A randomized trial to evaluate the preventive effect of lafutidine on chemotherapy-induced peripheral neuropathy in patients treated with carboplatin and paclitaxel for lung cancer.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) has a significant impact on the therapeutic efficacy of chemotherapy and patients' quality of life. The aim of this study was to assess the preventive effect of lafutidine on CIPN. METHODS: Patients were randomly assigned (1:1) to carboplatin and paclitaxel chemotherapy with lafutidine 10 mg twice daily (lafutidine group) or without lafutidine (control group). Peripheral neuropathy in both groups was assessed with the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and two patient-based questionnaires, the Patient Neurotoxicity Questionnaire (PNQ) and the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx). The primary outcome was the incidence of grade 2 or higher peripheral neuropathy in CTCAE version 5.0. The target number of cases was set at approximately 40. RESULTS: In total, 18 patients were screened, and 16 patients were assigned to the lafutidine group (n=9) or control group (n=7) between January 2021 and January 2023. Due to poor recruitment, the target number of cases was not reached. Grade 2 or higher neuralgia was 22.2% in the lafutidine group and 14.3% in the control group. Grade 2 or higher peripheral sensory neuropathy was 100% in the lafutidine group and 71.4% in the control group (P=0.175). Grade 3 or higher peripheral neuropathy was not detected in either group. There was no significant difference in PNQ scores between the two groups. Median FACT/GOG-Ntx scores after the fourth cycle tended to be lower in the lafutidine group than in the control group. There was no statistically significant difference in progression free survival (PFS) between the two groups. There were no adverse events due to lafutidine administration. CONCLUSIONS: Although the preventive effect of lafutidine on CIPN could not be demonstrated statistically, lafutidine FACT/GOG-Ntx scores showed a trend toward decreased neurotoxicity as chemotherapy proceeded. More reliable studies using lafutidine on the prevention of CIPN should be conducted. TRIAL REGISTRATION: Japan Registry of Clinical Trials, identifier: jRCTs021200031.

Correlation of tumor microenvironment-related markers with clinical outcomes in patients with squamous cell carcinoma of the lung.

Background: Squamous cell carcinoma (SCC) is the major histological type in lung cancer (LC). The tumor microenvironment (TME) drives tumor progression and metastasis. In the TME, cancer-associated fibroblasts (CAFs) play key roles in carcinogenesis. However, the roles of CAFs in lung SCC remain unknown. In this study, we evaluated whether the CAF phenotype was determined by various CAF-related proteins and whether CAF-related protein expression contributed to clinical outcomes in patients with lung SCC. Methods: We examined the associations of CAF- and epithelial-mesenchymal transition (EMT)-related markers expressed in CAFs, including α-smooth muscle actin (α-SMA), CD10, podoplanin, fibroblast-specific protein 1 (FSP1), platelet-derived growth factor receptor (PDGFR) α, PDGFRß, adipocyte enhancer-binding protein 1 (AEBP1), fibroblast activation protein (FAP), tenascin-C, Zinc finger E-box binding homeobox 1 (ZEB1), and twist homolog 1 gene (TWIST1), in 108 lung SCC tissues using immunohistochemistry. In addition, cluster analysis was used to identify objective expression patterns of immunohistochemical markers. Finally, the CD3/CD8 ratio was evaluated in order to identify the associations of CAF-related proteins with the CD3/CD8 ratio using immunohistochemistry. Results: SCC samples were classified into two subgroups (CAF-phenotype), which were significantly correlated with disease-free and overall survival using univariate and multivariate analyses. Moreover, high AEBP1 expression was identified as an independent prognostic marker in this cohort by univariate and multivariate analyses. The CD3/CD8 ratio was not correlated with the CAF-phenotype. Conclusions: The presence of a specific subgroup defined by multiple markers could be used for prediction of prognosis in patients with lung SCC. In addition, AEBP1 overexpression played key roles in prediction of a poor prognosis in patients with lung SCC.

Relationship between Trace Element in Tumor and Prognosis in Lung Cancer Patients.

