Approach To The Diagnosis

Of A Cancer Patient
Felycette Gay P. Martinez-Lapus, M.D., FPCP, FPSMO, FPSO
Internal Medicine Medical Oncology

CANCER CARE CONTINUUM

Prevention
Screening
Diagnosis
Pre-treatment evaluation
Therapy
Continuing care and rehabilitation
Terminal care

PREVENTION
Primary Prevention

Efforts to reduce or eliminate exposures to

carcinogens in order to prevent the
initiation or promotion of the fundamental
carcinogenic processes:
Tobacco use
Alcohol consumption
Diet modification
Radiation exposure
Infections
Medications
Occupational & environmental exposures

PREVENTION

Chemoprevention
Involves the use of specific natural or
synthetic chemical agents to reverse,
suppress or prevent carcinogenesis before
the development of invasive malignancy.
Tamoxifen for Breast CA
NSAIDs for Colon CA
Vaccines

PREVENTION

Secondary Prevention
Screening & early detection programs that
seek to identify cases early in their
development, so that chances for cure are
enhanced:
Breast self-examination/Mammogram
Pap smear
Digital rectal exam/FOBT + Sigmoidoscopy
Oral exam
PSA determination

PREVENTION

Tertiary Prevention
Treatment of cancer patients that seek
to prevent undue clinical complications or
premature deaths

CANCER CARE CONTINUUM

Prevention
Screening
Diagnosis
Pre-treatment evaluation
Therapy
Continuing care and rehabilitation
Terminal care

DIAGNOSIS
Pathological or tissue diagnosis is CRITICAL
Anatomic origin
Type/classification
Grade
Pathological & clinical diagnosis MUST be
consistent
It is RARELY ACCEPTABLE to initiate
treatment based solely on clinical exam,
radiologic evidence and nontissue laboratory
evidence like tumor markers

DIAGNOSIS
RARELY, treatment without a pathological
diagnosis is done only if:
clinical features strongly suggest the
diagnosis of cancer and the likelihood of a
benign diagnosis is remote
withholding prompt treatment or carrying
out procedures required to establish a
diagnosis would greatly increase a patients
morbidity or risk of mortality

DIAGNOSIS
Investigations
Careful history & PE
Tissue biopsy
Blood sampling

Hematologic
Biochemical
Tumor markers
Radiologic studies

TUMOR MARKERS
Cellular products that are helpful in the
detection and diagnosis of certain cancers.
Types
Cell surface markers
Genetic markers

Tumor markers found in blood & other

body fluids

Oncofetal proteins
Hormones
Enzymes
Cancer antigens

DIAGNOSTIC IMAGING
Radiography
Routine flat plate studies
Mammography
Angiography
Computed tomography
Ultrasonography

DIAGNOSTIC IMAGING
Radioisotopes
PET
Lymphoscintigraphy
Bone scan
Thyroid scan
Magnetism
MRI

CANCER CARE CONTINUUM

Prevention
Screening
Diagnosis
Pre-treatment evaluation
Therapy
Continuing care and rehabilitation
Terminal care

PRE-TREATMENT EVALUATION
Patient Factors

Tumor Factors

Age & gender

Nutritional status
Weight
Performance status
Co-morbidity
Emotional factors
Socioeconomic status

Histology
Stage
Tempo

DECISION
Curative Intent Therapy

Palliative Intent Therapy

PERFORMAMCE STATUS
refers to the level of activity of which a
patient is capable
it is a measure independent from:
the anatomic extent
histologic characteristics
how much the cancer or co-morbid
conditions have affected the patient
prognostic indicator of how well the patient is
likely to respond to treatment

ECOG PERFORMANCE STATUS SCALE

(Eastern Cooperative Oncology Group)
GRADE
0
1
2
3
4

ACTIVITY
normal activity
symptomatic but
ambulatory; able to carry
out daily activities
out of bed >50%;
occasionally needs assistance
in bed >50%; needs skilled care
100% bedridden

PRE-TREATMENT EVALUATION
Patient Factors

Tumor Factors

Age & gender

Nutritional status
Weight
Performance status
Co-morbidity
Emotional factors
Socioeconomic status

Histology
Stage
Tempo

DECISION
Curative Intent Therapy

Palliative Intent Therapy

HISTOLOGY
Tumor type
Classification
Grade

PRE-TREATMENT EVALUATION
Patient Factors

Tumor Factors

Age & gender

Nutritional status
Weight
Performance status
Co-morbidity
Emotional factors
Socioeconomic status

