Eiji Takeuchi, Hirokazu Ogino, Kensuke Kondo, Yoshio Okano, Seiya Ichihara, Michihiro Kunishige, Naoki Kadota, Hisanori Machida, Nobuo Hatakeyama, Keishi Naruse, Hiroshi Nokihara, Tsutomu Shinohara and Yasuhiko Nishioka : An increased relative eosinophil count as a predictive dynamic biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors., Thoracic Cancer, Vol.15, No.3, 248-257, 2024.
(要約)
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). 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. 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 < 0.001). Disease control rates (DCR) were significantly higher in patients with than in those without an increased REC (84% vs. 47%, p < 0.001). The median overall survival (OS) of lung cancer patients with or without an increased REC were 674 and 234 days, respectively. A Kaplan-Meier univariate analysis revealed a significant difference in OS between the two groups (p < 0.001). A Cox proportional regression analysis identified an increased REC as an independent predictor of OS (p = 0.003). ICI-treated NSCLC patients with an increased REC after 4 weeks of treatment had a better DCR and prognosis than the other patients examined.
Eiji Takeuchi, Kensuke Kondo, Yoshio Okano, Seiya Ichihara, Michihiro Kunishige, Naoki Kadota, Hisanori Machida, Nobuo Hatakeyama, Keishi Naruse, Hirokazu Ogino, Hiroshi Nokihara, Tsutomu Shinohara and Yasuhiko Nishioka : Pretreatment eosinophil counts as a predictive biomarker in non-small cell lung cancer patients treated with immune checkpoint inhibitors., Thoracic Cancer, Vol.14, No.30, 3042-3050, 2023.
(要約)
OS was significantly longer in ICI-treated NSCLC patients with a pretreatment eosinophil count of 100 ≤ Eo <500 than in the other patients and, thus, has potential as a new predictive biomarker.
Michihiro Kunishige, Seiya Ichihara, Naoki Kadota, Yoshio Okano, Hisanori Machida, Nobuo Hatakeyama, Keishi Naruse, Tsutomu Shinohara and Eiji Takeuchi : Non-small cell lung cancer with EGFR (L858R and E709X) and CNNB1 mutations responded to afatinib., Thoracic Cancer, Vol.14, No.4, 423-426, 2022.
(要約)
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.
Seiya Ichihara, Michihiro Kunishige, Naoki Kadota, Yoshio Okano, Hisanori Machida, Nobuo Hatakeyama, Keishi Naruse, Tsutomu Shinohara and Eiji Takeuchi : Late-onset acute type 1 diabetes mellitus 7 months after discontinuation of pembrolizumab against lung cancer., Thoracic Cancer, Vol.14, No.1, 81-84, 2022.
(要約)
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.
Yoshihiro Kondo, Michihiro Kunishige, Naoki Kadota, Yoshio Okano, Hisanori Machida, Nobuo Hatakeyama, Keishi Naruse, Tsutomu Shinohara and Eiji Takeuchi : A single dose of pembrolizumab treatment causing a profound and durable response in lung cancer., Thoracic Cancer, Vol.13, No.4, 648-652, 2022.
(要約)
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.
Yoshio Okano, Michihiro Kunishige, Yoshihiro Kondo, Naoki Kadota, Atsushi Morishita, Keishi Naruse, Hisanori Machida, Nobuo Hatakeyama, Hiroyuki Hino, Tsutomu Shinohara, Shoji Sakiyama and Eiji Takeuchi : Dramatic response to immunochemotherapy followed by salvage surgery in an elderly lung cancer patient., Thoracic Cancer, Vol.13, No.3, 510-513, 2021.
(要約)
F-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.
Naoki Kadota, Nobuo Hatakeyama, Hiroyuki Hino, Michihiro Kunishige, Yoshihiro Kondo, Yoshio Okano, Hisanori Machida, Keishi Naruse, Tsutomu Shinohara, Shoji Sakiyama, Fumitaka Ogushi and Eiji Takeuchi : Complete and durable response of pulmonary large-cell neuroendocrine carcinoma to pembrolizumab., Cancer Reports, Vol.5, No.8, 2021.
(要約)
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.