315 results on '"Yusuke Okuma"'
Search Results
2. Distinct Progression and Efficacy of First-Line Osimertinib Treatment According to Mutation Subtypes in Metastatic NSCLC Harboring EGFR Mutations
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Yuki Takeyasu, MD, Tatsuya Yoshida, MD, Ken Masuda, MD, Yuji Matsumoto, MD, Yuki Shinno, MD, Yusuke Okuma, MD, Yasushi Goto, MD, Hidehito Horinouchi, MD, Noboru Yamamoto, MD, and Yuichiro Ohe, MD
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Non–small cell lung cancer ,Epidermal growth factor receptor ,EGFR TKI ,Osimertinib ,Central nervous system ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Osimertinib (OSI), a third-generation EGFR tyrosine kinase inhibitor, is the standard treatment for patients with naive EGFR-mutant NSCLC. Nevertheless, information on how the mutation subtype affects disease progression after the failure of OSI treatment is scarce. Methods: We retrospectively reviewed patients with EGFR-mutant NSCLC who received OSI as a first-line treatment between April 2015 and December 2021. Results: This study included 229 patients. The objective response rate was 71%, with intracranial and extracranial response rates of 71% and 90%, respectively. The median progression-free survival was 23.3 mo (95% confidence interval [CI]: 19.6–26.7), and the median overall survival was 33.7 mo (95% CI: 31.3–58.6). Multivariate analysis revealed that the EGFR exon 21 L858R point mutation (L858R) (hazard ratio [HR] = 1.56, 95% CI: 1.04–2.34, p = 0.0328) and liver metastasis (HR = 2.63, 95% CI: 1.53–4.49, p = 0.0004) were significant predictors of progression-free survival in OSI treatment. The concomitant disease progression involving the central nervous system metastasis was significantly more common in patients with L858R (p = 0.048), whereas concomitant disease progression involving primary lesions was significantly more common in patients with exon 19 deletion mutation (p = 0.01). In addition, the probability of disease progression over time was higher for L858R compared with that for exon 19 deletion mutation, in patients with central nervous system metastasis (log-rank test, p = 0.027). Conclusions: The mutation subtype had an impact not only on the clinical outcome of the first-line OSI treatment but also on progression patterns after OSI treatment in patients with NSCLC harboring EGFR mutations.
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- 2024
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3. Disease progression status during initial immune checkpoint inhibitor (ICI) affects the clinical outcome of ICI retreatment in advanced non‐small cell lung cancer patients
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Masahiro Torasawa, Tatsuya Yoshida, Yuki Takeyasu, Yukiko Shimoda, Akiko Tateishi, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Kazuhisa Takahashi, and Yuichiro Ohe
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immune checkpoint inhibitor ,immune‐related adverse events ,non‐small cell lung cancer ,PD‐L1 ,retreatment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background It is still unclear whether patients with advanced non‐small cell lung cancer (NSCLC), with disease progression after initial immune checkpoint inhibitor (ICI) therapy, would benefit from ICIs readministration. Patients and Methods We retrospectively collected data from patients with advanced NSCLC who received ICI retreatment. Depending on the disease status at the discontinuation of the initial ICI therapy, the patients were divided into two groups: with disease progression (PD group) and without disease progression (Without PD group). Patients in the Without PD group were required to experience disease progression during the treatment‐free period. Efficacy was assessed by measuring the objective response rate (ORR) and progression‐free survival in retreatment (PFS‐R), while safety was assessed using the incidence of immune‐related adverse events (irAEs). Results 30 (46.7%) of 64 eligible patients were included in the PD group and 34 (53.1%) in the Without PD group. Patients in the Without PD group had better clinical outcomes than those in the PD group (ORR, 29.4% vs. 6.7%; p = 0.03, median PFS‐R, 4.1 months vs. 2.2 months, hazard ratio [HR], 0.61; 95% confidence interval [CI], 0.36–1.04; p = 0.07). Multivariate Cox regression analysis showed that patients in the Without PD group had significantly longer PFS‐R than those in the PD group (HR 0.42, 95% CI, 0.21–0.85; p = 0.015). In terms of safety, 28.1% of patients observed irAEs during ICI retreatment, and the incidence rate of grade 3 or higher irAEs was 7.8%. Specifically, of the 28 patients who discontinued their initial ICI treatment because of irAEs, 35.7% developed irAEs, and 28.6% experienced relapsed irAEs during ICI retreatment. Conclusion Immune checkpoint inhibitor retreatment demonstrated efficacy in patients who discontinued initial ICI therapy for reasons other than disease progression. However, ICI retreatment was ineffective in patients with disease progression during the initial ICI treatment.
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- 2023
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4. Prospective exosome-focused translational research for afatinib (EXTRA) study of patients with nonsmall cell lung cancer harboring mutation: an observational clinical study
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Saori Takata, Kei Morikawa, Hisashi Tanaka, Hidetoshi Itani, Masashi Ishihara, Kazuya Horiuchi, Yasuhiro Kato, Shinnosuke Ikemura, Hideyuki Nakagawa, Yoshiro Nakahara, Yoshitaka Seki, Akihiro Bessho, Nobumasa Takahashi, Kentaro Hayashi, Takeo Endo, Kiyoshi Takeyama, Toshiya Maekura, Nagio Takigawa, Akikazu Kawase, Makoto Endoh, Kenji Nemoto, Kazuma Kishi, Kenzo Soejima, Yusuke Okuma, Kenichi Yoshimura, Daisuke Saigusa, Yae Kanai, Koji Ueda, Akira Togashi, Noriyuki Matsutani, and Nobuhiko Seki
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The exosome-focused translational research for afatinib (EXTRA) study is the first trial to identify novel predictive biomarkers for longer treatment efficacy of afatinib in patients with epidermal growth factor receptor ( EGFR ) mutation-positive nonsmall cell lung cancer (NSCLC) via a comprehensive association study using genomic, proteomic, epigenomic, and metabolomic analyses. Objectives: We report details of the clinical portion prior to omics analyses. Design: A prospective, single-arm, observational study was conducted using afatinib 40 mg/day as an initial dose in untreated patients with EGFR mutation-positive NSCLC. Dose reduction to 20 mg every other day was allowed. Methods: Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were evaluated. Results: A total of 103 patients (median age 70 years, range 42–88 years) were enrolled from 21 institutions in Japan between February 2017 and March 2018. After a median follow-up of 35.0 months, 21% remained on afatinib treatment, whereas 9% had discontinued treatment because of AEs. The median PFS was 18.4 months, with a 3-year PFS rate of 23.3%. The median afatinib treatment duration in patients with final doses of 40 ( n = 27), 30 ( n = 23), and 20 mg/day ( n = 35), and 20 mg every other day ( n = 18) were 13.4, 15.4, 18.8, and 18.3 months, respectively. The median OS was not reached, with a 3-year OS rate of 58.5%. The median OS in patients who did ( n = 25) and did not ( n = 78) receive osimertinib during the entire course of treatment were 42.4 months and not reached, respectively ( p = 0.654). Conclusions: As the largest prospective study in Japan, this study confirmed favorable OS following first-line afatinib in patients with EGFR mutation-positive NSCLC in a real-world setting. Further analysis of the EXTRA study is expected to identify novel predictive biomarkers for afatinib. Trial registration: UMIN-CTR identifier (UMIN000024935, https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_his_list.cgi?recptno=R000028688
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- 2023
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5. Clinical Characteristics and Pharmacokinetics Change of Long-Term Responders to Antiprogrammed Cell Death Protein 1 Inhibitor Among Patients With Advanced NSCLC
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Hitomi Jo, MD, PhD, Tatsuya Yoshida, MD, PhD, Shigehiro Yagishita, MD, PhD, Mayu Ohuchi, PhD, Yuji Matsumoto, MD, PhD, Yuki Shinno, MD, PhD, Yusuke Okuma, MD, PhD, Yasushi Goto, MD, PhD, Hidehito Horinouchi, MD, PhD, Noboru Yamamoto, MD, PhD, Kazuhisa Takahashi, MD, PhD, Noriko Motoi, MD, PhD, Akinobu Hamada, PhD, and Yuichiro Ohe, MD, PhD
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Anti–PD-1 inhibitor ,Non–small cell lung cancer ,Long-term response ,Pharmacokinetics ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Immune checkpoint inhibitors (ICIs) induce long-term, durable responses in patients with advanced NSCLC. Nevertheless, these responses are limited to a few patients, and most responders have disease progression. The purpose of this study was to determine the differences in clinical factors and blood drug concentrations between long-term responders (LTRs) and non-LTRs. Methods: We retrospectively analyzed consecutive patients with advanced NSCLC who received antiprogrammed cell death protein 1 (PD-1) inhibitor monotherapy (nivolumab) from December 22, 2015, to May 31, 2017. Patients who obtained a clinical benefit for more than 6 months were referred to as “responders”; among these, individuals who had a durable response for more than 2 years were defined as “LTRs.” Those with a clinical benefit for less than 2 years were defined as “non-LTRs.” Results: A total of 212 patients received anti–PD-1 inhibitor monotherapy. The responders accounted for 35% (75 of 212) of the patients. Of these, 29 (39%) were LTRs and 46 (61%) were non-LTRs. The overall response rate and median tumor shrinkage in the LTR group were significantly higher than those in the non-LTR group (76% versus 35%, p < 0.0001, and 66% versus 16%, p < 0.001, respectively). The groups had no significant difference in PD-L1 expression and serum drug concentration at 3- and 6-month post-treatment initiation. Conclusions: Significant tumor shrinkage was associated with a long-term response to an anti–PD-1 inhibitor. Nevertheless, the PD-L1 expression level and pharmacokinetic profile of the inhibitor could not be used to predict the durable response among the responders.
