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PURPOSE:Merkel cell carcinoma (MCC) is an aggressive skin cancer often caused by the Merkel cell polyomavirus. Clinical trials of programmed cell death-1 pathway inhibitors for advanced MCC (aMCC) demonstrate increased progression-free survival (PFS) compared with historical chemotherapy data. However, response durability and overall survival (OS) data are limited. PATIENTS AND METHODS:In this multicenter phase II trial (Cancer Immunotherapy Trials Network-09/Keynote-017), 50 adults naïve to systemic therapy for aMCC received pembrolizumab (2 mg/kg every 3 weeks) for up to 2 years. Radiographic responses were assessed centrally per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. RESULTS:Among 50 patients, the median age was 70.5 years, and 64% had Merkel cell polyomavirus-positive tumors. The objective response rate (ORR) to pembrolizumab was 56% (complete response [24%] plus partial response [32%]; 95% CI, 41.3% to 70.0%), with ORRs of 59% in virus-positive and 53% in virus-negative tumors. Median follow-up time was 14.9 months (range, 0.4 to 36.4+ months). Among 28 responders, median response duration was not reached (range, 5.9 to 34.5+ months). The 24-month PFS rate was 48.3%, and median PFS time was 16.8 months (95% CI, 4.6 months to not estimable). The 24-month OS rate was 68.7%, and median OS time was not reached. Although tumor viral status did not correlate with ORR, PFS, or OS, there was a trend toward improved PFS and OS in patients with programmed death ligand-1-positive tumors. Grade 3 or greater treatment-related adverse events occurred in 14 (28%) of 50 patients and led to treatment discontinuation in seven (14%) of 50 patients, including one treatment-related death. CONCLUSION:Here, we present the longest observation to date of patients with aMCC receiving first-line anti-programmed cell death-1 therapy. Pembrolizumab demonstrated durable tumor control, a generally manageable safety profile, and favorable OS compared with historical data from patients treated with first-line chemotherapy.

The chief goal of the Blood Profiling Atlas in Cancer (BloodPAC) consortium is to promote collaborative efforts that support the development and implementation of liquid biopsy tests. Here, we report the results of a pilot study conducted by three BloodPAC members that aimed to demonstrate a multisite liquid biopsy testing framework using longitudinal blood specimens from 38 patients with metastatic breast cancer. Three laboratories receiving identical samples from two clinical sites each applied a different targeted sequencing platform to analyze mutations in cell-free DNA (cfDNA). The resulting mutational profiles reflected common breast cancer alterations, including clinically actionable mutations for 40% of hormone- receptor-positive patients. In 12 genes with shared target regions across sequencing panels, perfect inter-assay concordance was also observed for mutations detected above the lowest common assay limit of detection. Whole-genome copy number profiling of cfDNA and circulating tumor cells (CTCs) further revealed marked heterogeneity in copy number alterations and cfDNA tumor fractions across patients. Additionally, comparison of tumor fraction and CTC abundance demonstrated the complementary nature of cfDNA and CTC analyses. Overall, the framework described in this study may serve as a resource for future trials aiming to identify multimodal liquid biopsy biomarkers to guide clinical care. [ABSTRACT FROM AUTHOR]

Background: Imiquimod is a topical cream approved by the US Food and Drug Administration for treatment of superficial basal cell carcinoma, actinic keratosis, and genital-perianal warts. Its successful use in patients with persistently positive margins of melanoma in situ (MIS) after surgical excision has been previously reported. Case Report: A 75-year-old female presented with a primary melanoma that was removed through an elliptical excision with 1 cm margins. Pathology revealed 3 involved margins with residual MIS without an invasive component. After a second operation removed an additional 1 cm margin, pathology revealed 2 positive margins with residual MIS. Rather than undergoing a third excision, the patient decided to pursue a nonsurgical approach with topical imiquimod, and at the 4-month follow-up examination, the incision was completely healed with no clinical evidence of tumor recurrence. Conclusion: A nonsurgical approach with 5% topical imiquimod cream applied along the incision was utilized. In specific patient populations, the use of imiquimod is a reasonable alternative approach for the management of persistently positive MIS margins. Long-term follow-up is necessary to assess for evidence of recurrence and the ultimate success of this nonsurgical approach. [ABSTRACT FROM AUTHOR]

Background: Formerly, anesthetized patients who received intraoperative radiation therapy (IORT) had to be transported from the operating room (OR) to the location of the linear accelerator. With the advent of mobile accelerators, therapy is delivered directly to the patient in the OR, presenting specific challenges for the anesthesiologist. Methods: We review the uses and benefits, operative and anesthetic challenges, and unique issues associated with IORT. Results: Patient safety and precise delivery of the radiation dose are the primary goals of IORT. The anesthesiologist's role in ensuring the success of these two outcomes includes selecting the optimal anesthetic technique to prevent patient movement and permit sentinel node mapping, monitoring the patient's vital signs throughout the procedure, and ensuring that the sterile field is maintained in the OR. Conclusion: Although keeping patients in the OR has simplified the process of providing IORT, the anesthesiologist must be aware of potential problems and plan accordingly. [ABSTRACT FROM AUTHOR]