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Abstract Background An increased relative eosinophil count (REC) has potential as a predictive biomarker for a beneficial clinical response and outcome to cancer immunotherapies. Therefore, the present study investigated the impact of an increased posttreatment REC on the prognosis of non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs). Methods We retrospectively reviewed all 151 patients diagnosed with NSCLC and treated with ICI monotherapy and blood test data between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Results A total of 151 patients with a mean age of 69 years were included. REC after 4 weeks of initial ICI monotherapy was higher than pretreatment REC in 87 patients but not in 64. REC after 4 weeks of the ICI treatment with and without an increased REC were 4.4 and 1.8%, respectively (p

Abstract Background Although the incidence of lung cancer in elderly individuals has been increasing in recent years, the number of clinical trials designed specifically for elderly patients with advanced non‐small cell lung cancer (NSCLC) is still limited. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of pemetrexed (PEM) plus bevacizumab (Bev) combination chemotherapy in elderly patients with nonsquamous NSCLC. Methods A total of 29 elderly patients (≥75 years old) with nonsquamous NSCLC were enrolled in this multicenter, open‐label, phase II study, and 27 patients were finally analyzed. PEM at 500 mg/m2 on day 1 plus Bev at 15 mg/kg on day 1 were administered triweekly. The primary endpoint was the investigator‐assessed objective response rate. Results The median age at initiating chemotherapy was 80 years old. Almost all patients (92.6%) had adenocarcinoma histology. The median number of cycles administered was 6, and the objective response rate was 40.7%. The median progression‐free survival, overall survival and 1‐year survival were 8.8 months, 27.2 months and 79%, respectively. The treatment was well‐tolerated, and no treatment‐related death was observed. Conclusion Combination chemotherapy with PEM plus Bev in elderly patients with previously untreated advanced non‐squamous NSCLC exhibited favorable antitumor activity and tolerability, suggesting that a combination of PEM plus Bev might be a promising treatment option for this population.

Abstract Background The peripheral blood eosinophil count prior to treatment has potential as a predictive biomarker for a beneficial clinical response to cancer immunotherapies. Therefore, the present study investigated the impact of the eosinophil count on overall survival (OS) in non‐small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICI). Methods We retrospectively reviewed all patients diagnosed with NSCLC and treated with ICI monotherapy between March 2016 and August 2021 at National Hospital Organization Kochi Hospital and Tokushima University. Results A total of 166 patients were included. Fifty‐five patients had an eosinophil count of less than 100 cells/μL (Eo

Abstract Lung cancer with complex epidermal growth factor receptor (EGFR) and CTNNB1 comutations is rare, and the efficacy of tyrosine kinase inhibitors (TKIs) is generally poor. Here, we encountered a lung cancer patient with complex EGFR (L858R and E709X) and CTNNB1 comutations who successfully responded to afatinib. A 78‐year‐old woman visited our hospital with a cough and bloody sputum that had worsened over the past year. She had multiple mass shadows in both lungs and nodular shadows in the bronchi. The patient was diagnosed with lung adenocarcinoma cT4N3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx target test multi‐CDx system revealed positivity for EGFR (L858R and E709X) and CTNNB1 mutations. The expression of programmed death ligand 1 (22C3 clones) in tumor cells was negative by immunostaining. The patient was treated with afatinib as first‐line therapy and achieved clinical improvement and a partial response and is continuing treatment 1 year later. Case reports of lung cancer patients with EGFR/CTNNB1 comutations are rare, and TKIs are not considered to be effective. We herein present the first case report of lung cancer with the co‐occurrence of uncommon and complex EGFR (L858R and E709X) and CTNNB1 mutations that was successfully treated with afatinib.

Abstract Immune‐related adverse events (irAEs) occur in rare cases, even after the completion of immune checkpoint inhibitor (ICI) therapy. We encountered a lung cancer patient diagnosed with acute‐onset type 1 diabetes mellitus (DM) 7 months after the cessation of ICI. A 68‐year‐old woman was referred to our hospital for chest abnormalities. She was diagnosed with lung adenocarcinoma cT4N2M1c, stage IVB. Immunostaining showed that the expression of programmed death ligand 1 in tumor cells was negative. A genetic analysis using the Oncomine Dx Target Test Multi‐CDx System revealed that the primary tumor was positive for ERBB2. Combined immunotherapy with carboplatin, pemetrexed, and pembrolizumab was performed as first‐line therapy, followed by maintenance therapy with pemetrexed plus pembrolizumab, which was successful. After the seventh course, maintenance therapy was stopped because only the primary tumor showed local enlargement. Local chest radiotherapy (66 Gy/33 Fr) was performed, and the patient was followed up. HbA1c was 4.9% 3 months after the completion of pembrolizumab, and dry mouth and polyuria occurred after 5 months. Seven months later, the patient developed diabetic ketoacidosis with a blood glucose of 348 mg/dL and an HbA1c of 11.3%. Antiglutamic acid decarboxylase antibodies were negative and urinary C‐peptide was 9.3 μg/day. The patient was diagnosed with acute‐onset type 1 diabetes and received insulin therapy. There has been no case report of type 1 diabetes diagnosed 7 months after the last administration of an ICI. These results indicate that irAE needs to be considered even after the cessation of ICI.