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- 2023
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6. Whole Exome Sequencing of Thymoma Patients Exhibiting Exceptional Responses to Pemetrexed Monotherapy
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Tomohiro Tanaka, Yasushi Goto, Masafumi Horie, Ken Masuda, Yuki Shinno, Yuji Matsumoto, Yusuke Okuma, Tatsuya Yoshida, Hidehito Horinouchi, Noriko Motoi, Yasushi Yatabe, Shunichi Watanabe, Noboru Yamamoto, and Yuichiro Ohe
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thymoma ,whole-exome sequencing ,pemetrexed ,copy number variations ,exceptional response ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Pemetrexed is used for the chemotherapy of advanced thymoma. Exceptional responses of thymoma to pemetrexed treatment are not frequently observed. The underlying genetic mechanism of the exceptional responses remains unclear. We used whole-exome sequencing to explore the specific genomic aberrations that lead to an extreme and durable response. Methods: Whole-exome sequencing using NovaSeq6000 (150 bp paired-end sequencing) was performed on nine formalin-fixed paraffin-embedded tissues from patients with advanced thymomas treated with pemetrexed (two exceptional responders and seven typical responders). Results: We identified 284 somatic single-nucleotide variants (SNVs; 272 missense, 8 missense/splice-site, 3 stop-gain, and 1 stop-gain/splice-site), 34 insertions and deletions (Indels; 33 frameshift and one splice region), and 21 copy number variations (CNVs; 15 gains and six losses). No difference in the number of SNVs variants and distribution of deleterious Indels was observed between the exceptional and typical responders. Interestingly, arm-level chromosomal CNVs (15 gains and six losses) were detected in four patients, including an exceptional responder. The highest number of arm-level CNVs was observed in an exceptional responder. Conclusion: Exceptional responders to pemetrexed for metastatic thymomas may be characterized by arm-level CNVs. Further, whole-genome and RNA sequencing studies should be performed.
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- 2023
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7. Clinical characteristics of advanced non-small cell lung cancer patients with EGFR exon 20 insertions
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Chie Morita, Tatsuya Yoshida, Masayuki Shirasawa, Ken Masuda, Yuji Matsumoto, Yuki Shinno, Shigehiro Yagishita, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Noriko Motoi, Yasushi Yatabe, and Yuichiro Ohe
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Medicine ,Science - Abstract
Abstract Epidermal growth factor receptor (EGFR) exon 20 insertion mutations (Exon20ins) account for 4–12% of all EGFR mutations in non-small cell lung cancer (NSCLC) patients. Data on the differences in clinical characteristics between patients with Exon20ins and major mutations (M-mut) such as exon 19 deletion and L858R are limited. We retrospectively reviewed advanced NSCLC patients with EGFR mutations, who were treated with systemic therapy between January 2011 and December 2019. We identified 23 patients with Exon20ins and 534 patients with M-mut. In Exon20ins patients, the median age was 60 (range 27–88) years, and females and never-smokers were predominant. Clinical characteristics were similar in the two groups. In Exon20ins patients, 17 patients received platinum doublet as first-line therapy, and the overall response rate (ORR) and median progression-free survival (mPFS) were 11.8% and 8.9 months. Additionally, seven patients received conventional EGFR-tyrosine kinase inhibitors (TKIs), and eight patients anti-PD-1 antibodies in any-line therapy. ORR and mPFS of EGFR-TKIs and anti-PD-1 antibodies were 0%, 2.2 months and 25%, 3.1 months, respectively. Overall survival was significantly shorter in Exon20ins patients than in M-mut patients (29.3 vs. 43.4 months, p = 0.04). The clinical outcomes in Exon20ins patients were not satisfactory compared to M-mut patients.
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- 2021
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8. Characteristics of Japanese cypress pollen-induced allergic rhinitis by environmental challenge chamber
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Minami Koriyama, Yoshitaka Okamoto, Takeshi Suzuki, Tomohisa Iinuma, Heizaburou Yamamoto, Yusuke Okuma, Sawako Hamasaki, Daiju Sakurai, Toyoyuki Hanazawa, and Syuji Yonekura
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Immunologic diseases. Allergy ,RC581-607 - Published
- 2022
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9. Premature phase II study of amrubicin as palliative chemotherapy for previously treated malignant pleural mesothelioma
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Kageaki Watanabe, Yusuke Okuma, Shoko Kawai, Makoto Nagamata, and Yukio Hosomi
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amrubicin ,anthracyclines ,case series ,malignant pleural mesothelioma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Treatment options for malignant pleural mesothelioma (MPM) are limited. Anthracyclines are considered key drugs for treating MPM. However, their use is limited by severe cardiac toxicities. Amrubicin (AMR) is a next‐generation anthracycline that is commonly used to treat lung cancer. Here, we conducted a phase II trial of this drug in patients with previously treated MPM. Methods Eligible patients with MPM having adequate organ function and a performance status of 0–2 were enrolled after disease progression following pemetrexed/platinum therapy. Patients received 35 mg/m2 AMR on days 1–3 every three weeks until tumor progression or the appearance of unacceptable toxicities. The primary endpoint was the objective response rate. Median progression‐free survival (PFS), overall survival (OS), number of treatment cycles, and adverse events were evaluated as secondary endpoints. Results This trial was discontinued because of low accrual. From September 2013 to July 2018, five patients with MPM were enrolled. Stable disease (SD) was observed in three patients (60%), and progressive disease was noted in two patients (40%). The median PFS was 2.4 (range, 1.2–11.2) months, and the median OS was 9.1 (range, 6.2–22.0) months. The median number of treatment cycles was three (range, 2–11). Grade 1/2 toxicities were observed in all patients. Grade 3/4 neutropenia was observed in four patients (80%), but there were no cases of febrile neutropenia. Conclusions Despite the absence of the responders, the observation of SD in three patients suggests that AMR could have potential for treating MPM.
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- 2021
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10. Lorlatinib Versus Pemetrexed-Based Chemotherapy in Patients With ALK-rearranged NSCLC Previously Treated With Alectinib
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Yuki Takeyasu, MD, Tatsuya Yoshida, MD, Ken Masuda, MD, Yuji Matsumoto, MD, Yuki Shinno, MD, Yusuke Okuma, MD, Yasushi Goto, MD, Hidehito Horinouchi, MD, Noboru Yamamoto, MD, and Yuichiro Ohe, MD
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Non–small cell lung cancer ,Anaplastic lymphoma kinase ,Lorlatinib ,Chemotherapy ,Pemetrexed ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Introduction: Lorlatinib (LOR) or pemetrexed-based chemotherapy (PEM) is the standard treatment after failure of a second-generation ALK tyrosine kinase inhibitor, such as alectinib, in patients with ALK-positive NSCLC. Nevertheless, there have been few data on the clinical outcomes of these treatments after alectinib failure. Methods: We retrospectively analyzed patients with ALK-rearranged NSCLC who received LOR (LOR group) or PEM (PEM group) as post-treatment after alectinib failure between December 2012 and August 2020. Results: Among 90 patients who experienced disease progression during alectinib treatment, 38 of them received either PEM (n = 22) or LOR (n = 16) as subsequent treatment. The objective response rate and the median progression-free survival were similar in the PEM and LOR groups (objective response rate: 45% versus 44%, p = 0.92; median progression-free survival: 6.9 mo versus 6.2 mo, p = 0.83, respectively). Disease progression during treatment occurred in 22 patients with PEM and 14 patients with LOR. The central nervous system (CNS) was the most common site of progression in both groups. In patients without CNS metastasis at baseline, the cumulative incidence rate of CNS progression was lower over time in the LOR group compared with the PEM group (p = 0.045), whereas in patients with CNS metastasis at baseline, there were no significant differences in cumulative incidence rate of CNS progression between both groups (p = 0.43). Conclusions: Clinical outcomes of PEM and LOR after failure of alectinib were similar in patients with ALK-positive NSCLC.
