161 results on '"Akihiro Tamiya"'
Search Results
2. The Impact of Estrogen Receptor Expression on Mutational Status in the Evolution of Non-Small Cell Lung Cancer
- Author
-
Yoko Tani, Hiroyasu Kaneda, Yasuhiro Koh, Akihiro Tamiya, Shunichi Isa, Akihito Kubo, Koichi Ogawa, Yoshiya Matsumoto, Kenji Sawa, Naoki Yoshimoto, Shigeki Mitsuoka, and Tomoya Kawaguchi
- Subjects
Pulmonary and Respiratory Medicine ,Cancer Research ,Oncology - Published
- 2023
3. Bevacizumab Plus Carboplatin Plus Nab-paclitaxel for Non-squamous Non-small Cell Lung Cancer in a Real-world Setting
- Author
-
AKIHIRO TAMIYA, MOTOHIRO TAMIYA, YUJI INAGAKI, YOSHIHIKO TANIGUCHI, KEIKO NAKAO, YOSHINOBU MATSUDA, TAKAHISA KAWAMURA, KEI KUNIMASA, TAKAKO INOUE, KAZUMI NISHINO, and KYOICHI OKISHIO
- Subjects
Cancer Research ,Oncology ,General Medicine - Published
- 2023
4. Cerebral infarction after treatment with dabrafenib plus trametinib for <scp>BRAF‐V600E</scp> ‐positive non–small cell lung cancer: A case report
- Author
-
Yoshihiko Taniguchi, Akihiro Tamiya, Atsushi Yanagisawa, Minako Shimaya, Mayu Kawakami, Yuji Inagaki, Nobuhiko Saijo, Yoshinobu Matsuda, and Kyoichi Okishio
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,General Medicine - Published
- 2023
5. Right‐sided vocal cord paralysis following stereotactic body radiation therapy for non–small‐cell lung cancer: A case report
- Author
-
Kensuke Kanaoka, Shoich Fukuda, Yuji Inagaki, Yoshihiko Taniguchi, Keiko Nakao, Akihiro Tamiya, Yoshinobu Matsuda, and Kyoichi Okishio
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,General Medicine - Published
- 2023
6. Supplementary Figures S1-8 from Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non–Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR
- Author
-
Yasuhiro Koh, Akihide Matsumura, Kazuhiro Sakamoto, Yukiyasu Takeuchi, Yukito Ichinose, Kazuhiko Kataoka, Motohiro Yamashita, Seiichi Kakegawa, Tsutomu Tagawa, Hirofumi Adachi, Sadanori Takeo, Hideo Saka, Akihito Kubo, Akihiro Tamiya, Masahiko Ando, Shun-ichi Isa, Tomoya Kawaguchi, and Masaru Watanabe
- Abstract
Supplementary Figures S1-8. Figure S1: Flowchart for mutation call. Figure S2: Quantification of performance of ddPCR analysis for EGFR T790M mutation. Figure S3: Analytical sensitivity of 0.001% for the ddPCR assay. Figure S4: Determination of false-positive events from wild-type control DNA and normal human genomic DNA. Figure S5: Determination of false-positive events in genomic DNA from formalin-fixed paraffin-embedded (FFPE) A549 cells. Figure S6: Detection of EGFR T790M mutant alleles in patients with EGFR T790M-containing primary tumors. Figure S7: Comparison of T790M mutation detection in 6 samples by different operators. Figure S8: Reproducibility of ddPCR analysis from 16 T790M-positive samples.
- Published
- 2023
7. Data from Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non–Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR
- Author
-
Yasuhiro Koh, Akihide Matsumura, Kazuhiro Sakamoto, Yukiyasu Takeuchi, Yukito Ichinose, Kazuhiko Kataoka, Motohiro Yamashita, Seiichi Kakegawa, Tsutomu Tagawa, Hirofumi Adachi, Sadanori Takeo, Hideo Saka, Akihito Kubo, Akihiro Tamiya, Masahiko Ando, Shun-ichi Isa, Tomoya Kawaguchi, and Masaru Watanabe
- Abstract
Purpose: The resistance to the EGFR tyrosine kinase inhibitors (TKI) is a major concern in non–small cell lung cancer (NSCLC) treatment. T790M mutation in EGFR accounts for nearly 50% of the acquired resistance to EGFR-TKIs. Earlier studies suggested that T790M mutation was also detected in TKI-naïve NSCLCs in a small cohort. Here, we use an ultra-sensitive droplet digital PCR (ddPCR) technique to address the incidence and clinical significance of pretreatment T790M in a larger cohort.Experimental Design: ddPCR was established as follows: wild-type or T790M mutation-containing DNA fragments were cloned into plasmids. Candidate threshold was identified using wild-type plasmid, normal human genomic DNA, and human A549 cell line DNA, which expresses wild type. Surgically resected tumor tissues from 373 NSCLC patients with EGFR-activating mutations were then examined for the presence of T790M using ddPCR.Results: Our data revealed a linear performance for this ddPCR method (R2 = 0.998) with an analytical sensitivity of approximately 0.001%. The overall incidence of the pretreatment T790M mutation was 79.9% (298/373), and the frequency ranged from 0.009% to 26.9%. The T790M mutation was detected more frequently in patients with a larger tumor size (P = 0.019) and those with common EGFR-activating mutations (P = 0.022), as compared with the others.Conclusions: The ultra-sensitive ddPCR assay revealed that pretreatment T790M was found in the majority of NSCLC patients with EGFR-activating mutations. ddPCR should be utilized for detailed assessment of the impact of the low frequency pretreatment T790M mutation on treatment with EGFR-TKIs. Clin Cancer Res; 21(15); 3552–60. ©2015 AACR.
