Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer

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; Peter Gibbs; Desmond Yip

doi:10.1016/j.currproblcancer.2020.100637

Metastasectomy and BRAF mutation; an analysis of survival outcome in metastatic colorectal cancer

Curr Probl Cancer. 2021 Feb;45(1):100637. doi: 10.1016/j.currproblcancer.2020.100637. Epub 2020 Aug 14.

Authors

Thiru Prasanna¹, Rachel Wong², Timothy Price³, Jeremy Shapiro⁴, Jeanne Tie⁵, Hui-Li Wong⁶, Louise Nott⁷, David Roder⁸, Margaret Lee⁹, Suzanne Kosmider¹⁰, Azim Jalali¹¹, Matthew Burge¹², Robert Padbury¹³, Guy Maddern¹⁴, Scott Carruthers¹⁵, James Moore¹⁶, Michael Sorich¹⁷, Christos S Karapetis¹⁸, Peter Gibbs¹¹, Desmond Yip¹⁹

Affiliations

¹ Department of Medical Oncology, The Canberra Hospital, Garran, ACT, Australia; ANU Medical School, Australian National University, Australia; University of Canberra, ACT, Australia. Electronic address: Thiru.prasanna@act.gov.au.
² Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Eastern Health, Melbourne, Australia; Monash University, Faculty of Medicine, Nursing and Health Sciences, Melbourne, Australia.
³ The Queen Elizabeth Hospital and University of Adelaide, Adelaide, Australia.
⁴ Cabrini Haematology and Oncology Centre, Melbourne, Australia.
⁵ Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Western Hospital, Melbourne, Australia; Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia.
⁶ Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia.
⁷ Department of Medical Oncology, Royal Hobart Hospital, Hobart, Tasmania, Australia; Menzies Research institute, Hobart, Australia.
⁸ South Australian Health & Medical Research Institute (SAHMRI), Australia; University of South Australia, Adelaide, Australia.
⁹ Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Eastern Health, Melbourne, Australia.
¹⁰ Department of Medical Oncology, Western Hospital, Melbourne, Australia.
¹¹ Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Oncology, Western Hospital, Melbourne, Australia.
¹² Department of Medical Oncology, Royal Brisbane Hospital, Brisbane, Australia.
¹³ Flinders University, Bedford Park, Australia; Department of Surgery, Flinders Medical Centre, Australia.
¹⁴ University of Adelaide Discipline of Surgery, The Queen Elizabeth Hospital, Adelaide, Australia.
¹⁵ Department of Radiation Oncology, Royal Adelaide Hospital, Adelaide, Australia.
¹⁶ Department of Surgery, Royal Adelaide Hospital, Adelaide, Australia.
¹⁷ College of Medicine and Public Health, Flinders University, Adelaide, Australia.
¹⁸ Flinders University, Bedford Park, Australia; Department of Medical Oncology, Flinders Medical Centre, Australia.
¹⁹ Department of Medical Oncology, The Canberra Hospital, Garran, ACT, Australia; ANU Medical School, Australian National University, Australia.

PMID: 32826083
DOI: 10.1016/j.currproblcancer.2020.100637

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.

Keywords: BRAF V600E mutation; Metastasectomy; Metastatic colorectal cancer; Survival.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't
Review

MeSH terms

Aged
Australia / epidemiology
Colorectal Neoplasms / epidemiology*
Colorectal Neoplasms / genetics*
Colorectal Neoplasms / pathology
Colorectal Neoplasms / surgery
Female
Humans
Male
Metastasectomy / statistics & numerical data*
Middle Aged
Neoplasm Metastasis
Proto-Oncogene Proteins B-raf / genetics*
Registries
Retrospective Studies
Risk Factors
Survival Rate

Substances

BRAF protein, human
Proto-Oncogene Proteins B-raf