PURPOSE Neoadjuvant chemotherapy plus nivolumab has been shown to be effective in resectable non–small-cell lung cancer (NSCLC) in the NADIM trial (ClinicalTrials.gov identifier: NCT03081689 ). The 3-year overall survival (OS) and circulating tumor DNA (ctDNA) analysis have not been reported. METHODS This was an open-label, multicenter, single-arm, phase II trial in which patients with stage IIIA NSCLC, who were deemed to be surgically resectable, were treated with neoadjuvant paclitaxel (200 mg/m2 once a day) and carboplatin (area under curve 6) plus nivolumab (360 mg) once on day 1 of each 21-day cycle, for three cycles, followed by adjuvant nivolumab monotherapy for 1 year (240 mg once every 2 weeks for 4 months, followed by 480 mg once every 4 weeks for 8 months). The 3-year OS and ctDNA analysis were secondary objectives of the trial. RESULTS OS at 36 months was 81.9% (95% CI, 66.8 to 90.6) in the intention-to-treat population, rising to 91.0% (95% CI, 74.2 to 97.0) in the per-protocol population. Neither tumor mutation burden nor programmed cell death ligand-1 staining was predictive of survival. Conversely, low pretreatment levels of ctDNA were significantly associated with improved progression-free survival and OS (hazard ratio [HR]: 0.20; 95% CI, 0.06 to 0.63, and HR: 0.07; 95% CI, 0.01 to 0.39, respectively). Clinical responses according to RECIST v1.1 criteria did not predict survival outcomes. However, undetectable ctDNA levels after neoadjuvant treatment were significantly associated with progression-free survival and OS (HR: 0.26; 95% CI, 0.07 to 0.93, and HR: 0.04; 95% CI, 0.00 to 0.55, respectively). The C-index to predict OS for ctDNA levels after neoadjuvant treatment (0.82) was superior to that of RECIST criteria (0.72). CONCLUSION The efficacy of neoadjuvant chemotherapy plus nivolumab in resectable NSCLC is supported by 3-year OS. ctDNA levels were significantly associated with OS and outperformed radiologic assessments in the prediction of survival.

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Pulmonary megakaryocytes participate in the pathogenesis of lung damage, particularly in acute lung injury. Although megakaryocytes are not mentioned as a characteristic histologic finding associated to pulmonary injury, a few studies reveal that their number is increased in diffuse alveolar damage (DAD). In this autopsy study, we have observed a relevant number of pulmonary megakaryocytes in COVID-19 patients dying with acute lung injury (7.61 ± 5.59 megakaryocytes per 25 high-power fields vs. 1.14 ± 0.86 for the control group, p < 0.05). We analyzed samples of 18 patients, most of whom died after prolonged disease and use of mechanical ventilation. Most patients showed advanced DAD and abnormal coagulation parameters with high levels of fibrinogen, D-dimers, and variable thrombocytopenia. For comparison, pulmonary samples from a group of 14 non-COVID-19 patients dying with DAD were reviewed. They showed similar pulmonary histopathologic findings and an increase in the number of megakaryocytes (4 ± 4.17 vs. 1.14 ± 0.86 for the control group, p < 0.05). Megakaryocyte count in the COVID-19 group was greater but did not reach statistical significance (7.61 ± 5.59 vs. 4 ± 4.17, p = 0.063). Regardless of the cause, pulmonary megakaryocytes are increased in patients with DAD. Their high number seen in COVID-19 patients suggests a relation with the thrombotic events so often seen these patients. Since the lung is considered an active site of megakaryopoiesis, a prothrombotic status leading to platelet activation, aggregation and consumption may trigger a compensatory pulmonary response.

AimThe aim of this study was to describe the testing rate and frequency of molecular alterations observed in the Lung Cancer Biomarker Testing Registry (LungPath).MethodsA descriptive study of NSCLC biomarker determinations collected from March 2018 to January 2019, from 38 Spanish hospitals, was carried out. Only adenocarcinoma and not otherwise specified histologies were included for epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and programmed death ligand-1 (PD-L1) expression. The testing rate and the positivity rate were calculated. Multivariate logistic regression was used to explore the joint relationship between independent explanatory factors and both testing and positivity rates. Two models were adjusted: one with sample type and histology as independent factors, and the other adding the testing rate or the positivity rate of the other biomarkers.Results3226 patient samples were analysed, where EGFR, ALK, ROS1 and PD-L1 information was collected (a total of 12 904 determinations). Overall, 9118 (71.4%) determinations were finally assessed. EGFR (91.4%) and ALK (80.1%) were the mainly tested biomarkers. Positivity rates for EGFR, ALK, ROS1 and PD-L1 were 13.6%, 3.4%, 2.0% and 49.2%, respectively. Multivariate models showed a lower testing rate for ALK in surgical pieces, fine-needle aspiration or other types of samples versus biopsies.ConclusionsDespite the high testing rate in EGFR and ALK in NSCLC, the real-world evidence obtained from the LungPath demonstrates that ROS1 and PD-L1 were not determined in a significant portion of patients. LungPath provides crucial information to improve the coverage in molecular testing in lung cancer, to monitor the positivity rate and the introduction of new biomarker testing in clinical practice.

IntroductionPressure ulcers are a prevalent health problem in today's society. The shortage of suitable animal models limits our understanding and our ability to develop new therapies. This study aims to report on the development of a novel and reproducible human skin pressure ulcer model in mice.Material and MethodsMale non-obese, diabetic, severe combined immunodeficiency mice (n = 22) were engrafted with human skin. A full-thickness skin graft was placed onto 4×3 cm wounds created on the dorsal skin of the mice. Two groups with permanent grafts were studied after 60 days. The control group (n = 6) was focused on the process of engraftment. Evaluations were conducted with photographic assessment, histological analysis and fluorescence in situ hybridization (FISH) techniques. The pressure ulcer group (n = 12) was created using a compression device. A pressure of 150 mmHg for 8 h, with a total of three cycles of compression-release was exerted. Evaluations were conducted with photographic assessment and histological analysis.ResultsSkin grafts in the control group took successfully, as shown by visual assessment, FISH techniques and histological analysis. Pressure ulcers in the second group showed full-thickness skin loss with damage and necrosis of all the epidermal and dermal layers (ulcer stage III) in all cases. Complete repair occurred after 40 days.ConclusionsAn inexpensive, reproducible human skin pressure ulcer model has been developed. This novel model will facilitate the development of new clinically relevant therapeutic strategies that can be tested directly on human skin.