in diagnosis, shortage of trained staff, and insufficient liver transplant facilities. Furthermore, costs associated with molecular and targeted therapies
are an increasing concern. A committee was formed, consisting
of leading specialists and decision-makers from the region, with
each member being tasked to suggest modifications to the existing guidelines based on review of the literature and consultations
From the aDepartment of Gastroenterology, Shaukat Khanum

Memorial Cancer Hospital and Research Centre, Lahore, Pakistan;
b
Surgical Gastroenterology, Sanjay Gandhi Postgraduate Institute
of Medical Sciences, Lucknow, India; cHepatobiliary Surgery &
Liver Transplantation, Ein Shams University, Cairo, Egypt; dClinical
Oncology, Shaukat Khanum Memorial Cancer Hospital and
Research Centre, Lahore, Pakistan; eInterventional Radiology,
Shaukat Khanum Memorial Cancer Hospital and Research Centre,
Lahore, Pakistan; fMedical Oncology, Aga Khan University Hospital,
Karachi, Pakistan; and gDepartment of Hepatobiliary Sciences and
Liver Transplantation, King Abdul Aziz Medical City, King Fahad
National Guard Hospital, Riyadh, Kingdom of Saudi Arabia.
arrangements, or affiliations with the manufacturers of any
products discussed in this article or their competitors.
Correspondence: Muhammed Aasim Yusuf, FRCP Edin, Shaukat
Khanum Memorial Cancer Hospital and Research Centre, Lahore,
Pakistan. E-mail: aasim@skm.org.pk
with local colleagues. This committee met as a group, and then

continued to discuss and debate the suggested modifications electronically. Several recommendations were finalized after vigorous
debate. The final approved recommendations were then presented in April 2009 to the chair of the NCCN Hepatobiliary Cancers
Panel for onward transmission and approval. This project represents an effort to modify and implement the NCCN Guidelines on
Hepatobiliary Cancers in the MENA region, while taking into consideration local differences in patient and disease characteristics.
The hope is that this will form the basis of future local, regional,
and international cooperation in guideline development and research. (JNCCN 2010;8[Suppl 3]:S36S40)
The 2009 version of the NCCN Clinical Practice Guide-
lines in Oncology (NCCN Guidelines) on Hepatobiliary Cancers (to view the most recent version of these
guidelines, visit the NCCN Web site at www.NCCN.
org) addresses 4 main tumor groups: hepatocellular cancer, cancer of the gallbladder, extrahepatic cholangiocarcinoma, and intrahepatic cholangiocarcinoma.
The incidence of hepatocellular cancer seems to be
significantly higher in the Middle East and North Africa (MENA) region than in the West. The age-standardized incidence rate is 12.8 per 100,000 population in
Egypt,1 8 per 100,000 in Pakistan,2 and 4.2 per 100,000
in Saudi Arabia,3 compared with 2.5 per 100,000 in the
United States.4
The region also shares some unique regional risk
factors. Hepatitis B and C infections seem to be particularly important. A predominance of hepatitis B virus
surface antigen is seen in patients with hepatocellular
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Hepatobiliary Cancer
cancer from most Asian, African, and Latin American countries; hepatitis C predominates in Japan,
Pakistan, Mongolia, and Egypt.5
Although the MENA region is not homogeneous, most countries represented in the committee have some common issues, albeit to a variable
extent. These include delay in diagnosis, often from
an absence of screening programs in those infected
with hepatitis B or C, and a shortage of trained staff
required for diagnosis and treatment, including gastroenterologists/hepatologists, radiologists, hepatobiliary surgeons, and oncologists. Furthermore, insufficient or, in some cases, nonexistent liver transplant
facilities are a serious limitation to treatment for
some patients. Pakistan, with a population of more
than 170 million, has no liver transplant program.
India has 3 centers, performing a total of 550 transplants annually. Egypt has 10 centers, with 150 to 200
transplants performed per year, whereas Saudi Arabia
has 3 centers, performing 120 transplants annually.
The costs associated with diagnosis and treatment
are an increasing concern in an age of molecular and
targeted therapies. Sorafenib for treating hepatocellular
carcinoma, for example, is too expensive to be used by
most eligible patients in many countries. It is currently
recommended primarily in patients with Childs A disease, precluding its use in most patients in the MENA
region. Additionally, the modest benefit in survival
improvement means that both patients and physicians
question the cost/benefit analysis.
Shortage of trained staff is a major problem in
many countries in the region. Interventional radiologists are a rare species in many countries. Currently,
only 4 centers in Pakistan offer transarterial chemoembolization, with each performing fewer than 500
procedures per year, for an estimated 15,000 new cases
per year. A dearth of surgical expertise for liver resection and transplantation exists across the region.
Therefore, numerous challenges exist in the region. A large number of patients have hepatitis B
and C infections, suggesting a huge tumor load in
the future. Patients present at an advanced stage,
with poor background liver function in up to half,
thus precluding many treatment options. A culture
of cooperation between different specialties is often
lacking, with multidisciplinary care the exception
rather than the norm. This results in squandering of
research opportunities and lack of progress at the local, national, and regional levels.
Typical Journey of a Patient With

