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1. Tumor microenvironment disparity in multiple primary lung cancers: Impact of non-intrinsic factors, histological subtypes, and genetic aberrations

Author

Izumi, Motohiro, Sawa, Kenji, Oyanagi, Jun, Noura, Ikue, Fukui, Mitsuru, Ogawa, Koichi, Matsumoto, Yoshiya, Tani, Yoko, Suzumura, Tomohiro, Watanabe, Tetsuya, Kaneda, Hiroyasu, Mitsuoka, Shigeki, Asai, Kazuhisa, Nishiyama, Noritoshi, Ohsawa, Masahiko, Yamamoto, Nobuyuki, Koh, Yasuhiro, and Kawaguchi, Tomoya

Published
2021
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3. Safe Concurrent Use of Anti-tuberculosis Drugs and Pembrolizumab in a Patient with Non-small-cell Lung Cancer Who Was Infected with Mycobacterium tuberculosis

Author

Nakahama, Kenji, primary, Kaneda, Hiroyasu, additional, Ogawa, Koichi, additional, Matsumoto, Yoshiya, additional, Tani, Yoko, additional, Suzumura, Tomohiro, additional, Mitsuoka, Shigeki, additional, Watanabe, Tetsuya, additional, Asai, Kazuhisa, additional, and Kawaguchi, Tomoya, additional

Published
2022
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8. Repeat lung cancer screenings reveal less CXR abnormalities with different variations than first-time screening

Author

Kimura, Tatsuo, primary, Fukumoto, Shinya, additional, Nakano, Akemi, additional, Fujii, Hideki, additional, Nadatani, Yuji, additional, Tauchi, Yukie, additional, Takashima, Shingo, additional, Nishii, Yuko, additional, Otani, Koji, additional, Ageshio, Naomi, additional, Suzumura, Tomohiro, additional, and Kawada, Norifumi, additional

Published
2021
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10. Abstract 2333: Mutational landscape of multiple primary lung cancers and its correlation with environmental factors

Author

Izumi, Motohiro, primary, Oyanagi, Jun, additional, Sawa, Kenji, additional, Fukui, Mitsuru, additional, Ogawa, Koichi, additional, Matsumoto, Yoshiya, additional, Tani, Yoko, additional, Suzumura, Tomohiro, additional, Watanabe, Tetsuya, additional, Kaneda, Hiroyasu, additional, Mitsuoka, Shigeki, additional, Asai, Kazuhisa, additional, Kimura, Tatsuo, additional, Yamamoto, Nobuyuki, additional, Kawaguchi, Tomoya, additional, and Koh, Yasuhiro, additional

Published
2020
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12. Reduced CYP2D6 function is associated with gefitinib-induced rash in patients with non-small cell lung cancer

Author

Suzumura Tomohiro, Kimura Tatsuo, Kudoh Shinzoh, Umekawa Kanako, Nagata Misato, Matsuura Kuniomi, Tanaka Hidenori, Mitsuoka Shigeki, Yoshimura Naruo, Kira Yukimi, Nakai Toshiyuki, and Hirata Kazuto

Subjects
CYP2D6, Non-small cell lung cancer, Gefitinib, Erlotinib, Adverse events, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Rash, liver dysfunction, and diarrhea are known major adverse events associated with erlotinib and gefitinib. However, clinical trials with gefitinib have reported different proportions of adverse events compared to trials with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib but not erlotinib. It has been hypothesized that CYP2D6 phenotypes may be implicated in different adverse events associated with gefitinib and erlotinib therapies. Methods The frequency of each adverse event was evaluated during the period in which the patients received gefitinib or erlotinib therapy. CYP2D6 phenotypes were determined by analysis of CYP2D6 genotypes using real-time polymerase chain reaction techniques, which can detect single-nucleotide polymorphisms. The CYP2D6 phenotypes were categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of the adverse events associated with each factor, including CYP2D6 activities and treatment types. Results A total of 232 patients received gefitinib therapy, and 86 received erlotinib therapy. Reduced function of CYP2D6 was associated with an increased risk of rash of grade 2 or more (OR, 0.44; 95% confidence interval [CI], 0.21–0.94; *p = 0.03), but not diarrhea ≥ grade 2 (OR, 0.49; 95% CI, 0.17–1.51; *p = 0.20) or liver dysfunction ≥ grade 2 (OR, 1.08; 95% CI, 0.52–2.34; *p = 0.84) in the gefitinib cohort. No associations were observed between any adverse events in the erlotinib cohort and CYP2D6 phenotypes (rash: OR, 1.77; 95% CI, 0.54–6.41; *p = 0.35/diarrhea: OR, 1.08; 95% CI, 0.21–7.43; *p = 0.93/liver dysfunction: OR, 0.93; 95% CI, 0.20–5.07; *p = 0.93). Conclusions The frequency of rash was significantly higher in patients with reduced CYP2D6 activity who treated with gefitinib compared to patients with functional CYP2D6. CYP2D6 phenotypes are a risk factor for the development of rash in response to gefitinib therapy.

