Toshirou Nishida1,2,3, Shinsuke Sato4, Masato Ozaka5, Yujiro Nakahara6, Yoshito Komatsu7, Masato Kondo8, Haruhiko Cho9, Seiichi Hirota10, Tatsuo Kagimura11, Yukinori Kurokawa12, Yuko Kitagawa13. 1. Department of Surgery, Japan Community Health-Care Organization Osaka Hospital, 4-2-78 Fukushima, Fukushima-ku, Osaka, 553-0003, Japan. tnishida@ncc.go.jp. 2. Department of Surgery, National Cancer Center Hospital, Tokyo, Japan. tnishida@ncc.go.jp. 3. Laboratory of Nuclear Transport Dynamics, National Institute of Biomedical Innovation, Health and Nutrition, Osaka, Japan. tnishida@ncc.go.jp. 4. Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan. 5. Department of Gastroenterological Medicine, Cancer Institute Hospital Japanese Foundation for Cancer Research, Tokyo, Japan. 6. Department of Surgery, Osaka Police Hospital, Osaka, Japan. 7. Hokkaido University Hospital, Sapporo, Hokkaido, Japan. 8. Department of Surgery, Kobe City Medical Center General Hospital, Kobe, Japan. 9. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, Tokyo, Japan. 10. Department of Surgical Pathology, Hyogo College of Medicine, Nishinomiya, Japan. 11. Foundation for Biomedical Research and Innovation at Kobe, Translational Research Center for Medical Innovation, Kobe, Japan. 12. Department of Gastroenterological Surgery, Osaka University Graduate School of Medicine, Suita, Japan. 13. Department of Surgery, Keio University Hospital, Tokyo, Japan.
Abstract
PURPOSE: Three years of adjuvant imatinib is the standard therapy for gastrointestinal stromal tumors (GISTs) with high-risk features. The prognostic effects of long-term adjuvant therapy are unknown. PATIENTS AND METHODS: The prospective registry study recruited 515 patients with high-risk GISTs between Dec. 2012 and Dec. 2015 were analyzed. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints include overall survival (OS) and safety. The study was designed to compare RFS after 3.5 years of 3-year adjuvant therapy (3.0 ± 0.5 years: 3-year group) with that of more than 3.5 years (median 5.2 years: longer group). RESULTS: Five-year RFS and 5-year OS were 68.2% (95% confidence interval [CI] 63.8-72.1) and 92.3% (95% CI 89.5-94.4), respectively. The recurrence rate during adjuvant was estimated to be 2.9/100 person-years (95% CI 2.0-4.1) and those after the end of adjuvant, which appeared similar irrespective of the adjuvant duration or reason to stop adjuvant, were estimated 12.0/100 person-years (95% CI 10.2-14.0). The 5-year RFS rates of 3-year and longer groups were 78.7% (95% CI 70.8-84.7) and 92.7% (95% CI 85.2-96.4), respectively. RFS after 3.5 years of the longer group was significantly better than that of the 3-year group (adjusted hazard ratio [HR] 0.56; 95% CI 0.39-0.78; P < 0.001). CONCLUSION: The recurrence risk of high-risk GISTs after adjuvant therapy is similar irrespective of the adjuvant duration and imatinib adjuvant may not cure but may delay recurrence. RFS after long-term adjuvant therapy appeared better than that after 3-year adjuvant.
PURPOSE: Three years of adjuvant imatinib is the standard therapy for gastrointestinal stromal tumors (GISTs) with high-risk features. The prognostic effects of long-term adjuvant therapy are unknown. PATIENTS AND METHODS: The prospective registry study recruited 515 patients with high-risk GISTs between Dec. 2012 and Dec. 2015 were analyzed. The primary endpoint was recurrence-free survival (RFS), and secondary endpoints include overall survival (OS) and safety. The study was designed to compare RFS after 3.5 years of 3-year adjuvant therapy (3.0 ± 0.5 years: 3-year group) with that of more than 3.5 years (median 5.2 years: longer group). RESULTS: Five-year RFS and 5-year OS were 68.2% (95% confidence interval [CI] 63.8-72.1) and 92.3% (95% CI 89.5-94.4), respectively. The recurrence rate during adjuvant was estimated to be 2.9/100 person-years (95% CI 2.0-4.1) and those after the end of adjuvant, which appeared similar irrespective of the adjuvant duration or reason to stop adjuvant, were estimated 12.0/100 person-years (95% CI 10.2-14.0). The 5-year RFS rates of 3-year and longer groups were 78.7% (95% CI 70.8-84.7) and 92.7% (95% CI 85.2-96.4), respectively. RFS after 3.5 years of the longer group was significantly better than that of the 3-year group (adjusted hazard ratio [HR] 0.56; 95% CI 0.39-0.78; P < 0.001). CONCLUSION: The recurrence risk of high-risk GISTs after adjuvant therapy is similar irrespective of the adjuvant duration and imatinib adjuvant may not cure but may delay recurrence. RFS after long-term adjuvant therapy appeared better than that after 3-year adjuvant.
Authors: Chandrajit P Raut; N Joseph Espat; Robert G Maki; Dejka M Araujo; Jonathan Trent; Toni Faith Williams; D Das Purkayastha; Ronald P DeMatteo Journal: JAMA Oncol Date: 2018-12-13 Impact factor: 31.777