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Background: Risk factors for predicting pneumonitis during durvalumab consolidation after chemoradiotherapy (CRT) in locally advanced non‐small cell lung cancer (LA‐NSCLC) are still lacking. Extracellular vesicles (EVs) play a crucial role in intercellular communication and are potential diagnostic tools for various diseases. Methods: We retrospectively collected predurvalumab treatment serum samples from patients treated with durvalumab for LA‐NSCLC, isolated EVs using anti‐CD9 and anti‐CD63 antibodies, and performed proteomic analyses. We examined EV proteins that could predict the development of symptomatic pneumonitis (SP) during durvalumab treatment. Potential EV‐protein biomarkers were validated in an independent cohort. Results: In the discovery cohort, 73 patients were included, 49 with asymptomatic pneumonitis (AP) and 24 with SP. Of the 5797 proteins detected in circulating EVs, 33 were significantly elevated (fold change [FC] > 1.5, p < 0.05) in the SP group, indicating enrichment of the nuclear factor kappa B (NF‐κB) pathway. Patients with high levels of EV‐RELA, an NF‐κB subunit, had a higher incidence of SP than those with low levels of EV‐RELA (53.8% vs. 13.4%, p = 0.0017). In the receiver operating characteristic analysis, EV‐RELA demonstrated a higher area under the curve (AUC) than lung V20 (0.76 vs. 0.62) and was identified as an independent risk factor in the multivariate logistic regression analysis (p = 0.008, odds ratio 7.72). Moreover, high EV‐RELA was also a predictor of SP in the validation cohort comprising 43 patients (AUC of 0.80). Conclusions: Circulating EV‐RELA may be a predictive marker for symptomatic pneumonitis in patients with LA‐NSCLC treated with durvalumab. [ABSTRACT FROM AUTHOR]

A 66-year old man with non-smoking history was diagnosed with pulmonary pleomorphic carcinoma of the right lower lobe. The carcinoma metastasized to the brain, lungs, pleura, and mediastinal lymph nodes. It was positive for epidermal growth factor receptor (EGFR) L858R mutation, and tumor cells highly expressed programmed death-ligand 1(PD-L1). Atezolizumab was initiated as the fourth treatment. After three days, he developed cardiac tamponade and immediately underwent pericardial drainage. Computed tomography showed bilateral ground-glass opacity (GGO), significant worsening of multiple lung metastases, and increased size of metastatic lesions. Newly developed metastasis was noted in the lung, and the patient's respiratory condition rapidly deteriorated. He died of respiratory failure on day 13 after atezolizumab administration. The autopsy showed widespread metastasis in all lobes of the bilateral lungs, cardiac tamponade due to carcinomatous pericarditis, carcinomatous lymphangiopathy, and multiple lung metastases, which were thought to be comprehensively the cause of death. These symptoms suggested hyperprogressive disease (HPD). Hence, we report the first case of HPD following atezolizumab therapy for pulmonary pleomorphic carcinoma with EGFR mutation. [ABSTRACT FROM AUTHOR]

The prevalence of lung cancer in idiopathic pulmonary fibrosis (IPF) patients ranges from 9.8 to 38%. Nintedanib, a small molecule receptor tyrosine kinase inhibitor (TKI) of platelet‐derived growth factor receptor (PDGFR), fibroblast growth factor receptor (FGFR), and vascular endothelial growth factor receptor (VEGFR), has been approved for IPF after phase III INPULSIS trials in 2014. Ramucirumab, a monoclonal antibody for VEGFR‐2, combined with docetaxcel, has been approved for advanced non‐small cell lung cancer (NSCLC) after the phase III REVEL trail in 2014. Physicians will have more IPF patients being treated with nintedanib, who subsequently develop NSCLC, and therefore will likely be treated with ramucirumab plus docetaxel. We report the first case of 70‐year‐old man taking nintedanib for his IPF and treated with ramucirumab plus docetaxel as a seventh‐line therapy for his pulmonary adenocarcinoma. On day 15 of his chemotherapy treatment cycle 2, after taking nintedanib for nine days, he developed gastric perforation. We report the first case of 70‐year‐old man taking nintedanib for his progressive idiopathic pulmonary fibrosis (IPF) and treated with ramucirumab plus docetaxel as a seventh line therapy for his pulmonary adenocarcinoma. On day15 of chemotherapy treatment cycle2, after taking nintedanib for nine days, he developed gastric perforation. [ABSTRACT FROM AUTHOR]