Cancer Treatment Reviews 39 (2013) 534540

Contents lists available at SciVerse ScienceDirect

Cancer Treatment Reviews

journal homepage: www.elsevierhealth.com/journals/ctrv

Laboratory-Clinic Interface

The systemic inammation-based Glasgow Prognostic Score: A decade

of experience in patients with cancer
Donald C. McMillan
Academic Unit of Surgery, School of Medicine-University of Glasgow, Royal Inrmary, Glasgow G31 2ER, United Kingdom

a r t i c l e i n f o s u m m a r y

Article history: Since the initial work, a decade ago that the combination of C-reactive protein and albumin, the Glasgow
Received 23 July 2012 Prognostic Score (GPS), had independent prognostic value in patients with cancer, there have been more
Received in revised form 21 August 2012 than 60 studies (>30,000 patients) that have examined and validated the use of the GPS or the modied
Accepted 22 August 2012
GPS (mGPS) in a variety of cancer scenarios. The present review provides a concise overview of these
studies and comments on the current and future clinical utility of this simple objective systemic
inammation-based score. The GPS/mGPS had independent prognostic value in (a) unselected cohorts
Keywords:
(4 studies, >19,400 patients) (b) operable disease (28 studies, >8,000 patients) (c) chemo/radiotherapy
Cancer
Tumour stage
(11 studies, >1500 patients) (d) inoperable disease (11 studies, >2,000 patients). Association studies
Systemic inammation (15 studies, >2,000 patients) pointed to an increased GPS/mGPS being associated with increased weight
Glasgow Prognostic Score and muscle loss, poor performance status, increased comorbidity, increased pro-inammatory and angio-
Survival genic cytokines and complications on treatment. These studies have originated from 13 different coun-
tries, in particular the UK and Japan. A chronic systemic inammatory response, as evidenced by the
GPS/mGPS, is clearly implicated in the prognosis of patients with cancer in a variety of clinical scenarios.
The GPS/mGPS is the most extensively validated of the systemic inammation-based prognostic scores
and therefore may be used in the routine clinical assessment of patients with cancer. It not only identies
patients at risk but also provides a well dened therapeutic target for future clinical trials. It remains to
be determined whether the GPS has prognostic value in other disease states.
2012 Elsevier Ltd. All rights reserved.

Introduction Currently, the cornerstone of cancer prognosis is accurate stag-

Cancer remains the leading cause of death worldwide in indi-
viduals aged 3564 years and globally accounts for at least
500,000 deaths each year. In the UK approximately one in three
develops cancer and one in four dies of cancer. Despite this rela-
tively poor outcome for most common cancers, much high prole
research is carried out with a view to cure whereas the reality
for most patients with cancer is disease progression and death.
Therefore, against this background, predicting the likely out-
come of the patient with cancer is of considerable importance since
even without improvements in treatment, if patients are given the
appropriate treatment, then outcomes will improve for all patients.
Unfortunately, without objective measures of likely outcome, the
allocation of treatment will continue to be suboptimal. For exam-
ple, Temel and coworkers1 recently reported that, in patients with
metastatic lung cancer randomised to palliative care vs standard
care, palliative care was associated with better quality of life and
increased survival.
Tel.: +44 141 211 5435; fax: +44 141 552 4943.
E-mail address: Donald.McMillan@glasgow.ac.uk
ing of the tumour and establishing whether there has been tumour
spread. However, there is increasing recognition that patient re-
lated factors, in particular nutritional and functional decline, are
associated with poorer outcome independent of tumour stage.
The most commonly used measures of this decline, weight loss
and performance status, are recognised to be subjective and
therefore their reliability in predicting outcome is compromised.
Moreover, they do not provide objective therapeutic targets.
There is now good consistent evidence that the presence of a
systemic inammatory response is a major factor underlying such
patient decline.25 Since the initial studies of using C-reactive pro-
tein, as a sensitive measure of the systemic inammatory response,
reported independent prognostic value in operable colorectal
cancer6,7 there have been a plethora of studies reporting the prog-
nostic value of C-reactive protein and other markers of the sys-
temic inammatory response in a wide variety of operable8 and
inoperable9 cancers.
In this early work it was noted as circulating C-reactive protein
concentrations increased albumin concentrations fell and this rela-
tionship was similar across different tumour types.10 Also, given
that albumin concentrations reected both systemic inammation

