Reanalysis of the NCCN PD-L1 Companion Diagnostic Assay Study for Lung Cancer in the Context of PD-L1 Expression Findings in Triple-Negative Breast Cancer

The companion diagnostic test for checkpoint inhibitor immune therapy is an immunohistochemical test for PD-L1. The test has been shown to be reproducible for expression in tumor cells, but not in immune cells. Immune cells were used in the IMpassion130 trial which showed PD-L1 expression was associated with a better outcome. Two large studies have been done assessing immune cell PD-L1 expression in lung cancer. Here, we reanalyze one of those studies, to show that, even with an easier scoring method, there is still only poor agreement between assays and pathologist for immune cell PD-L1 expression

Novel MIR143HG::PLAG1 gene fusion identified in a rectal myxoid leiomyosarcoma

Myxoid leiomyosarcoma (MLS) is a rare but well-documented tumor that often portends a poor prognosis compared to the conventional leiomyosarcoma. This rare sarcoma has been reported in the uterus, external female genitalia, soft tissue, and other locations. However, a definite rectal MLS has not been reported. Recently five cases of MLS were reported to harbor PLAG1 fusions (TRPS1::PLAG1, RAD51B::PLAG1, and TRIM13::PLAG1). In this report, we present a case of rectal MLS with a novel MIR143HG::PLAG1 fusion detected by RNA next-generation sequencing

Dysplasia at the margin? Investigating the case for subsequent therapy in \u27low-risk\u27 squamous cell carcinoma of the oral tongue.

PURPOSE: This is a retrospective analysis of the impact of moderate dysplasia at the resection margin for early stage cancer of the oral tongue. MATERIALS AND METHODS: Patients with T1-2N0 oral tongue cancer treated with surgery alone at Fox Chase Cancer Center (FCCC) from 1990 to 2010 were reviewed. Tumor and margin characteristics were abstracted from the pathology report. Overall survival (OS), disease-free survival (DFS) and local control (LC) were calculated using the Kaplan Meier method. Predictors of LC, OS and DFS were analyzed. RESULTS: 126 Patients met the inclusion criteria. Dysplasia was present at the final margin in 36% of the cases (severe: 9%, moderate: 15%, mild: 12%). Median follow-up was 52 months. 3 and 5-year actuarial LC for the entire cohort was 77% and 73%, respectively. Actuarial 5-year LC and DFS were significantly worse for patients with moderate or severe dysplasia at the margin vs. none or mild dysplasia at the margin (49% vs 82%, p=0.005 and 49% vs 80%, p=0.008, respectively); 3-year comparisons were not significant. When analyzed separately, the detrimental local effect of moderate dysplasia at the margin persisted (p=0.02) and the effect of severe dysplasia at the margin was approaching significance (p=0.1). Mild dysplasia at the margin did not significantly impair LC or DFS. Multivariate analysis demonstrated worse LC (HR: 2.99, p=0.006) and DFS (HR: 2.84, p=0.008) associated with severe or moderate dysplasia at the margin. CONCLUSIONS: Both severe and moderate dysplasia at the margin appear to be correlated with inferior LC and DFS. Additional therapy may be justified, despite added morbidity

MMP-13 In-Vivo Molecular Imaging Reveals Early Expression in Lung Adenocarcinoma

International audienceSeveral matrix metalloproteinases (MMPs) are overexpressed in lung cancer and may serve as potential targets for the development of bioactivable probes for molecular imaging

Survival Impact of Increasing Time to Treatment Initiation for Patients With Head and Neck Cancer in the United States

PURPOSE: To estimate the overall survival (OS) impact from increasing time to treatment initiation (TTI) for patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Using the National Cancer Data Base (NCDB), we examined patients who received curative therapy for the following sites: oral tongue, oropharynx, larynx, and hypopharynx. TTI was the number of days from diagnosis to initiation of curative treatment. The effect of TTI on OS was determined by using Cox regression models (MVA). Recursive partitioning analysis (RPA) identified TTI thresholds via conditional inference trees to estimate the greatest differences in OS on the basis of randomly selected training and validation sets, and repeated this 1,000 times to ensure robustness of TTI thresholds. RESULTS: A total of 51,655 patients were included. On MVA, TTI of 61 to 90 days versus less than 30 days (hazard ratio [HR], 1.13; 95% CI, 1.08 to 1.19) independently increased mortality risk. TTI of 67 days appeared as the optimal threshold on the training RPA, statistical significance was confirmed in the validation set (P < .001), and the 67-day TTI was the optimal threshold in 54% of repeated simulations. Overall, 96% of simulations validated two optimal TTI thresholds, with ranges of 46 to 52 days and 62 to 67 days. The median OS for TTI of 46 to 52 days or fewer versus 53 to 67 days versus greater than 67 days was 71.9 months (95% CI, 70.3 to 73.5 months) versus 61 months (95% CI, 57 to 66.1 months) versus 46.6 months (95% CI, 42.8 to 50.7 months), respectively (P < .001). In the most recent year with available data (2011), 25% of patients had TTI of greater than 46 days. CONCLUSION: TTI independently affects survival. One in four patients experienced treatment delay. TTI of greater than 46 to 52 days introduced an increased risk of death that was most consistently detrimental beyond 60 days. Prolonged TTI is currently affecting survival