Published
2012
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13. Impact of tumor microenvironment on the efficacy of epidermal growth factor receptor‐tyrosine kinase inhibitors in patients withEGFR‐mutant non‐small cell lung cancer

Author

Matsumoto, Yoshiya, primary, Sawa, Kenji, additional, Fukui, Mitsuru, additional, Oyanagi, Jun, additional, Izumi, Motohiro, additional, Ogawa, Koichi, additional, Suzumura, Tomohiro, additional, Watanabe, Tetsuya, additional, Kaneda, Hiroyasu, additional, Mitsuoka, Shigeki, additional, Asai, Kazuhisa, additional, Kimura, Tatsuo, additional, Yamamoto, Nobuyuki, additional, Koh, Yasuhiro, additional, and Kawaguchi, Tomoya, additional

Published
2019
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14. Efficacy and safety of ultrasound (US) guided percutaneous needle biopsy for peripheral lung or pleural lesion: comparison with computed tomography (CT) guided needle biopsy

Author

Yamamoto, Norio, primary, Watanabe, Tetsuya, additional, Yamada, Kazuhiro, additional, Nakai, Toshiyuki, additional, Suzumura, Tomohiro, additional, Sakagami, Kazuki, additional, Yoshimoto, Naoki, additional, Sato, Kanako, additional, Tanaka, Hidenori, additional, Mitsuoka, Shigeki, additional, Asai, Kazuhisa, additional, Kimura, Tatsuo, additional, Kanazawa, Hiroshi, additional, Hirata, Kazuto, additional, and Kawaguchi, Tomoya, additional

Published
2019
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15. The Macroscopic Appearance of Computed Tomography-guided Needle Biopsy Specimens Correlates with Tumor Metastasis in Non-small Cell Lung Cancer

Author

Nakai, Toshiyuki, Kimura, Tatsuo, Suzumura, Tomohiro, Yoshimoto, Naoki, Oka, Takako, Yamamoto, Norio, Matsuura, Kuniomi, Mitsuoka, Shigeki, Asai, Kazuhisa, Tochino, Yoshihiro, Yoshimura, Naruo, Kawaguchi, Tomoya, Kudoh, Shinzoh, Matsuoka, Toshiyuki, Ohsawa, Masahiko, and Hirata, Kazuto

Subjects
Non-small cell lung cancer, Computed tomography (CT)-guided needle biopsy, Tumor metastasis
Abstract

Background : Computed tomography (CT)-guided needle biopsy is a well-established and dependable procedure for the diagnosis of pulmonary lesions. Some tissue biopsy samples have loose cohesion and disintegrate into tiny pieces before formalin fixation. The purpose of this study was to assess the association between the fresh macroscopic appearance of samples obtained using CT-guided needle biopsy and the clinicopathological features of non-small cell lung cancer (NSCLC). / Methods : A total of 111 patients who underwent CT-guided lung needle biopsy at Osaka City University Hospital between May 2009 and May 2013 were enrolled. Macroscopic appearance was categorized as either loose or tight cohesion. Samples were evaluated using Azan staining to detect collagen fibers. The staining intensity was multiplied by the percentage of positive cells, and the specimen was categorized as having either low (

Published
2015

16. Abstract 2613: Predictive impact of low-frequency pretreatment T790M mutation in patients with EGFR-mutated non-small cell lung cancer treated with EGFR tyrosine kinase inhibitors

Author

Matsumoto, Yoshiya, primary, Sawa, Kenji, additional, Oyanagi, Jun, additional, Fukui, Mitsuru, additional, Yoshimoto, Naoki, additional, Suzumura, Tomohiro, additional, Mitsuoka, Shigeki, additional, Asai, Kazuhisa, additional, Kimura, Tatsuo, additional, Yamamoto, Nobuyuki, additional, Kawaguchi, Tomoya, additional, Hirata, Kazuto, additional, and Koh, Yasuhiro, additional