Histology
Stage
Tempo

DECISION
Curative Intent Therapy

Palliative Intent Therapy

STAGE
Definition: the anatomic extent of the
disease
Reasons:
Measure and follow results of
treatment
Standardize the description of the
extent of disease in order to
accurately compare results of
treatment in different institutions

STAGE
Systems
AJCC & TNM Committee of the UICC
T
N
M

location, size, adjacent tissue involvement

loco-regional involvement with tumor
presence or absence of metastasis and
their location

Others
Ann Arbor
Dukes Classification
FIGO

PRE-TREATMENT EVALUATION
Patient Factors

Tumor Factors

Age & gender

Nutritional status
Weight
Performance status
Co-morbidity
Emotional factors
Socioeconomic status

Histology
Stage
Tempo

DECISION
Curative Intent Therapy

Palliative Intent Therapy

TEMPO
Severity of signs & symptoms
Duration of signs & symptoms
Interval of time between first diagnosis &
treatment, and the time of first recurrence

CANCER CARE CONTINUUM

Prevention
Screening
Diagnosis
Pre-treatment evaluation
Therapy
Continuing care and rehabilitation
Terminal care

MODALITIES OF TREATMENT
Surgery
Radiotherapy
Systemic therapy
Chemotherapy
Hormone therapy
Biologic therapy

SURGERY
A.

Diagnosis

Fine needle aspiration cytology

Core needle biopsy
Cutaneous punch biopsy
Incisional biopsy
Excisional biopsy

B. Staging
Mediastinoscopy
Laparotomy
Laparoscopy
Lymphadenectomy
Sentinel node biopsy

SURGERY
C. Treatment

Primary
Reduction of bulky disease
Resection for recurrent locoregional disease
Metastectomy with curative intent
Vascular access
Enteral feeding tubes
Palliation
Oncologic emergencies
Reconstruction

RADIATION THERAPY
Primary
In combination
Surgery + Radiotherapy
Chemotherapy + Radiotherapy
Surgery + Chemotherapy + Radiotherapy

RADIATION THERAPY
Palliation
Increase intracranial pressure
Obstruction of a conduit such as the esophagus,
bile duct or ureter
Pain or neurological impairment from lesions
involving the central or peripheral nervous
system
Bone pain
Airway obstruction, hemoptysis, stridor, pain,
dyspnea from lung & mediastinal tumors
Swelling, compression, pain from lymph node
metastases

RADIATION THERAPY
Emergency Situations:
spinal cord, cranial or peripheral nerve
compression
severe airway compromise
superior vena caval syndrome
massive bleeding
malignant cardiac tamponade

MEDICAL ONCOLOGY
Discipline that specializes in the use of
systemic forms of treatment for cancer
management
Systemic rather than localized
Tissue diagnosis
Efficient staging
Review of prognosis & treatment options with
the patient & family
Effective relief of pain
Coordination of various auxillary sevices

CHEMOTHERAPY
Use of systemic chemicals that have cytotoxic
effects which interfere with cell reproduction
Most effective in early stage disease because
of a low tumor cell burden
Lethal to both cancer and normal cells
Dose computation is based on BSA
Cell kill theory
a fixed percentage of the total number
of cancer cells present is killed with
each chemotherapuetic dose
Combination chemotherapy provides a better
response than single agent chemotherapy

CHEMOTHERAPY
Common routes of administration:
oral
parenteral

intramuscular
intravenous
subcutaneous
intracavitary
intrapleural
intra-abdominal
intravesical
intrathecal
intra-arterial

TUMOR CELL KINETICS &

CHEMOTHERAPY
Tumor Growth
cell cycle time
growth fraction
total number of cells in the population
intrinsic cell death rate
Cell Cycle
Phase & Cell Cycle Specificity
phase specific drugs
cell cycle specific drugs
cell cycle nonspecific drugs

CELL CYCLE
G2
S

G0
G1
S
G2
M

G0: Cells are reversibly out

of cycle, e.g., as the result of nutrient

G1

deprivation; may serve as a reserve

for repopulation of tissue
Cell Death
Cells are irreversibly out of cycle, e.g.,
as the result of maturation /
differentation

resting phase
RNA & protein synthesis (18-30 hours)
DNA synthesis (16 20 hours)
RNA & protein synthesis (2 10 hours)
Mitosis (30 minutes 1 hour)

