Checkpoint inhibitor pneumonitis (CIP) is an immunerelated adverse event that can occur after initiation of anti-programmed death 1/programmed death ligand 1 immune checkpoint inhibitor (ICI) therapy for the treatment of multiple malignancies, including NSCLC. However, the incidence of CIP has not been previously examined in a population that included both trial-enrolled and non-trialenrolled patients with advanced NSCLC. Furthermore, risk factors and other clinical characteristics associated with CIP severity are not known. In this study, we retrospectively examined clinical characteristics, incidence, and risk factors for CIP in a cohort of 205 patients with NSCLC, all of whom received anti-programmed death 1/programmed death ligand 1 ICIs. Our results demonstrate a higher incidence of CIP (19%) than previously reported in clinical trials (3%-5%). Our data also suggest that tumor histologic type may be a risk factor for CIP development. We observed a wide range of time to onset of CIP (median 82 days), with high morbidity and mortality associated with higher-grade CIP regardless of degree of immunosuppression. Our data provide new insight into the epidemiology and clinical

With increasing use of immune checkpoint inhibitors (ICIs) for advanced NSCLC, there is increasing recognition of immune-related adverse events associated with ICI use. We recently reported increased incidence of checkpoint inhibitor pneumonitis (CIP) in ICI-treated NSCLC patients. Since development of immune-related adverse events in other organ systems has been associated with either no change or even improvement in tumor response/cancer outcomes, we sought to better understand the impact of CIP development on overall survival in ICI-treated NSCLC patients. Using baseline and follow-up data collected on a cohort of 205 ICI-treated NSCLC patients, we used a multistate modeling approach to understand the effect of developing CIP on the risk of death. We observed timedependent changes in risk of developing and recovery from CIP, with an increased risk of both developing and recovering from CIP in the first year after initiating ICI. We found that developing CIP independently increased the risk of transitioning to death in both adjusted and unadjusted models. In the multivariate model, we found that the increase in mortality associated with CIP was only seen in patients with adenocarcinoma tumor histology. Collectively, these findings suggest that in NSCLC, development of CIP worsens survival in patients receiving immunotherapy.

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Summary Pancreatic adenosquamous carcinoma is a rare morphological variant of pancreatic adenocarcinoma with an especially poor prognosis. The purpose of this study is to identify clinicopathologic features associated with prognosis, assess whether the percentage of squamous differentiation in pancreatic adenosquamous carcinoma is associated with an inferior prognosis, and examine the impact of adjuvant chemoradiation therapy on overall survival. Forty-five (1.2%) of 3651 patients who underwent pancreatic resection at the Johns Hopkins Hospital, Baltimore, MD, between 1986 and 2007 were identified with adenocarcinoma of the pancreas with any squamous differentiation. All pathologic specimens were re-reviewed. Statistical analyses were performed on the 38 patients amenable to adjuvant chemoradiation therapy for whom clinical outcome data could be obtained. Median age was 68 years (61% male). Sixty-one percent underwent pancreaticoduodenectomy. Median tumor size was 5.0 cm. Seventy-six percent of carcinomas were node positive, 37% were margin-positive resections, and 68% had 30% or more squamous differentiation. Median overall survival of the pancreatic adenosquamous carcinoma cohort was 10.9 months (range, 2.1-140.6 months; 95% confidence interval, 8.2-12.5 months). Adjuvant chemoradiation therapy was associated with superior overall survival in patients with pancreatic adenosquamous carcinoma (P = .005). Adjuvant chemoradiation therapy was associated with improved survival in patients with tumors 3 cm or larger and vascular or perineural invasion (P = .02, .03, .02, respectively). The proportion of squamous differentiation was not associated with median overall survival (<30% versus ≥30%, P = .82). Survival after pancreatic resection of pancreatic adenosquamous carcinoma is poor. Treatment with adjuvant chemoradiation therapy is associated with improved survival. The proportion of squamous differentiation in resected pancreatic adenosquamous carcinoma specimens does not appear to impact overall survival.

The results of this randomized trial demonstrate superior cancer control for men with localized prostate cancer who receive dose-escalated moderately hypofractionation radiotherapy while shortening treatment duration.

PurposeHigh cure rates for Hodgkin’s lymphoma must be balanced with long-term treatment-related toxicity. Here we report an intensity-modulated radiation therapy (IMRT) technique that achieves adequate target coverage for mediastinal disease while minimizing high- and low-dose exposure of critical organs.Methods and materialsTreatment plans for IMRT and conventional anteroposterior-posteroanterior (AP-PA) techniques, with comparable coverage of the planning target volume (PTV), were generated for 9 female patients with mediastinal Hodgkin’s lymphoma assuming use of inclined positioning, daily breath-hold, and CT-on-rails verification. Our “butterfly” IMRT beam arrangement involved anterior beams of 300°−30° and posterior beams of 160°−210°. Percentages of normal structures receiving 30 Gy (V30), 20 Gy (V20), and 5 Gy (V5) were tabulated for the right and left breasts, total lung, heart, left and right ventricles, left anterior descending coronary artery (LAD), and spinal cord. Differences in each variable, conformity index, homogeneity index, and V107% between the two techniques were calculated (IMRT minus conventional).ResultsUse of IMRT generally reduced the V30 and V20 to critical structures: −1.4% and +0.1% to the right breast, −1.7% and −0.9% to the left breast, −14.6% and −7.7% to the total lung, −12.2% and −10.5% to the heart, −2.4% and −14.2% to the left ventricle, −16.4% and −8.4% to the right ventricle, −7.0% and −14.2% to the LAD, and −52.2% and −13.4% to the spinal cord. Differences in V5 were +6.2% for right breast, +2.8% for left breast, +12.9% for total lung, −3.5% for heart, −8.2% for left ventricle, −1.5% for right ventricle, +0.1% for LAD, and −0.1% for spinal cord. Use of IMRT significantly reduced the volume of tissue receiving 107% of the dose (mean 754 cm3 reduction).ConclusionsThis butterfly technique for IMRT avoids excess exposure of heart, breast, lung, and spinal cord to doses of 30 or 20 Gy; mildly increases V5 to the breasts; and decreases the V107%.

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Recently, a firmer understanding of tumor immunology and tumor escape mechanisms has led to the development of immune checkpoint inhibitors, antibodies against programmed death-1 (PD-1) and its ligand (PD-L1). Nivolumab, pembrolizumab, and atezolizumab have dramatically altered the treatment paradigm in non-small cell lung cancer (NSCLC) and have each demonstrated improvements in outcomes and quality of life when compared to chemotherapy. Enrichment strategies to better select those patients more likely to respond have identified PD-L1 staining by immunohistochemistry (IHC) to be a predictive biomarker in both treatment naïve and refractory patients. Unfortunately, many challenges exist with this strategy and underscore the need for further exploration for more reliable biomarkers. Multiple tissue and plasma-based enrichment strategies have been identified in the hope of identifying patients more likely to benefit from checkpoint inhibitors. These include tumor mutational load; the "inflamed phenotype" including tumor infiltrating lymphocytes (TILS) and immunoscore; T-cell receptor clonality; gene signatures, and several plasma biomarkers. Several studies have revealed many of these biomarkers to be reliable predictors of response to immune checkpoint inhibitors across multiple tumor types. Given the small nature of these studies, additional prospective studies are warranted to formalize and validate each of these enrichment strategies.