Published
2018
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17. Reaction of Plasma Adiponectin Level in Non-small Cell Lung Cancer Patients Treated with EGFR-TKIs

Author

Umekawa, Kanako, Kimura, Tatsuo, Kudoh, Shinzoh, Suzumura, Tomohiro, Nagata, Misato, Mitsuoka, Shigeki, Matsuura, Kuniomi, Oka, Takako, Yoshimura, Naruo, Kira, Yukimi, and Hirata, Kazuto

Subjects
Adipokines, Adiponectin, NSCLC, EGFR-TKIs, respiratory tract diseases
Abstract

Background : Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) are routinely used to treat advanced non-small cell lung cancer (NSCLC) patients with activated EGFR mutations, and are associated with excellent response and improvement of performance status. Adipose tissue produces and releases substances called adipokines, which include adiponectin, leptin, resistin, and hepatocyte growth factor (HGF), etc. Previously, we reported that high levels of plasma HGF at diagnosis indicated intrinsic resistance to EGFR-TKIs. EGFR-TKIs have been hypothesized to affect these adipokines. / Methods : This prospective study, to evaluate the correlation between plasma adiponectin and insulin levels and non-hematological adverse effects in advanced NSCLC following EGFR-TKIs administration, was conducted at the Osaka City University Hospital. Plasma adiponectin and insulin levels were determined at diagnosis and on treatment day 30....

Published
2013

18. Skeletal-related Events in Advanced Lung Adenocarcinoma Patients Evaluated EGFR Mutations

Author

Nagata, Misato, Kudoh, Shinzoh, Mitsuoka, Shigeki, Suzumura, Tomohiro, Umekawa, Kanako, Tanaka, Hidenori, Matsuura, Kuniomi, Kimura, Tatsuo, Yoshimura, Naruo, and Hirata, Kazuto

Subjects
Non-small cell lung cancer, Skeletal-related event, Bone metastasis, EGFR mutation, Adenocarcinoma, respiratory tract diseases
Abstract

Background : The rate of lung cancer metastasis to the bone is high and skeletal-related events (SREs) decrease the quality of life in many patients. Recently, it was found that a subgroup of patients with non-small cell lung cancer (NSCLC) have specific mutations in the EGFR (epidermal growth factor receptor) gene. We assessed the SREs in advanced lung adenocarcinoma patients that evaluated EGFR mutations in whom bone metastasis was present. / Methods : We retrospectively investigated the clinical records of 377 patients with advanced NSCLC. Patients were evaluated for the presence of EGFR mutations, bone metastases, the incidence of SREs, and treatment history before the first SRE....

Published
2013

19. Comparison of Adverse Events of Erlotinib with those of Gefitinib in Patients with Non-small Cell Lung Cancer : A Case-control Study in a Japanese Population

Author

Suzumura, Tomohiro, Kimura, Tatsuo, Kudoh, Shinzoh, Umekawa, Kanako, Nagata, Misato, Tanaka, Hidenori, Mitsuoka, Shigeki, Yoshimura, Naruo, Kira, Yukimi, and Hirata, Kazuto

Subjects
Non-small cell lung cancer, Erlotinib, Adverse events, heterocyclic compounds, Gefitinib, skin and connective tissue diseases, neoplasms, respiratory tract diseases
Abstract

Background : Rash, liver dysfunction, and diarrhea are known as adverse events of erlotinib and gefitinib. However, clinical trials with gefitinib have reported different adverse events compared to those with erlotinib. In an in vitro study, cytochrome P450 (CYP) 2D6 was shown to be involved in the metabolism of gefitinib and not of erlotinib. It has been hypothesized that gefitinib therapy results in different adverse events compared to erlotinib therapy. / Methods : The frequency of each adverse event was evaluated in a case-control study on Japanese patients who were treated with gefitinib or erlotinib. The CYP2D6 phenotype was categorized into 2 groups according to functional or reduced metabolic levels. In addition, we evaluated the odds ratio (OR) of adverse events with each factor, including CYP2D6 activities as well as treatment types....