TUMOR CELL KINETICS &

CHEMOTHERAPY
Tumor Growth
cell cycle time
growth fraction
total number of cells in the population
intrinsic cell death rate
Cell Cycle
Phase & Cell Cycle Specificity
phase specific drugs
cell cycle specific drugs
cell cycle nonspecific drugs

PHASE SPECIFIC DRUGS

are most effective against cells that are in a
specific phase of the cell cycle
best for rapidly dividing tumors
Phase
G1

Class

Type

Agent

natural product

enzyme

asparaginase

hormone

steroid

prednisone

PHASE SPECIFIC DRUGS

Phase
S

Class

Type

antimetabolite pyrimidine
analog

Agent
cytarabine
5FU

antimetabolite folic acid analog methotrexate

G2
M

antimetabolite purine analog

thioguanine

miscellaneous

hydroxyurea

substituted

urea
natural product antibiotic
natural product mitotic
inhibitor

bleomycin
etoposide
vincristine
vinblastine

CELL CYCLE SPECIFIC DRUGS

are effective while cells are actively in cycle,
but not dependent on a particular phase
best for large tumors with fewer actively
dividing cells
Class
Type
Agent
alkylating agent nitrogen
chlorambucil
mustard
melphalan
cyclophosphamide
natural product antibiotic

dactinomycin
doxorubicin

CELL CYCLE NON-SPECIFIC DRUGS

are effective whether cells are in cycle or

resting

Class

Type

alkylating agent

nitrogen
nitrosurea

Agent
Mechlorethamine mustard
BCNU, CCNU

EFFECT OF CHEMOTHERAPY
C
E
L
L
N
U
M
B
E
R

1012
1011
1010
109
108
107
106
105
104
103
102
1011
00

3 log cell kill

1 log cell regrowth

Clinically overt disease

Disease in remission
Tumor
regrowth
following
premature
cessation
of therapy

2
3
4
5
CYCLES OF CHEMOTHERAPY

USES OF CHEMOTHERAPY
Definitive therapy
Hodgkins Disease
Non-Hodgkins Lymphoma
Childhood Leukemias & Lymphomas
Wilms Tumor
Embryonal Rhabdomyosarcoma
Small Cell Lung CA

USES OF CHEMOTHERAPY
Adjuvant therapy
Breast CA
Colorectal CA
Osteogenic Sarcoma
Ovarian CA
Curative intent w/ surgery
Testicular CA
Choriocarcinoma
Palliative therapy

LIMITATIONS OF
CHEMOTHERAPY

Resistance
Dose limiting toxicities
Immune response
Accessibility
Vascular supply

COMMON ADVERSE EFFECTS

complications at the injection site
myelosupression
granulocytopenia
thrombocytopenia
anemia
skin changes
mucosal changes
oral mucositis
pharyngitis, esophagitis, enteritis
vaginitis

COMMON ADVERSE EFFECTS

gastrointestinal changes
nausea & vomiting
diarrhea
constipation
germinal cell effects
on the fetus
on menses
on fertility
alopecia

LESS FREQUENT SIDE EFFECTS

cardiomyopathy
pulmonary fibrosis
hepatotoxicity
nephrotoxicity or hemorrhagic cystitis
neurotoxicity
peripheral
autonomic
cranial nerves
second malignancies

Molecular Targeted Therapy (MTT)

Drugs designed to specifically target
molecules that are uniquely or abnormally
expressed within cancer cells while sparing
normal cells
Characteristics:
the molecule is uniquely expressed in
cancer cells.
the molecule is important for the
maintenance of the malignant phenotype

Classification & Type of MTT

Function-directed therapy
Cell signaling-targeted therapy
Angiogenesis-targeted therapy
Protein degradation-targeted therapy
Immune modulation-targeted therapy
Phenotype-directed therapy
Nonreceptor protein-directed MoAbs
Immunotoxins
Cancer vaccines

Tumor Angiogenesis

RESPONSE CRITERIA
Survival
Objective Response
tumor size

complete response
(CR)
partial response
(PR)
stable disease
(SD)
progressive disease (PD)

tumor products
evaluable disease
performance status
Subjective change