Hepatocellular Carcinoma in Pakistan
Abdominal pain leads to investigation, and usually
the discovery of hepatitis C infection. Abdominal
imaging, usually with ultrasonography, leads to the
finding of a mass or masses in the liver. Most patients
will have access to biphasic CT scanning, usually at
a referral center or in the private sector. However, up
to 85% may be unsuitable for treatment based on extent of disease or poor liver function. The remainder
are offered various treatments, but cost issues often
limit patient acceptance, especially for sorafenib,
which only 1 in 8 patients will accept at Shaukat
Khanum Memorial Cancer Hospital in Lahore.
In a single-center experience in Pakistan,2 586
patients were diagnosed with hepatocellular cancer
over a 10-year period. Most presented with large,
multifocal tumors (mean cross-sectional diameter, 8
cm). Background liver function, assessed according
to Child-Pugh status, was poor (B to C) in 46%. Median survival after diagnosis was 10.5 months, with
1-, 3-, and 5-year survival rates of 45%, 20%, and
10%, respectively (Figure 1).
Regarding gall bladder cancer, the highest incidence rates worldwide were reported for women in Delhi, India (21.5/100,000); South Karachi, Pakistan (13.8/100,000); and Quito, Ecuador
(12.9/100,000).6 Risk factors for gallbladder cancer
include gallstones, particularly those associated with
chronic cholecystitis; calcified (porcelain) gallbladder; gallbladder polyps; typhoid carrier; obesity; multiparity; and chronic infection with Helicobacter bilis
and H pylori.6,7 Gallstone disease has been shown to
start at a younger age in Northern India and Kashmir.8 Decreasing biliary tract cancer mortality worldwide reflects more widespread and earlier adoption of
cholecystectomy. However, in many high-risk areas,
including Pakistan and India, access to gallbladder
surgery remains patchy and inadequate.9
Methods
After the successful development of regional NCCN
guidelines for Korea and China, a committee was formulated in November 2008 to begin developing regional guidelines for the MENA region. The committee also had major representation from South Asia.
The initial group consisted of the various committee
chairs. Each committee chair then began identifying
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Yusuf et al.
1.0
.9
.8
Cumulative Survival
.7
.6
Median survival time: 10.5 months
.5
.4
.3
.2
.1
0
12
24
36
48
60
72
84
96
108
Months
Figure 1 Overall survival of patients with hepatocellular

carcinoma.
From Yusuf MA, Badar F, Meerza F, et al. Survival from hepatocellular carcinoma at a cancer hospital in Pakistan. Asian Pac J
Cancer Prev 2007;8:273; with permission.
and inviting leading specialists and decision-makers

from the region to participate. Each member was
asked to suggest modifications to the existing guidelines, based on review of the literature and after consultations with local colleagues. The committee met
in Dubai in January 2009 to discuss and debate the
various suggested modifications. Further modifications
followed, with most discussion and changes occurring by email. All members were required to provide
references from the literature for any modifications
to be approved. The committee then met again, on
the sidelines of the NCCNMENA meeting in Abu
Dhabi in April 2009, to finalize the presentation and
recommendations. These were then presented to the
chair of the NCCN Hepatobiliary Cancers Panel for
onward transmission and approval.
Recommended Modifications
Table of Contents
The committee suggested adding The NCCN believes that all cancer patients should be managed
by a multidisciplinary team, and preferably in a
specialist center.
Hepatocellular Carcinoma
Screening: The committee suggested modifying

footnote b to read Imaging of those with elevated
AFP [alpha-fetoprotein] should be with CT/MR,
and not with ultrasound scan [USS]. If CT/MR is

normal, then follow-up imaging will be with USS.10
This recommendation was made because contrastenhanced ultrasound scan is not widely available in
the MENA region.
Diagnosis: The committee suggested amending biopsy to read FNAC/biopsy and adding a footnote
stating that FNAC appropriate if cytopathology expertise available. The rationale for this recommendation is that fine-needle aspiration (FNA) may be
easier and safer and requires less monitoring. Furthermore, it may be associated with fewer complications
and is often less expensive than liver biopsy.
Workup: The committee recommended amending
footnote g to read assess liver reserve using combination of Child-Pugh score, estimation of residual
liver volume, and assessment of portal hypertension
(e.g., varices, splenomegaly, thrombocytopenia, and
measurement of portal vein pressure, where available).1012 The committee believed that these additional modalities helped to more appropriately
select patients who would be suitable for surgery,
particularly resection.
The committee also suggested adding a footnote
after AFP stating AFP > 1000 is suggestive of microvascular invasion in tumors > 5 cm. These patients are not suitable for transplantation.13
Surgical Assessment: The committee suggested replacing Childs A, B with Childs A because they
believed that this was more in agreement with the
American Association for the Study of Liver Disease
(AASLD) guidelines, which state that Patients
who have a single lesion can be offered surgical resection if they are noncirrhotic or have cirrhosis
but still have well-preserved liver function, normal
bilirubin, and hepatic vein pressure gradient < 10
mm Hg.10 The committee believed that those with
poorer liver function (i.e., patients with Childs B)
probably should be considered for transplantation
rather than resection.
For transplant candidates, the committee suggested adding a footnote stating Ablation techniques can be considered in selected patients waiting
for a transplant, especially when the waiting time is
more than 6 months.10,14 The committee also suggested adding a footnote stating Patients originally
deemed unsuitable for transplant may be reconsidered for transplant after ablative therapies.15
Unresectable Clinical Presentation: The commit-
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Hepatobiliary Cancer
tee recommended changing footnote r, dealing