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- 2022
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11. Phase II trial of S‐1 treatment as palliative‐intent chemotherapy for previously treated advanced thymic carcinoma
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Yusuke Okuma, Yasushi Goto, Fumiyoshi Ohyanagi, Kuniko Sunami, Yoshiro Nakahara, Satoru Kitazono, Keita Kudo, Yuichi Tambo, Shintaro Kanda, Noriko Yanagitani, Atsushi Horiike, Hidehito Horinouchi, Yutaka Fujiwara, Hiroshi Nokihara, Noboru Yamamoto, Makoto Nishio, Yuichiro Ohe, and Yukio Hosomi
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chemotherapy ,phase II ,rare cancer ,S‐1 ,thymic carcinoma ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival following palliative‐intent chemotherapy. Sunitinib, everolimus, and pembrolizumab have been proposed as active agents based on previous phase II trials. In this phase II study, TC patients previously treated with platinum‐based chemotherapy were enrolled. The patients received S‐1 orally twice daily at a dose of 40‐60 mg/m2 for 4 weeks, followed by 2 weeks off until the progression of the disease or the presence of unacceptable toxicities. The primary endpoint was the objective response rate (ORR), and secondary endpoints were progression‐free survival (PFS), overall survival (OS), and safety. The sample size of 26 patients was planned to reject the ORR of 10% under the expectation of 30% with a power of 0.80 and a type I error of 0.05 (one‐sided). Twenty‐six patients were recruited between 2013 and 2016; 23 patients had squamous cell carcinoma and 10 had an ECOG performance status of 0. One patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (90% confidence interval [CI], 18.3‐46.9) and an 80.8% disease control rate (90% CI, 65.4‐90.3). The median PFS was 4.3 months (95% CI, 2.3‐10.3 months) and median OS was 27.4 months (95% CI, 16.6‐34.3). Adverse events of grade ≥ 3 included neutropenia (12%), skin rash (8%), elevated alanine aminotransferase, and fatigue (4%). No treatment‐related death was observed. S‐1 confirmed clinical activity with tolerability in patients with previously treated TC. (UMIN000010736).
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- 2020
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12. Cisplatin and Irinotecan as First-Line Chemotherapy for Previously Untreated Metastatic Thymic Carcinoma: Updated Analysis
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Akito Fukuda, Yusuke Okuma, Taiki Hakozaki, Kie Mirokuji, Makiko Yomota, Tsunekazu Hishima, and Yukio Hosomi
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thymic carcinoma ,cisplatin ,irinotecan ,first-line chemotherapy ,metastasis ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Platinum-based chemotherapy is the de facto standard treatment for metastatic or unresectable thymic carcinoma. The optimal chemotherapy regimen has not yet been determined, including whether this should be combined with a second- or third-generation anti-cancer agent. We retrospectively evaluated the data of patients with metastatic or unresectable thymic carcinoma who were treated with a combination of cisplatin and irinotecan as first-line chemotherapy between 2002 and 2021 (trial registration UMIN000012175). The primary endpoint was response rate according to the RECIST criteria version 1.1. Secondary endpoints were disease control rate, progression-free survival (PFS), overall survival (OS), and toxicity (adverse events). Some patients analyzed in this study were also included in the previous trial, which was terminated early. For this analysis, we included 18 patients with a median age of 56 years and an Eastern Cooperative Oncology Group performance status of 0 or 1. All patients had clinical stage IVa or IVb thymic carcinoma according to the Masaoka-Koga staging system. The response rate was 44% and the disease control rate was 89%. The median PFS was 8.4 months (95% confidence interval (CI): 2.7–11.6 months) and the median OS was 45.6 months (95% CI: 15.7–69.1 months). Grade 3 or worse hematological toxicity was observed in 5 patients and grade 3 or worse non-hematological toxicity was observed in 3 patients. None of the patients developed febrile neutropenia, and no treatment-related deaths occurred. Thus, the combination of cisplatin and irinotecan as first-line chemotherapy for metastatic thymic carcinoma showed efficacy and acceptable toxicity.
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- 2022
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13. CD70 in Thymic Squamous Cell Carcinoma: Potential Diagnostic Markers and Immunotherapeutic Targets
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Jumpei Kashima, Tsunekazu Hishima, Yusuke Okuma, Hirotoshi Horio, Masumi Ogawa, Yukiko Hayashi, Shin-ichiro Horiguchi, Toru Motoi, Tetsuo Ushiku, and Masashi Fukayama
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thymic carcinoma ,CD70 ,CD27 ,immunohistochemistry ,tumor-infiltrating lymphocyte ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
CD70 – a ligand protein of CD27 on lymphocytes – is expressed in a large spectrum of malignancies. It is an attractive target for antibody-based therapy and several clinical trials are currently being conducted. However, there is no evidence regarding the expression of CD70 and its relationship with expression of programmed death ligand-1 (PD-L1) and CD27+ tumor-infiltrating lymphocytes (TIL) in formalin-fixed paraffin-embedded (FFPE) tissues of thymic tumors. FFPE tissues of thymic squamous cell carcinoma (TSCC) (operative specimens, n = 31; biopsy specimens, n = 11), thymoma (n = 60), thymic carcinoid (n = 3), and lung squamous cell carcinoma (LSCC) (n = 30) were analyzed immunohistochemically. Immunoreactivity for CD70 was semi-quantitatively scored according to the proportion of positive tumor cells. Moreover, the densities of CD27-positive intratumoral TIL (iTIL) and stromal TIL of TSCC were assessed and survival was compared. Most TSCC cases (87%; 27/31) were CD70-positive. In contrast, all thymoma and thymic carcinoid cases were CD70-negative. In LSCC cases, CD70-positivity was significantly lower than TSCC cases (20%; 6/30). Biopsy and resected specimens obtained from the same patients demonstrated a consistent staining pattern (6/6 patients). The proportion of CD70-positive TSCC was comparable with those of CD5 (87%) and CD117 (90%). Correlation between CD70 and PD-L1 expression score was observed. There was no significant difference in survival between the CD70-high and CD70-low expression groups. Meanwhile, patients with CD27-positive iTIL-high tumors exhibited better survival than those with iTIL-low tumors. This tendency was weaker in the CD70-high subset. CD70 immunohistochemistry is useful in diagnosing TSCC. CD70 may prevent anti-tumor immunity via CD27. Immunotherapy targeting the CD70–CD27 axis may be a promising option for the treatment of TSCC.
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- 2022
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14. Durvalumab Consolidation Treatment after Chemoradiotherapy for an HIV-Positive Patient with Locally Advanced Non-Small Cell Lung Cancer
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Shoko Kawai, Hiroe Suzuki, and Yusuke Okuma
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locally advanced non-small cell lung cancer ,immune checkpoint inhibitor ,anti-programmed cell death ligand-1 agent ,human immunodeficiency virus infection ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Due to antiretroviral therapy, human immunodeficiency virus (HIV) patients and non-HIV patients have a similar life expectancy. The leading cause of death among HIV patients is lung cancer. However, clinical toxicities with immune checkpoint inhibitors, including durvalumab, in HIV-positive patients with non-small cell lung cancer (NSCLC) remain unknown. We report a 45-year-old Japanese HIV patient, who was safely treated with durvalumab consolidation therapy after concurrent chemoradiotherapy (CCRT) for locally advanced NSCLC without significant toxicities until his disease progressed. This case demonstrates the safety of durvalumab consolidation therapy for HIV-positive patients after CCRT for locally advanced NSCLC.
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- 2020
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15. Cancer Cachexia among Patients with Advanced Non-Small-Cell Lung Cancer on Immunotherapy: An Observational Study with Exploratory Gut Microbiota Analysis
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Taiki Hakozaki, Alexis Nolin-Lapalme, Masato Kogawa, Yusuke Okuma, Shohei Nakamura, Danielle Moreau-Amaru, Taichi Tamura, Yukio Hosomi, Haruko Takeyama, Corentin Richard, Masahito Hosokawa, and Bertrand Routy
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non-small-cell lung cancer ,cancer cachexia ,immunotherapy ,prognosis ,gut microbiota ,biomarker ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Cancer cachexia exerts a negative clinical influence on patients with advanced non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICI). The prognostic impact of body weight change during ICI treatment remains unknown. The gut microbiota (GM) is a key contributor to the response to ICI therapy in cancer patients. However, the association between cancer cachexia and GM and their association with the response to ICIs remains unexplored. This study examined the association of cancer cachexia with GM composition and assessed the impact of GM on clinical outcomes in patients with NSCLC treated with ICIs. In this observational, prospective study, which included 113 Japanese patients with advanced NSCLC treated with ICIs, the prevalence of cachexia was 50.4% (57/113). The median progression-free survival (PFS) and overall survival (OS) were significantly shorter in the cachexia group than in the non-cachexia group (4.3 vs. 11.6 months (p = 0.003) and 12.0 months vs. not reached (p = 0.02), respectively). A multivariable analysis revealed that baseline cachexia was independently associated with a shorter PFS. Moreover, a gain in body weight from the baseline (reversible cachexia) was associated with a significantly longer PFS and OS compared to irreversible cachexia. Microbiome profiling with 16S rRNA analysis revealed that the cachexia group presented an overrepresentation of the commensal bacteria, Escherichia-Shigella and Hungatella, while the non-cachexia group had a preponderance of Anaerostipes, Blautia, and Eubacterium ventriosum. Anaerostipes and E. ventriosum were associated with longer PFS and OS. Moreover, a cachexia status correlated with the systemic inflammatory marker-derived-neutrophil-to-lymphocytes ratio (dNLR) and Lung Immune Prognostic Index (LIPI) indexes. Our study demonstrates that cachexia and longitudinal bodyweight change have a prognostic impact on patients with advanced NSCLC treated with ICI therapy. Moreover, our study demonstrates that bacteria associated with ICI resistance are also linked to cachexia. Targeted microbiota interventions may represent a new type of treatment to overcome cachexia in patients with NSCLC.
