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Introduction: Current recommendations regarding the size of wide local excision (WLE) margins for Merkel cell carcinoma (MCC) are not well established. Methods: WLE and pathologic margins were respectively reviewed from 79 patients with stage I or II MCC, who underwent WLE at Washington University in St Louis from 2005 to 2019. Outcomes included local recurrence-free survival (LRFS), regional recurrence-free survival (RRFS), distant recurrence-free survival (DRFS), disease-free survival (DFS), and disease-specific survival (DSS). Results: Thirty-two percent of patients received adjuvant radiotherapy (aRT). At 1 year, DFS was 51.3%, 71.4%, and 87.8% for patients with WLE margins < 1 cm, 1–1.9 cm, and ≥ 2 cm, respectively (p = 0.02). At 3 years, the DSS was 57.7%, 82.6%, and 100% for patients with WLE margins < 1 cm, 1–1.9 cm, and ≥ 2 cm, respectively (p = 0.02). Multivariable Cox analysis demonstrated that every 1-cm increase in WLE margins was associated with improved RRFS [hazard ratio (HR) = 0.28, 95% confidence interval (CI): 0.11–0.75], DRFS (HR 0.30, CI 0.08–0.99), DFS (HR 0.42, CI 0.21–0.86), and DSS (HR 0.16, CI 0.04–0.61). WLE and pathologic margin size were moderately-to-strongly correlated (r = 0.66). Close or positive pathologic margins (< 3 mm) were associated with reduced DRFS (HR 6.83, CI 1.80–25.9), DFS (HR 2.98, CI 1.31–6.75), and DSS (HR 3.52, CI 1.14–10.9). Conclusion: Reduced WLE and pathologic margins were associated with higher risk of relapse and death from MCC. Larger WLE margins are important in populations with lower rates of adjuvant radiation. [ABSTRACT FROM AUTHOR]

Anti-programmed death 1 (PD-1) immune checkpoint inhibitors enhance the antitumour activity of the immune system and have produced durable tumour responses in several solid tumours including non-small cell lung cancer (NSCLC). However, PD-1 inhibitors can lead to immune-related adverse events, including pneumonitis, which is typically mild, but can be severe and potentially fatal. Pneumonitis often resolves with steroids, but some cases are steroid refractory, leading to a relapsing and remitting course in milder cases or the need for salvage therapies in more severe cases. Here, we present two patients with NSCLC who developed severe pneumonitis following therapy with nivolumab and pembrolizumab. While one patient improved with steroids and infliximab, the other patient failed to respond to steroids and subsequently died. These cases demonstrate the highly variable presentation and therapeutic responses seen in patients with pneumonitis following anti-PD-1 therapy and illustrate that severe cases can often present refractory to steroid therapy. [ABSTRACT FROM AUTHOR]

Cancer cell proliferation is regulated by oncogenes, such as c-Myc. An alternative approach to directly targeting individual oncogenes is to target IMP-1, an oncofetal protein that binds to and stabilizes messenger RNAs (mRNAs), leading to elevated expression of c-Myc and other oncogenes. Expression of IMP-1 is tightly correlated with a poor prognosis and reduced survival in ovarian, lung, and colon cancer. Small-molecule inhibitors of IMP-1 have not been reported. We established a fluorescence anisotropy/polarization microplate assay (FAMA) for analyzing binding of IMP-1 to a fluorescein-labeled 93 nucleotide c-Myc mRNA target (flMyc), developed the assay as a highly robust (Z′ factor = 0.60) FAMA-based high-throughput screen for inhibitors of binding of IMP-1 to flMyc, and carried out a successful pilot screen of 17,600 small molecules. Our studies support rapidly filtering out toxic nonspecific inhibitors using an early cell-based assay in control cells lacking the target protein. The physiologic importance of verified hits from the in vitro high-throughput screen was demonstrated by identification of the first small-molecule IMP-1 inhibitor, a lead compound that selectively inhibits proliferation of IMP-1–positive cancer cells with very little or no effect on proliferation of IMP-1–negative cells. [ABSTRACT FROM PUBLISHER]

Infection is a common cause of morbidity and mortality in chronic lymphocytic leukemia and should be considered when examining bone marrow specimens to identify a potentially treatable pathogen. [ABSTRACT FROM AUTHOR]