0305-7372/$ - see front matter 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.ctrv.2012.08.003
 D.C. McMillan / Cancer Treatment Reviews 39 (2013) 534540 535

Table 1 reporting the prognostic value of the GPS/mGPS in relation to can-

Systemic inammation based prognostic scores, the Glasgow Prognostic Scores. cer outcome (September 2003 to July 2012 inclusive).
The Glasgow Prognostic Score (GPS) Points allocated On completion of the online search, the title and abstract of
C-Reactive protein P10 mg/l and albumin P35 g/l 0 each identied study was examined for relevance. Full text was ob-
C-Reactive protein >10 mg/l 1 tained for all studies deemed potentially relevant. Of these, studies
Albumin <35 g/l 1 that had examined the prognostic value of the GPS/mGPS in solid
C-Reactive protein >10 mg/l and albumin <35 g/l 2 organ malignant disease were included while studies relating to
The modied Glasgow Prognostic Score (mGPS) duplicate datasets, studies not available in English language and
C-Reactive protein 6 10 mg/l and albumin P35 g/l 0 those published in abstract form only were excluded. The bibliog-
C-Reactive protein >10 mg/l 1
C-Reactive protein >10 mg/l and albumin <35 g/l 2
raphies of all included articles were subsequently hand searched to
identify any additional studies. Studies were selected after review
by the author.
Study heterogeneity precluded a meaningful meta-analysis and
and the amount of lean tissue,11 it was of interest to examine the the results are presented in descriptive form only. For each group
prognostic value of the combination of an elevated C-reactive pro- of studies a weighted average hazard ratio for an incremental in-
tein concentration (>10 mg/l) and hypoalbuminaemia (<35 g/l). In crease in the mGPS was calculated by multiplying the hazard ratio
the rst report by Forrest and coworkers in Glasgow, this objective reported in the study by the number of patients in the study. The
combination compared favourably with the clinical standard product of this multiplication was added to the products of other
combination of stage and performance status.12 The resultant studies in the group and the total was divided by the total number
prognostic score (0, 1, 2) was dened as follows; patients with both of all the patients in the group studies.
an elevated C-reactive protein (>10 mg/l) and hypoalbuminaemia
(<35 g/l) were allocated a score of 2. Patients in whom only one
of these biochemical abnormalities was present were allocated a Studies of the prognostic value of the GPS/mGPS, in an
score of 1. Patients in whom neither of these abnormalities was unselected cohort of patients with cancer
present were allocated a score of 0. However, the score of 1 was
most commonly due to an elevated C-reactive protein emphasising Four studies, comprising data on 19,481 patients, reported
the inammatory basis of the GPS (Table 1,12). prognostic value of the GPS/mGPS in unselected cohorts of patients
This systemic inammation based prognostic score was subse- with cancer (Table 2,1518). All studies used the mGPS and reported
quently termed the Glasgow Prognostic Score (GPS,13). On further prognostic value independent of tumour site (breast, bladder,
investigation the GPS was modied, termed the mGPS, to reect gynaecological, prostate, gastro-oesophageal, haematological, re-
the observation that hypoalbuminaemia without an elevated nal, colorectal, head and neck, hepatopancreaticobiliary and pul-
C-reactive protein concentration was rare and that hypoalbumina- monary) and were from the Glasgow group. Two studies
emia on its own was not associated with poor survival (Table 1,14). compared the prognostic value of the GPS/mGPS with that of other
The GPS/mGPS being simple to measure, routinely available and markers of the systemic inammatory response including the neu-
well standardised world-wide has subsequently been the subject trophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR),
of prognostic studies in wide variety of operable and inoperable prognostic index (PI) and the prognostic nutritional index (PNI).
cancers. Since the initial work, a decade ago, there have been more The mGPS predicted survival superior to NLR, PLR, PI and PNI. Over
than 60 studies (>30,000 cancer patients) that have examined and the studies the weighted average hazard ratio for an incremental
validated the use of the GPS/mGPS in a variety of clinical scenarios. increase in the mGPS was 1.8.
The present review provides a concise overview of these studies In conclusion, there is increasing evidence that the mGPS pre-
and comments on the current and future clinical utility of this sim- dicts poor survival in patients with cancer, independent of tumour
ple objective systemic inammation-based score. site.

