Shin Kobayashi1, Shinichiro Takahashi2, Naoki Takahashi3, Toshiki Masuishi4, Hirokazu Shoji5, Eiji Shinozaki6, Tatsuro Yamaguchi7, Motohiro Kojima8, Naoto Gotohda2, Shogo Nomura9, Takayuki Yoshino10, Hiroya Taniguchi10. 1. Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Kashiwa, Japan. shkobaya@east.ncc.go.jp. 2. Department of Hepatobiliary and Pancreatic Surgery, National Cancer Center Hospital East, Chiba, Kashiwa, Japan. 3. Department of Gastroenterology, Saitama Cancer Center, Saitama, Japan. 4. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 5. Department of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Gastrointestinal Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 7. Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Tokyo, Japan. 8. Division of Pathology, Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 9. Clinical Research Support Office, National Cancer Center Hospital East, Kashiwa, Japan. 10. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Abstract
BACKGROUND: Although the prognosis for patients with resected BRAF mutant colorectal liver metastases (CRLM) is poor, the survival impact of the BRAF V600E mutation in such cases remains unclear. METHODS: A multicenter retrospective cohort study was performed to investigate the survival outcomes of patients who underwent initial hepatectomy for histologically confirmed BRAF V600E mutant CRLM between January 2005 and December 2017. RESULTS: Thirty-three patients from 6 institutions were included in this study. During the median duration of the post-hepatectomy follow-up period of 49.2 months, 31 patients (93.9%) developed recurrence after a median period of 5.3 months and the 1-year recurrence-free survival (RFS) rate was 24.2%. Only two patients underwent repeated surgery for recurrence. The other 29 patients had unresectable recurrent lesions, and 27 of them received systemic chemotherapy. The median overall survival (OS) period was 31.1 months and the 5-year OS rate was 18.2%. The factors for a poor RFS prognosis were an elevated serum CA19-9 level (≥ 37 IU/ml) at hepatectomy (HR: 2.139, 95% CI: 1.009-4.534, P = 0.047) and R1 resection (HR: 5.827, 95% CI: 1.585-21.42, P = 0.008), and that for OS was R1 resection only (HR: 4.129, 95% CI: 1.104-15.45, P = 0.035). CONCLUSIONS: Since the early onset unresectable recurrence rate was very high, systemic chemotherapy should be considered for resectable BRAF V600E mutant CRLM. A novel perioperative treatment strategy is needed to improve the survival of such patients.
BACKGROUND: Although the prognosis for patients with resected BRAF mutant colorectal liver metastases (CRLM) is poor, the survival impact of the BRAFV600E mutation in such cases remains unclear. METHODS: A multicenter retrospective cohort study was performed to investigate the survival outcomes of patients who underwent initial hepatectomy for histologically confirmed BRAFV600E mutant CRLM between January 2005 and December 2017. RESULTS: Thirty-three patients from 6 institutions were included in this study. During the median duration of the post-hepatectomy follow-up period of 49.2 months, 31 patients (93.9%) developed recurrence after a median period of 5.3 months and the 1-year recurrence-free survival (RFS) rate was 24.2%. Only two patients underwent repeated surgery for recurrence. The other 29 patients had unresectable recurrent lesions, and 27 of them received systemic chemotherapy. The median overall survival (OS) period was 31.1 months and the 5-year OS rate was 18.2%. The factors for a poor RFS prognosis were an elevated serum CA19-9 level (≥ 37 IU/ml) at hepatectomy (HR: 2.139, 95% CI: 1.009-4.534, P = 0.047) and R1 resection (HR: 5.827, 95% CI: 1.585-21.42, P = 0.008), and that for OS was R1 resection only (HR: 4.129, 95% CI: 1.104-15.45, P = 0.035). CONCLUSIONS: Since the early onset unresectable recurrence rate was very high, systemic chemotherapy should be considered for resectable BRAFV600E mutant CRLM. A novel perioperative treatment strategy is needed to improve the survival of such patients.