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Objective To develop a combinatorial panel of salivary cytokines that manifests the presence of non-small cell lung cancer (NSCLC) that will eventually improve prognosis by facilitating the early diagnosis and management of this common cancer. Methods We performed a case-control study comparing salivary cytokine profiles of 35 adult subjects with NSCLC with those of 35 matched, healthy nonsmokers. Multiplex bead array assays were used to quantify 27 cytokines in saliva, serum, and oral mucosal transudate samples. Logistic regression analysis was used to develop an informative cytokine panel. Receiver operating characteristic (ROC) curves were generated to evaluate the discriminant ability of the panel. Results A combinatorial 12-cytokine panel (interleukin receptor antagonist [IL1RN], IL1B, IL6, IL7, IL8, IL10, C-C motif chemokine ligand 11 [CCL11], tumor necrosis factor, C-X-C motif chemokine ligand 10 [CXCL10], C-C motif chemokine ligand 3, C-C motif chemokine ligand 4, and platelet-derived growth factor-BB) distinguished patients with NSCLC from healthy controls. Further, ROC analysis revealed that a cytokine panel comprising IL10 (odds ratio, 1.156) and CXCL10 (odds ratio, 1.000) discriminated NSCLC with a sensitivity of 60.6% and specificity of 80.8% (area under the ROC curve, 0.701). Conclusion A combinatorial panel of select salivary cytokines indicates the presence of NSCLC.

Thymic carcinoma is a highly malignant tumor and treatment options are limited. Lenvatinib, a novel multitargeted kinase inhibitor, has recently been approved for the treatment of unresectable thymic carcinoma. There are no reports of complete surgical resection after the administration of first‐line lenvatinib in advanced thymic carcinoma. A 50‐year‐old man visited our hospital because a computed tomography (CT) scan of the chest showed a large thymic squamous cell carcinoma. We suspected malignant pericardial effusion, invasion of the left upper lobe of the lung, and left mediastinal lymph node metastases. The patient was diagnosed with WHO classification stage IVb disease. Lenvatinib therapy was started at 24 mg/day as first‐line therapy. Gradual dose reduction to 16 mg/day was required because of hypertension, diarrhea, and palmar‐plantar erythrodysesthesia syndrome as side effects. Chest CT findings after 6 months of lenvatinib therapy showed reduction of the main tumor, disappearance of the mediastinal lymph node metastases, and pericardial effusion. Complete salvage resection was successfully performed a month after discontinuation of lenvatinib. The patient has been disease‐free for 1 year without adjuvant therapy. Lenvatinib therapy is one of the promising therapeutic options for thymic carcinoma and may make salvage surgery increasingly useful for advanced thymic carcinoma. [ABSTRACT FROM AUTHOR]

Treatment of synchronous multiple primary cancers is clinically difficult. We report four cases of synchronous primary cancers, including advanced and metastatic non-small cell lung cancer (NSCLCs) highly positive for programmed death ligand-1 (PD-L1) expression and initially treated with pembrolizumab. Pembrolizumab was efficacious in 2 patients with NSCLC lesions, followed by chemoradiotherapy for esophageal cancer (case 1) and chemotherapy for gastric cancer (case 2). Both cancers in case 1 showed a complete response for 3 years, while progression of the accompanying gastric cancer resulted in mortality at 20 months in case 2. Both NSCLC and gastric cancer in case 3 failed to respond to pembrolizumab, but the accompanying laryngeal cancer in case 4 showed a complete response, and cytotoxic chemotherapy for NSCLC was continued for 18.0 months. Our clinical experience suggests that pembrolizumab is a useful therapeutic approach for patients with synchronous cancers, including NSCLC that highly expresses PD-L1. [ABSTRACT FROM AUTHOR]

