University of Canberra, Canberra, ACT, Australia
Thiru Prasanna , Rachel Wong , Timothy Jay Price , Jeremy David Shapiro , Jeanne Tie , Hui-Li Wong , Louise M. Nott , David Roder , Margaret Lee , Suzanne Kosmider , Azim Jalali , Matthew E. Burge , Robert Padbury , Guy Maddern , James Moore , Scott Carruthers , Michael Sorich , Christos Stelios Karapetis , Peter Gibbs , Desmond Yip
Background: Surgical resection of oligometastases improves survival in metastatic colorectal cancer (mCRC). It is unclear whether such benefit is consistently observed for BRAF V600E mutant (MT) and wild type (WT) mCRC. We conducted a retrospective analysis to explore the influence of BRAF mutation status on survival outcomes after metastasectomy. Methods: Data collected from two large prospective population databases in Australia (Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) and South Australian cancer registry). Overall survival (OS) and recurrence free survival (RFS) for BRAF MT and WT mCRC were evaluated by Kaplan-Meier method and compared by log-rank test. Results: 513 patients who had undergone metastasectomy were identified, 6% were BRAF MT. Median age 63. Metastasectomy rate was lower in BRAF MT (13 v 27%). In BRAF WT, 4% underwent resection of metastases (mets) in >1 organ at diagnosis and 5% had 3 or 4 metastasectomies versus none in BRAF MT. Median OS in BRAF MT v WT: 25.7 v 48.5 months (HR 1.95; 1.18-3.22). In a multivariate model adjusting for variables which were significant on univariate analysis, OS differences were not statistically significant. Right primary tumor, intact primary, >1 metastatic sites at diagnosis, non R0 resection, peritoneal mets and synchronous mets were independent predictors of worse OS. Among 364 patients with RFS data there was no difference between BRAF MT and WT (16 v 19 months, p=0.09). Rate of downsizing was higher with triplet chemo than doublet +/- bevacizumab or doublet/EGFR in BRAF WT (50 v 30%) as well as MT (33 v 11%). Conclusions: Median OS was > 2 years in BRAF MT V600E after metastasectomy in this study consistent with an OS benefit. OS did not differ after metastasectomy between BRAF MT and WT in a multivariate model. Presence of BRAF MT should not impact patient selection for metastasectomy.
BRAF MT n=31 (%) | BRAF WT n=483 (%) | p | |
---|---|---|---|
Resected primary | 90 | 85 | 0.6 |
Synchronous met | 57 | 51 | 0.5 |
MSI-H | 13 | 3 | 0.02 |
Right primary | 70 | 28 | 0.001 |
Rectal primary | 10 | 31 | 0.001 |
Liver met at diagnosis | 40 | 66 | 0.005 |
Lung met at diagnosis | 13 | 26 | 0.19 |
Peritoneal mets at diagnosis | 60 | 31 | 0.002 |
Complete resection | 73 | 76 | 0.8 |
1st metastasectomy | |||
-Liver | 40 | 62 | 0.02 |
-Lung | 7 | 17 | 0.2 |
-Peritoneum | 53 | 24 | 0.001 |
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