Background and Objectives: This study aimed to observe the relationship between trace element concentrations in lung tissue from lung non-small cell lung carcinoma (NSCLC) patients and prognosis. Materials and Methods: The concentrations of various trace elements in the lung tissues were measured by a particle-induced X-ray emission (PIXE) system, and the results were analyzed for statistical significance. Eight essential trace elements, Cr, Mn, Fe, Co, Cu, Zn, Se, and Mo, were analyzed. We investigated the relationship between trace element concentrations and disease-free survival (DFS) and overall survival (OS) in NSCLC patients. Results: A total of 129 NSCLC patients and 20 control patients were included in this study. As for DFS, Co was the only element that showed a significant difference, and the high Co group had better DFS (HR: 0.352, 95% CI = 0.128-0.97). No significant difference was observed for Cr, Mn, Fe, Se, or Mo, but DFS tended to be better in the high trace element group. No significant difference was observed for Cu and Zn, but DFS tended to be good in the low trace element group. As for OS, Cr was the only element that showed a significant difference, and the high Cr element group had better OS (HR: 0.477, 95% CI = 0.128-0.97). Conclusions: This study suggests that the prognosis is good in lung cancer cases with high intratumoral concentrations of Co and Cr. The dynamics of trace elements in body and in tumor tissue have not been well established, and we consider that more research is necessary in the future.

Analysis of bevacizumab treatments and metastatic sites of lung cancer.

INTRODUCTION: Liver metastasis has not been sufficiently evaluated in lung cancer so far. We retrospectively analyzed the distant metastasis of Non-squamous non-small cell lung cancer (NSQ-NSCLC), including liver metastasis, and association between prognosis and therapeutic effect of bevacizumab treatment. PATIENTS AND METHODS: Clinical data were collected from 1954 patients with lung cancer admitted in our hospital between 1st April 2011 and 31 March 2019. Information is extracted from the electronic medical record. Main collection data was the age, gender, smoking history, performance status, histology and driver mutation, distant metastasis site. Efficacy data of treatment including treatment duration and survival time were obtained from medical record, image data and local registry. RESULTS: Total 366 patients receiving any chemotherapy with NSQ-NSCLC were eligible for this study. Most frequent extrathoracic metastasis is bone (N = 59) followed by brain (37), liver (18), adrenal gland (23), and OS analysis showed liver metastasis was worse prognosis compared to brain and bone metastasis (median OS: 11.6, 18.9, 15.0, respectively). Bevacizumab treatment was tend to have favorable efficacy in patients with each metastatic sites, especially, induced significant longer OS for patients with liver metastasis. CONCLUSION;: Though this study was retrospective study for small sized metastatic patients, the study suggested that liver metastasis was refractory, and that bevacizumab treatment might improve the worse prognosis.

Pleomorphic carcinoma of the trachea after chemoradiotherapy for laryngeal cancer.

A 66-year-old male patient who had received chemoradiotherapy (CRT) for laryngeal cancer 2 years ago visited a local doctor complaining of dyspnoea and wheezing. CT scan showed narrowing of the trachea caused by a tumour. We intubated the trachea over the tumour using a bronchoscope. A week later, the truncated tracheal tumour obstructed the tracheal tube, compromising the patient's breathing. We removed the obstructed tube and inserted a new one. We submitted the tissue from the tube to a pathologist. Histopathological diagnosis was pleomorphic carcinoma, a subtype of sarcomatoid carcinoma. The mechanism of epithelial-mesenchymal transition (EMT) occurring after CRT was detected in the tumour. Because he had undergone CRT for laryngeal cancer, surgery was not indicated, and we started radiation therapy. Sarcomatoid carcinomas including pleomorphic carcinoma of the trachea are extremely rare, with few reported cases, and EMT is associated with this histological type and CRT.

Acute cerebellar ataxia due to Epstein-Barr virus under administration of an immune checkpoint inhibitor.

A 71-year-old male patient with adenocarcinoma of the lung and contralateral lung metastasis under administration of pembrolizumab had symptoms of cerebellar ataxia. We suspected that the symptoms were immune-related adverse events (irAE), but the patient was subsequently diagnosed as cerebellitis due to Epstein-Barr virus (EBV) infection. After steroid pulse therapy, the symptoms of cerebellar ataxia improved immediately. Immune checkpoint inhibitors (ICI) can induce neurological adverse events and cause acute cerebellar ataxia. Initially, irAEs were suspected in this case. His clinical data suggested that reactivation of the virus had occurred because the ICI affected his immune system. This is the first report of a case of acute cerebellar ataxia due to EBV under administration of an ICI.