Methods Studies of the prognostic value of the GPS/mGPS in patients

This systematic review of published literature was undertaken
according to a pre-dened protocol. The primary outcome of inter-
est was the relationship between the GPS/mGPS and cancer out-
come (overall survival, cancer specic survival, disease recurrence
or response to treatment). The secondary outcomes of interest were
the associations between the GPS/mGPS and other clinical, patho-
logical or inammatory characteristics.
A literature search, using appropriate free text and medical sub-
ject heading (MeSH) terms, was made of the US National Library of
Medicine (MEDLINE), the Excerpta Medica database (EMBASE) and
the Cochrane Database of Systematic Reviews (CDSR) for articles
with operable cancer
Twenty-eight studies, comprising data on 8,333 patients, re-
ported prognostic value of the GPS/mGPS in patients with operable
cancer (Table 3,14,1946). Fourteen studies were in colorectal
(including liver metastases) cancer and the GPS/mGPS was re-
ported to have prognostic value independent of tumour stage
and pathological features, comorbidity and other measures of the
systemic inammatory response. These studies were from groups
in the UK (9 studies), Japan (5 studies). Over these 14 studies the
weighted average hazard ratio for an incremental increase in the
GPS/mGPS was 2.0.

Table 2
Studies (n = 4) of the prognostic value of the GPS/mGPS, in unselected cohorts of patients with cancer (n > 19,400).

Study Centre Tumour site n HR (p-value) Comments

Crumley et al.15 Glasgow, UK Gastro-oesophageal 217 1.7 (<0.001) mGPS predicted survival independent of tumour site/stage/treatment
Proctor et al.16 Glasgow, UK 11 sites 9608 1.9 (<0.001) mGPS predicted survival independent of tumour site
Proctor et al.17 Glasgow, UK 11 sites 8759 1.7 (<0.001) mGPS predicted survival superior to NLR, PLR, PI, PNI
Shaque et al.18 Glasgow, UK Prostate 897 1.8 (<0.05) mGPS predicted survival superior to NLR

HR multivariate hazard ratio for incremental change of GPS/mGPS.

536 D.C. McMillan / Cancer Treatment Reviews 39 (2013) 534540

Table 3
Studies (n = 28) of the prognostic value of the GPS/mGPS in patients with operable cancer (n > 8,000).