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- 2022
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16. Sublingual administration of liposomes enclosing alpha-galactosylceramide as an effective adjuvant of allergen immunotherapy in a murine model of allergic rhinitis
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Satoshi Suzuki, Daiju Sakurai, Toshioki Sakurai, Syuji Yonekura, Tomohisa Iinuma, Yusuke Okuma, Fumie Ihara, Tomoyuki Arai, Toyoyuki Hanazawa, Emi Fukuda-Kawaguchi, Yasuyuki Ishii, and Yoshitaka Okamoto
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Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: Sublingual immunotherapy (SLIT) is an established efficacious approach for the treatment of allergic rhinitis (AR). However, SLIT requires a long administration period to establish stable and adequate responses. This study investigated the efficacy of the sublingual administration of an allergen with liposomes enclosing α-GalCer (α-GC-liposome) as a potential adjuvant in mice with AR. Methods: Mice with AR induced by OVA received the sublingual administration of OVA, α-GC-liposomes, or OVA plus α-GC-liposomes for 7 days. After nasal re-challenge with OVA, nasal symptoms were evaluated. The serum levels of OVA-specific Ig, the cytokine production of CD4+ T cells in the cultures of cervical lymph node (CLN) cells, and the gene expression of CLNs were analyzed. Results: Although IL-4, IL-5 and IL-13 production from CD4+ T cells in CLN cells was significantly inhibited by the sublingual administration of OVA alone in mice with AR induced by OVA, their nasal symptoms were not significantly diminished. However, the combined sublingual administration of α-GC-liposomes and OVA completely suppressed nasal symptoms, downregulated Th2 and Th17 type cytokine production in CD4+ T cells as well as Th2 and Th17 gene expressions, and upregulated Th1 type cytokine production as well as Th1 gene expressions in CLN cells. Additionally, the serum levels of specific IgG2a were promoted, and specific IgE and IgG1 were inhibited. Conclusions: Our findings suggest that the sublingual administration of an allergen with α-GC-liposomes as an adjuvant might increase the therapeutic efficacy and effectiveness of this treatment method. Keywords: Allergic, Liposome, Mice, Natural killer T-Cells, Rhinitis
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- 2019
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17. Prospective exosome‐focused translational research for afatinib study of non‐small cell lung cancer patients expressing EGFR (EXTRA study)
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Yusuke Okuma, Kei Morikawa, Hisashi Tanaka, Takuma Yokoyama, Hidetoshi Itani, Kazuya Horiuchi, Hideyuki Nakagawa, Nobumasa Takahashi, Akihiro Bessho, Kenzo Soejima, Kazuma Kishi, Akira Togashi, Yae Kanai, Koji Ueda, Katsuhisa Horimoto, Noriyuki Matsutani, and Nobuhiko Seki
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Afatinib ,epidermal growth factor receptor ,exosome ,OMIC ,translational research ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Patients with EGFR‐mutated non‐small cell lung cancer (NSCLC) exhibit resistance to EGFR‐tyrosine kinase inhibitors (TKIs) within 9–14 months of therapy. Recently, EGFR‐mutated NSCLC has demonstrated the potential for heterogeneity; therefore, the manner of clonal heterogeneity may impact the duration of progression‐free and overall survival and other parameters affecting EGFR‐TKI treatment efficacy. However no predictive biomarker of these favorable treatment efficacies has been identified to date. The exosome‐focused translational research for afatinib (EXTRA) study aims to identify a novel predictive biomarker and a resistance marker for afatinib by analyzing data from association studies of the clinical efficacy of afatinib and four “OMICs” (genomics, proteomics, epigenomics, and metabolomics) using peripheral blood from patients treated with afatinib. This study aims to: (i) conduct comprehensive multi‐OMIC analyses in a prospective clinical trial, and (ii) focus on both sera/plasma and exosome as a source for OMIC analyses to identify a novel predictor of the efficacy of a specific drug. To eliminate the carryover bias of prior treatment, systemic treatment‐naïve patients were enrolled. The candidates to be screened for biomarkers comprise a discovery cohort of 60 patients and an independent validation cohort of 40 patients. The EXTRA study is the first trial to screen novel biomarkers of longer treatment efficacy of EGFR‐TKIs using four‐OMICs analyses, focusing on both “naked or free” molecules and “capsulated” exosomal components in serially collected peripheral blood.
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- 2019
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18. Gingival Metastasis of ALK Rearranged Non-Small Cell Lung Cancer
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Rui Kitadai, Yusuke Okuma, and Jumpei Kashima
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Lung cancer ,ALK rearrangement ,Gingival metastasis ,Heterogeneity ,Molecular targeted therapy ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: Metastasis to oral soft tissues is rare and account for only 0.1% of all oral malignancies. Oral cavity metastasis tends to be male-predominant, and lung cancer is the leading cause. Targeted therapies for advanced ALK rearranged non-small cell lung cancer (NSCLC) have shown a promising higher response than cytotoxic chemotherapy. Gingival metastasis usually shows poor prognosis. However using ALK inhibitor to ALK-positive advanced NSCLC may show longer survival. Case: A 64-year-old male who was diagnosed non-small cell carcinoma (NSCC) favoring adenocarcinoma presented with gingival metastasis. After first-line chemotherapy, ALK rearrangement was revealed in both primary lesion and gingival metastasis, and therefore the patient was treated with alectinib. Tumor response of the primary site and gingival lesion were obtained, however he presented with intestinal metastasis that lead to bowel obstruction and passed away. Conclusion: Our case showed good response to primary tumor and gingival metastasis but not to intestinal obstruction. ALK inhibitor often shows high response rate and long survival for ALK rearrangement NSCLC, however ALK rearranged positive NSCLC with gingival metastasis may have poor prognosis.
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- 2019
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19. Treatment Strategies for Non-Small Cell Lung Cancer Harboring Common and Uncommon EGFR Mutations: Drug Sensitivity Based on Exon Classification, and Structure-Function Analysis
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Rui Kitadai and Yusuke Okuma
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common EGFR mutation ,uncommon EGFR mutation ,non-small cell lung cancer ,EGFR-TKI ,structural feature ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The identification of epidermal growth factor receptor (EGFR) mutations and development of EGFR tyrosine kinase inhibitors (EGFR-TKIs) have dramatically improved the prognosis of advanced EGFR-mutated non-small cell lung cancer (NSCLC), setting a landmark in precision oncology. Exon 19 deletions and exon 21 L858R substitutions, which comprise the majority of common EGFR mutations, are predictors of good sensitivity to EGFR-TKIs. However, not all cancers harboring EGFR mutations are sensitive to EGFR-TKIs. Most patients harboring uncommon EGFR mutations demonstrate a poorer clinical response than those harboring common EGFR mutations. For example, cancers harboring exon 20 insertions, which represent approximately 4–12% of EGFR mutations, are generally insensitive to first- and second-generation EGFR-TKIs. Although understanding the biology of uncommon EGFR mutations is essential for developing treatment strategies, there is little clinical data because of their rarity. Moreover, clarifying the acquired resistance of EGFR-mutated NSCLC may lead to more precise treatments. Sequencing and structure-based analyses of EGFRmutated NSCLC have revealed resistance mechanisms and drug sensitivity. In this review, we discuss the strategies in development for treating NSCLC harboring common and uncommon EGFR mutations. We will also focus on EGFR-TKI sensitivity in patients harboring EGFR mutations based on the structural features.