Abstract An 83‐year‐old Japanese man visited our hospital with dyspnea and general fatigue. Computed tomography (CT) revealed a tumor in the anterior mediastinum, bilateral pleural effusion, pericardial fluid, and multiple liver nodules. We performed a CT‐guided tumor biopsy, and the patient was diagnosed with thymic small‐cell carcinoma, Masaoka–Koga stage classification IVb. The patient received four cycles of carboplatin and etoposide, and all lesions disappeared on CT. However, after 6 months, CT revealed a recurrent tumor in the anterior mediastinum. After one cycle of rechallenge chemotherapy, we performed extended total thymectomy followed by another three cycles of chemotherapy. More than 2.5 years after the last chemotherapy session, the patient's carcinoma did not recur. Thus, this case suggests that salvage surgery may be a treatment option for local recurrence of thymic carcinoma after complete remission with chemotherapy, even in patients with stage IV cancer.

Abstract A 76‐year‐old man was referred to our hospital with a cough. Chest computed tomography (CT) revealed a 45‐mm mass in the lingular segment of the left upper lobe. Transbronchial tumor biopsies showed adenocarcinoma. Contrast‐enhanced CT and bone scintigraphy revealed lung, pleura, and bone metastases. The patient was diagnosed with left upper lobe adenocarcinoma cT2bN3M1c stage IVB. A genetic analysis of the primary tumor using the Oncomine Dx Target Test Multi‐CDx system revealed positivity for epidermal growth factor receptor (EGFR) (L858R) and CTNNB1 mutations. Based on these findings, the patient was treated with osimertinib (80 mg/day) as first‐line therapy. Six months later, the tumor increased in size, indicating progressive disease. Osimertinib was stopped and second‐line therapy with carboplatin (area under the curve 5) and pemetrexed (500 mg/m2) was initiated. After three cycles of chemotherapy, the patient developed dementia and disorientation. Contrast‐enhanced magnetic resonance imaging of the head showed miliary brain metastases. Miliary dissemination is a rare form of brain metastasis. Miliary patterns of lung metastases have been strongly associated with the EGFR exon 19 deletion. The radiological features of miliary brain metastases of non‐small cell lung cancer with the exon 19 deletion have been reported. To the best of our knowledge, this is the first case report of lung cancer with miliary brain metastases and co‐mutations of EGFR (L858R) and CTNNB1. In conclusion, co‐mutations of EGFR (L858R) and CTNNB1 and the discontinuation of EGFR‐tyrosine kinase inhibitor may contribute to the development of miliary brain metastases. Further case studies are warranted.

Abstract Background The prognosis of thymoma with cardiac tamponade is generally poor. Most of the reported thymomas with cardiac tamponade were type B or type AB (mixed thymoma), and cardiac tamponade due to type A thymoma, which has a better prognosis compared to type B thymoma, is extremely rare. Case presentation We encountered a case of cardiac tamponade in a 71-year-old male. He visited our emergency department due to exacerbation of fatigue and dyspnea on exertion that lasted for two weeks. Chest imaging revealed a large amount of pericardial fluid and a contrast-enhanced tumor with calcification in the anterior mediastinum. The patient underwent thoracoscopic tumor biopsy and pathological examinations revealed type A thymoma. In this case, long-term disease-free survival (7.5 years) was achieved by multidisciplinary treatment (preoperative chemotherapy, surgical excision, and postoperative radiation therapy), in accordance with the histological type. Conclusions This case indicates that neoplastic cardiac tamponade, even in elderly patients, should not necessarily be regarded as a terminal cancer and requires a systematic investigation for underlying causes.

Abstract Immune checkpoint inhibitors (ICIs) have caused a paradigm shift in the treatment of lung cancer. Here, we encountered a case of inoperable locally advanced squamous cell carcinoma of the lung that became operable with pembrolizumab‐based immunochemotherapy and achieved a pathological complete response. An 82‐year‐old man suspected of having lung cancer was referred to our hospital. The patient was clinically diagnosed with left upper lobe squamous cell carcinoma cT2aN3M0 c‐stage IIIC. Immunostaining revealed the expression of programmed death‐ligand 1 in 60% of tumor cells. The cancer cells disappeared after two cycles of chemotherapy with carboplatin and nanoparticle albumin‐bound paclitaxel plus pembrolizumab. As the abnormal accumulation of 18F‐fluorodeoxyglucose (FDG) on FDG‐positron emission tomography/computed tomography before chemotherapy almost disappeared after pembrolizumab‐based immunochemotherapy, left upper lobectomy and lymph node dissection were performed. No cancer cells were pathologically detected from the resected tissue. Therefore, ICIs combined with chemotherapy may enable inoperable advanced lung cancer patients to undergo surgery and achieve a complete response.