Study Centre Tumour site n HR (p-value) Comments

14
McMillan et al. Glasgow, UK Colorectal 316 1.7 (<0.001) mGPS predicted survival independent of stage/treatment
Leitch et al.19 Glasgow, UK Colorectal 233 2.1 (<0.001) mGPS predicted survival superior to WCC/lymphocytes
Ishizuka et al.20 Tochigi, Japan Colorectal 315 1.5 (<0.01) GPS predicted survival independent of stage/treatment
Crozier et al.21 Glasgow, UK Colorectal 188 2.2 (<0.05) mGPS predicted survival independent of emergency presentation
Roxburgh et al.22 Glasgow, UK Colorectal 244 2.3 (<0.001) mGPS predicted survival independent of Petersen Index
Moyes et al.23 Glasgow, UK Colorectal 455 1.8 (<0.01) mGPS predicted post-operative infective complications
Roxburgh et al.24 Glasgow, UK Colorectal 287 2.7 (<0.001) mGPS predicted survival independent of tumour inammatory inltrate
Ishizuka et al.25 Tochigi, Japan Colorectal liver 300 2.1 (<0.05) GPS predicted survival independent of CLIP score
Ishizuka et al.26 Tochigi, Japan Colorectal 156 24.5 (<0.05) GPS predicted survival in T1/T2 stage disease
Kobayashi et al.27 Tokyo, Japan Oesophageal 65 NR (<0.001) GPS predicted survival independent of lymph node status
Polterauer et al.28 Vienna, Austria Cervical 244 NR (<0.05) GPS predicted survival independent of FIGO stage
Kobayashi et al.29 Tokyo, Japan Colorectal liver 63 3.1 (<0.01) GPS predicted survival independent of number of liver metastases
Knight et al.30 Manchester, UK Pancreas 99 4.3 (<0.05) GPS predicted post-operative morbidity
Richards et al.31 Glasgow, UK Colorectal 320 1.8 (<0.001) mGPS predicted survival independent of POSSUM
Nozoe et al.32 Koga, Japan Gastric 232 4.1 (<0.001) mGPS predicted survival independent of tumour stage
Moug et al.33 Kilmarnock, UK Colorectal 206 1.6 (<0.05) mGPS predicted survival independent of LNR
Roxburgh et al.34 Glasgow, UK Colorectal 302 1.6 (<0.001) mGPS predicted survival independent of comorbidity indices
Vashist et al.35 Hamburg, Germany Oesophageal 495 3.0 (<0.001) GPS predicted peri-operative morbidity and survival
Ishizuka et al.36 Tochigi, Japan Hepatocellular 300 2.1 (<0.05) GPS predicted survival independent of post-operative mortality
Dutta et al.37 Glasgow, UK Oesophageal 112 4.3 (<0.001) mGPS predicted survival independent of LNR, NLR and PLR
Jamieson et al.38 Glasgow, UK Pancreas 135 2.3 (<0.001) GPS predicted survival independent of margin status/adjuvant therapy
Ishizuka et al.39 Tochigi, Japan Hepatocellular 398 2.5 (<0.05) GPS predicted survival independent of CLIP score
Lamb et al.40 Glasgow, UK Renal 169 5.1 (<0.001) GPS predicted survival independent of established scoring systems
La Torre et al.41 Rome, Italy Pancreas 101 1.8 (<0.01) mGPS predicted survival independent of LNR and margin status
Wang et al.42 Guangzhou, China Gastric 324 1.4 (<0.01) GPS predicted survival independent of TNM stage, NLR and PLR
Jamieson et al.43 Glasgow, UK Pancreas 173 1.8 (<0.01) mGPS predicted survival independent of LIR
Ishizuka et al.44 Tochigi, Japan Colorectal 271 2.0 (<0.05) mGPS predicted survival in patients with normal CEA
Dutta et al.45 Glasgow, UK Gastric 120 2.2 (<0.01) mGPS predicted survival independent of LNR, NLR and PLR
Jiang et al.46 Tokyo, Japan Gastric 1710 1.8 (<0.01) mGPS predicted survival independent of TNM stage

HR, multivariate hazard ratio for incremental change of GPS/mGPS; NR, not reported; LNR, lymph node ratio; NLR, neutrophil lymphocyte ratio; PLR, platelet lymphocyte
ratio; CLIP, cancer of the liver Italian program; LIR, local inammatory response; POSSUM.

Table 4
Studies (n = 11) of the prognostic value of the GPS/mGPS, in cancer patients receiving chemo/radiotherapy (n > 1500).