Published
2012

20. Clinical Outcome of Amrubicin Therapy According to the Prior Chemotherapy Sensitivities of Extensive Small Cell Lung Cancer

Author

Mitsuoka, Shigeki, Kudoh, Shinzoh, Kimura, Tatsuo, Yoshimura, Naruo, Tanaka, Hidenori, Suzumura, Tomohiro, Umekawa, Kanako, Nagata, Misato, Ueda, Takako, and Hirata, Kazuto

Subjects
Refractory, 肺がん, Lung cancer, Second-line chemotherapy, Amrubicin, Topoisomerase II inhibitor
Abstract

Background : Amrubicin (AMR) is an active agent for relapsed small cell lung cancer (SCLC). However, the activity of AMR in refractory relapsed patients is controversial. The objective of this retrospective analysis was to evaluate the efficacy and safety of AMR as second-line chemotherapy in SCLC, especially refractory relapsed SCLC. / Methods : Between July 2003 and February 2009, a total of 27 patients were treated with AMR at a dosage of 40 mg・m^-2・day^-1 on days 1-3 every 3 weeks. Safety was assessable for all patients. Efficacy was evaluated in 26 patients (one patient was not assessable for response), in 12 patients with chemotherapy-sensitive relapse and 14 patients with chemotherapy-refractory relapse. Sensitive relapse means that a first-line response lasted more than 90 days. Refractory relapse means that either did not respond to first-line chemotherapy or responded initially but relapsed within 90 days....

Published
2011

21. Interstitial Lung Disease Induced by Osimertinib for Epidermal Growth Factor Receptor (EGFR) T790M-positive Non-small Cell Lung Cancer

Author

Matsumoto, Yoshiya, primary, Kawaguchi, Tomoya, additional, Yamamoto, Norio, additional, Sawa, Kenji, additional, Yoshimoto, Naoki, additional, Suzumura, Tomohiro, additional, Watanabe, Tetsuya, additional, Mitsuoka, Shigeki, additional, Asai, Kazuhisa, additional, Kimura, Tatsuo, additional, Yoshimura, Naruo, additional, Kuwae, Yuko, additional, and Hirata, Kazuto, additional

Published
2017
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22. Impact of tumor microenvironment on the efficacy of epidermal growth factor receptor‐tyrosine kinase inhibitors in patients with EGFR‐mutant non‐small cell lung cancer.

Author

Matsumoto, Yoshiya, Sawa, Kenji, Fukui, Mitsuru, Oyanagi, Jun, Izumi, Motohiro, Ogawa, Koichi, Suzumura, Tomohiro, Watanabe, Tetsuya, Kaneda, Hiroyasu, Mitsuoka, Shigeki, Asai, Kazuhisa, Kimura, Tatsuo, Yamamoto, Nobuyuki, Koh, Yasuhiro, and Kawaguchi, Tomoya

Abstract

We retrospectively investigated the impact of the tumor microenvironment (TME) on the efficacy of epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors (TKIs) as first‐line treatment in 70 patients with advanced EGFR‐mutant non‐small cell lung cancer and who were seen at Osaka City University Hospital (Osaka, Japan) between August 2013 and December 2017. Using immunohistochemical staining with 28‐8 and D7U8C Abs, the tumor proportion score was assessed for programmed cell death‐1 ligand‐1 (PD‐L1), as high (50% or more) or low (less than 50%), and ligand‐2 (PD‐L2) expression, respectively. The extent of CD8+ tumor‐infiltrating lymphocytes was evaluated on a scale of 0‐3, with 0‐1 as low and 2‐3 as high. The TME of the 52 evaluable pretreatment specimens was categorized into 4 subtypes, according to the respective PD‐L1 tumor proportion and CD8+ scores, as follows: (a) high/high (13.5%, n = 7); (b) low/low (42.3%, n = 22); (c) high/low (17.3%, n = 9); and (d) low/high (26.9%, n = 14). Expression of PD‐L2 was significantly the highest in type 1 (57.1% vs 4.5% vs 11.1% vs 7.1%, respectively; P = .0090). Response rate was significantly the lowest in type 1 (14.3% vs 81.8% vs 66.7% vs 78.6%, respectively; P = .0085). Progression‐free survival was the shortest in type 1 and the longest in type 4 (median, 2.4 vs 11.3 vs 8.4 vs 17.5 months, respectively; P = .00000077). The efficacy of EGFR‐TKIs differed according to the TME, and the phenotype with high PD‐L1 and CD8+ expression might be the subset that would poorly benefit from such treatment. [ABSTRACT FROM AUTHOR]

Published
2019
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23. Abdominal pain under immunosuppressive conditions

Author

Ota, Takayo, primary, Nakano, Masanobu, additional, Tanaka, Noriko, additional, Suzumura, Tomohiro, additional, Miyatake, Nozomi, additional, Hasegawa, Yoshikazu, additional, Ozaki, Tomohiro, additional, Tsukuda, Hiroshi, additional, and Fukuoka, Masahiro, additional