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- 2022
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20. Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations
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Kiichiro Ninomiya, MD, PhD, Shunsuke Teraoka, MD, Yoshitaka Zenke, MD, PhD, Hirotsugu Kenmotsu, MD, PhD, Yukiko Nakamura, MD, Yusuke Okuma, MD, PhD, Akihiro Tamiya, MD, Kaname Nosaki, MD, Masahiro Morise, MD, PhD, Keiju Aokage, MD, Yuko Oya, MD, Toshiyuki Kozuki, MD, PhD, Tomohiro Sakamoto, MD, PhD, Kentaro Tanaka, MD, PhD, Hisashi Tanaka, MD, PhD, Junko Tanizaki, MD, PhD, Satoru Miura, MD, PhD, Hideaki Mizutani, MD, Eisaku Miyauchi, MD, PhD, Ou Yamaguchi, MD, PhD, Noriyuki Ebi, MD, Yasushi Goto, MD, PhD, Takaaki Sasaki, MD, PhD, Haruko Daga, MD, PhD, Satoshi Morita, PhD, Takeharu Yamanaka, PhD, Shinsuke Amano, BCom, Kazuo Hasegawa, BFA, Chiyo K. Imamura, PhD, Kenichi Suzuki, PhD, Kazuko Nakajima, PhD, Hitomi Nishimoto, MN, Satoshi Oizumi, MD, PhD, Toyoaki Hida, MD, PhD, Katsuyuki Hotta, MD, PHD, MPH, and Yuichi Takiguchi, MD, PhD
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Non–small cell lung cancer ,Epidermal growth factor receptor ,Systematic review ,Guidelines ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Patients with NSCLC in East Asia, including Japan, frequently contain EGFR mutations. In 2018, we published the latest full clinical practice guidelines on the basis of those provided by the Japanese Lung Cancer Society Guidelines Committee. The purpose of this study was to update those recommendations, especially for the treatment of metastatic or recurrent EGFR-mutated NSCLC. We conducted a literature search of systematic reviews of randomized controlled and nonrandomized trials published between 2018 and 2019 that multiple physicians had reviewed independently. On the basis of those studies and the advice from the Japanese Society of Lung Cancer Expert Panel, we developed updated guidelines according to the Grading of Recommendations, Assessment, Development, and Evaluation system. We also evaluated the benefits of overall and progression-free survival, end points, toxicities, and patients’ reported outcomes. For patients with NSCLC harboring EGFR-activating mutations, the use of EGFR tyrosine kinase inhibitors (EGFR TKIs), especially osimertinib, had the best recommendation as to first-line treatment. We also recommended the combination of EGFR TKI with other agents (platinum-based chemotherapy or antiangiogenic agents); however, it can lead to toxicity. In the presence of EGFR uncommon mutations, except for an exon 20 insertion, we also recommended the EGFR TKI treatment. However, we could not provide recommendations for the treatment of EGFR mutations with immune checkpoint inhibitors, including monotherapy, and its combination with cytotoxic chemotherapy, because of the limited evidence present in the literature. The 2020 Japanese Lung Cancer Society Guidelines can help community-based physicians to determine the most appropriate treatments and adequately provide medical care to their patients.
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- 2021
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21. 681 Single pipeline re-analysis revises microbiome associations with anti-tumor response to checkpoint inhibitors
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James White, Jarushka Naidoo, Jeffrey Weber, Evan Lipson, Cynthia Sears, Bertrand Routy, Fyza Shaikh, Joell Gills, Taiki Hakozaki, Richard Corentin, Yusuke Okuma, Mykhaylo Usyk, Abhishek Pandey, and Jiyoung Ahn
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Published
- 2020
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22. Clinical Significance of Tumor Markers for Advanced Thymic Carcinoma: A Retrospective Analysis from the NEJ023 Study
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Tomoyasu Mimori, Takehito Shukuya, Ryo Ko, Yusuke Okuma, Tomonobu Koizumi, Hisao Imai, Yuichi Takiguchi, Eisaku Miyauchi, Hiroshi Kagamu, Tomohide Sugiyama, Keisuke Azuma, Yukiko Namba, Masahiro Yamasaki, Hisashi Tanaka, Yuta Takashima, Sayo Soda, Osamu Ishimoto, Nobuyuki Koyama, Kunihiko Kobayashi, and Kazuhisa Takahashi
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advanced thymic carcinoma ,prognostic factor ,tumor marker ,neuron-specific enolase ,squamous cell carcinoma antigen ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The optimal tumor marker for predicting the prognosis of advanced thymic carcinoma (ATC) remains unclear. We conducted a multi-institutional retrospective study of patients with ATC. A total of 286 patients were treated with chemotherapy. Clinicopathological information, including serum tumor markers, was evaluated to determine the overall survival (OS) and progression-free survival (PFS). The carcinoembryonic antigen, cytokeratin-19 fragment, squamous cell carcinoma (SCC) antigen, progastrin-releasing peptide, neuron-specific enolase (NSE), and alpha-fetoprotein levels were evaluated. In the Kaplan–Meier analysis, the OS was significantly shorter in the patients with elevated NSE levels than in those with normal NSE levels (median, 20.3 vs. 36.8 months; log-rank test p = 0.029; hazard ratio (HR), 1.55; 95% confidence interval (CI), 1.05–2.31 (Cox proportional hazard model)); a similar tendency regarding the PFS was observed (median, 6.4 vs. 11.0 months; log-rank test p = 0.001; HR, 2.04; 95% CI, 1.31–3.18). No significant differences in the OS and PFS were observed among the other tumor markers. In both univariate and multivariate analyses of the patients with SCC only, the NSE level was associated with the OS and PFS. Thus, the NSE level may be a prognostic tumor marker for thymic carcinoma, regardless of histology.
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- 2022
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23. Re-challenging immune checkpoint inhibitor in a patient with advanced non-small cell lung cancer: a case report
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Taiki Hakozaki, Yusuke Okuma, and Jumpei Kashima
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Nivolumab ,Immune checkpoint inhibitor ,Non-small cell lung cancer ,Immune-related adverse events ,Re-challenge ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Currently, immune checkpoint (ICP) inhibitors are essential drugs for the treatment of non-small cell lung cancer (NSCLC). However, in patients previously treated with ICP inhibitors, the efficacy and safety of re-challenging the same or another ICP inhibitor remain unclear. Case presentation We present the case of a patient treated with nivolumab for advanced NSCLC who was previously treated with an ICP inhibitor as the first-line chemotherapy along with heavy cytotoxic chemotherapy. After the failure of five lines of chemotherapy, 3 cycles of nivolumab, as the ICP inhibitor re-challenge, the patient achieved a partial response. Conclusions This case might suggest that re-challenging an ICP inhibitor could be clinically active in selected patients with advanced NSCLC who progress after achieving an initial clinical benefit with an ICP inhibitor.
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- 2018
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24. Future Perspective of Chemotherapy and Pharmacotherapy in Thymic Carcinoma
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Rui Kitadai and Yusuke Okuma
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thymic carcinoma ,chemotherapy ,molecular targeted agent ,immune checkpoint inhibitor ,clinical trial ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Thymic carcinoma is a rare cancer that arises from thymic epithelial cells. Its nature and pathology differ from that of benign thymoma, presenting a poorer prognosis. If surgically resectable, surgery alone or surgery followed by chemoradiotherapy or radiotherapy is recommended by the National Comprehensive Cancer Network Guidelines. Metastatic and refractory thymic carcinomas require systemic pharmacotherapy. Combined carboplatin and paclitaxel, and cisplatin and anthracycline-based regimens have been shown a fair response rate and survival to provide a de facto standard of care when compared with other drugs employed as first-line chemotherapy. Cytotoxic agents have been pivotal for treating thymic carcinoma, as little is known regarding its tumorigenesis. In addition, genetic alterations, including driver mutations, which play an important role in treatments, have not yet been discovered. However, molecular pathways and biomarker studies assessing thymic epithelial tumors have been reported recently, resulting in the development of new agents, such as molecular targeted agents and immune checkpoint inhibitors. As treatment options are currently limited and the prognosis remains poor in metastases and recurrent thymic carcinoma, genetic alterations need to be assessed. In the present review, we focused on the current role of targeted therapies and immune checkpoint inhibitors in treating thymic carcinoma.
