Risk Factors for Gastrointestinal Stromal Tumor Recurrence in Patients Treated With Adjuvant Imatinib

Heikki Joensuu, Mikael Eriksson, Kirsten Sundby Hall, Joerg T. Hartmann, Daniel Pink, Jochen Schuette, Giuliano Ramadori, Peter Hohenberger, Justus Duyster, Salah-Eddin Al-Batran, Marcus Schlemmer, Sebastian Bauer, Eva Wardelmann, Maarit Sarlomo-Rikala, Bengt Nilsson, Harri Sihto, Karla V. Ballman, Mika Leinonen, Ronald P. DeMatteo, Peter Reichardt

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Abstract

BACKGROUND: Little is known about the factors that predict for gastrointestinal stromal tumor (GIST) recurrence in patients treated with adjuvant imatinib. METHODS: Risk factors for GIST recurrence were identified, and 2 risk stratification scores were developed using the database of the Scandinavian Sarcoma Group (SSG) XVIII trial, where 358 patients with high-risk GIST with no overt metastases were randomly assigned to adjuvant imatinib 400 mg/day either for 12 or 36 months after surgery. The findings were validated in the imatinib arm of the American College of Surgeons Oncology Group Z9001 trial, where 359 patients with GIST were randomized to receive imatinib and 354 were to receive placebo for 12 months. RESULTS: Five factors (high tumor mitotic count, nongastric location, large size, rupture, and adjuvant imatinib for 12 months) were independently associated with unfavorable recurrence-free survival (RFS) in a multivariable analysis in the SSGXVIII cohort. A risk score based on these 5 factors had a concordance index with GIST recurrence of 78.9%. When a simpler score consisting of the 2 strongest predictive factors (mitotic count and tumor site) was devised, the groups with the lowest, intermediate high, and the highest risk had 5-year RFS of 76.7%, 47.5%, and 8.4%, respectively. Both scores were strongly associated with RFS in the validation cohort (P<.001 for each comparison). CONCLUSIONS: The scores generated were effective in stratifying the risk of GIST recurrence in patient populations treated with adjuvant imatinib. Patients with nongastric GIST with a high mitotic count are at a particularly high risk for recurrence. (C) 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
Original languageEnglish
Pages (from-to)2325-2333
JournalCancer
Volume120
Issue number15
DOIs
Publication statusPublished - 2014

Subject classification (UKÄ)

  • Cancer and Oncology

Keywords

  • gastrointestinal stromal tumor
  • imatinib
  • adjuvant therapy
  • predictive
  • score

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