with the use of sorafenib, from There are limited
safety data available for patients with Child-Pugh
class B. Use with extreme caution in patients with
elevated bilirubin levels to read There are limited
safety data available for patients with Child-Pugh
class B and dosing is uncertain. Extreme caution is
required and participation in clinical trials is recommended. The committee members believed that
data were insufficient to recommend anything more
than this.
Gallbladder
For workup of jaundiced patients, the committee suggested changing cholangiography to ERCP/PTC
+ biliary drainage (+ biopsy if possible) if obstruction confirmed. The committee members believed
that magnetic resonance cholangiopancreatography
was less likely to be useful in jaundiced patients,
because many or most would also require a biliary
drainage procedure.
The committee also believed that biliary drainage should be removed from the primary treatment
column, because this should be performed normally
during the diagnostic workup.
Intrahepatic Cholangiocarcinoma
Although not disagreeing with resection as a possible

treatment for intrahepatic cholangiocarcinoma, the
committee believed it important to add a footnote
stating that There is no level 1 data with regard to
the value of hepatic resection in this situation.
Extrahepatic Cholangiocarcinoma
In workup, the committee suggested changing cholangiography to ERCP/PTC + biliary drainage (+

biopsy if possible) if obstruction confirmed. The
committee also believed that biliary drainage
should be removed from the primary treatment column, because this should be performed normally during the diagnostic workup.
For Resected, negative margin (R0), negative regional nodes, the committee recommended
removing the chemotherapy option because they
believed the benefit of adjuvant chemotherapy remains unproven, and the only randomized trial examining this did not show any benefit in treating
cholangiocarcinoma.16 The committee also recommended that the chemotherapy + radiation therapy
(XRT) option be removed because of conflicting
data regarding adjuvant chemoradiation. No ran-
domized trials specifically address this treatment,

and most retrospective series consisted of a mix of
R0 and R1 tumors. No clear evidence shows that
adjuvant chemoradiation improves outcomes in
patients with R0 cancers. The committee believed
it reasonable to leave Observe or clinical trial as
the only 2 available options.
Conclusions
This initiative represents the first effort in the
MENA region to implement transnational guidelines, with content based on the NCCN guidelines
but modified to take into consideration local differences in patient and disease characteristics. Every
effort was made to recommend modifications based
on the literature or, at the minimum, best practice
in the region, and backed by expert opinion. This
project could form the basis of future cooperation,
not only in guideline development and modification, but also in research. It became painfully obvious to all involved in this effort that little local
research data was available on which to base suggested modifications. This finding highlighted the
need for regional cooperation and the development
of research protocols to study these common diseases in the MENA region. Great disparity exists
within the MENA region in terms of patients and
resources, but many similarities are also present.
The committee members hope to revisit this subject at regular intervals, and look forward to when
all cancer care in this region follows treatment
guidelines derived from robust local data.
Acknowledgments
The following also contributed to the process of
guideline formulation and revision, as members of
the NCCNMENA Hepatobiliary Guidelines Review Committee: Khalid Omer Abdullah, King Fahad National Guard Hospital, Riyadh, Kingdom of
Saudi Arabia; Hassan Jaafar, Tawam Hospital, AlAin, United Arab Emirates; Kakil Ibrahim Rasul,
Hamad Medical Corporation, Doha, Qatar; Suayib
Yalcin, Hacettepe University Institute of Oncology,
Ankara, Turkey; and Abdel-Rahman El-Zayadi, Ain
Shams University, Cairo, Egypt.
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Yusuf et al.
References
1. Ibrahim AS. Liver and intrahepatic bile duct cancer. Available at:
http://seer.cancer.gov/publications/mecc/mecc_liver.pdf. Accessed
March 31, 2010.
9. Randi G, Malvezzi M, Levi F, et al. Epidemiology of biliary tract

cancers: an update. Ann Oncol 2009;20:146159.
10. Bruix, J, Sherman, M. AASLD practice guideline: management of
hepatocellular carcinoma. Hepatology 2005;42:12081236.
2. Yusuf MA, Badar F, Meerza F, et al. Survival from hepatocellular

carcinoma at a cancer hospital in Pakistan. Asian Pac J Cancer
Prev 2007;8:272274.
11. Llovet JM, Fuster J, Bruix J. Intention-to-treat analysis of surgical

treatment for early hepatocellular carcinoma: resection versus
transplantation. Hepatology 1999;30:14341440.
3. Kindgom of Saudi Arabia Ministry of Health National Cancer

Registry. Cancer incidence report Saudi Arabia 2003. Available at:
http://www.kfshrc.edu.sa/oncology/files/NCR2003.pdf. Accessed
March 31, 2010.
12. Bruix J, Castells A, Bosch J, et al. Surgical resection of hepatocellular

carcinoma in cirrhotic patients: prognostic value of preoperative
portal pressure. Gastroenterology 1996;111:10181022.
4. Carr BI, ed. Hepatocellular cancer: diagnosis and treatment.