Abstract Profound and durable responses to a single dose of pembrolizumab in lung cancer are rare. We encountered a non‐small cell lung cancer patient showing a deep and durable response with a single dose of pembrolizumab. A 79‐year‐old man reported bloody sputum for several weeks and visited a general physician. A chest x‐ray revealed a tumor shadow in the right middle lung field at that time, and the patient was referred to our hospital. He was diagnosed with adenocarcinoma of the lung by transbronchial biopsy. The expression of programmed death ligand 1 in tumor cells was 100% by immunostaining. Based on the above, immunotherapy with pembrolizumab was performed as first‐line therapy. Cancer cells had significantly shrunk at the end of the first cycle. The patient had grade‐3 immune‐related hepatitis at the end of the first cycle. Pembrolizumab treatment was stopped and prednisolone (80 mg/body) was initiated. Subsequently, liver function normalized, and prednisolone was tapered and discontinued. Since then, no tumor recurrence has been detected for 1.5 years without treatment. There have been few reports of profound and durable responses to a single dose of pembrolizumab in lung cancer. The results indicate that a single dose of pembrolizumab alone may be sufficient to cause durable response and serious immune‐related adverse events in some cases.

Abstract Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. Case A 65‐year‐old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD‐L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3‐positive T cells and CD138‐positive plasma cells. Second‐line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. Conclusion Pembrolizumab may be used as a treatment option for pulmonary LCNEC.

Malignant tumors are often associated with eosinophilic pleural effusion. Here, we encountered a case of interleukin‐5 (IL‐5)‐producing malignant pleural mesothelioma with eosinophilic pleural effusion. The patient was a 50‐year‐old male. He had a history of a cough for several weeks and had visited a local doctor. Left pleural effusion was noted, and the patient was referred to our hospital. He was diagnosed with malignant pleural mesothelioma by pleural biopsy, with eosinophilic pleural effusion. IL‐5 in the pleural effusion increased, and tumor cells were IL‐5‐positive by immunostaining. There have been few reports of IL‐5‐producing tumors, and this is the first report of IL‐5‐producing malignant pleural mesothelioma. Host‐tumor cell interactions cause eosinophilic pleural effusion. In patients with eosinophilic pleural effusion, malignant pleural effusion should be considered. It is necessary to clarify the pathophysiology of malignant tumors and eosinophils.

Sarcomatoid malignant pleural mesothelioma (SMPM) is a rare disease with no effective treatment and a poor prognosis. Here, we encountered a case of programmed death ligand 1 (PD-L1)-negative SMPM with a favorable and sustained response to second-line nivolumab. Nivolumab is a human mAb to the PD-1 receptor that inhibits the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Nivolumab showed promising results in several phase II trials on pretreated malignant pleural mesothelioma (MPM) patients. The patient was an 82-year-old male. He had a complaint of dyspnea on exertion and visited a local doctor. Left pleural effusion was noted, and the patient was referred to our hospital. He was diagnosed with SMPM by pleural biopsy. The patient received four cycles of chemotherapy (carboplatin and pemetrexed); however, his condition progressed. Nivolumab was selected as the second-line treatment. CT imaging showed a clear improvement in pleural thickening, and thus, the administration of nivolumab was continued. PD-L1 IHC tests (SP142 and 22C3 clones) have been negative. SMPM does not respond well to systemic chemotherapy. In epithelioid MPM and SMPM, anti-tumor immune responses by hosts differed. SMPM patients may be better candidates for immune checkpoint inhibitors (ICIs). Nivolumab needs to be considered for patients with SMPM. Further studies are needed to identify predictive biomarkers of ICIs for SMPM.

ObjectivesTo identify blood cell markers that predict the long-term outcomes of patients with colorectal cancer.MethodsData from 892 stage II and III colorectal cancer patients who underwent R0 resection were included. We analyzed the correlations of the preoperative blood data, previously reported prognostic indices, and clinicopathologic factors with the long-term outcomes, such as relapse-free survival and overall survival, using univariate and multivariate analyses.ResultsMultivariate analysis showed that tumor location, stage, mean corpuscular volume, neutrophil-to-lymphocyte ratio, and lymphocyte-to- monocyte ratio were significantly correlated with relapse-free survival. A mean corpuscular volume ≥80.5 fL, neutrophil-to-lymphocyte ratio ≥5.5, and lymphocyte-to- monocyte ratio ConclusionThe mean corpuscular volume, neutrophil-to-lymphocyte ratio, and lymphocyte-to- monocyte ratio can serve as blood cell markers to predict the long-term outcomes of patients who underwent R0 resection for stage II/III colorectal cancer.

Aspergillus nodules (AN) are an unusual form of chronic pulmonary aspergillosis. On the other hand, pulmonary nodular lymphoid hyperplasia (PNLH) is classified as a reactive pulmonary lymphoproliferative disorder. A 65-year-old male was referred to our hospital due to a nodule in the left upper lobe. Histologically, a mixture of prominent lymphoid follicular formation, and hyaline necrosis were observed. Grocott staining revealed morphological forms of Aspergillus spp. in the necrosis. The final clinical diagnosis was suspected AN histologically consistent with PNLH. This case suggests that there may be PNLH cases in which local infection with Aspergillus contributes to its pathophysiology. [ABSTRACT FROM AUTHOR]