- Published
- 2023
8. Supplemental Materials from Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non–Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR
- Author
-
Yasuhiro Koh, Akihide Matsumura, Kazuhiro Sakamoto, Yukiyasu Takeuchi, Yukito Ichinose, Kazuhiko Kataoka, Motohiro Yamashita, Seiichi Kakegawa, Tsutomu Tagawa, Hirofumi Adachi, Sadanori Takeo, Hideo Saka, Akihito Kubo, Akihiro Tamiya, Masahiko Ando, Shun-ichi Isa, Tomoya Kawaguchi, and Masaru Watanabe
- Abstract
Supplementary Materials and Methods, Reference and Supplementary Figure Legends
- Published
- 2023
9. Supplementary Tables S1-5 from Ultra-Sensitive Detection of the Pretreatment EGFR T790M Mutation in Non–Small Cell Lung Cancer Patients with an EGFR-Activating Mutation Using Droplet Digital PCR
- Author
-
Yasuhiro Koh, Akihide Matsumura, Kazuhiro Sakamoto, Yukiyasu Takeuchi, Yukito Ichinose, Kazuhiko Kataoka, Motohiro Yamashita, Seiichi Kakegawa, Tsutomu Tagawa, Hirofumi Adachi, Sadanori Takeo, Hideo Saka, Akihito Kubo, Akihiro Tamiya, Masahiko Ando, Shun-ichi Isa, Tomoya Kawaguchi, and Masaru Watanabe
- Abstract
Supplementary Tables S1-5. Table S1: Primers and probes used for droplet digital PCR (ddPCR). Table S2: Determination of the limit of blank (LOB) from wild-type control DNA, normal human genomic DNA, and EGFR wild-type A549 genomic DNA. Table S3: Determination of the limit of blank (LOB) using genomic DNA from adjacent normal tissue samples of EGFR-activating mutation positive adenocarcinoma and EGFR wild-type squamous cell carcinoma. Table S4: Concordance between ddPCR and deep sequencing of EGFR T790M mutation. Table S5: Distribution of amplifiable DNA concentrations in the 377 analyzed samples.
- Published
- 2023
10. Pneumonitis associated with pembrolizumab plus chemotherapy for non-squamous non-small cell lung cancer
- Author
-
Daichi Fujimoto, Satoru Miura, Keisuke Tomii, Hiromitsu Sumikawa, Kenichi Yoshimura, Kazushige Wakuda, Yuko Oya, Toshihide Yokoyama, Takashi Kijima, Tetsuhiko Asao, Motohiro Tamiya, Atsushi Nakamura, Hiroshige Yoshioka, Takaaki Tokito, Shuji Murakami, Akihiro Tamiya, Hiroshi Yokouchi, Satoshi Watanabe, Ou Yamaguchi, Ryotaro Morinaga, Takayuki Jodai, Kentaro Ito, Yoshimasa Shiraishi, Yoshihito Kogure, Ryota Shibaki, and Nobuyuki Yamamoto
- Subjects
Multidisciplinary - Abstract
Studies elucidating detailed characteristics of pneumonitis in association with chemo-immunotherapy are limited. We aimed to investigate the characteristics of images, prognostic factors, and clinical course of combination therapy associated with pneumonitis. A multicenter, retrospective cohort study of patients with non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed, and pembrolizumab was conducted. Patients with confirmed pneumonitis established by an independent multidisciplinary team were enrolled. For 53 patients with pneumonitis, radiographic features at diagnosis predominantly comprised an organizing pneumonia pattern (62%, 33/53). Twelve (23%) patients experienced a worsening respiratory status during pneumonitis management, which was associated with a high mortality rate (58%, 7/12) during treatment. Severe grade at pneumonitis diagnosis (p p = 0.002), and disease extent ≥ 25% in the lungs (p = 0.009) were significantly associated with worsening respiratory status. Furthermore, post-diagnosis survival was significantly worse in severe pneumonitis (p = 0.02) than in mild and in patients with the DAD pattern than in those without (p
- Published
- 2023
11. Immune checkpoint inhibitor-related pneumonitis in lung cancer patients with interstitial lung disease: Significance of radiological pleuroparenchymal fibroelastosis
- Author
-
Megumu Osaki, Toru Arai, Hiromitsu Sumikawa, Takayuki Takimoto, Naoko Takeuchi, Akihiro Tamiya, Kyoichi Okishio, and Yoshikazu Inoue
- Subjects
Cancer Research ,Oncology ,General Medicine - Abstract