Study Centre Tumour site n HR (p-value) Comments

13
Forrest et al. Glasgow, UK Lung (NSCLC) 109 1.9 (<0.01) GPS predicted survival independent of ECOG-ps/platinum therapy
Crumley et al.,47 Glasgow, UK Gastro-oesophageal 65 1.7 (<0.05) mGPS predicted survival independent of ECOG-ps/platinum therapy
Kobayashi et al.48 Tokyo, Japan Oesophageal 48 5.9 (<0.01) GPS predicted toxicity in patients receiving neoadjuvant therapy
Sharma et al.49 London/Sydney Colorectal 52 NR GPS predicted toxicity and survival independent of stage/treatment
Ishizuka et al.50 Tochigi, Japan Colorectal 112 6.0 (<0.01) GPS predicted survival in patients receiving adjuvant therapy
Wang et al.51 Kaohsiung, Taiwan Oesophageal 123 3.4 (<0.001) GPS predicted survival in patients receiving radiotherapy
Roxburgh et al.52 Glasgow, UK Colon 348 3.2 (<0.01) mGPS predicted survival in patients receiving adjuvant therapy
Chau et al.53 Sydney, Australia Various 68 4.1 (<0.01) GPS predicted survival in patients receiving docetaxel
Hwang et al.54 Gwangui, South Korea Gastric 402 1.8 (<0.01) GPS predicted survival independent of performance status
Morimoto et al.55 Yokohama, Japan Hepatocellular 81 5.5 (<0.001) GPS predicted survival in patients receiving sorafenib
Gioulbasanis et al.56 Heraklion, Greece Lung (metastatic) 96 1.9 (<0.01) GPS) predicts toxicity and efcacy in platinum-based treatment

HR, multivariate hazard ratio for incremental change of GPS; NR, not reported.

There were seven studies in gastro-oesophageal cancer and the
GPS/mGPS was reported to have prognostic value independent of
tumour stage and pathological features and other measures of
the systemic inammatory response. These studies were from
groups in the UK (2 studies), Japan (3 studies), China (1 study)
and Germany (1 study). Over these seven studies the weighted
average hazard ratio for an incremental increase in the GPS/mGPS
was 2.2.
There were four studies in pancreatic cancer and the GPS/mGPS
was reported to have prognostic value independent of tumour
stage and pathological features and other measures of the systemic
inammatory response. These studies were from groups in the UK
(3 studies) and Italy (1 study). Over these 6 studies the weighted
average hazard ratio for an incremental increase in the GPS/mGPS
was 2.4.
There were also 2 studies in hepatocellular cancer, 1 study in
cervical cancer and 1 study in renal cancer.
In conclusion, there is good evidence that the GPS/mGPS reli-
ably predicts poor survival in patients with operable colorectal,
gastro-oesophageal and pancreatic cancer and may be incorpo-
rated into the routine clinical assessment of these patients.
Studies of the prognostic value of the GPS/mGPS, in cancer
patients receiving chemo/radiotherapy
Eleven studies, comprising data on 1,504 patients, reported
prognostic value of the GPS/mGPS in cancer patients receiving
chemo/radiotherapy (Table 4,13,4756). Four studies were in gas-
tro-oesophageal cancer and the GPS/mGPS was reported to have
prognostic value independent of tumour stage and performance
status. These studies were from groups in the UK (1 study), Japan
(1 study), Taiwan (1 study) and South Korea (1 study). Over these
four studies the weighted average hazard ratio for an incremental
increase in the GPS/mGPS was 2.4.
There were three studies in colorectal cancer and the GPS/mGPS
was reported to have prognostic value independent of tumour
stage and adjuvant therapy. These studies were from groups in
 D.C. McMillan / Cancer Treatment Reviews 39 (2013) 534540 537

Table 5
Studies (n = 11) of the prognostic value of the GPS/mGPS, in patients with inoperable cancer (n > 2000).