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- 2021
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25. Phase I/II study of induction chemotherapy using carboplatin plus irinotecan and sequential thoracic radiotherapy (TRT) for elderly patients with limited-disease small-cell lung cancer (LD-SCLC): TORG 0604
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Yuki Misumi, Hiroaki Okamoto, Jiichiro Sasaki, Noriyuki Masuda, Mari Ishii, Tsuneo Shimokawa, Yukio Hosomi, Yusuke Okuma, Makoto Nagamata, Takashi Ogura, Terufumi Kato, Masafumi Sata, Sakiko Otani, Akira Takakura, Koichi Minato, Yosuke Miura, Takuma Yokoyama, Saori Takata, Katsuhiko Naoki, and Koshiro Watanabe
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LD-SCLC ,Irinotecan ,Sequential radiotherapy ,Elderly ,Carboplatin ,Phase I ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background The role of irinotecan for elderly patients with LD-SCLC has been unclear, and the timing of TRT combined with chemotherapy has not been fully evaluated. Methods Patients aged > 70 years with untreated, measurable, LD-SCLC, performance status (PS) 0–2, and adequate organ function were eligible. Treatment consisted of induction with carboplatin on day 1 and irinotecan on days 1 and 8, every 21 days for 4 cycles, and sequential TRT (54Gy in 27 fractions). Carboplatin doses were based on AUC of 4 and 5 (levels 1 and 2, respectively), with a fixed irinotecan dose (50 mg/m2). Primary objective of the phase II study was overall responce rate. Results Forty-three patients were enrolled and forty-one were finally analyzed (median age: 75 years [range 70–86 years); males 31; PS 0/1/2, n = 22/18/1]. Two patients were excluded because of protocol violation (ascertained to be extensive disease). Twelve patients were accrued at phase I and the number of patients with carboplatin dose-limiting toxicities at levels-1 (n = 6) and −2 (n = 6) were 1(grade 3 hypertension) and 2 (grade 4 thrombocytopenia), respectively. The phase II trial was expanded to 29 additional patients receiving the level 1 carboplatin dose, total of 35 patients. The median number of chemotherapy cycles was 4 (range 1–4), and the median radiation dose was 54Gy (range 36–60). Toxicities were generally mild. There were 4 complete and 27 partial responses (response rate 88.6%). With a median follow-up of 52 months, the median progression-free and overall survival times of phase II were 11.2 and 27.1 months, respectively. Conclusions Induction chemotherapy of carboplatin plus irinotecan and sequential TRT was well tolerated and effective for elderly patients with LD-SCLC. Additional confirmatory studies are warranted. Trial registration Trial registration number: UMIN000007352 Name of registry: UMIN. Date of registration: 1/Dec/2006. Date of enrolment of the first participant to the trial: 6/Feb/2007. Clinical trial registration date: 1/Feb/2006 (prospective).
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- 2017
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26. Pneumothorax during Pazopanib Treatment in Patients with Soft-Tissue Sarcoma: Two Case Reports and a Review of the Literature
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Yoshiro Nakahara, Tomoya Fukui, Ken Katono, Yuuki Nishizawa, Yusuke Okuma, Masachika Ikegami, Jiichiro Sasaki, and Noriyuki Masuda
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Pneumothorax ,Soft-tissue sarcoma ,Pazopanib ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Pazopanib, a multitargeting tyrosine kinase inhibitor, has single-agent activity in patients with advanced soft-tissue sarcoma. Herein, we describe 2 cases of pneumothorax that occurred during pazopanib treatment in patients with soft-tissue sarcoma. These 2 patients had multiple lung metastases. According to previous reports and our past experience, the risk of pneumothorax may be higher in patients with multiple lung metastases. Although a causal relationship is uncertain, the risk of pneumothorax when prescribing pazopanib for these patients should be considered.
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- 2017
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27. Genetic and immunohistochemical analyses of ciliated muconodular papillary tumors of the lung: A report of five cases
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Jumpei Kashima, Tsunekazu Hishima, Akiko Tonooka, Shin-ichiro Horiguchi, Toru Motoi, Yusuke Okuma, Yukio Hosimi, and Hirotoshi Horio
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Medicine (General) ,R5-920 - Abstract
Ciliated muconodular papillary tumors are benign lesions located in the peripheral lung field. Recent studies revealed BRAF and epidermal growth factor receptor gene mutations and anaplastic lymphoma kinase gene rearrangement. Five ciliated muconodular papillary tumors were screened for the BRAF V600E and EGFR mutations via polymerase chain reaction. Immunohistochemical analysis was performed for the detection of the BRAF V600E and anaplastic lymphoma kinase proteins, as well as other markers including phosphorylated extracellular signal-regulated protein kinase. Three tumors (60%) harbored the BRAF V600E mutation. Immunohistochemical analysis confirmed this mutation in all of the tumor cell types. EGFR mutation and immunoactivity of the anaplastic lymphoma kinase protein were not detected. Phosphorylated extracellular signal-regulated protein kinase was negative both in the cytoplasm and nucleus of the BRAF V600E–positive tumors. Mucin 1, mucin 4, thyroid transcription factor 1, and cytokeratin 7 were positive, and mucin 5AC was partially positive, whereas napsin A and cytokeratin 20 were negative. Ciliated muconodular papillary tumor may originate from the terminal bronchioles, and the status of ERK activation reflects its benign behavior.
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- 2019
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28. Characteristics of the Chiba Environmental Challenge Chamber
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Sawako Hamasaki, Yoshitaka Okamoto, Syuji Yonekura, Yusuke Okuma, Toshioki Sakurai, Tomohisa Iinuma, Heizaburo Yamamoto, Daiju Sakurai, Shigetoshi Horiguchi, and Masahiko Yokota
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environmental challenge chamber (ECC) ,Japanese cedar pollinosis ,seasonal allergic rhinitis (SAR) ,validation study ,α chamber ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Background: An environmental challenge chamber (ECC), which we refer to as the α-chamber, was built at Chiba University in 2008. The aim of this study was to validate the functionality of the ECC. Methods: The stability of the pollen distribution and concentration in the ECC and symptoms of patients with Japanese cedar pollinosis induced by cedar pollen exposure were examined. Carryover effects of symptoms induced by different exposure protocols and correlations between symptoms induced in the ECC and those in the natural cedar pollen season were also determined. All the studies using the α-chamber were conducted out of the cedar pollen season. Results: The severity of symptoms in the chamber reached a peak about 2 hours after the start of pollen exposure and plateaued thereafter. After subjects left the chamber, the symptoms persisted for several days. There was no significant difference between the severity of symptoms at exposure levels of 8000 and 12000 grains/m3. The symptoms were significantly increased by exposure for 3 consecutive days; however, there were no carryover effects in a study performed with a two-week interval. The total nasal symptom score (TNSS) in the natural pollen season showed a weak correlation with the mean TNSS on the day of exposure and the following 3 days. Symptoms in the ECC also had weak correlations with those in the early natural pollen season. Conclusions: The ECC under well-controlled conditions is suitable for clinical studies and might accelerate development of treatment for seasonal allergic rhinitis. A complete evaluation requires inclusion of the persistent reaction after subjects leave the ECC.
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- 2014
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29. Molecular and Morphological Profiling of Lung Cancer: A Foundation for 'Next-Generation' Pathologists and Oncologists
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Jumpei Kashima, Rui Kitadai, and Yusuke Okuma
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histological subtype ,molecular pathology ,targeted therapy ,lung cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The pathological diagnosis of lung cancer has largely been based on the morphological features observed microscopically. Recent innovations in molecular and genetic technology enable us to compare conventional histological classifications, protein expression status, and gene abnormalities. The introduction of The Cancer Genome Atlas (TCGA) project along with the widespread use of the next-generation sequencer (NGS) have facilitated access to enormous data regarding the molecular profiles of lung cancer. The World Health Organization classification of lung cancer, which was revised in 2015, is based on this progress in molecular pathology; moreover, immunohistochemistry has come to play a larger role in diagnosis. In this article, we focused on genetic and epigenetic abnormalities in non-small cell carcinoma (adenocarcinoma and squamous cell carcinoma), neuroendocrine tumor (including carcinoids, small cell carcinoma, and large cell neuroendocrine carcinoma), and carcinoma with rare histological subtypes. In addition, we summarize the therapeutic targeted reagents that are currently available and undergoing clinical trials. A good understanding of the morphological and molecular profiles will be necessary in routine practice when the NGS platform is widely used.
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- 2019
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30. Eligibility for bevacizumab as an independent prognostic factor for patients with advanced non-squamous non-small cell lung cancer: a retrospective cohort study.