Totowa (NJ): Humana Press; 2005.
5. Raza SA, Clifford GM, Franceschi S. Worldwide variation in
the relative importance of hepatitis B and hepatitis C viruses
in hepatocellular carcinoma: a systematic review. Br J Cancer
2007;96:11271134.
6. Randi G, Franceschi S, La Vecchia C. Gallbladder cancer
worldwide: geographical distribution and risk factors. Int J Cancer
2006;118:15911602.
7. Kapoor VK, McMichael AJ. Gallbladder cancer: an Indian
disease. Natl Med J India 2003;16:209213.
8. Khuroo MS, Mahajan R, Zargar SA, et al. Prevalence of biliary
tract disease in India: a sonographic study in adult population in
Kashmir. Gut 1989;30:201205.
13. Pawlik TM, Delman KA, Vauthey JN, et al. Tumor size predicts
vascular invasion and histologic grade: implications for selection
of surgical treatment for hepatocellular carcinoma. Liver Transpl
2005;11:10861092.
14. Llovet JM, Mas X, Aponte JJ, et al. Cost effectiveness of adjuvant
therapy for hepatocellular carcinoma during the waiting list for
liver transplantation. Gut 2002;50:123128.
15. Yao FY, Kerlan RK Jr, Hirose R, et al. Excellent outcome
following down-staging of hepatocellular carcinoma prior to
liver transplantation: an intention-to-treat analysis. Hepatology
2008;48:819827.
16. Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant
chemotherapy useful for gallbladder carcinoma? A phase III
multicenter prospective randomized controlled trial in patients with
resected pancreatobiliary carcinoma. Cancer 2002;95:16851695.
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Guidelines on Palliative Care in the
Omar Shamieh, MD, and Abdul-Rahman Jazieh, MD, MPH, Riyadh, Kingdom of Saudi Arabia
Key Words
Middle East and North Africa, palliative care, cancer
Abstract
Palliative care is an important component of cancer treatment.
Advancing palliative care in the developing countries is essential
to improving patient care. The issues limiting its practice must be
addressed, especially in light of the initiative to adapt the NCCN
Clinical Practice Guidelines in Oncology (NCCN Guidelines) to the
Middle East and North Africa (MENA) region. Palliative care is in
its early stage of evolution in the MENA region, and its practice
encounters many challenges and barriers. Adaptation of guidelines should take into consideration the situation and conditions
in the targeted region to improve the standard of care to an internationally acceptable level. A group of experts in the MENA
region reviewed the literature and collaborated to assess the current status of palliative care and recommend modifications to the
NCCN Guidelines based on the unique needs of the region. (JNCCN
2010;8[Suppl 3]:S41S47)
SAn initiative was launched to adapt several of the

NCCN Clinical Practice Guidelines in Oncology
(NCCN Guidelines) to the Middle East and North
Africa (MENA) region. Palliative care was one area
of cancer treatment selected because of its high level
of importance. To better understand how to adapt the
From the Department of Oncology, King Saud bin Abdulaziz
University for Health Sciences, Riyadh, Kingdom of Saudi Arabia.
arrangements, or afiliations with the manufacturers of any
products discussed in the article or their competitors.
Correspondence: Omar Shamieh, MD, Department of Oncology,
King Saud bin Abdulaziz University for Health Sciences, Mail Code
1777, P.O. Box 22490, Riyadh 11426, Kingdom of Saudi Arabia.
E-mail: shamieho@ngha.med.sa
NCCN Guidelines on Palliative Care in this region, the

current status of palliative care had to be assessed. This
article addresses the practice of palliative care in the
MENA region.
Population and Religion

In our review, we evaluated 19 Arab countries of the
MENA region, with 12 of these in Asia (Saudi Arabia,
Kuwait, Qatar, United Arab Emirates, Bahrain, Oman,
Yemen, Iraq, Palestinian Authorities, Jordan, Syria, and
Lebanon) and the remainder in Northern Africa (Egypt,
Sudan, Libya, Morocco, Tunisia, Algeria, and Djibouti).1,2 The total population of the MENA region exceeds
326 million (Table 1), with Arabic the official and most
common language. The predominant religion is Islam,
although other religions exist for the native population
or expatriates. These countries have a wide heterogeneity of culture, religious practices and adherence, and
social issues.
Palliative care principles are aligned and applicable
to all religions and faiths.3 Although palliative care
concepts and practice are more accepted by health care
professionals, patients, and families, than in the past,
families may tend to withhold, and persuade health care
providers to withhold, information from patients, even
at end of life. Furthermore, resistance to opioid use by
individuals and providers in this region is usually a result of misconceptions and attitude, in addition to religious misinterpretation.4
Economy and Health Care Finance

The economic classifications of these countries vary
widely, ranging from those that are wealthy to those
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Shamieh and Jazieh
Table 1 Cancer Mortality and Opioid Consumption in the Middle East and North Africa Countries
Country
Population19
Mortality From Cancer5

