Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer

Crumley, A B C; McMillan, D C; McKernan, M; McDonald, S A C; Stuart, R C

doi:10.1038/sj.bjc.6602998

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Evaluation of an inflammation-based prognostic score in patients with inoperable gastro-oesophageal cancer

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Author(s): A B C Crumley ¹ , D C McMillan ¹ ^, ^* , M McKernan ¹ , A C McDonald ² , R C Stuart ¹

Publication date (Electronic): 07 March 2006

Journal: British Journal of Cancer

Keywords: gastro-oesophageal cancer, TNM stage C-reactive protein, albumin, survival

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Abstract

There is increasing evidence that the presence of an ongoing systemic inflammatory response is associated with poor outcome in patients with advanced cancer. The aim of the present study was to examine whether an inflammation-based prognostic score (Glasgow Prognostic score, GPS) was associated with survival, in patients with inoperable gastro-oesophageal cancer. Patients diagnosed with inoperable gastro-oesophageal carcinoma and who had measurement of albumin and C-reactive protein concentrations, at the time of diagnosis, were studied ( n=258). Clinical information was obtained from a gastro-oesophageal cancer database and analysis of the case notes. Patients with both an elevated C-reactive protein (>10 mg l ⁻¹) and hypoalbuminaemia (<35 g l ⁻¹) were allocated a GPS score of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS score of 1, and patients with a normal C-reactive protein and albumin were allocated a score of 0. On multivariate survival analysis, age (hazard ratio (HR) 1.22, 95% CI 1.02–1.46, P<0.05), stage (HR 1.55, 95% CI 1.30–1.83, P<0.001), the GPS (HR 1.51, 95% CI 1.22–1.86, P<0.001) and treatment (HR 2.53, 95% CI 1.80–3.56, P<0.001) were significant independent predictors of cancer survival. A 12-month cancer-specific survival in patients with stage I/II disease receiving active treatment was 67 and 60% for a GPS of 0 and 1, respectively. For stage III/IV disease, 12 months cancer-specific survival was 57, 25 and 12% for a GPS of 0, 1 and 2, respectively. In the present study, the GPS predicted cancer-specific survival, independent of stage and treatment received, in patients with inoperable gastro-oesophageal cancer. Moreover, the GPS may be used in combination with conventional staging techniques to improve the prediction of survival in patients with inoperable gastro-oesophageal cancer.

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Most cited references 12

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Multivariate prognostic factor analysis in locally advanced and metastatic esophago-gastric cancer--pooled analysis from three multicenter, randomized, controlled trials using individual patient data.

David Cunningham, Peadar S Waters, R. Norman … (2004)

To identify baseline prognostic factors and assess whether pretreatment quality of life (QoL) predicts survival in patients with locally advanced or metastatic esophago-gastric cancer. Between 1992 and 2001, 1,080 patients were enrolled into three randomized, controlled trials assessing fluorouracil-based combination chemotherapy. All patients were required to complete the European Organization for Research and Treatment of Cancer core QoL questionnaire before random assignment. Of the 1080 patients randomly assigned, 979 (91%) died. Four independent poor prognostic factors were identified by multivariate analysis: performance status >or= 2 (hazard ratio [HR], 1.58; 99% CI, 1.25 to 1.98), liver metastases (HR, 1.41; 99%CI, 1.14 to 1.74), peritoneal metastases (HR, 1.33; 99%CI, 1.01 to 1.74) and alkaline phosphatase >or= 100 U/L (HR, 1.41; 99% CI, 1.14 to 1.76). A prognostic index was constructed dividing patients into good (no risk factor), moderate (one or two risk factors) or poor (three or four risk factors) risk groups. One-year survival for good, moderate, and poor risk groups were 48.5%, 25.7%, and 11%, respectively, and the survival differences among these groups were highly significant (P <.00001). Compared with the good risk group, the moderate risk group had nearly twice the risk of death, and the poor risk group had 3.5-fold increased risk of death. Pretreatment physical (P =.003), role functioning (P <.001), and global QoL (P <.001) predicted survival. Four poor prognostic factors were identified and a simple prognostic index was devised. Information from this analysis can be used to aid clinical decision-making, help individual patient risk stratification, and serve as benchmark for the planning for future phase III trials.