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Yusuke Takagi, Akira Toriihara, Yoshiro Nakahara, Makiko Yomota, Yusuke Okuma, Yukio Hosomi, Masahiko Shibuya, and Tatsuru Okamura
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Medicine ,Science - Abstract
BACKGROUND: Bevacizumab requires some unique eligibility criteria, such as absence of hemoptysis and major blood vessel invasion by the tumor. The prognostic impact of these bevacizumab-specific criteria has not been evaluated. METHODS: Patients with stage IIIB/IV, non-squamous non-small cell lung cancer who started chemotherapy before the approval of bevacizumab were reviewed. Patients with impaired organ function, poor performance status or untreated/symptomatic brain metastasis were excluded before the evaluation of bevacizumab eligibility. We compared overall survival and time to treatment failure among patients who were eligible (Group A) or ineligible (Group B) to receive bevacizumab. RESULTS: Among 283 patients with stage IIIB/IV non-squamous non-small cell lung cancer, eligibility for bevacizumab was evaluated in 154 patients. Fifty-seven patients were considered ineligible (Group B) based on one or more of a history of hemoptysis (n = 20), major blood vessel invasion (n = 43) and cardiovascular disease (n = 8). The remaining 97 patients were classified into Group A. Overall survival was significantly better in Group A (median, 14.6 months) than in Group B (median, 7.1 months; p
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- 2013
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31. Impact of ramucirumab pharmacokinetics in combination with docetaxel on the efficacy and survival in patients with advanced non-small cell lung cancer
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Kazumasa Akagi, Shigehiro Yagishita, Mayu Ohuchi, Yoshiharu Hayashi, Yuki Takeyasu, Ken Masuda, Yuki Shinno, Yusuke Okuma, Tatsuya Yoshida, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Hiroshi Mukae, Yuichiro Ohe, and Akinobu Hamada
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Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
32. Real-world Data on the Incidence of Coronavirus Disease (COVID-19) in Patients With Advanced Thoracic Cancer During the Early Phase of the Pandemic in Japan
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AKITO FUKUDA, TATSUYA YOSHIDA, SHIGEHIRO YAGISHITA, MIKA SHIOTSUKA, OSAMU KOBAYASHI, SATOSHI IWATA, HITOMI UMEGUCHI, MASATOSHI YANAGIDA, YASUHIRO IRINO, KEN MASUDA, YUKI SHINNO, YUSUKE OKUMA, YASUSHI GOTO, HIDEHITO HORINOUCHI, AKINOBU HAMADA, NOBORU YAMAMOTO, and YUICHIRO OHE
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Cancer Research ,Oncology ,General Medicine - Published
- 2023
33. High levels of <scp>AXL</scp> expression in untreated <scp> EGFR </scp> ‐mutated non‐small cell lung cancer negatively impacts the use of osimertinib
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Akihiro Yoshimura, Tadaaki Yamada, Masakuni Serizawa, Hisanori Uehara, Keiko Tanimura, Yusuke Okuma, Akito Fukuda, Satoshi Watanabe, Naoya Nishioka, Takayuki Takeda, Yusuke Chihara, Shinnosuke Takemoto, Taishi Harada, Osamu Hiranuma, Yukina Shirai, Takehito Shukuya, Akihiro Nishiyama, Yasuhiro Goto, Shinsuke Shiotsu, Kei Kunimasa, Kenji Morimoto, Yuki Katayama, Kenichi Suda, Tetsuya Mitsudomi, Seiji Yano, Hirotsugu Kenmotsu, Toshiaki Takahashi, and Koichi Takayama
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Cancer Research ,Oncology ,General Medicine - Abstract
For non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations, the initial therapeutic interventions will have crucial impacts on their clinical outcomes. Drug tolerant factors reportedly have an impact on EGFR-tyrosine kinase inhibitor sensitivity. This prospective study investigated the impacts of drug tolerant-related protein expression in tumors based on the efficacy of osimertinib in the first-setting of EGFR-mutated advanced NSCLC patients. A total of 92 patients with EGFR-mutated advanced or postoperative recurrent NSCLC were analyzed and treated with osimertinib at 14 institutions in Japan. AXL, p53, and programmed death-ligand 1 (PD-L1) expression in patient tumors was determined using immunohistochemistry. The AXL signaling pathway was investigated using a cell line-based assay and AXL-related gene expression in The Cancer Genome Atlas (TCGA) database. High levels of AXL and positive-p53 expression were detected in 26.1% and 53.3% of the pretreatment EGFR-mutated NSCLC tumors, respectively. High AXL expression levels were significantly associated with a shorter progression-free survival compared with low AXL expression levels, irrespective of the EGFR activating mutation status (p = 0.026). Cell line-based assays indicated that the overexpression of AXL protein accelerated PD-L1 expression, which induced insensitivity to osimertinib. In the TCGA database, AXL RNA levels were positively correlated with PD-L1 expression in the lung adenocarcinoma cohort. The results show that high AXL expression levels in tumors impact clinical predictions when using osimertinib to treat EGFR-mutated NSCLC patients. Trial Registration: UMIN000043942.
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- 2022
34. C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
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Takashi Kohno, Mamoru Kato, Shinji Kohsaka, Tomohisa Sudo, Ikuo Tamai, Yuichi Shiraishi, Yusuke Okuma, Daisuke Ogasawara, Tatsuya Suzuki, Teruhiko Yoshida, and Hiroyuki Mano
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Genomic Medicine ,Japan ,Oncology ,Neoplasms ,Humans ,Genomics - Abstract
Summary: Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates “C-CAT Findings” reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.
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- 2022
35. Early change in the clearance of pembrolizumab reflects the survival and therapeutic response: A population pharmacokinetic analysis in real-world non-small cell lung cancer patients
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Mayu, Ohuchi, Shigehiro, Yagishita, Hitomi, Jo, Kazumasa, Akagi, Ryoko, Inaba Higashiyama, Ken, Masuda, Yuki, Shinno, Yusuke, Okuma, Tatsuya, Yoshida, Yasushi, Goto, Hidehito, Horinouchi, Yoshinori, Makino, Noboru, Yamamoto, Yuichiro, Ohe, and Akinobu, Hamada
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,Lung Neoplasms ,Cachexia ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Humans ,Antibodies, Monoclonal, Humanized - Abstract
The dosing pattern of pembrolizumab is based on population pharmacokinetic (Pop-PK) analysis of clinical trials. Data for Japanese patients or patient populations with poor conditions such as cachexia are scarce. In this study, we performed a Pop-PK analysis of Japanese non-small cell lung cancer patients and analyzed the relationship between exposure, treatment effect, and survival.A total of 270 blood samples from 76 patients who received 200 mg pembrolizumab every 3 weeks between March 2017 and December 2018 were included. Blood concentrations of pembrolizumab were measured using mass spectrometry, and Pop-PK analysis was conducted using the Phoenix NLME software with a one-compartment model.The estimated median of clearance (CL) in this analysis population was 0.104 L/day, about half of the historical data for Western data. Overall, pembrolizumab CL decreased over time, with some populations showing increased CL early in the treatment and others showing decreased CL over time. When the time-varying CL was stratified by quartile, the group with decreasing CL showed significantly better treatment response and survival than the group with increasing CL, even though the group included more patients with cachexia. Detailed analysis suggested that the patient population that responded to pembrolizumab treatment had an improved general condition and reduced protein catabolism, further decreasing CL.In populations that benefit from pembrolizumab treatment, CL may be reduced early in their treatment, which may be a predictive and prognostic factor. However, further prospective validation of our findings is needed.
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- 2022
36. Liquid biopsy for the detection of resistance mutations to ROS1 and RET inhibitors in non-small lung cancers: A case series study
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Yoshitaka Seki, Tatsuya Yoshida, Takashi Kohno, Ken Masuda, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Kazuyoshi Kuwano, and Yuichiro Ohe
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Pulmonary and Respiratory Medicine - Published
- 2022
37. Advances in biology and novel treatments of SCLC: The four-color problem in uncharted territory
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Jumpei, Kashima and Yusuke, Okuma
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Cancer Research ,Lung Neoplasms ,Carcinoma, Non-Small-Cell Lung ,Humans ,Immunotherapy ,Small Cell Lung Carcinoma ,Biology - Abstract
Treatment for small cell lung cancer (SCLC) has not changed significantly compared to the overwhelming development of targeted therapies for non-small cell lung cancer. However, recent epigenetic and expressional analyses have revealed that SCLC can be divided into four distinct subtypes, which may lead to precision treatments. The situation appears slightly similar to the "four-color problem," a classic mathematical problem stating that no more than four colors are required to color the regions so that no two adjacent areas have the same color. This review introduces the framework for subtyping SCLC into four molecular subtypes and the promising targeted treatment for each subtype.
- Published
- 2022
38. Safety Implications of Switching Pembrolizumab Dosage From 200 mg Every 3 Weeks to 400 mg Every 6 Weeks in Patients With Advanced NSCLC
- Author
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Ryoko Inaba Higashiyama, Tatsuya Yoshida, Shigehiro Yagishita, Mayu Ohuchi, Naomi Sakiyama, Masahiro Torasawa, Masayuki Shirasawa, Ken Masuda, Yuki Shinno, Yuji Matsumoto, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Akinobu Hamada, and Yuichiro Ohe
- Subjects
Adult ,Aged, 80 and over ,Male ,Pulmonary and Respiratory Medicine ,Lung Neoplasms ,Treatment Outcome ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Humans ,Female ,Middle Aged ,Antibodies, Monoclonal, Humanized ,Aged - Abstract
Administration of 400 mg pembrolizumab every 6 weeks (400 mg Q6W) has been approved on the basis of the results of simulated pharmacokinetic modeling and exposure-response analyses. Nevertheless, the safety of switching dosage from 200 mg every 3 weeks (Q3W) to 400 mg Q6W during treatment remains unclear.This study involved patients (N = 45) with advanced NSCLC, in whom the pembrolizumab dosage was switched from 200 mg Q3W to 400 mg Q6W between August 2020 and November 2021 in our institute.At the time of switching, the median age of the patients was 71 (range: 32-84) years, and 32 patients (71.1 %) were males. The median number of cycles of 200 mg Q3W before switching was six (range: 1-31). After switching, new or worsening immune-related adverse events (irAEs) occurred in 17 of the 45 patients (37.8%) within three cycles. The irAEs were pneumonitis in 11 patients (24.4%), diarrhea in three patients (6.7%), renal dysfunction in two patients (4.4%), adrenal dysfunction in two patients (4.4%), a skin rash in one patient (2.2%), fulminant type 1 diabetes mellitus in one patient (2.2%).The switching of pembrolizumab dosage from 200 mg Q3W to 400 mg Q6W resulted in the occurrence of new or worsening irAEs, in particular, pneumonitis, in the early cycles even in patients who had received stable treatment with 200 mg Q3W.
