Purpose: Patients with lung cancer and interstitial lung disease treated with radiotherapy have been reported to be at a risk of developing radiation pneumonitis. However, the association between interstitial lung abnormalities (ILA) and radiation pneumonitis in patients with limited-stage small cell lung cancer (LS-SCLC) remains unclear. Furthermore, the prognosis is unclear for patients with SCLC and ILA treated with chemoradiotherapy. We investigated the impact of ILA on radiation pneumonitis and assessed the prognosis of patients with LS-SCLC and ILA treated chemoradiotherapy. Methods and materials: We retrospectively reviewed the medical records of 149 patients with LS-SCLC who received first-line treatment between January 2009 and December 2016. Results: In a univariate analysis, the patients with ILA showed a higher incidence rate of radiation pneumonitis compared with those without ILA (64% vs. 10%); multivariate analysis confirmed that ILA was significantly associated with the incidence of radiation pneumonitis. In the univariate analysis, patients with ILA showed poorer overall survival than those without ILA (median, 18.9 vs. 67.9 months). Multivariate analysis showed that ILA was a significant independent negative prognostic factor. However, the 2-year and 5-year survival rates for the patients with ILA treated with chemoradiotherapy were 36% and 26%, respectively; for those treated with chemotherapy alone were 8% and 0%, respectively.Conclusions: ILA was a predictive factor for radiation pneumonitis in patients with LS-SCLC treated with chemoradiotherapy. The prognosis of the patients with LS-SCLC and ILA was poor; however, some patients with ILA treated chemoradiotherapy achieved long-term survival.

Background Immune-related hepatotoxicity is often regarded as immune-related hepatitis (irHepatitis) despite including immune-related sclerosing cholangitis (irSC). This study examined the clinical differences between irSC and irHepatitis.Methods A single-center retrospective study of 530 consecutive patients who received immunotherapy between August 2014 and April 2020 was performed. IrSC and irHepatitis were respectively defined as the radiological presence and absence of bile duct dilation and wall thickness.Results Forty-one patients (7.7%) developed immune-related hepatotoxicity. A CT scan was performed on 12 patients, including 11 of 12 with ≥grade 3 aminotransferase elevations. IrSC and irHepatitis were diagnosed in 4 (0.8%) and 8 (1.5%) patients, respectively. All the irSC patients had been treated with anti-PD-1. IrHepatitis was more common among patients receiving anti-CTLA-4 than among those receiving anti-PD-1/PD-L1 inhibitors (14%, 7/50 vs. 0.2%, 1/480, P <0.001). A ≥grade 2 alkaline phosphatase (ALP) elevation resulting in a cholestatic pattern was seen in all 4 irSC patients. Among the irSC patients, 3 (3/4, 75%) developed ≥grade 3 aminotransferases elevation. The median duration from the start of immunotherapy until ≥grade 2 liver enzymes elevation was 257 and 55.5 days in irSC and irHepatitis patients. The median times for progression from grade 2 to 3 liver enzyme elevation were 17.5 and 0 days, respectively.Conclusions IrSC and irHepatitis have different characteristics in the class of immune checkpoint inhibitor and onset pattern. Radiological examination for the diagnosis of irSC should be considered for patients with ≥grade 2 ALP elevation resulting in a cholestatic pattern. (Registration number J2020-36, Date of registration June 3, 2020)

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Background When a patient has multiple tumors in different organs, it is very important to identify whether the tumors are multiple cancers or metastasis from one tumor in order to establish an optimal treatment strategy. However, it is difficult to obtain an accurate diagnosis from conventional diagnostic strategies, including immunohistochemistry. We report two patients with multiple tumors in which a somatic mutation comparison using next-generation sequencing (NGS) was useful for the diagnosis of a metastatic tumor. Case presentations Patient 1: A 64-year-old man was diagnosed with gastric and lung cancer. After radical chemoradiotherapy for lung cancer, gastrectomy was planned for gastric cancer. At gastrectomy, the patient underwent a multiple omics analysis for “Project HOPE”. The gene mutational signature of the gastric tumor showed signature 4 of COSMIC mutational signature version 2, which was associated with smoking and has not been found in gastric cancer. To confirm that the gastric tumor was metastasis from lung cancer, we conducted a somatic mutation comparison of the two tumors with 409-gene panel sequencing, which revealed that 28 of 97 mutations in the lung tumor completely matched those of the gastric tumor. Based on these findings, the gastric tumor was diagnosed as metastasis from lung cancer. Patient 2: A 47-year-old woman underwent distal gastrectomy for gastric cancer. A colon tumor was detected 6 years after gastrectomy. The colon lesion was a submucosal tumor-like elevated tumor, and was suspected to be metastasis from gastric cancer. The patient underwent sigmoidectomy, and participated in “Project HOPE”. The possibility of primary colon cancer could not be ruled out, and we conducted a somatic mutation comparison of the two tumors as we did with Patient 1. Panel sequencing revealed 11 mutations in the gastric tumors, 4 of which completely matched those of the colon tumor. The colon tumor was diagnosed as metastasis from gastric cancer. Conclusion We reported two patients with multiple tumors in which a somatic mutation comparison using NGS was useful for the diagnosis of a metastatic tumor.

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