Here, we report a case of mediastinal mesenchymal tumor with a pericytic neoplasm feature that responded to radiation therapy. A 43‐year‐old man visited our hospital with a complaint of esophageal obstruction and chest pain. Chest computed tomography revealed a middle mediastinal tumor and a mesenchymal tumor was diagnosed with a pericytic neoplasm feature by video‐assisted thoracoscopic biopsy. The definitive treatment for soft tissue tumor is surgical resection; however, the mediastinal tumor was unresectable because of esophageal and tracheal invasion. Radiation therapy was administered and there was a partial tumor response and 2 years disease‐free status. With a review of the literature, we discuss the clinical and pathological characteristics of this rare tumor and its treatment. [ABSTRACT FROM AUTHOR]

Epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) elicit potent cell cycle arrest in EGFR‐mutant non–small‐cell lung cancer (NSCLC) cells. However, little is known about the mechanisms through which these drugs alter the tumor phenotype that contributes to the immune escape of EGFR‐mutant cells. Using EGFR‐mutant NSCLC cell lines and tissue samples from patients, we investigated the changes in immune checkpoints expressed in tumor cells following EGFR inhibition. Subsequently, we also analyzed the role of soluble factors from the dying tumor cells in the activation of immune signaling pathways involved in therapy resistance. Upon EGFR‐TKI treatment, we found that EGFR‐mutant cells upregulated the expression of innate immune checkpoint CD24 in vitro. We then analyzed biopsy samples from six patients who developed resistance to a first‐generation EGFR‐TKI without the acquired T790M mutation. Immunohistochemistry revealed that levels of tumor CD24 expression were increased upon treatment compared with those from pre‐treatment samples. Monocyte‐derived macrophages facilitated antibody‐dependent cellular phagocytosis when EGFR‐TKI‐treated EGFR‐mutant cells were incubated with anti‐CD24 antibodies in vitro, suggesting that CD24 may be a therapeutical target for EGFR‐mutant lung cancer. Moreover, EGFR inhibition accelerated the release of cell‐free DNA (cfDNA) from dying tumor cells, which activated the type I interferon signaling pathways in human THP‐1 monocytes in a stimulator of interferon genes‐dependent manner. Our study indicates that EGFR inhibition in EGFR‐mutant NSCLC cells fosters a tumor microenvironment associated with immune escape. Thus, CD24 targeted therapy and cfDNA monitoring may contribute to improved treatment outcomes in patients with EGFR‐mutant NSCLC. [ABSTRACT FROM AUTHOR]

Introduction: Extrapulmonary neuroendocrine carcinoma (EPNEC) is a clinicopathological entity distinct from neuroendocrine carcinoma of the lung. Here, we reviewed the clinical features, treatment modalities, and prognosis of EPNEC patients in a single-institution series. Methods: We retrospectively reviewed the medical records of EPNEC patients and examined the clinical profiles and treatment outcomes at our hospital between 2013 and 2021. Results: Thirty-one EPNEC patients (21 men and 10 women) with a median age of 65 years were included. The primary sites were as follows: stomach (n = 7); rectum and bladder (n = 3 each); prostate, esophagus, cervix, and pancreas (n = 2 each); maxillary sinus, parotid gland, gallbladder, anal canal, larynx, uterine body, ovary, appendix, anterior mediastinum, and unknown primary lesion (n = 1 each). Thirteen patients had locally advanced stage and 18 cases had distant metastases. Chemotherapy using platinum-combined CPT-11 or VP-16 was mainly performed. Various therapeutic modalities were used, especially in locally advanced cases. Ten patients underwent surgery, including initial surgery in 5 and conversion in 5 after chemotherapy. The response rate to initial chemotherapy was 56.5%, and the median overall survival in all patients was 12.8 (95% CI: 9.6–34.5) months. Survival was significantly longer in patients with locally advanced stage (80.3 months) and receiving surgery (not reached) than in those with metastatic disease (9.9 months) and without surgery (9.6 months). Conclusion: EPNEC occurs in various organs and has poor prognosis. Long-term survival may be possible with surgical resection in cases with early-stage disease or tumor shrinkage due to chemotherapy. [ABSTRACT FROM AUTHOR]