Study Centre Tumour site n HR (p-value) Comments

57
Forrest et al. Glasgow, UK Lung (NSCLC) 109 1.7 (<0.001) GPS predicted survival independent of ECOG-ps/stage/treatment
Al Murri et al.58 Glasgow, UK Breast 96 2.3 (<0.001) GPS predicted survival independent of stage/treatment
Crumley et al.59 Glasgow, UK Gastro-oesophageal 258 1.5 (<0.001) GPS predicted survival independent of stage/treatment
Glen et al.60 Glasgow, UK Pancreas 187 1.7 (<0.001) GPS predicted survival independent of stage
Read et al.61 Sydney, Australia Colorectal 84 2.3 (<0.05) GPS independent of stage/treatment
Ramsey et al.62 Glasgow, UK Renal 119 2.4 (<0.001) GPS predicted survival independent of scoring systems
Sharma et al.63 Sydney, Australia Ovarian 154 1.7 (<0.01) GPS independent of stage/treatment
Pinato et al.64 London, UK Lung (mesothelioma) 171 2.6 (<0.001) mGPS predicted survival independent of NLR and EPS
Leung et al.65 Glasgow, UK Lung (NSCLC) 261 1.7 (<0.001) mGPS predicted survival independent of ECOG-ps/stage/treatment
Pinato et al.66 London, UK Hepatocellular 578 2.7 (<0.01) GPS predicted survival in training and validation datasets
Partridge et al.67 Edinburgh, UK 5 sites 102 2.7 (<0.01) mGPS predicted survival independent of tumour site in palliative care

HR, multivariate hazard ratio for incremental change of GPS; NR, not reported; NLR, neutrophil lymphocyte ratio; EPS, European organisation for the research and treatment
of cancer Prognostic Score.

Table 6
Studies (n = 15) of associations with the GPS/mGPS in patients with cancer (n > 2000).

Study Centre Tumour site n Comments

Brown et al.68 Glasgow, UK Lung and colorectal 50 GPS associated with weight loss, poor performance status and biochemical disturbance
K-Korpacka69 Wroclaw, Poland Gastro-oesophageal 96 GPS associated with weight loss, transferrin, IL-1, IL-6, IL-8, TNF, VEGF-A and midkine
concentrations
Leung et al.70 Glasgow, UK Colorectal 106 mGPS associated with plasma retinol, lutein, lycopene, alpha and beta carotene
Kerem et al.71 Ankara, Turkey Gastric 60 GPS associated with weight loss, ghrelin, resistin, adiponectin and leptin
Fujiwara et al.72 Tokyo, Japan Hepatocellular 66 GPS associated with blood transfusion and post-operative complications
Meek et al.73 Glasgow, UK Lung (NSCLC) 56 mGPS associated with haemoglobin and IGFBP-3
Skipworth Edinburgh, UK Gastro-oesophageal 293 mGPS associated with weight loss, dietary intake, MAMC and KPS
et al.74
Shimoda et al.75 Tochigi, Japan Pancreas 83 GPS associated with responses to treatment
(unresectable)
Diakowska Wroclaw, Poland Gastro-oesophageal 135 GPS associated with cachexia in cancer and controls
et al.76
Giannousi Heraklion, Greece Lung (metastatic) 122 GPS associated with MNA, anxiety, depression and survival
et al.77
Blomberg et al.78 Stockholm, ENT and non-cancer 484 Combination of C-reactive protein and albumin associated with mortality following PEG
Sweden
Richards et al.79 Glasgow, UK Colorectal 343 mGPS associated with tumour necrosis
Naito et al.80 Shizuoka, Japan Gastro-oesophageal 47 GPS associated with clinical responses to oxycodone
Leung et al.81 Glasgow, UK Colorectal 108 mGPS associated with plasma B6
Richards et al.82 Glasgow, UK Colorectal 174 mGPS associated with skeletal muscle index

NSCLC, non-small cell lung cancer; MNA, mini-nutritional assessment; IGFBP-3, insulin like growth factor binding protein-3.

