BACKGROUND:Immune-checkpoint inhibitors (ICIs) often cause immune-related adverse events (irAEs). The spectrum of irAEs and their managements has been partially clarified, however the knowledge on time-course of irAEs is not well understood. METHODS:A retrospective study based on the medical record was performed. The study subjects were consisting of patients with various types of solid tumors for whom ICIs (nivolumab, pembrolizumab, durvalumab, atezolizumab, nivolumab plus ipilimumab) were used between April 2016 and October 2021. We focused on irAEs developed more than 1-year after commencement ICIs (delayed irAE group) and compared with irAEs developed within 1-year (non-delayed irAE group) in terms of types and severity of irAEs. RESULTS:A total of 336 patients were enrolled in the study. Eighty-eight patients (26.2%) developed irAEs and 248 did not. Most of the patients developing irAEs were treated using PD-L1/PD-1 inhibitors. Eighty-one patients (24.1%) in non-delayed irAE group and 7 patients (2.1%) in delayed irAE group developed irAEs. The median onset of irAEs in the delayed irAE group was 18.6 months (range: 13.5-24.3). The types of irAEs observed in delayed irAE group were dermatitis (2 cases), pneumonitis (2 cases), nephritis (1 case), arthritis (1 case), and gastritis (1 case). The severity of irAEs was almost mild (≤G2), but one patient (.3%) developed G3 nephritis. CONCLUSION:PD-L1/PD-1 inhibitors frequently caused various irAEs but their severities were mostly tolerable. Few patients developed delayed irAE with mild toxities.

AbstractBackgroundThe recurrence rate of non‐small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high‐risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis.Materials and MethodsA cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer‐associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA).ResultsMutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse‐free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log‐rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log‐rank test, p = 0.10).ConclusionMutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.

━━ Background. Lung typical carcinoids with spontaneous regression or paraneoplastic syndromes other than carcinoid syndromes are relatively rare. Case. A 69-year-old man was found to have a chest abnormal-ity during a medical checkup. Chest computed tomography (CT) showed nodules in the right S 5 and 8/9th inter-costal space and a mass in the right parietal pleura, near the 9-10th thoracic spine. The paravertebral mass re-gressed on chest CT, but right pleural effusion appeared three months later. He was transferred to our hospital and found to have peripheral eosinophilia and eosinophilic pleural effusion. A CT-guided biopsy was performed, as chest CT showed an increase in the size of the nodule at the right chest wall. However, the diagnosis was difficult due to an insufficient sample volume, and thoracoscopic partial lung resection with pleural tumor resection was performed. The histopathological samples showed tumor cells that were positive for neuroendocrine markers. The cell division was extremely low, and the patient was diagnosed with lung typical carcinoid (pT1cN0M1a pStage IVA). After resection, the peripheral eosinophilia improved spontaneously, and the right pleural effusion did not relapse. Despite the advanced stage, the target lesion was resected, and careful follow-up is being con-ducted. Conclusion. We experienced a very rare case of a patient with lung typical carcinoid with spontaneous regression and paraneoplastic syndromes.