Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib

Heikki Joensuu, Mikael Eriksson, Kirsten Sundby Hall, Jörg T. Hartmann, Daniel Pink, Jochen Schütte, 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.

Original languageEnglish (US)
Pages (from-to)2325-2333
Number of pages9
JournalCancer
Volume120
Issue number15
DOIs
StatePublished - Aug 1 2014

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Gastrointestinal Stromal Tumors
Recurrence
Survival
Imatinib Mesylate
Sarcoma
Rupture
Neoplasms
Placebos
Databases
Neoplasm Metastasis

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Joensuu, H., Eriksson, M., Hall, K. S., Hartmann, J. T., Pink, D., Schütte, J., ... Reichardt, P. (2014). Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer, 120(15), 2325-2333. https://doi.org/10.1002/cncr.28669

Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. / Joensuu, Heikki; Eriksson, Mikael; Hall, Kirsten Sundby; Hartmann, Jörg T.; Pink, Daniel; Schütte, Jochen; Ramadori, Giuliano; Hohenberger, Peter; Duyster, Justus; Al-Batran, Salah Eddin; Schlemmer, Marcus; Bauer, Sebastian; Wardelmann, Eva; Sarlomo-Rikala, Maarit; Nilsson, Bengt; Sihto, Harri; Ballman, Karla V.; Leinonen, Mika; Dematteo, Ronald P.; Reichardt, Peter.

In: Cancer, Vol. 120, No. 15, 01.08.2014, p. 2325-2333.

Research output: Contribution to journalArticle

Joensuu, H, Eriksson, M, Hall, KS, Hartmann, JT, Pink, D, Schütte, J, Ramadori, G, Hohenberger, P, Duyster, J, Al-Batran, SE, Schlemmer, M, Bauer, S, Wardelmann, E, Sarlomo-Rikala, M, Nilsson, B, Sihto, H, Ballman, KV, Leinonen, M, Dematteo, RP & Reichardt, P 2014, 'Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib', Cancer, vol. 120, no. 15, pp. 2325-2333. https://doi.org/10.1002/cncr.28669
Joensuu H, Eriksson M, Hall KS, Hartmann JT, Pink D, Schütte J et al. Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. Cancer. 2014 Aug 1;120(15):2325-2333. https://doi.org/10.1002/cncr.28669
Joensuu, Heikki ; Eriksson, Mikael ; Hall, Kirsten Sundby ; Hartmann, Jörg T. ; Pink, Daniel ; Schütte, Jochen ; Ramadori, Giuliano ; Hohenberger, Peter ; Duyster, Justus ; Al-Batran, Salah Eddin ; Schlemmer, Marcus ; Bauer, Sebastian ; Wardelmann, Eva ; Sarlomo-Rikala, Maarit ; Nilsson, Bengt ; Sihto, Harri ; Ballman, Karla V. ; Leinonen, Mika ; Dematteo, Ronald P. ; Reichardt, Peter. / Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib. In: Cancer. 2014 ; Vol. 120, No. 15. pp. 2325-2333.
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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.",
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T1 - Risk factors for gastrointestinal stromal tumor recurrence in patients treated with adjuvant imatinib

AU - Joensuu, Heikki

AU - Eriksson, Mikael

AU - Hall, Kirsten Sundby

AU - Hartmann, Jörg T.

AU - Pink, Daniel

AU - Schütte, Jochen

AU - Ramadori, Giuliano

AU - Hohenberger, Peter

AU - Duyster, Justus

AU - Al-Batran, Salah Eddin

AU - Schlemmer, Marcus

AU - Bauer, Sebastian

AU - Wardelmann, Eva

AU - Sarlomo-Rikala, Maarit

AU - Nilsson, Bengt

AU - Sihto, Harri

AU - Ballman, Karla V.

AU - Leinonen, Mika

AU - Dematteo, Ronald P.

AU - Reichardt, Peter

PY - 2014/8/1

Y1 - 2014/8/1

N2 - 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.

AB - 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.

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KW - predictive score

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