Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer |
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| Authors: | Thiru Prasanna Rachel Wong Timothy Price Jeremy Shapiro Jeanne Tie Hui-Li Wong Louise Nott David Roder Margaret Lee Suzanne Kosmider Azim Jalali Matthew Burge Robert Padbury Guy Maddern Scott Carruthers James Moore Michael Sorich Christos S Karapetis Desmond Yip |
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| Institution: | 1. Department of Medical Oncology, The Canberra Hospital, Garran, ACT, Australia;2. ANU Medical School, Australian National University, Australia;3. University of Canberra, ACT, Australia;4. Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia;5. Department of Medical Oncology, Eastern Health, Melbourne, Australia;6. Monash University, Faculty of Medicine, Nursing and Health Sciences, Melbourne, Australia;7. The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia;8. Cabrini Haematology and Oncology Centre, Melbourne, Australia;9. Department of Medical Oncology, Western Hospital, Melbourne, Australia;10. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia;11. Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia;12. Menzies Research institute, Hobart, Australia;13. South Australian Health & Medical Research Institute (SAHMRI), Australia;14. University of South Australia, Adelaide, Australia;15. Department of Medical Oncology, Royal Brisbane Hospital, Brisbane, Australia;p. Flinders University, Bedford Park, Australia;q. Department of Surgery, Flinders Medical Centre, Australia;r. University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Adelaide, Australia;s. Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia;t. Department of Surgery, Royal Adelaide Hospital, Adelaide, Australia;u. College of Medicine and Public Health, Flinders University, Adelaide, Australia;v. Department of Medical Oncology, Flinders Medical Centre, Australia;1. Australian Research Center for Population Oral Health, Adelaide Dental School, University of Adelaide, Australia;2. Consultant Oral Pathologist, Waryam Singh Yamunanagar, Haryana 135001 Desh Bhagat Dental Hospital, Ludhiana, Punjab, India;3. Adelaide Dental School, University of Adelaide, Adelaide, Australia;4. Head and Neck Surgical Oncology Unit, Punjab Institute of Medical Sciences, Jalandhar, Punjab, India;1. Department of Oncology, Portuguese Institute of Oncology Francisco Gentil, Porto, Portugal;2. Department of Neurology, Portuguese Institute of Oncology Francisco Gentil, Porto, Portugal;3. Department of Neurosurgery, Portuguese Institute of Oncology Francisco Gentil, Porto, Portugal;4. Intensive care department, Portuguese Institute of Oncology Francisco Gentil, Porto, Portugal;5. Department of Pathology, Portuguese Institute of Oncology Francisco Gentil, Porto, Portugal;1. Department of Family Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;2. Department of Statistics and Actuarial Science, Soongsil University, Seoul, Republic of Korea;3. Department of Family Medicine & Supportive Care Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;4. Department of Digital Health, Samsung Advanced Institute of Health Science and Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea;5. Department of Biostatistics, The Catholic University of Korea, Seoul, Republic of Korea;6. Department of Thoracic and Cardiovascular Surgery, Armed Forces Capital Hospital, Seongnam, Republic of Korea;7. Department of Family Medicine, Boramae Medical Center, Seoul, Republic of Korea;8. Department of Thoracic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea;1. Department of General Surgery, Tongji Hospital, Medical School of Tongji University, Shanghai, PR China;2. Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou, PR China;3. Department of General Surgery, The First Affiliated Hospital of Xingjiang Medical University, Urumqi, Xinjiang Province, PR China;4. Department of Gastrointestinal Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, PR China;5. Department of Gastrointestinal Surgery, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, PR China;6. School of Clinical Medicine, Dali University, Dali, Yunnan 671000, PR China;7. Yizheng People''s Hospital, Clinical Medical College, Yangzhou University, Yangzhou 211400, Jiangsu Province, China;8. Changzhi People''s Hospital, The Affiliated Hospital of Changzhi Medical College, Changzhi 046000, Shanxi Province, China;1. Division of Dermatology, IRCCS Policlinico di Sant''Orsola, via Massarenti 9, 40138 Bologna, Italy;2. Division of Dermatology, Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, 40138 Bologna, Italy;3. Division of Oncology, IRCCS Policlinico di Sant''Orsola, via Massarenti 9, 40138 Bologna, Italy;1. Bezmialem Vakif University, School of Medicine Hospital, Department of Medical Oncology, Istanbul, Turkey;2. Necmettin Erbakan University, Meram School of Medicine Hospital, Department of Medical Oncology, Konya, Turkey;3. Trakya University School of Medicine Hospital, Department of Medical Oncology, Edirne, Turkey;4. Van Yüzünzü Y?l University Hospital, Department of Medical Oncology, Van, Turkey;5. Bezmialem Vakif University, School of Medicine Hospital, Department of Pathology, Istanbul, Turkey;6. Bezmialem Vakif University, School of Medicine Hospital, Department of Urology, Istanbul, Turkey |
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| Abstract: | Background: Resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether the benefit is consistent for BRAF V600E mutant (MT) and wild type (WT) mCRC. This retrospective analysis explores the influence of BRAF MT on survival after metastasectomy. Methods: Overall survival (OS) and recurrence-free survival (RFS) for BRAF MT and WT mCRC were evaluated. Survival was also analyzed in the cohort of BRAF MT with or without metastasectomy. Results: Five hundred and thirteen patients who had undergone metastasectomy were identified, 6% were BRAF-MT. Median age 63. Median OS in BRAF MT vs WT: 25.7 vs 48.5 months (hazard ratio HR] 1.95; 1.18-3.22). However, difference was not significant in a multivariate model. Right primary tumor, intact primary, >1 metastatic site, non-R0 resection, peritoneal metastasis, and synchronous metastasis were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 vs 19 months, p=0.09). In another cohort of 158 BRAF-MT patients, OS was significantly better after metastasectomy compared to “no metastasectomy” (HR 0.34; 0.18-0.65, P= 0.001). Proficient mismatch repair status showed a trend toward worse survival after metastasectomy in BRAF MT (HR 1.71, P = 0.08). Conclusion: OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Median OS was >2 years in this study after metastasectomy among BRAFV600E MT patients suggesting a survival benefit of metastasectomy in this group where systemic therapeutic options are limited. Metastasectomy may be considered in carefully selected BRAF-MT patients. |
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