the UK (2 studies) and Japan (1 study). Over these three studies the
weighted average hazard ratio for an incremental increase in the
GPS/mGPS was 3.9.
There were also 2 studies in lung cancer, 1 study in hepatocel-
lular cancer and 1 study in various cancers.
In conclusion, there is some evidence that the GPS/mGPS
reliably predicts poor survival/response to treatment in patients
receiving chemo/radiotherapy for colorectal and gastro-oesopha-
geal cancer. Further work is required particularly in the context
of randomised clinical trials.
Studies of the prognostic value of the GPS/mGPS, in patients
with inoperable cancer
Eleven studies, comprising data on 2,119 patients, reported
prognostic value of the GPS/mGPS in patients with inoperable can-
cer (Table 5,5767). Three studies were in lung cancer and the GPS/
mGPS was reported to have prognostic value independent of tu-
mour stage, performance status and treatment and other measures
of the systemic inammatory response. These 3 studies were from
groups in the UK. Over these three studies the weighted average
hazard ratio for an incremental increase in the GPS/mGPS was 2.0.
There were also single studies in inoperable breast, gastro-
esophageal, hepatocellular, pancreatic, renal and ovarian cancer.
In conclusion, there is good evidence that the GPS/mGPS
reliably predicts poor survival in patients with inoperable cancer.
Further work is required to dene the clinical utility of the GPS/
mGPS within individual tumour sites.
Studies of the associations with the GPS/mGPS in patients with
cancer
Fifteen studies, comprising data on 2,215 patients, reported
associations between the GPS/mGPS and weight and muscle loss,
nutritional status, performance status, biochemical and cytokine
disturbances (Table 6,6882). This was particularly evident in gas-
tro-oesophageal (5 studies), colorectal (5 studies) and lung (2 stud-
ies) cancer. There were also single studies in hepatocellular cancer,
pancreas and ear nose and throat cancers. These fourteen studies
were from groups in the UK (7 studies), Japan (3 studies), Poland
(2 studies), Turkey (1 study), Greece (1 study) and Sweden (1
study).
In conclusion, there is good evidence that the GPS/mGPS is
reliably associated with weight and muscle loss and poor perfor-
mance status in gastrointestinal and lung cancers. This is consis-
tent with the use of the GPS/mGPS to objectively dene the
cachexia syndrome.
538 D.C. McMillan / Cancer Treatment Reviews 39 (2013) 534540
Discussion
From the present review and given that the HR was similar
across different tumours, countries and clinical scenarios it can
be concluded that GPS/mGPS is a reliable independent prognostic
factor in patients with cancer. Its use has been reported in (a) unse-
lected cohorts (4 studies, >19,400 patients) (b) operable disease
(28 studies, >8,000 patients) (c) chemo/radiotherapy (11 studies,
>1500 patients) (d) inoperable disease 11 studies, >2,000 patients).
Also, association studies (15 studies, >2,000 patients) pointed to an
increased GPS/mGPS being associated with increased weight loss,
poor performance status, increased comorbidity, increased pro-
inammatory and angiogenic cytokines and complications on
treatment. It was notable that no reports originated from the
USA. Irrespective, it is reasonable to conclude that the simple
GPS/mGPS may be included, in addition or in preference to the
current denitions of cachexia, with tumour staging as part of
the routine assessment of all cancer patients. Also, MacDonald83
recently concluded that particularly in the more aggressive tu-
mour types (e.g. pancreas and lung), the future of patients with ele-
vated mGPS scores is so grim that they should be given precachexia
status and offered multimodal therapy which may delay the onset
of cachexia and/or death. As a consequence this will highlight the
need not only to treat the tumour but also the systemic inamma-
tory response, a potentially less intractable target compared with
established weight loss and/or poor performance status. Indeed,
the rst such studies using the GPS/mGPS have recently been
reported.84,85
Further work is required to dene the value of GPS/mGPS as a
stratication factor, as a selection criteria in randomised clinical
trials and as a therapeutic target in patients with cancer. Also,
how the prognostic value of the GPS/mGPS compares with that
of other measures of the systemic inammatory response, such
as the neutrophil/lymphocyte ratio.17,19,37,42,45,64
It remains to be determined whether the GPS will also have
prognostic utility in disease states other than cancer.
Acknowledgements
The author gratefully acknowledges the support and advice of
clinical and scientic colleagues at Glasgow Royal Inrmary, in
particular Professors of Surgery Clem Imrie and Paul Horgan, and
funding from Glasgow Royal Inrmary Endowment Funds, the
Chief Scientist Ofce and Cancer Research UK.
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