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Background and purpose: In clinical studies, checkpoint inhibitor-related pneumonitis (CIP) ranks first among the causes of death in programmed cell death protein-1 (PD-1)/programmed death ligand-1 (PD-L1) inhibitor immune-related adverse events. Real-world CIP situations lack extensive population reports. This study aimed to understand the incidence of CIP in the real world of lung cancer in China, and to summarize its characteristics, treatment status and outcomes. Methods: This study retrospectively collected the essential clinical information of patients with an initral diagnosis of lung cancer who received treatment with immune checkpoint inhibitors (ICIs) at the First Affiliated Hospital of Guangzhou Medical University and Shanghai Pulmonary Hospital between January 2019 and September 2021. For patients with CIP, we also collected the time of its onset, grade, treatment regimen and outcome. The analyses of incidence, patient’s characteristics and the risk factors of CIP in overall and subgroup were carried out. Moreover, we analyzed the outcomes of patients treated with immunosuppressive therapy. Results: A total of 2 031 patients with immunotherapy were enrolled, with a CIP incidence rate of 7.2% (147/2 031), a severe CIP rate of 2.6% (52/2 031) and a mortality rate of 0.4% (9/2 031). The rate of severe grade in the population with CIP was 35.4%, and the mortality rate was 6.1% (9/147). Compared with non-CIP patients, more CIP patients were male, older (>65 years), with combination therapy, and on first- and second-line immunotherapy in advanced treatment. In subgroup analyses, the incidence of CIP was higher in men, the elderly (>65 years), squamous cancer, combination therapy, anti-PD-1 inhibitors, and first- and second-line therapy in advanced treatment. The median onset time of CIP in the real world was 148 days, with a double-peak characteristic, that was, 60-90 days and 150-210 days after immunotherapy were both the peak time periods for CIP onset. The incidence of CIP was also influenced by seasonality, with a high incidence in autumn and winter. All treated patients used corticosteroids as first-line treatment; the immunosuppressive treatment rate of CIP in this study was 76.2%. After treatment, 97.9% of mild CIP patients and 81.2% of severe CIP patients had a good prognosis, and 17.3% of severe CIP patients died due to CIP. Conclusion: In the real world, the incidence of CIP for lung cancer patients was 7.2%, incidence of severe CIP was 2.6%, and mortality rate was 0.4%; the incidence of severe disease in the population with CIP was 35.4%, and mortality rate was 6.1%. The median onset time of CIP was characterized by a double peak, and incidence of CIP was higher in autumn and winter. Men, the elderly, squamous cancer patients, patients on combination therapy, patients who used anti-PD-1 inhibitors, and patients with advanced treatment had higher incidence of CIP. Most patients with CIP had good outcomes after immunosuppressive therapy.

Background: Epidemiological surveys have suggested that lung cancer has inherited susceptibility and shows familial aggregation. However, the distribution and prevalence of epidermal growth factor receptor (EGFR) germline variants and their roles in lung cancer genetic predisposition in Chinese population remain to be elucidated. Methods: In this study, EGFR germline and somatic variants were retrospectively reviewed from the next-generation sequencing results of 31,906 patients with lung cancer. Clinical information was also collected for patients with confirmed EGFR germline mutations. Results: A total of 22 germline EGFR variants were identified in 64 patients with lung cancer, accounting for 0.2% of the total cases studied. Five patients were diagnosed as multiple primary carcinomas. Family history was documented in 31.3% (20/64) of patients, 55% of which were diagnosed as lung cancer. G863D was the most frequent EGFR germline mutation, followed by P848L, D1014N, and K757R. Somatic EGFR -sensitive mutations were identified in 51.6% of patients with germline EGFR mutations. The proportion of L858R mutation, exon 19 deletion, and rare sensitive mutation was 50%, 17.6%, and 32.4%, respectively. D1014N and T790M mutations were common in young patients. The family members of patients with P848L, R776H, V769M, and V774M mutations were more commonly diagnosed with cancers. A total of 19 patients were confirmed to have received EGFR tyrosine kinase inhibitors (TKIs), but the response to EGFR-TKIs differed among patients with different EGFR mutations. Conclusion: Chinese patients with lung cancer harbored unique and dispersive EGFR germline mutations and showed unique clinical and genetic characteristics, with varied response patterns to EGFR-TKI treatment. [ABSTRACT FROM AUTHOR]

A novel current treatment, immunotherapy, is normally effective for pulmonary lymphoepithelial carcinoma (pLELC). However, it is frequently accompanied by responses such as immune checkpoint inhibitor-associated pneumonitis (CIP), a rare immune adverse reaction that may be fatal in severe cases. pLELC is known to be linked to Epstein-Barr virus (EBV), while associations between EBV and CIP in clinical settings have rarely been reported. A 57-year-old male patient with pLELC presented at our hospital with cough, expectoration, fever and dyspnea following his third course of immunotherapy at another hospital. Diagnosis of grade 4 CIP was confirmed. Simultaneously, a rapid increase in the EBV titer and response of CIP to corticosteroids were observed. The corticosteroids and antiviral drugs were then increased. In spite of his severe condition, the patient recovered within eight days. After discontinuing antiviral drugs, chest computed tomography indicated rapid lesion progression and significantly increased bilateral multiple metastases. To our knowledge, the present study was the first to report a case of CIP caused by EBV during immune checkpoint inhibitor treatment. It indicates that EBV may be associated with CIP development. As immunotherapy has off-target effects, clinicians should remain aware of combined corticosteroids and antivirals in similar cases. [ABSTRACT FROM AUTHOR]