INTRODUCTION Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine neoplasm with propensity for lymphatic spread. The rarity of MCC has limited analysis of factors associated with a positive sentinel lymph node biopsy (SLNB) and survival. METHODS Review of a prospective MCC database was performed. Factors associated with +SLNB were analyzed. Univariate and multivariate analyses of factors associated with recurrence and survival were performed using the cumulative incidence (CI) function, treating death from other causes (DOC) as a competing risk. RESULTS From 1996–2010, 153 patients with localized MCC underwent SLNB, of whom 45 (29%) were positive. Factors associated with +SLNB were primary tumor size (25% ≤2 cm v. 45% >2 cm; p=0.02) and presence of lymphovascular invasion (LVI; 55% +LVI v. 4% −LVI; p<0.01). +SLNB patients were more likely to receive radiation or chemotherapy (60% vs. 7%, p<0.01). With median follow-up of 41 months, there were 16 nodal/distant recurrences (10%), 11 deaths from MCC (7%), and 27 DOC’s (18%). The 2-year CI’s of recurrence or death from MCC were 12% and 6%, respectively. There was no difference in recurrence or death from MCC between +SLNB and −SLNB patients. The 2-year CI’s of recurrence or death from MCC for +LVI patients were 30% and 15%, respectively. No −LVI patient recurred or died of MCC. CONCLUSION SLNB identifies occult nodal metastases in 29% of patients with localized MCC. Predictors of +SLNB are tumor size and presence of LVI. Patients with +SLNB are more likely to receive further treatment; however, SLN status is not associated with recurrence or survival. In contrast, LVI is strongly associated with both recurrence and survival.

Using common clinicopathologic factors, the recurrence nomogram is better able to account for tumor and patient heterogeneity, thereby providing a more individualized outcome prognostication than that afforded by the AJCC categoric system. By identifying both the high- and low-risk patients within any particular stage, the nomogram is expected to aid in treatment planning and future trial design.

BACKGROUND BRAF mutations occur in 5% to 11% of patients with metastatic colorectal cancer (mCRC) and have been associated with poor prognosis. The current study was undertaken to determine the clinicopathologic characteristics, PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) mutation frequency, and outcomes after metastasectomy in patients with BRAF-mutant mCRC. METHODS Data from 1941 consecutive patients with mCRC who underwent KRAS/BRAF mutation testing between 2009 and 2012 at a single institution were identified to identify BRAF-mutant mCRC cases (92 cases). BRAF wild-type mCRC cases from 2011 (423 cases) served as a control group. RESULTS BRAF-mutated mCRC was found to be significantly associated with older age at diagnosis, female sex, right-sided location, poorly differentiated morphology, and mucinous histology compared with wild-type cases. BRAF-mutant cases more frequently progressed from stage III disease (32% vs 17%; P =.003) and among those patients with stage III disease, T4 disease was more common (48% vs 27%; P =.05). PIK3CA was found to be co-mutated in 5% of BRAF-mutant tumors versus 17% of KRAS-mutant tumors (P <.01) and 4% of BRAF/KRAS wild-type cases. Patients with BRAF-mutated mCRC presented more frequently with peritoneal involvement (26% vs 14%; P <0.01) and less frequently with liver-limited metastases (41% vs 63%; P <.01). Patients with BRAF-mutated mCRC were less likely to undergo metastasectomy (41% vs 26% at 2 years from diagnosis of metastatic disease; P <.01) and were found to have lower overall survival (P <.01) after metastasectomy. CONCLUSIONS BRAF-mutant mCRC is associated with worse clinical outcome. Patients with BRAF-mutant tumors more commonly develop peritoneal metastases, less frequently present with disease limited to the liver, and have shorter survival after metastasectomy compared with patients with BRAF wild-type tumors.

Among women treated for childhood cancer with chest radiation therapy, those treated with whole-lung irradiation have a greater risk of breast cancer than previously recognized, demonstrating the importance of radiation volume. Importantly, mortality associated with breast cancer after childhood cancer is substantial.