(Estimated Cause of Death 2005)
Opioid Consumption
2007 (kg)12
Algeria
33.4 M
19,000
Bahrain
0.7 M
370
Djibouti
0.5 M
460
NA
Egypt
83 M
42,000
Iraq
27.5 M
15,000
NA
Jordan
6M
3700
11
Kuwait
2.5 M
700
11
Lebanon
4M
2600
Libya
6M
2700
NA
Morocco
33 M
13,000
Oman
3.2 M
1200
Palestinian Authority
4M
NA
NA
Qatar
0.9 M
160
Saudi Arabia
27.6
12,000
13
Sudan
39 M
22,000
NA
Syria
19 M
5000
NA
Tunisia
10.1 M
6000
20
United Arab Emirates
4.4 M
1200
Yemen
22 M
10,000
NA
TOTAL
326.8 M
157,090*
85
Abbreviation: NA, not available.

*Cancer mortality exceeds 200,000 accounting for all MENA countries.
with very limited resources. Household incomes,

health care expenditure, and human development
also vary widely. People tend to migrate from rural
to urban areas, increasing the isolation of the rural
areas and placing more governmental focus on large
cities, resulting in an underserved rural population.3
Health care systems in many countries havelimited resources and low expenditures. The government may provide most cancer care, either
partly or fully, to a portion of the population based
on available resources and services; however, many
countries may not have access to all treatment modalities. In view of this fact and other constraints,
many patients are unable to access the system or
afford treatment.3
Private cancer care is provided on an out-ofpocket basis rather than through organized insurance, and most countries do not a have a national
cancer control program.
Family Model
An obvious shift is occurring from the traditional
extended family model to a more nuclear, mobile,
and isolated family structure. Families and individuals tend to rely more and more on the health care
system and hospitals for the care of sick loved ones.
This shift has resulted in overuse of health care resources, emergency visits, and in-patient beds for
chronic and palliative care needs.3
Cancer Epidemiology
Despite the advancement in medical technology
and innovative therapeutics and pharmaceutical
products, a huge increase in cancer incidence has occurred not only in the MENA region but also worldwide. Cancer ranges from the third to the fifth leading cause of death.5 In 2005, approximately 200,000
cancer deaths occurred in MENA countries, with
approximately 60% of deaths in individuals younger
Supplement
Palliative Care
than 70 years (Table 1).5

Cancer incidence is underreported in most of
these countries, either because of the lack of cancer
registries or the absence of effective data collection.
Traditional Cancer Care Model

The traditional cancer care model in MENA countries almost follows an older cancer care model,
which is marked by delayed patient presentation as
a result of late detection, poor access, and late referrals, followed by an active anticancer treatment approach at diagnosis, ending with death or cessation
of anticancer therapy. Less attention is paid to pain
and symptom management, and poor end-of-life
care is available, if at all. Except for a few centers
mentioned later, no hospice palliative care model
exists in most of these countries. Even in countries
in which palliative care service is available, patients tend to be referred to palliative care late in
the trajectory of their illness.
Need for Palliative Care

The needs of patients with cancer in the MENA region does not differ greatly from those of patients in
the rest of the world. Patients diagnosed with cancer
have multiple domains of suffering, including physical, social, spiritual, practical, and psychological, as
a result of multiple levels of interactions with the
disease itself, or with relatives, care providers, health
care systems, and the community.
Palliative care should start from cancer diagnosis
for all patients, regardless of the type or stage, and
continue through the cancer journey for both survivors and advanced cases to end-of-life care. Palliative care should be delivered simultaneously with
disease-modifying treatment. The need for palliative
care increases as the disease progresses, until it is the
only focus of care.6
More than 80% of cancer cases are advanced
at presentation, making palliative care the only option for patients and highlighting the importance of
making palliative care services available for those
patients and their families.6
Using the WHO formula6 and multiplying cancer mortality (Table 1)5 by the percentage of advanced cases provides an approximate number of
patients in the MENA region needing palliative
care before they die in the given year, which was

160,000 for 2005 (200,000 x 0.8 = 160,000). Similarly, assuming one caregiver is needed per patient
with advanced cancer, the number of caregivers can
be estimated (> 160,000 in 2005).6
WHO Definition of Palliative Care

The WHO defines palliative care7 by noting that
palliative care improves quality of life of patients and
families facing a life-threatening illness by preventing and relieving suffering through early identification, assessment, and treatment of pain and other
physical, psychosocial, and spiritual problems. Palliative care:
Provides relief from pain and other distressing
symptoms;
Affirms life and considers dying a normal process;
Intends neither to hasten nor postpone death;
Integrates the psychological and spiritual aspects
of patient care;
Offers a support system to help patients live as
actively as possible until death;
Offers a support system to help the patients family
cope during the illness and through bereavement;
Uses a team approach to address the needs of patients and their families, including bereavement
counselling, if indicated;
Will enhance quality of life and may also positively influence the course of illness; and
Is applicable early in the course of illness, in conjunction with other therapies that are intended
to prolong life, such as chemotherapy or radiation therapy, and includes investigations needed
to better understand and manage distressing
clinical complications.
Current Palliative Care Services

