Zachary Zihui Yong1, Jolene Si Min Wong1, Melissa Ching Ching Teo1,2, Claramae Shulyn Chia1,2, Chin-Ann Johnny Ong1,2,3,4, Mohamad Farid5, Grace Hwei Ching Tan6,7. 1. Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, 169610, Singapore. 2. SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore. 3. Laboratory of Applied Human Genetics, Division of Medical Sciences, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, 169610, Singapore. 4. Institute of Molecular and Cell Biology, A*STAR Research Entities, 61 Biopolis Drive, Singapore, 138673, Singapore. 5. Division of Medical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, 169610, Singapore. 6. Department of Sarcoma, Peritoneal and Rare Tumours (SPRinT), Division of Surgery and Surgical Oncology, National Cancer Centre Singapore, 11 Hospital Crescent, Singapore, 169610, Singapore. grace.tan.h.c@singhealth.com.sg. 7. SingHealth Duke-NUS Oncology Academic Clinical Program, Duke-NUS Medical School, 8 College Road, Singapore, 169857, Singapore. grace.tan.h.c@singhealth.com.sg.
Abstract
BACKGROUND: The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs. METHODS: A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared. RESULTS: Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1-3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group. CONCLUSIONS: Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.
BACKGROUND: The role of tyrosine kinase inhibitors (TKI) in the neoadjuvant setting and the optimal duration of therapy remains poorly defined. As such, we aim to evaluate the impact of neoadjuvant TKI on oncological and functional outcomes in our cohort of patients with rectal GISTs. METHODS: A retrospective analysis of 36 consecutive patients who underwent treatment for rectal GIST at the National Cancer Centre Singapore from February 1996 to October 2017 was analysed. Surgical, recurrence and survival outcomes between the groups who underwent neoadjuvant therapy and those who underwent upfront surgery were compared. RESULTS:Patients who received neoadjuvant treatment had significantly larger tumours (median size 7.1 vs. 6.0 cm, p = 0.04) and lower mitotic count (> 10 per 50 HPF, 14 vs. 70%, p = 0.03) when compared with the non-neoadjuvant group. With TKI pre-treatment (median duration 8.8 months), majority of patients (82%) achieved at least partial response to the therapy coupled with a significant downsizing effect of up to 39% (median size of 7.1-3.6 cm), resulting in similar rates of sphincter-sparing surgery (75 vs. 76%, p = 0.94) when compared with the non-neoadjuvant group. In general, neoadjuvant group had lower rates of local recurrence (0 vs. 69%, p = 0.04) and higher overall survival (7.4 vs. 5.7 years, p = 0.03) as compared to the non-neoadjuvant group. CONCLUSIONS: Neoadjuvant TKI has the benefit of downsizing unresectable rectal GIST to benefit from sphincter-sparing procedure and also confers protection against local recurrence and improves overall survival.
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