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To offer evidence-based clinical recommendations concerning prognosis in advanced cancer patients. A Working Group of the Research Network of the European Association for Palliative Care identified clinically significant topics, reviewed the studies, and assigned the level of evidence. A formal meta-analysis was not feasible because of the heterogeneity of published studies and the lack of minimal standards in reporting results. A systematic electronic literature search within the main available medical literature databases was performed for each of the following four areas identified: clinical prediction of survival (CPS), biologic factors, clinical signs and symptoms and psychosocial variables, and prognostic scores. Only studies on patients with advanced cancer and survival < or = 90 days were included. A total of 38 studies were evaluated. Level A evidence-based recommendations of prognostic correlation could be formulated for CPS (albeit with a series of limitations of which clinicians must be aware) and prognostic scores. Recommendations on the use of other prognostic factors, such as performance status, symptoms associated with cancer anorexia-cachexia syndrome (weight loss, anorexia, dysphagia, and xerostomia), dyspnea, delirium, and some biologic factors (leukocytosis, lymphocytopenia, and C-reactive protein), reached level B. Prognostication of life expectancy is a significant clinical commitment for clinicians involved in oncology and palliative care. More accurate prognostication is feasible and can be achieved by combining clinical experience and evidence from the literature. Using and communicating prognostic information should be part of a multidisciplinary palliative care approach.

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Randomised comparison of fluorouracil, epidoxorubicin and methotrexate (FEMTX) plus supportive care with supportive care alone in patients with non-resectable gastric cancer.

S. Pyrhönen, T. Kuitunen, P. Nyandoto … (1995)

A phase III randomised study, comparing treatment with fluorouracil, epidoxorubicin and methotrexate (FEMTX) with the best supportive care, was conducted in patients with unresectable or metastatic gastric cancer. During the period from July 1986 to June 1992, 41 patients were randomised to receive FEMTX or best supportive care. MTX was given in a dose of 1500 mg m-2 intravenously (i.v.) followed after 1 h by 5-FU 1500 mg m-2 i.v. on day 1; leucovorin rescue was started after 24 h (30 mg orally every 6 h for 48 h) and epidoxorubicin 60 mg m-2 i.v. was administered on day 15. In addition both groups received tablets containing vitamins A and E. Response rates for FEMTX were as follows: complete response (CR), 19% (4/21); partial response (PR), 10% (2/21); no change (NC), 33% (7/21); and progressive disease (PD), 24% (5/21). Response rates in the control group were: NC, 20% (4/20); and PD, 80% (16/20). Increased pain was observed in one patient in the treated group and in 11 patients in the control group within the first 2 months. WHO grade III/IV toxicity in the chemotherapy group was as follows: nausea/vomiting 40%, diarrhoea 10%, stomatitis 15%, leucopenia 50% and thrombocytopenia 10%. One possible treatment-related death was due to sepsis. The median time to progression in the FEMTX group was 5.4 months [95% confidence interval (CI) 3.1-11.7 months], but only 1.7 months in the control group (95% CI 1.2-2.7 months) (P = 0.0013). Similarly, the FEMTX group displayed significantly (P = 0.0006) prolonged survival compared with the control group, i.e. median survival 12.3 months (95% CI 7.1-15.6 months) vs 3.1 months (95% CI 1.6-4.6 months). In conclusion, FEMTX combined with vitamin A and E is a fairly well-tolerated treatment, giving a response rate of 29% in patients with advanced gastric cancer, and also prolonging patients' survival. It can be used as a reference treatment in testing new investigational combinations.

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Author and article information

Journal

Journal ID (nlm-ta): Br J Cancer

Title: British Journal of Cancer

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Electronic): 07 March 2006

Publication date (Print): 13 March 2006

Volume: 94

Issue: 5

Pages: 637-641

Affiliations

[1 ]University Department of Surgery, Royal Infirmary, Glasgow G31 2ER, UK

[2 ]Beatson Oncology Centre, Western Infirmary, Glasgow G11 6NT, UK

Author notes

[* ]Author for correspondence: d.c.mcmillan@ 123456clinmed.gla.ac.uk

Article

Publisher Item ID: 6602998

DOI: 10.1038/sj.bjc.6602998

PMC ID: 2361199

PubMed ID: 16479253

SO-VID: 1202d4ea-2a5b-4e90-81b7-b6a4c8365f41

History

Date received : 04 October 2005

Date revision received : 20 December 2005

Date accepted : 17 January 2006

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