Successful Tepotinib Challenge After Capmatinib-Induced Interstitial Lung Disease in a Patient With Lung Adenocarcinoma Harboring MET Exon 14 Skipping Mutation: Case Report.

MET tyrosine kinase inhibitors, capmatinib and tepotinib, have been recently introduced for the treatment of advanced NSCLC with MET exon 14 skipping mutations. Although interstitial lung disease (ILD) induced by these drugs is reported, its optimal management and whether they can be rechallenged remain unclear. We report the first successful case of tepotinib treatment after capmatinib-induced ILD. Switching MET tyrosine kinase inhibitors after drug-induced ILD could be a clinical option, which warrants further investigation.

[Early diagnosis of metastatic spinal tumor is a key for effective palliative radiotherapy in patients with lung cancer].

Patients with metastatic spinal tumor are the largest in number among the patients with bone tumor. It causes a severe bone pain, pathological fracture and spinal cord compression. Thus it harshly hampers patient's quality of life. We report 3 patients with lung cancer whose initial manifestation was metastatic spinal tumor. We treated the 3 patients with palliative radiotherapy and medication. Although the severe pain has improved on a numerical rating scale(NRS), but performance status(PS)and activity of daily living(ADL)of the 3 patients got worse because the disease was progressed and complicated. Generally, PS of cancer patients found by bone matastasis is low. However, it is difficult to take an effective treatment, which leads to ADL improvement. There are many choices for treating metastatic bone tumors including pain control, bisphosphonate administration, radiation therapy, strontium radiotherapy, bone cement, palliative surgery and orthotics. In addition, a development of molecular target drugs, such as Denosmab, is expected as future modality of palliative care. In conclusion, we should detect a bone metastasis in the patient with lung cancer as early as possible, and select an appropriate treatment in collaboration with each specialist for achieving the ADL and PS improvement.

Standard therapy-resistant small cell lung cancer showing dynamic transition of neuroendocrine fate during the cancer trajectory: A case report.

While small cell lung cancer (SCLC) has been treated as a single disease historically, recent studies have suggested that SCLC can be classified into molecular subtypes based on the expression of lineage transcription factors such as achaete-scute homolog 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), POU domain class 2 transcription factor 3 (POU2F3) and transcriptional coactivator YAP1 (YAP1). These transcription factor-based subtypes may be specifically targeted in therapy, and recent studies have suggested that the SCLC subtypes represent different stages of dynamic evolution of SCLC rather than independent diseases. Nevertheless, evidence of shift in neuroendocrine differentiation during SCLC evolution has been lacking in the clinical setting. In the present study, a 60-year-old male was diagnosed with extensive SCLC. The tumor responded not to the standard SCLC regimen of carboplatin, etoposide and atezolizumab, but to the non-SCLC regimen of carboplatin, nab-paclitaxel and pembrolizumab. The patient succumbed 5 months after the initial diagnosis and a pathological autopsy was performed. The tumor was originally negative for all four transcription factors, ASCL1, NEUROD1, POU2F3 and YAP1, in the biopsy specimens at diagnosis. Loss of synaptophysin expression and emergence of Myc proto-oncogene protein and YAP1 expression was recorded in the autopsy specimens, suggesting the transition to a decreased neuroendocrine fate during the disease trajectory. This case provides clinical evidence of dynamic transition of neuroendocrine fate during SCLC evolution. In light of SCLC heterogeneity and plasticity, development of precision medicine is required.

A case of lung adenocarcinoma with a novel CD74-ROS1 fusion variant identified by comprehensive genomic profiling that responded to crizotinib and entrectinib.

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.

Pulmonary inflammatory pseudotumor observed by bronchoscopy and resected using video-assisted thoracic surgery.

Pulmonary inflammatory pseudotumor is rare. A 34-year-old woman visited our hospital due to an abnormal chest shadow. Computed tomograhy showed a nodule in the right upper lobe. Bronchoscopy showed a polypoid endobronchial nodule obstructing most of the orifice of B2a. The nodule was white, glossy, and smooth, and it seemed to be covered with bronchial mucosa. However, transbronchial biopsy could not facilitate a diagnosis. To obtain a definitive diagnosis, we performed lobectomy of the right upper lobe using video-assisted thoracic surgery and removed the nodule completely. The pathologic diagnosis made during surgery was inflammatory pseudotumor. Immunohistochemical examination showed proliferating spindle cells were positive for vimentin and smooth muscle actin, but negative for epithelial markers. These findings were consistent with the staining pattern of inflammatory pseudotumor previously reported. Careful follow-up is necessary to detect any sign of local recurrence and distant metastases.