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Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts - 28/02/12

Doi : 10.1016/S1470-2045(11)70299-6 
Heikki Joensuu, ProfMD a, , Aki Vehtari, DSci b, Jaakko Riihimäki, MSc b, Toshirou Nishida, MD c, Sonja E Steigen, MD d, Peter Brabec, MSci e, Lukas Plank, ProfMD f, Bengt Nilsson, MD g, Claudia Cirilli, BSc h, Chiara Braconi, MD i, Andrea Bordoni, MD j, Magnus K Magnusson, MD k, Zdenek Linke, MD m, Jozef Sufliarsky, MD l, Massimo Federico, MD n, Jon G Jonasson, MD o, Angelo Paolo Dei Tos, MD p, Piotr Rutkowski, MD q
a Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland 
b Department of Biomedical Engineering and Computational Science, Aalto University, Espoo, Finland 
c Osaka Police Hospital, Osaka, Japan 
d University Hospital of Northern Norway and University of Tromsø, Tromsø, Norway 
e Institute of Biostatistics and Analyses, Masaryk University, Czech Republic 
f Department of Pathology, Jessenius Medical Faculty of Comenius University and University Hospital, Martin, Slovak Republic 
g Department of Surgery, Sahlgrenska University Hospital, Gothenburg, Sweden 
h Registro Tumori della provincia di Modena, Modena, Italy 
i Centro Regionale di Genetica Oncologica, Oncologia Medica, Ancona, Italy 
j Ticino Cancer Registry, Insitute of Pathology South of Switzerland, Locarno, Switzerland 
k Department of Laboratory Hematology and Pathology, Landspitali University Hospital, Reykjavik, Iceland 
l Department of Internal Medicine, National Cancer Institute, Bratislava, Slovak Republic 
m Faculty Hospital Motol, Radiotherapeutical-Oncological Department, Prague, Czech Republic 
n Department of Oncology and Hematology, University of Modena and Reggio Emilia, Modena, Italy 
o Department of Pathology, Landspitali University Hospital and the Faculty of Medicine, University of Iceland, Reykjavik, Iceland 
p General Hospital of Treviso, Treviso, Italy 
q Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Warsaw, Poland 

* Correspondence to: Prof Heikki Joensuu, Department of Oncology, Helsinki University Central Hospital, Haartmaninkatu 4, POB 180, FIN-00029 Helsinki, Finland

Summary

Background

The risk of recurrence of gastrointestinal stromal tumour (GIST) after surgery needs to be estimated when considering adjuvant systemic therapy. We assessed prognostic factors of patients with operable GIST, to compare widely used risk-stratification schemes and to develop a new method for risk estimation.

Methods

Population-based cohorts of patients diagnosed with operable GIST, who were not given adjuvant therapy, were identified from the literature. Data from ten series and 2560 patients were pooled. Risk of tumour recurrence was stratified using the National Institute of Health (NIH) consensus criteria, the modified consensus criteria, and the Armed Forces Institute of Pathology (AFIP) criteria. Prognostic factors were examined using proportional hazards and non-linear models. The results were validated in an independent centre-based cohort consisting of 920 patients with GIST.

Findings

Estimated 15-year recurrence-free survival (RFS) after surgery was 59·9% (95% CI 56·2–63·6); few recurrences occurred after the first 10 years of follow-up. Large tumour size, high mitosis count, non-gastric location, presence of rupture, and male sex were independent adverse prognostic factors. In receiver operating characteristics curve analysis of 10-year RFS, the NIH consensus criteria, modified consensus criteria, and AFIP criteria resulted in an area under the curve (AUC) of 0·79 (95% CI 0·76–0·81), 0·78 (0·75–0·80), and 0·82 (0·80–0·85), respectively. The modified consensus criteria identified a single high-risk group. Since tumour size and mitosis count had a non-linear association with the risk of GIST recurrence, novel prognostic contour maps were generated using non-linear modelling of tumour size and mitosis count, and taking into account tumour site and rupture. The non-linear model accurately predicted the risk of recurrence (AUC 0·88, 0·86–0·90).

Interpretation

The risk-stratification schemes assessed identify patients who are likely to be cured by surgery alone. Although the modified NIH classification is the best criteria to identify a single high-risk group for consideration of adjuvant therapy, the prognostic contour maps resulting from non-linear modelling are appropriate for estimation of individualised outcomes.

Funding

Academy of Finland, Cancer Society of Finland, Sigrid Juselius Foundation and Helsinki University Research Funds.

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Vol 13 - N° 3

P. 265-274 - mars 2012 Retour au numéro
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