Preclinical data suggest that oncogene (EGFR and KRAS) events regulate tumor procoagulant activity. However, few studies have prospectively investigated the clinical relevance between the presence of EGFR or KRAS mutations and occurrence of venous thromboembolism(VTE) in patients with non-small cell lung cancer (NSCLC). A total of 605 Chinese patients with newly diagnosed NSCLC were included and were followed for a maximum period of 4.5 years. EGFR and KRAS mutations were determined by amplification refractory mutation system polymerase chain reaction method at inclusion. The main outcome was objectively confirmed VTE. Of the 605 patients, 40.3% (244) had EGFR mutations and 10.2% (62) of patients had KRAS mutations. In multivariable analysis including age, sex, tumor histology, tumor stage, performance status, EGFR and KRAS status, EGFR wild-type (sub-distribution hazard ratio 1.81, 95% confidence interval 1.07–3.07) were associated with the increased risk of VTE. In competing risk analysis, the probability of developing VTE was 8.3% in those with and 13.2% in those without EGFR mutations after 1 year; after 2 years, the corresponding risks were 9.7 and 15.5% (Gray test P = 0.047). EGFR mutations have a negative association with the risk of VTE in Chinese patients with NSCLC.

Introdution: Immune checkpoint inhibitors (ICIs) have significantly improved clinical outcomes for a wide range of cancers but can also lead to serious or fatal immune-related adverse events (irAEs). Although ICI-related pericardial toxicities have been reported, the clinical features are not well characterized in real-world studies.Objective: To characterize the main features of ICI-related pericardial toxicities and identify factors associated with death.Methods: Data from January 1, 2011 to March 31, 2020 in the FDA Adverse Event Reporting System database were retrieved for disproportionality analysis. We used the reporting odds ratio and the information component (IC) to evaluate the association between ICIs and pericardial adverse events. Clinical characteristics of patients with ICI-associated pericardial toxicities were collected and compared between fatal and non-fatal groups. The time to onset following different ICI regimens was further investigated.Results: We identified a total of 705 ICI-associated pericardial toxicities which appeared to influence more men (53.90%) than women (36.03%), with a median age of 63 (interquartile range [IQR] 54–69) years. Patients with lung cancer accounted for the largest proportion (55.6%). ICI therapies were detected with pharmacovigilance signals of pericardial toxicities, corresponding to IC₀₂₅ = 2.11 and ROR 4.87 [4.51–5.25]. Nevertheless, there was a lack of association between anti-CTLA-4 and pericardial toxicities. There was no difference in onset time among all ICI regimens. However, TTO of fatal cases (25 days (interquartile range [IQR] 6–70)) occurred statistically earlier than non-fatal cases (42 days (IQR 12–114), p = 0.003).Conclusion: ICI monotherapy (PD-1/PD-L1 therapy) and combination therapy can lead to pericardial toxicities that can result in serious outcomes and tend to occur early. Early recognition and management of ICI-related pericardial disorders should attract clinical attention. The findings require further clinical surveillance for the quantification.

Primary pulmonary angiosarcoma is a rare type of malignant vascular tumor with a very aggressive clinical course and a grim prognosis. To date, only a handful of cases have been reported in English literature. Its rarity and consequent low index of suspicion makes clinical diagnosis difficult. In this report we present three cases of primary pulmonary angiosarcoma with cough, hemoptysis, and progressive dyspnea to contribute to the sparse literature on this disease. A review is made of previous reports of primary pulmonary angiosarcomas, and the clinical characteristics, diagnosed method, treatment options, and prognosis of pulmonary angiosarcoma are also discussed.

Background The association between immune checkpoint inhibitors (ICIs) and thromboembolic events (TEEs) remains controversial. Objective The goal of this study was to assess the risk of major TEEs associated with ICIs. Methods We explored ICI-related TEEs in randomized controlled trials available in ClinicalTrials.gov and electronic databases up to June 30, 2021. Meta-analysis was performed by using Peto odds ratios (ORs) with 95% confidence intervals (CIs). Results A total of 61 studies were included. Patients treated with ICIs had a similar risk of venous thromboembolism (VTE) but a significantly increased risk of arterial thromboembolism (ATE) (Peto OR: 1.58 [95% CI: 1.21–2.06]) compared with non-ICI regimens. Stratified by different regimens, only PD-L1 (programmed cell death ligand 1) inhibitors showed a significant increase in ATE (Peto OR: 2.07 [95% CI: 1.26–3.38]). The incidence of VTE was higher in PD-1/PD-L1 inhibitor and CTLA-4 (cytotoxic T lymphocyte antigen 4) inhibitor combination therapies compared with monotherapies (Peto OR: 2.23 [95% CI: 1.47–3.37]). Stratified by tumor, for pulmonary embolism (PE) and cerebral ATE, the statistically significant results were only seen in lung cancer patients (Peto OR: 1.42 [95% CI: 1.02–1.97]; Peto OR: 2.10 [1.07–4.12]), and for myocardial infarction, the statistically significant result was only seen in other tumor types (Peto OR: 2.66 [95% CI: 1.68–4.20], p < 0.0001). Conclusion There was no significant increase in the overall risk of VTE in patients treated with ICIs; however, special attention should be given to the risk of VTE in PD-1/PD-L1 inhibitor and CTLA-4 inhibitor combination therapy and PE in lung cancer patients. PD-L1 inhibitors were associated with a significant increase in ATE. YH.Z. and ZL.A. were responsible for the conception and design of the study. Z.M. and XM.S. did the data extraction, statistical analysis, and drafted the original writing of the manuscript. Y.Z., H.L., and D.S. contributed to the methodological support. All authors contributed to the critical review and editing of the manuscript and approved the final version of the manuscript. ^* Zhuo Ma and Ximu Sun are first co-authors. Received: 20 December 2021 Accepted: 28 March 2022 Article published online: 30 June 2022 © 2022. Thieme. All rights reserved. Georg Thieme Verlag KG Rüdigerstraße 14, 70469 Stuttgart, Germany