The incidence of melanoma is increasing worldwide. Advances in targeted agents and immunotherapy have improved outcomes in metastatic disease, but biomarkers are required to optimize treatment. We determined the prevalence of circulating tumor cells (CTCs) and explored their utility as prognostic and pharmacodynamic biomarkers. A total of 101 patients with metastatic cutaneous melanoma were recruited prospectively. CTC number was determined using the CellSearch platform and melanoma kits in samples taken at baseline and serially during treatment. CTC numbers ranged between 0 and 36 per 7.5 ml blood; 26% of patients had ≥ 2 CTCs. Baseline CTC number was prognostic for median overall survival (OS) in univariate analysis (2.6 vs. 7.2 months (P<0.011) for patients with ≥ 2 CTCs vs. <2 CTCs, respectively). In multivariate analysis, CTC number was an independent prognostic biomarker of OS (hazard ratio (HR) 2.403, 95% confidence interval (CI) 1.303-4.430, P=0.005). Patients receiving treatment in whom CTC number remained ≥ 2 CTCs during treatment had shorter median OS than those who maintained<2 CTCs (7 vs. 10 months, HR 0.34, 95% CI 0.14-0.81, log-rank test P=0.015). In conclusion, CTC number in metastatic cutaneous melanoma patients is prognostic for OS with a cutoff of 2 CTCs per 7.5 ml blood. CTC number measured before and throughout treatment provided additional prognostic information. Larger studies are warranted to confirm CTC biomarker utility in melanoma patients.

BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage response; however, selective small molecule inhibitors of defined mechanism are currently lacking. Here, we identify and characterise a specific inhibitor of BLM’s ATPase-coupled DNA helicase activity, by allosteric trapping of a DNA-bound translocation intermediate. Crystallographic structures of BLM-DNA-ADP-inhibitor complexes identify a hitherto unknown interdomain interface, whose opening and closing are integral to translocation of ssDNA, and which provides a highly selective pocket for drug discovery. Comparison with structures of other RECQ helicases provides a model for branch migration of Holliday junctions by BLM.

BLM (Bloom syndrome protein) is a RECQ-family helicase involved in the dissolution of complex DNA structures and repair intermediates. Synthetic lethality analysis implicates BLM as a promising target in a range of cancers with defects in the DNA damage response, however selective small molecule inhibitors of defined mechanism are currently lacking. Here we identify and characterise a specific inhibitor of BLM’s ATPase-coupled DNA helicase activity, by allosteric trapping of a DNA-bound translocation intermediate. Crystallographic structures of BLM-DNA-ADP-inhibitor complexes identify a hitherto unknown interdomain interface, whose opening and closing are integral to translocation of ssDNA, and which provides a highly selective pocket for drug discovery. Comparison with structures of other RECQ helicases provides a model for branch migration of Holliday junctions by BLM.

Objectives Basaloid nasopharyngeal carcinoma (BNPC) is an extremely rare malignancy with a paucity of cases reported in the literature. This analysis represents the largest cohort of BNPC to date. Study Design Retrospective population‐based analysis. Methods The Surveillance, Epidemiology, and End Results registry from 2001 to 2015 was utilized to extract a total of 82 cases of BNPC. Data were analyzed for incidence trends, demographic, and tumor characteristics, as well as potential outcome prognosticators. Results White male patients between the ages of 40 to 79 years were most commonly affected. The incidence was measured at 0.06 per 100 thousand people. The majority of tumors were considered high grade (grade III/IV; 92.2%). At presentation, patients were most commonly advanced stage (American Joint Committee on Cancer [AJCC] stage IV) at 29.3%, followed by AJCC stages II and III (20.7%, respectively). T2 tumors were most common at 28.8%. Cervical node involvement and distant metastasis were measured at 53.7% and 10.4%, respectively. One‐year, 5‐year, and 10‐year disease‐specific survival was 87.7%, 60.7%, and 29.8%, respectively. No prognostic factors were identified in this study. Conclusion Basaloid squamous cell carcinoma represents a histologic subtype of nasopharyngeal carcinoma with excellent short‐term outcomes but poor survival at 10 years when compared to conventional squamous cell carcinomas. Level of Evidence NA Laryngoscope, 129:2727–2732, 2019

Objectives/Hypothesis Salivary gland nasopharynx cancers (SGNPCs) are rare malignancies with few cases discussed in the literature. This study represents the largest cohort of SGNPC to date. Study Design Retrospective population-based analysis. Methods The Surveillance, Epidemiology, and End Results registry from 1973 to 2015 was utilized to extract 383 cases of SGNPC. Data were analyzed for demographic characteristics, incidence, clinicopathologic traits, and outcome prognosticators. Results White female patients aged >40 years were most commonly affected. The incidence was measured as 0.019 per 100,000 people. The majority of tumors presented at advanced stages (stage III/IV, 60.8%). Adenoid cystic carcinoma, adenocarcinoma, and mucoepidermoid carcinoma were the most commonly encountered histologies (43.1%, 31.6%, 13.3%, respectively). Cervical node involvement and distant metastasis were measured at 23% and 11.9%, respectively. Mucoepidermoid carcinomas presented with the best disease-specific survival at 5 and 10 years. Asian ethnicity, age <80 years, and earlier American Joint Committee on Cancer stages were positive prognostic factors. The inclusion of surgical therapy improved 5-year outcomes among the most common histologies, except for mucoepidermoid carcinoma. Conclusions Salivary gland nasopharyngeal cancer represents a group of rare histologies with similar outcomes as squamous cell carcinomas. However, prognosis is primarily dependent on histologic subtype, race, age, and American Joint Committee on Cancer stage.