Palliative care provision and development varies
widely among countries. Based on a pilot study report from the International Observatory on End of
Life Care, countries were divided into 4 categories
based on the level of hospice and palliative care development. Countries in the first level, or category 1,
have no available services for palliative care. Those
in the second level, or category 2, are in the capacity-building stage, in which the need for palliative
care is recognized and some awareness courses are
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Supplement
Shamieh and Jazieh
available. Countries in the third category, or level 3,

have a local provision, with one or more palliative
care programs established. Those in the fourth category, or level 4, have palliative care fully integrated
into the health care system.8
None of the MENA countries approached integration. Although some cancer centers in a few
countries have succeeded in integrating palliative
care into their existing institutions, the program is
not developed in the entire country.
An increasing number of countries are establishing a localized provision of palliative care, including Egypt, Iraq, Jordan, Morocco, Saudi Arabia, and
United Arab Emirates.9 At the time of this report,
Qatar, Tunisia, Sudan, and Kuwait started or are
starting to implement palliative care services.
Countries that have begun implementing various palliative capacity-building activities but have
no formal services available are Algeria, Bahrain,
Lebanon, Oman, and Palestinian Authority.9
Djibouti, Libya, and Syria have no known palliative care activities. Few countries are privileged
to have well-established centers of excellence for
comprehensive cancer care, such as the Kingdom of
Saudi Arabia.10
Most palliative care services in these countries
deliver excellent care to a certain portion of population, but do not offer wider coverage. In addition,
palliative care is still not included in the cancer control plan or any national health care policy.
Table 2 Barriers to Palliative Care Provisions in

Health care
professionals
Negative attitude to caring for the dying

patients
Fear of opioids use because of absence of
or inadequate training,
!!Fear of side effects
!!Fear of prosecution
Resources focused on cure and acute care
Perceived sense of failure
Patients and
families
Fear of addiction
Fear of abandoning
Unrealistic hope
Diversity in religious interpretation
Health care
system
Acute care focus dictates the allocation

of resources to acute care rather than
palliative care
Lack of space and resources for palliative
care
Less priority of palliative and end-of-life
care in the health care strategy
Scarce long-term and community services
Manpower
Lack of palliative care expert physicians,

nurses, medical social workers, and
medical religious advisors
Lack of interdisciplinary teams
Drugs
Lack of opioids
Very strict opioid prescriptions and
dispensing policies
Unavailability of opioids in peripheral
centers
Lack of essential medications
Barriers to Palliative Care Provision
Education
Many barriers exist to the availability, access, and

provision of palliative care, such as those summarized in Table 2.
Lack of palliative care education

programs and curriculum at all levels of
education
Funding
No funds for education, building

programs, or hiring experts
Policy
Lack of national policies, including those

regarding palliative care
Opioid Availability
Pain is underreported and undertreated in most of

the world.6 Morphine consumption has been used by
the WHO to measure pain control and, ultimately,
provision of palliative care.3 According to the International Narcotics Controlling Board report in 2007,
the total estimated reported morphine consumption
is 84 kg for all MENA countries.11,12
Opioid availability varies across the region.
Highest consumption has been reported in Tunisia
based on the absolute quantity, total population, and
total reported cancer mortality.
Barriers to pain control are almost universal, and
include fear of opioids, unavailability of medications,

poor access to medication, lack of education, and
fear of addiction.13
The amount of morphine needed can be predicted through calculating the estimated need of
oral morphine for each patient who died of cancer.
Assuming that each patient will require 100 mg/d of
oral morphine in the last 3 months of life, an estimated 10 g of oral morphine will be needed per patient. Then, in multiplying this number by the esti-
Supplement
Palliative Care
mated number of patients who died of cancer (Table

1; 200,000),14 the predicted need of oral morphine
required to control pain in those patients is determined to be approximately 2000 kg. This number
is less than 5% of the reported consumption of less
than 100 kg.
Notably, this estimation does not take into account the other needs for opioids to control pain
in cancer survivors, such as noncancer-related
or postoperative pain, further illustrating the huge
gap existing between the actual need and the
current consumption.
One major factor contributing to opioid underuse in the MENA countries is that they are not available. However, simply making opioids available will
not solve the problem; a simultaneous and effective
educational program is needed for health care workers, patients, families, communities, religious workers, government, and leaders, along with sufficient
manpower to develop palliative care initiatives.
Another important factor contributing to inadequate pain control is the existence of rigid and
strict opioid or narcotic policies (Table 2), which
are implemented as a result of fear regarding abuse
and misuse. These policies must be revised and
made flexible to allow sufficient supply and effective pain control, while at the same time maintaining accountability.11
Years ago, WHO advocated establishing recommendations and guidelines to improve cancer pain
control. The recommended strategy is summarized in
the following steps:15
The country should make cancer pain relief a
high priority in the form of health care policy.
An educational program should target officials,
policy makers, and regulators to increase awareness of the possibility and importance of managing cancer pain.
An educational program should be established to
train health care providers to treat cancer pain.
Analgesics, including opioids, should be made
available.
Education
Palliative care educational opportunities are scarce