Published
2016
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30. Magnesium supplementation and high volume hydration reduce the renal toxicity caused by cisplatin-based chemotherapy in patients with lung cancer: a toxicity study

Author

Oka, Takako, primary, Kimura, Tatsuo, additional, Suzumura, Tomohiro, additional, Yoshimoto, Naoki, additional, Nakai, Toshiyuki, additional, Yamamoto, Norio, additional, Matsuura, Kuniomi, additional, Mitsuoka, Shigeki, additional, Yoshimura, Naruo, additional, Kudoh, Shinzoh, additional, and Hirata, Kazuto, additional

Published
2014
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31. Striving for Palliative Care From the Early Stage of Cancer Therapy

Author

Hasegawa, Yoshikazu, primary, Tsukuda, Hiroshi, additional, Otsuka, Masatomo, additional, Yonesaka, Kimio, additional, Suzumura, Tomohiro, additional, Sugiura, Takamune, additional, Iwaya, Rikako, additional, Kawaguchi, Izumi, additional, Tanaka, Tomi, additional, and Fukuoka, Masahiro, additional

Published
2014
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33. Plasma RANTES, IL-10, and IL-8 levels in non–small-cell lung cancer patients treated with EGFR-TKIs

Author

Umekawa, Kanako, primary, Kimura, Tatsuo, additional, Kudoh, Shinzoh, additional, Suzumura, Tomohiro, additional, Oka, Takako, additional, Nagata, Misato, additional, Mitsuoka, Shigeki, additional, Matsuura, Kuniomi, additional, Nakai, Toshiyuki, additional, Yoshimura, Naruo, additional, Kira, Yukimi, additional, and Hirata, Kazuto, additional

Published
2013
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34. C609T polymorphism of NADPH Quinone Oxidoreductase 1 Correlates Clinical Hematological Toxicities in Lung Cancer Patients Treated with Amrubicin

Author

Nagata, Misato, primary, Kimura, Tatsuo, additional, Suzumura, Tomohiro, additional, Kira, Yukimi, additional, Nakai, Toshiyuki, additional, Umekawa, Kanako, additional, Tanaka, Hidenori, additional, Matsuura, Kuniomi, additional, Mitsuoka, Shigeki, additional, Yoshimura, Naruo, additional, Oka, Takako, additional, Kudoh, Shinzoh, additional, and Hirata, Kazuto, additional

Published
2013
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37. Erlotinib is a well-tolerated alternate treatment for non-small cell lung cancer in cases of gefitinib-induced hepatotoxicity.

Author

Yonesaka K, Suzumura T, Tsukuda H, Hasegawa Y, Ozaki T, Sugiura T, and Fukuoka M

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Agents administration & dosage, Antineoplastic Agents adverse effects, Carcinoma, Non-Small-Cell Lung complications, Carcinoma, Non-Small-Cell Lung pathology, Chemical and Drug Induced Liver Injury, Drug Substitution, Erlotinib Hydrochloride, Female, Gefitinib, Humans, Lung Neoplasms complications, Lung Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Protein Kinase Inhibitors administration & dosage, Protein Kinase Inhibitors adverse effects, Quinazolines administration & dosage, Quinazolines adverse effects, Treatment Outcome, Antineoplastic Agents therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Lung Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use, Quinazolines therapeutic use
Abstract

Aim: To evaluate the tolerability and efficacy of erlotinib treatment in advanced non-small cell lung cancer (NSCLC) patients who had previously experienced severe hepatotoxicity after gefitinib treatment., Patients and Methods: Twenty-five NSCLC patients with epidermal growth factor receptor (EGFR) mutation were initially treated with gefitinib (250 mg/day). However, 7 of these experienced severe hepatotoxicity. After recovery from hepatotoxicity, treatment was switched to erlotinib (150 mg/day) in all 7 patients. Toxicity and efficacy of erlotinib were analyzed., Results: None of the 7 patients reported severe hepatotoxicity with erlotinib despite gefitinib-induced severe hepatotoxicity. All patients achieved response with gefitinib or following erlotinib treatment. The response achieved with gefitinib was maintained after switching to erlotinib. Therefore, an excellent median progression-free survival of 372 days was achieved although gefitinib induced severe hepatotoxicity., Conclusion: Erlotinib treatment was efficient and well-tolerated in NSCLC patients with EGFR mutation, despite their severe hepatotoxicity with prior gefitinib treatment., (Copyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Published
2014

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