title: Differential Radiographic Appearance of BRAF V600E-Mutant Metastatic Colorectal Cancer in Patients Matched by Primary Tumor Location.
abstract: BRAF-mutant metastatic colorectal cancers (mCRCs) share many clinicopathologic features with right-sided colon tumors, including frequent peritoneal involvement. Because of the poorer outcomes associated with BRAF mutations, early enrollment in clinical trials has been encouraged. However, the use of standard eligibility and assessment criteria, such as measurable disease, has anecdotally impeded patient accrual and restricted appraisal of treatment response. We investigated whether the presence of a BRAF V600E mutation is differentially associated with sites and appearance of metastatic disease in patients matched by primary tumor location.
  
  
  
  A total of 40 patients with BRAF-mutant mCRC were matched to 80 patients with BRAF wild-type mCRC by location of primary tumor (right or left colon; rectum), sex, and age. Associations between BRAF mutation status and clinicopathologic characteristics and metastatic sites were analyzed using proportion tests. Survival was summarized with Kaplan-Meier and Cox regression methods.
  
  
  
  The distribution of primary tumor locations was: 60% right colon, 30% left colon, and 10% rectum. Compared with BRAF wild-type tumors, BRAF-mutant tumors more commonly associated with peritoneal metastases (50% vs 31%; P=.045) and ascites (50% vs 24%; P=.0038). In patients with left colon primaries, BRAF mutations were associated with more frequent ascites (58% vs 12%; P=.0038) and less frequent liver metastases (42% vs 79%; P=.024). Among patients with right colon primaries, no significant difference in sites of disease by BRAF mutation status was observed. Disease was not measurable by RECIST 1.1 in 24% of patients with right-sided primary tumors, irrespective of BRAF mutation status. In the BRAF-mutated cohort, ascites correlated unfavorably with survival (hazard ratio, 2.35; 95% CI, 1.14, 4.83; P=.02).
  
  
  
  Greater frequency of ascites and peritoneal metastases, which pose challenges for RECIST 1.1 interpretation of therapeutic outcomes, are seen with BRAF-mutant mCRC, even when patients are matched for primary tumor location.
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Chloe E
authors.initials: CE
authors.lastname: Atreya
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Claire
authors.initials: C
authors.lastname: Greene
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: McWhirter
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Nabia S
authors.initials: NS
authors.lastname: Ikram
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: I Elaine
authors.initials: IE
authors.lastname: Allen
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Katherine
authors.initials: K
authors.lastname: Van Loon
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Benjamin M
authors.initials: BM
authors.lastname: Yeh
authors.affiliation: From the Department of Medicine and Helen Diller Family Comprehensive Cancer Center; Department of Radiology and Biomedical Imaging; and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California.
authors.forename: Spencer C
authors.initials: SC
authors.lastname: Behr
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001201:Ascites / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000209:etiology; D014408:Biomarkers, Tumor / Q000235:genetics; D015179:Colorectal Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000556:secondary; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010534:Peritoneal Neoplasms / Q000000981:diagnostic imaging* / Q000453:epidemiology / Q000556:secondary; D011379:Prognosis; D016016:Proportional Hazards Models; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf