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ROS1 rearrangements are found in 1–2% of patients with non‐small‐cell lung cancer. The detection of the rearrangements is crucial since clinically effective molecular targeted drugs are available for them. We present a case of lung adenocarcinoma with a previously unknown ROS1‐CD74 fusion variant, CD74 exon 3 fused to ROS1 exon 34, which was not detected by a conventional RT‐PCR‐based test for ROS1 fusion gene detection but identified by hybrid capture‐based next‐generation sequencing. This tumor responded to crizotinib initially and to entrectinib after relapse with brain metastasis, indicating the oncogenic activity of this novel fusion variant., We present a case of lung adenocarcinoma with a novel ROS1‐CD74 fusion variant, CD74 exon 3 fused to ROS1 exon 34, which was not detected by a conventional RT‐PCR‐based testing but identified by hybrid capture‐based next‐generation sequencing. This tumor responded to crizotinib initially and to entrectinib after relapse with brain metastasis, indicating the oncogenic activity of this novel fusion variant.

Background Anti‐programmed death‐1 (PD‐1) immunotherapy can cause immune‐related pneumonitis, also known as checkpoint inhibitor pneumonitis (CIP). CIP that develops early after the initiation of anti‐PD‐1 immunotherapy is important because it is more severe than CIP that develops later. However, only a few studies have examined the risk factors for early‐onset CIP. Previous studies have reported several risk factors for CIP, including imaging findings of airway obstruction adjacent to lung tumors. However, the utility of this factor is debatable. Therefore, we investigated potential risk factors for early‐onset CIP, including tumor invasion in the central airway (TICA), in patients with non‐small cell lung cancer (NSCLC) receiving anti‐PD‐1 therapy. Methods We retrospectively analyzed the medical records and chest computed tomography scans of patients with NSCLC treated with anti‐PD‐1 antibodies at the Kanagawa Cancer Center in Japan between 1 January 2016, and 30 June 2018. The clinical characteristics and imaging findings, including TICA, were compared between patients with and without early‐onset CIP. Results Data from 181 eligible patients (114 receiving nivolumab and 67 receiving pembrolizumab) were analyzed. Early‐onset CIP occurred in 13 of 79 patients (16.5%) with TICA and 2 of 102 patients (2.0%) without TICA. In multivariate analysis, the odds ratio of early‐onset CIP for patients with TICA was 8.2 (95% confidence interval [CI]: 1.98–34.0, P = 0.0037). Conclusions TICA was strongly associated with early‐onset CIP in patients with NSCLC. Clinicians should carefully observe patients with TICA, especially within three months of anti‐PD‐1 antibody administration because of high CIP risk. Key points Significant study findings Tumor invasion in the central airway (TICA) was a predictor of early‐onset checkpoint inhibitor pneumonitis (CIP)TICA had good interobserver variability, indicating its utility in clinical practicePatients with TICA might have a higher immune status than patients without What this study adds This is the first study focusing on risk factors for CIP limited to early‐onset CIP., TICA was strongly associated with early‐onset CIP in patients with NSCLC. Clinicians should carefully observe patients with TICA, especially within three months of anti‐PD‐1 antibody administration because of high CIP risk.

Background Currently used biomarkers for immunotherapy are inadequate because they are only based on tumor properties. In view of microenvironment changes by tumors, host immunity should be considered, which may result in identifying more accurate and easily detectable biomarkers for daily clinical practice. Here, we assessed serum immune‐modulating factor levels for the response to anti‐PD‐1 antibodies during the first cycle in non‐small cell lung cancer (NSCLC) patients. Methods Serum was collected from patients with advanced NSCLC treated with nivolumab or pembrolizumab at several time points during the first cycle. We applied the enzyme‐linked immunosorbent assays (ELISAs) and multiplex assays to measure the levels of immune modulators. Results A total of 40 patients treated with nivolumab and 26 patients treated with pembrolizumab were studied. By ELISA, serum perforin, but not granzyme B, was measured in all samples. By multiplex assay, 10 immune modulators, including granzyme B, were measured in some, but not all, samples. Serum baseline perforin levels were strongly associated with increased progression‐free survival (PFS) and overall survival (OS) times. Sequential changes in perforin levels during the first cycle were weakly associated with the clinical outcome. Conclusions Serum baseline perforin levels may be used to predict the prognosis of NSCLC patients treated with anti‐PD‐1 antibody therapy. Key points To identify a useful predictive marker for anti‐PD‐1 antibody therapy, using blood samples might be helpful.Serum baseline perforin levels were closely associated with prognosis with anti‐PD‐1 antibody therapy in non‐small cell lung cancer., This study demonstrates immune‐modulator changes in serum during the first cycle of anti‐PD‐1 antibody therapy in non‐small cell lung cancer. Serum baseline perforin levels were found to be closely associated with clinical outcome with anti‐PD‐1 antibody therapies.

Background Treatment strategies for patients with non‐small cell lung cancer (NSCLC) depend on various factors including physical condition, complications, tumor histology, and molecular profiling. Even if initial chemotherapy is efficacious, almost all patients develop treatment resistance. Invasive rebiopsy from sites of recurrence might provide insight into resistance mechanisms and aid in the selection of suitable sequential antitumor drugs. However, invasive rebiopsy might be challenging because of limited tissue availability and patient burden. Therefore, this study aimed to assess awareness of invasive rebiopsy among non‐small cell lung cancer patients. Methods This prospective questionnaire survey was performed between June 2015 and March 2016 in patients with advanced non‐small cell lung cancer. The survey was carried out at two time points: before starting first‐line chemotherapy (cohort 1), and at the time of disease progression after initial chemotherapy, but before second‐line chemotherapy (cohort 2). Results In this study, 50 and 30 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, 37 (74%) patients agreed to rebiopsy, if disease progression occurred, whereas 18 (60%) patients in cohort 2 agreed to invasive rebiopsy at disease progression. The primary reasons for rebiopsy rejection were poor physical condition and patient burden related to the initial biopsy. Seven patients answered the survey questions during the treatment course, and the acceptance rate was lower among patients who agreed to rebiopsy at disease progression than before treatment. Conclusions Invasive rebiopsy can lead to distress in some patients. To improve the consent rate for tissue rebiopsy, treatment strategies including rebiopsy should be discussed with patients during the early treatment phase.

Background Malignant pleural effusion (MPE) can occur during the progression of various cancers. However, factors, such as the incidence of MPE associated with different types of cancers and its potential for diagnosing previously undetected cancers, are unknown. Moreover, MPE may accompany potentially curable cancers or those with a favorable survival prognosis with adequate treatment. The present study determined the types of cancers accompanied by MPE at initial diagnosis and investigated appropriate related methods for diagnosing previously unknown cancers. Methods We retrospectively reviewed the medical records of 35 patients with MPE at initial cancer diagnosis between 2004 and 2012. We evaluated the patient characteristics, final diagnosis, and diagnostic processes. Results Of the 35 patients, 10 had lung cancer, seven ovarian or peritoneal cancer, four malignant pleural mesothelioma, one breast cancer, one lymphoma, one pancreatic cancer, and 11 had cancers of unknown origin. Diagnoses of the primary lesions were confirmed using the MPE cellblock method for seven of 11 patients (63.6%), by excisional biopsy or aspiration from other sites in four of nine patients, by exploratory laparotomy in two of three patients, and by peritoneal washing cytology in five patients. Conclusion Lung cancer and cancer of unknown origin are major causes of MPE at initial presentation. However, these groups also contain cancers that are curable and those with good long-term prognosis. The MPE cellblock method represents an accurate method for identifying cancer origin.