- Published
- 2022
39. Concurrent High PD-L1 Expression and CD8+ Immune Cell Infiltration Predict PD-1 Blockade Efficacy in Advanced EGFR-Mutant NSCLC Patients
- Author
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Yukiko Shimoda, Ryota Shibaki, Tatsuya Yoshida, Shuji Murakami, Masayuki Shirasawa, Masahiro Torasawa, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Yuichiro Ohe, and Noriko Motoi
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2022
40. Unarranged territory in uncommon EGFR mutations
- Author
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Hiroyuki Fujii and Yusuke Okuma
- Subjects
Oncology - Published
- 2022
41. Efficacy of Immune Checkpoint Inhibitors in SMARCA4-Deficient Thoracic Tumor
- Author
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Yuki Shinno, Akihiko Yoshida, Ken Masuda, Yuji Matsumoto, Yusuke Okuma, Tastuya Yoshida, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, Yasushi Yatabe, and Yuichiro Ohe
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,Lung Neoplasms ,Carcinoma ,Programmed Cell Death 1 Receptor ,DNA Helicases ,Nuclear Proteins ,Thoracic Neoplasms ,B7-H1 Antigen ,Antineoplastic Agents, Immunological ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Biomarkers, Tumor ,Humans ,Immune Checkpoint Inhibitors ,Retrospective Studies ,Transcription Factors - Abstract
SMARCA4-deficient thoracic tumor is a novel disease entity characterized by mutations in SMARCA4 resulting in loss of its expression. They could be divided according to their phenotypes; carcinoma or sarcomatoid. It remains unclear how many patients with these SMARCA4-deficient tumors could benefit from inhibitors of programmed death 1 (PD-1) or programmed death ligand 1 (PD-L1).SMARCA4-deficient thoracic tumor cases were retrospectively identified from pathology and gene expression databases at the National Cancer Center Hospital in Japan. Clinical outcomes of patients treated with PD-1/PD-L1 inhibitors were reviewed.Eighteen patients with SMARCA4-deficient thoracic tumor [carcinoma (n = 10), sarcomatoid (n = 7), and ambiguous type (n = 1)] were identified. Of the twelve [carcinoma (n = 7), sarcomatoid (n = 5)] who had received immune checkpoint inhibitors (ICIs), 5 [carcinoma (n = 3), sarcomatoid (n = 2)] showed a partial response, all of whom had received an ICI as the first-line therapy. The overall response rate was The PD-L1 tumor proportion scores of the 5 responding patients were 100%, 80%, 5% (n = 2), and less than 1%. The median progression-free survival (PFS) of all the patients was 2.4 months [95% confidence interval (CI), 1.1 months-not achieved (NA)], while the median PFS of the 3 patients who received first-line ICIs was not reached (95% CI, 1.1 months-NA).PD-1/PD-L1 inhibitors showed promising results in the treatment of SMARCA4-deficient tumor. Further studies, especially on patient selection and combination therapy, are needed.
- Published
- 2022
42. Human resources for administrative work to carry out a comprehensive genomic profiling test in Japan
- Author
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Hidenori Kage, Katsutoshi Oda, Manabu Muto, Katsuya Tsuchihara, Natsuko Okita, Yusuke Okuma, Junko Kikuchi, Hidekazu Shirota, Hideyuki Hayashi, Toshio Kokuryo, Daisuke Sakai, Akira Hirasawa, Makoto Kubo, Hirotsugu Kenmotsu, Nana Akiyama, Aya Shinozaki‐Ushiku, Masahiko Tanabe, Tetsuo Ushiku, Kiyoshi Miyagawa, and Yasuyuki Seto
- Subjects
Cancer Research ,Oncology ,General Medicine - Published
- 2023
43. Incidence of serious adverse events caused by tyrosine kinase inhibitor treatment following immune checkpoint inhibitor therapy in advanced NSCLC patients with oncogenic driver alterations
- Author
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Yukiko Shimoda, Tatsuya Yoshida, Jun Miyakoshi, Masahiro Torasawa, Akiko Tateishi, Yuji Matsumoto, Ken Masuda, Yuki Shinno, Yusuke Okuma, Yasushi Goto, Hidehito Horinouchi, Noboru Yamamoto, and Yuichiro Ohe
- Subjects
Cancer Research ,Oncology ,Immunology ,Immunology and Allergy - Published
- 2023
44. Supplementary Figure 2 from The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non–Small Cell Lung Cancer
- Author
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Yusuke Okuma, Bertrand Routy, Laurence Zitvogel, Lisa Derosa, Safae Terrisse, Iris Mimpen, Myriam Benlaïfaoui, Yukio Hosomi, Arielle Elkrief, Corentin Richard, and Taiki Hakozaki
- Abstract
Supplementary Figure 2
- Published
- 2023
45. Supplementary Data from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
- Author
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Hiroyuki Mano, Teruhiko Yoshida, Tatsuya Suzuki, Daisuke Ogasawara, Yusuke Okuma, Yuichi Shiraishi, Ikuo Tamai, Tomohisa Sudo, Shinji Kohsaka, Mamoru Kato, and Takashi Kohno
- Abstract
Supplementary Data from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
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- 2023
46. Data from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
- Author
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Hiroyuki Mano, Teruhiko Yoshida, Tatsuya Suzuki, Daisuke Ogasawara, Yusuke Okuma, Yuichi Shiraishi, Ikuo Tamai, Tomohisa Sudo, Shinji Kohsaka, Mamoru Kato, and Takashi Kohno
- Abstract
Summary:Since June 2019, under the umbrella of the national health insurance system, Japan has started cancer genomic medicine (CGM) with comprehensive genomic profiling (CGP) tests. The Ministry of Health, Labour and Welfare (MHLW) of Japan constructed a network of CGM hospitals (a total of 233 institutes as of July 1, 2022) and established the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national datacenter for CGM. Clinical information and genomic data from the CGP tests are securely transferred to C-CAT, which then generates “C-CAT Findings” reports containing information of clinical annotation and matched clinical trials based on the CGP data. As of June 30, 2022, a total of 36,340 datapoints of clinical/genomic information are aggregated in C-CAT, and the number is expected to increase swiftly. The data are now open for sharing with not only the CGM hospitals but also other academic institutions and industries.
- Published
- 2023
47. Supplementary Figure Legends from The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non–Small Cell Lung Cancer
- Author
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Yusuke Okuma, Bertrand Routy, Laurence Zitvogel, Lisa Derosa, Safae Terrisse, Iris Mimpen, Myriam Benlaïfaoui, Yukio Hosomi, Arielle Elkrief, Corentin Richard, and Taiki Hakozaki
- Abstract
Supplementary Figure Legends
- Published
- 2023
48. Supplementary Figure 3 from The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non–Small Cell Lung Cancer
- Author
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Yusuke Okuma, Bertrand Routy, Laurence Zitvogel, Lisa Derosa, Safae Terrisse, Iris Mimpen, Myriam Benlaïfaoui, Yukio Hosomi, Arielle Elkrief, Corentin Richard, and Taiki Hakozaki
- Abstract
Supplementary Figure 3
- Published
- 2023
49. Supplementary Figure from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
- Author
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Hiroyuki Mano, Teruhiko Yoshida, Tatsuya Suzuki, Daisuke Ogasawara, Yusuke Okuma, Yuichi Shiraishi, Ikuo Tamai, Tomohisa Sudo, Shinji Kohsaka, Mamoru Kato, and Takashi Kohno
- Abstract
Supplementary Figure from C-CAT: The National Datacenter for Cancer Genomic Medicine in Japan
- Published
- 2023
50. Supplementary Figure 7 from The Gut Microbiome Associates with Immune Checkpoint Inhibition Outcomes in Patients with Advanced Non–Small Cell Lung Cancer
- Author
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Yusuke Okuma, Bertrand Routy, Laurence Zitvogel, Lisa Derosa, Safae Terrisse, Iris Mimpen, Myriam Benlaïfaoui, Yukio Hosomi, Arielle Elkrief, Corentin Richard, and Taiki Hakozaki
- Abstract
Supplementary Figure 7
- Published
- 2023
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