title: Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts.
abstract: 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  Academy of Finland, Cancer Society of Finland, Sigrid Juselius Foundation and Helsinki University Research Funds.
authors.affiliation: Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland. heikki.joensuu@hus.fi
authors.forename: Heikki
authors.initials: H
authors.lastname: Joensuu
authors.forename: Aki
authors.initials: A
authors.lastname: Vehtari
authors.forename: Jaakko
authors.initials: J
authors.lastname: Riihimäki
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Steigen
authors.forename: Peter
authors.initials: P
authors.lastname: Brabec
authors.forename: Lukas
authors.initials: L
authors.lastname: Plank
authors.forename: Bengt
authors.initials: B
authors.lastname: Nilsson
authors.forename: Claudia
authors.initials: C
authors.lastname: Cirilli
authors.forename: Chiara
authors.initials: C
authors.lastname: Braconi
authors.forename: Andrea
authors.initials: A
authors.lastname: Bordoni
authors.forename: Magnus K
authors.initials: MK
authors.lastname: Magnusson
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Linke
authors.forename: Jozef
authors.initials: J
authors.lastname: Sufliarsky
authors.forename: Massimo
authors.initials: M
authors.lastname: Federico
authors.forename: Jon G
authors.initials: JG
authors.lastname: Jonasson
authors.forename: Angelo Paolo
authors.initials: AP
authors.lastname: Dei Tos
authors.forename: Piotr
authors.initials: P
authors.lastname: Rutkowski
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016009:Chi-Square Distribution; D002648:Child; D018572:Disease-Free Survival; D005260:Female; D005743:Gastrectomy; D046152:Gastrointestinal Stromal Tumors / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D008940:Mitotic Index; D009364:Neoplasm Recurrence, Local; D017711:Nonlinear Dynamics; D016016:Proportional Hazards Models; D012372:ROC Curve; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D047368:Tumor Burden; D055815:Young Adult