in MENA countries. Formal palliative care education is minimal. Most palliative care expertise is
gained through education in countries with more
advanced palliative care programs, such as North
America and Europe. An increasing number of sen-
sitization courses are occurring in the MENA countries, such as in Jordan, Egypt, and Saudi Arabia.9
More formal palliative care training in the form
of advanced fellowships and well-developed palliative care curricula in medical schools do exist in
countries like Saudi Arabia; however, other countries have no educational provision at all.
Palliative care education is an integral part of establishing an effective palliative care program. The
level of educational needs varies among specialty
institutions and communities. Basic palliative care
knowledge is essential to all health care providers,
regardless of specialty, service, or settings.14 More
advanced skills and expert training will be needed
for services, with the highest demand in disciplines
such as oncology, intensive care, and infectious diseases to ensure implementation of best palliative
care practices.14
A palliative care curriculum should be incorporated into undergraduate nursing and medical school
education, residency training programs, and highdemanding fellowships such as oncology.
Funding
The field of palliative care seems to be a great opportunity for countries with limited resources to provide
care for patients while developing the other components of a comprehensive cancer control program,
ranging from prevention and early detection to optimal treatment.16 Palliative care should be delivered
in a cost-effective manner and can be provided in
less-served cities and communities in all countries,
not just those with limited resources.
However, funding for palliative care is challenging for many reasons, including underrecognition of
the importance of this field, resulting in inadequate
resource allocation and government support. Existing and evolving programs in countries with limited
resources must identify sources of financial support.
Establishing a national policy for palliative care
might allow governments to take some responsibility
for funding.
Countries with a disadvantaged financial and
economic situation may seek support and funding
from community resources, nongovernmental entities, local philanthropist associations, or international organizations, such as the International Association for Hospice and Palliative Care.16
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Supplement
Shamieh and Jazieh
Recommendations to Improve
Palliative Care in MENA Countries
Every country should aim to integrate pain relief and
palliative care into the mainstream of health care.
Pain relief and palliative care should be available
to all populations, although this article only focuses
on those with cancer. However, palliative care can
benefit all patients with advanced illness, including
those with HIV, dementia, and organ failure.17
Furthermore, palliative care should be available
to patients everywhere, not only those in major cities or tertiary cancer centers. Access to these services
should be available to peripheral cities and disadvantaged communities. Initiatives to improve palliative
care should include policy development, program
implementation, opioid availability, and education.14
Palliative care education should be available to all
health care providers, medical and nursing schools,
and training programs.
The most effective strategy for implementing a
palliative care program is a public health initiative
that incorporates all levels of the health care system,
government leadership, and the community. This
approach should benefit not only patients and families but also society as a whole.14
NCCN Guidelines for Palliative Care

and Cancer Pain Management
The successful implementation of NCCN palliative
care and cancer pain management guidelines depends on acceptance of the following principles:
Palliative care is an integral part of effective and
comprehensive cancer care.
Palliative care should be introduced as early as
the time of diagnosis.
All health care providers, health care leaders,
pharmaceutical leaders, government leaders,
and religious scholars dealing with patients with
cancer must be aware of the importance of palliative care.
Basic palliative care education is needed for all
oncologists and cancer care providers at all levels of care, including inpatient, outpatient, and
extended care facilities in both private and public sectors.18
Opioids and essential drugs must be available to
manage pain and distressing symptoms.
Cancer and palliative care should be delivered
using an interdisciplinary approach; treatment

programs should involve effective multidisciplinary teams to deliver the most comprehensive care.18
Adapting the NCCN guidelines to the MENA
region may trigger a systemic evaluation of the status
and needs regarding palliative care so that the highest possible standards of care can be implemented.
References
1. League of Arab States. Member Countries. Available at: http://
www.arableagueonline.org/las/index.jsp. Accessed March 31, 2010.
2. UNICEF. Middle East and North Africa. Available at: http://www.
unicef.org/infobycountry/northafrica.html. Accessed March 31,
2010.
3. De Lima L, Hamzah E. Socioeconomic, cultural and political issues
in palliative care. In: Bruera E, De Lima L, Wenk R, Farr W, eds.
Palliative Care in the Developing World: Principles and Practice.
Houston: IAHPC Press; 2004:2338.
4. Al-Shahri M, al-Khanizan A. Palliative care for Muslim patients. J
Support Oncol 2005;3:432436.
5. World Health Organization. WHO Global InfoBase: Data for
saving lives. Available at: https://apps.who.int/infobase/report.
aspx?rid=126. Accessed March 31, 2010.
6. Cancer Control: Knowledge Into Action: WHO Guide for Effective
Programmes: Palliative Care. Available at: http://www.who.int/
cancer/media/FINAL-PalliativeCareModule.pdf. Accessed March
31, 2010.
7. World Health Organization. WHO Definition of Palliative Care.
Available at: http://www.who.int/cancer/palliative/definition/en.
Accessed March 31, 2010.
8. Wright M, Wood J, Lynch T, Clark D. Mapping levels of palliative
care development: a global view. J Pain Symptom Manage
2008;35:469485.
9. Shamieh O. Building Capacity for Palliative Care at King Abdulaziz
Medical City, Riyadh, Saudi Arabia [International Association for
Hospice & Palliative Care Web site]. Available at: http://www.
hospicecare.com/news/09/03/regional_reports_saudi_arabia_asia.
html. Accessed March 31, 2010.
10. Stjernswrd J, Ferris FD, Khleif SN, et al. Jordan palliative care
initiative: a WHO Demonstration Project. J Pain Symptom
Manage 2007;33:628633.
11. International Narcotics Control Board. Report of the International
Narcotics Control Board for 2008. Available at: http://www.incb.
org/pdf/annual-report/2008/en/AR_08_English.pdf.
Accessed
March 31, 2010.
12. Table XII. Consumption of principal narcotic drugs, 20032007,
INCB statistical tables Available at: http://www.incb.org/incb/en/
narcotic_drugs_stat_tables.html. Accessed March 31, 2010.
13. Isbister WH, Bonifant J. Implementation of the World Health
Organization analgesic ladder in Saudi Arabia. Palliat Med
2001;15:135140.
14. Stjernswrd J, Foley KM, Ferris FD. The public health strategy for
palliative care. J Pain Symptom Manage 2007;33:486493.
15. Joranson D. Availability of Opioids for cancer pain: recent trends,
assessment of system barriers. New World Health Organization
Supplement
Palliative Care
guidelines and the risk of diversion. J Pain Symptom Manage
1993;8:353360.
hrsa.gov/publications/palliative/palliative_care-who_approach.
htm. Accessed March 31, 2010.
16. Callaway M, Foley K, De Lima L, et al. Funding for palliative

