Brief Report: Tepotinib as a Treatment Option in MET Exon 14 Skipping-Positive Lung Cancers-Investigating Discordance Between ArcherMET and the Oncomine Dx Target Test.

Introduction: NSCLC is a leading cause of cancer-related mortality worldwide. Specific genetic alterations, such as MET exon 14 (METex14) skipping, have been identified in NSCLC, allowing targeted therapy. Tepotinib, a highly selective MET inhibitor, has displayed promise in patients with advanced NSCLC. Nevertheless, challenges arise when identifying treatment strategies for patients with discordant results regarding METex14 skipping detection between diagnostic tests. Methods: We investigated patients with NSCLC and discordant results for METex14 skipping between the Oncomine Dx Target Test (ODxTT) and ArcherMET. Clinical response, adverse events, and the duration of tepotinib treatment were assessed, and statistical analysis was performed. Results: Among the 19 patients deemed METex14 skipping positive by ODxTT, only 10 had concordant results with ArcherMET. The number of METex14 skipping reads detected by ODxTT was significantly lower in discordant cases. Of the 19 patients, 14 received tepotinib, and comparable response and disease control rates were observed in both concordant and discordant cases. The duration of treatment did not significantly differ between the two groups. Conclusions: Our findings suggest that tepotinib has comparable therapeutic effects in patients with METex14 skipping-positive NSCLC irrespective of the concordance of results between ODxTT and ArcherMET. Tepotinib is a possible treatment option for patients with METex14 skipping, even in patients with discordant test results.

Cytokine release syndrome complicated with severe rashes induced by nivolumab plus ipilimumab therapy in a patient with non-small cell lung cancer: A case report.

Cytokine release syndrome (CRS) is a severe and life-threatening toxicity typically reported in chimeric antigen receptor T cell therapy and is rarely reported in immune checkpoint inhibitor (ICI) therapy. This study reports the case of a 75-year-old Japanese woman who received nivolumab plus ipilimumab therapy for the postoperative recurrence of non-small cell lung cancer. She was admitted to our hospital with fever, hypotension, hepatic disorder, and thrombocytopenia. We observed slight skin rashes on her neck on admission, which spread rapidly across her body within a few days. We diagnosed CRS complicated by severe rashes. CRS symptoms were resolved with corticosteroid therapy, and did not recur thereafter. CRS is a rare, but important, immune-related adverse event associated with ICI therapy.

[A CASE OF BIRD-RELATED HYPERSENSITIVITY PNEUMONITIS THAT DEVELOPED IN SUBACUTE COURSE AND PRESENTED WITH ACUTE FINDINGS].

A 52-year-old woman presented to a clinic in late August with exacerbated fatigue and dyspnea on exertion for several months. Then, she was referred and admitted to our hospital in late September. Her chest CT showed bilateral diffuse centrilobular micronodules. In her detailed clinical history, she had kept budgerigars indoors for 15 years. These findings suggested she had a bird-related hypersensitivity pneumonitis (BRHP). By a site environmental investigation, 40 budgerigars were kept in a single breeding room and there were large amounts of droppings on the floor. Serum specific antibody for bird antigens and an environmental provocation test were positive. Bronchoalveolar lavage fluid showed lymphocytosis and a low CD4/CD8 ratio. Trans-bronchial lung biopsy showed lymphocytic infiltration of the alveolar wall and interlobular septa. After antigen avoidance as hospitalization, her symptoms and abnormal shadow improved. From these results, the patient was diagnosed as an acute BRHP.BRHP often presents a chronic onset. This case was diagnosed as an acute type despite the 15-years of budgerigars breeding. Increased exposure of antigens due to lack of cleaning after several days' antigen avoidance was suspected with one of the causes of acute onset.

Cathepsin K Deficiency Suppresses Disuse-Induced Bone Loss.

Unloading induces bone loss and causes disuse osteoporosis. However, the mechanism underlying disuse osteoporosis is still incompletely understood. Here, we examined the effects of cathepsin K (CatK) deficiency on disuse osteoporosis induced by using sciatic neurectomy (Nx) model. After 4 weeks of surgery, CatK KO and WT mice were sacrificed and subjected to analyses. For cancellous bone rich region, Nx reduced the bone mineral density (BMD) compared to the BMD in the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in cancellous bone. Nx also reduced BMD in the mid shaft cortical bone compared to the BMD in the corresponding region on the sham operated side in wild type mice. In contrast, CatK deficiency suppressed such Nx-induced reduction of BMD in the mid shaft cortical bone. Bone volume (BV/TV) was reduced by Nx in WT mice. In contrast, Cat-K deficiency suppressed such reduction in bone volume. Interestingly, CatK deficiency suppressed osteoclast number and osteoclast surface in the Nx side compared to sham side. When bone marrow cells obtained from Nx side femur of CatK-KO mice were cultured, the levels of the calcified area in culture were increased. Further examination of gene expression indicated that Nx suppressed the expression of genes encoding osteoblast-phenotype-related molecules such as Runx2 and alkaline phosphatase in WT mice. In contrast, CatK deficiency suppressed such reduction. These data indicate that CatK is involved in the disuse-induced bone mass reduction.