care programs in developing countries. J Pain Symptom Manage
2007;33:509513.
18. Ferris F, Bruera E, Cherny N, et al. Palliative cancer care a decade

later: accomplishments, the need, next stepsfrom the American
Society of Clinical Oncology. J Clin Oncol 2009;27:30523058.
17. Sepulveda C. Palliative care in resource-constrained settings for

people living with HIV and other life threatening illnesses: the
World Health Organization approach. Available at: http://hab.
19. The World Factbook. Washington, DC: CIA, 2009. Available from
at: https://www.cia.gov/library/publications/the-world factbook/
region/region_mde.html. Accessed August 2009.
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S U P P L E M E N T

Journal of the National Comprehensive Cancer Network

The Abu Dhabi Declaration: Adapted

NonSmall Cell Lung Cancer

Fikri li, Hakan Akbulut, Shouki Bazarbashi, et al.

Volume 8 Supplement 3 Journal of the National Comprehensive Cancer Network

Postal and Contact Information

Volume 8 Supplement 3 Journal of the National Comprehensive Cancer Network

JNCCN is dedicated to improving the quality of cancer care locally,

About the NCCN

Volume 8 Supplement 3 Journal of the National Comprehensive Cancer Network

S-2 Editorial: The Abu Dhabi Declaration: Why the Hustle?

Volume 8 Supplement 3 Journal of the National Comprehensive Cancer Network

S-36 Modification and Implementation of NCCN Guidelines on Hepatobiliary Cancer in the

Omar Shamieh, MD, and Abdul-Rahman Jazieh, MD, MPH

Journal of the National Comprehensive Cancer Network

William T. McGivney, PhD

The ideas and viewpoints

Journal of the National Comprehensive Cancer Network

The Abu Dhabi Declaration: Why the Hustle?

Hamdy A. Azim, MD, PhD

Abdul-Rahman Jazieh, MD,

Differences in Racial, Genetic, and Environmental Factors

The Abu Dhabi Declaration

Differences in Presenting Features and Stage

Mohammad Jahanzeb, MD,

Differences in Access to Technology and Drugs

The ideas and viewpoints

The Abu Dhabi Declaration

technologies can then be channelled to the subsets of

small-cell lung cancer to gefitinib. N Engl J Med 2004;350:2129

The Process of NCCN Guidelines

From the aDepartment of Oncology, King Saud bin Abdulaziz

The National Comprehensive Cancer Network

The committee members reviewed the 2009 versions

List page number in

Write specific clinical

Explain the reason for

Process of NCCN Guidelines Adaptation to MENA Region

To maintain NCCN standards, the best available

Modification and Implementation of NCCN

on Breast Cancer for use in the MENA region to achieve common

Breast cancer is the most common malignant disease

countries, including the United States, Canada,

The GCCR data showed that breast cancer was

ASR per 100,000

suspicion by primary physicians.9

Figure 2 Stage distribution of breast cancer, 19982005.

because of lack of access to radiotherapy facilities

Follow Up Time (Years)

Figure 3 Relation of young age to worse prognosis in breast cancer.

Radiation Treatment Centers

*Source: International Atomic Energy Agency IAEA 2007 (www.iaea.org)

most commonly used drugs, either in combination or

Material and Methods

NCCN Clinical Practice Guidelines in Oncology

Specific Recommended Modifications

Invasive Breast Cancer

Recommendations: Delete lumpectomy without radiation.

Recommendations: Sentinel lymph node biopsy is

Recommendations: Setup for infrastructure, genetic

Recommendations: Treatment with adjuvant

Recommendations: Recommendation should read