Introduction Pleuroparenchymal fibroelastosis (PPFE) findings are associated with poor prognosis in interstitial lung disease (ILD). However, the effect of PPFE findings on the development of immune checkpoint inhibitor-related pneumonitis (ICI-pneumonitis), a life-threatening adverse event, in lung cancer patients with ILD has not been elucidated. We aimed to determine whether PPFE findings are a risk factor for ICI-pneumonitis in lung cancer patients with ILD. Methods We retrospectively examined 712 lung cancer patients, including 173 patients with background ILDs who received ICI therapy in our institute between December 2015 and May 2021. Background ILDs were radiologically classified into three types: lone PPFE, other ILDs with PPFE, and other ILDs without PPFE. The cumulative ICI-pneumonitis incidence curves and median overall survival (mOS) were compared between the three radiological types, and risk factors for ICI-pneumonitis were evaluated. Results Of 173 eligible patients with ILD, 23 patients (13.3%) experienced ICI-pneumonitis. The Kaplan–Meier method and the log-rank test showed that lone PPFE patients had significantly lower incidence of ICI-pneumonitis (p = 0.024) and longer mOS (575 versus 326 days; p = 0.0096) than other ILDs patients. ICI-pneumonitis (p = 0.35) and mOS (p = 0.29) were not significantly different between other ILDs with and without PPFE. A multivariate Cox proportional hazards regression analysis revealed that lone PPFE pattern was an independent predictive factor for ICI-pneumonitis (hazard ratio, 0.20; 95% confidence interval, 0.043 to 0.93; p = 0.040). Conclusion ICI therapy could be safer in lone PPFE patients than in other ILDs patients with lung cancer.
- Published
- 2023
12. Retrospective analysis of long‐term survival factors in patients with advanced non‐small cell lung cancer treated with nivolumab
- Author
-
Yusuke Murakami, Akihiro Tamiya, Yoshihiko Taniguchi, Yuichi Adachi, Takatoshi Enomoto, Koji Azuma, Yuji Inagaki, Shunichi Kouno, Yoshinobu Matsuda, Kyoichi Okishio, and Shinji Atagi
- Subjects
non‐small cell lung cancer ,Pulmonary and Respiratory Medicine ,Lung Neoplasms ,long‐term survivors ,overall survival ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,General Medicine ,neutrophil‐to‐lymphocyte ratio ,Prognosis ,Nivolumab ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Humans ,RC254-282 ,Retrospective Studies - Abstract
Background Nivolumab, an immune checkpoint inhibitor (ICI), has changed the treatment paradigm for advanced non‐small cell lung cancer (NSCLC). However, factors associated with long‐term survival in NSCLC patients treated with ICIs remain unknown. This study aimed to evaluate patient characteristics and clinical laboratory changes related to long‐term survival in NSCLC patients treated with nivolumab, using real‐world data. Methods We retrospectively reviewed the medical records of consecutive patients with advanced NSCLC with Eastern Cooperative Oncology Group performance status (ECOG‐PS) ≤1 treated with nivolumab. We defined patients with overall survival (OS) ≥3 years as long‐term survivors. We evaluated the differences in patient characteristics and tumor response between nonlong‐term survivors and long‐term survivors and performed univariate and multivariate analyses of factors associated with long‐term survival. Results Out of 213 patients with advanced NSCLC treated with nivolumab, 162 patients with ECOG‐PS ≤1 were included in the study. Young age, ECOG‐PS 0, absolute neutrophil count decrease, lymphocyte percentage increase, and neutrophil‐to‐lymphocyte ratio (NLR) change (ΔNLR)
- Published
- 2022
13. Clinical characteristics of COVID-19 in Osaka, Japan: Comparison of the first–third waves with the fourth wave
- Author
-
Sayoko Shintani, Kazunobu Tachibana, Akihiro Tamiya, Yoshinobu Matsuda, Kyoichi Okishio, Reiko Sugawara, Yu Kurahara, Kazunari Tsuyuguchi, Takehiko Kobayashi, Toru Arai, and Hideo Matsui
- Subjects
Comorbidity ,AST, aspartate aminotransferase ,Severity of Illness Index ,Pulmonary Disease, Chronic Obstructive ,Japan ,Risk Factors ,Interquartile range ,Fourth wave ,COVID-19, coronavirus disease 2019 ,Aged, 80 and over ,LDH, lactate dehydrogenase ,Mortality rate ,Middle Aged ,ICU, intensive care unit ,KL-6, Krebs von den Lungen-6 ,Hypertension ,Cohort ,CRP, C-reactive protein ,Original Article ,WBC, white blood cell ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,macromolecular substances ,SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 ,ALT, alanine aminotransferase ,Diabetes mellitus ,Internal medicine ,Severity of illness ,Diabetes Mellitus ,medicine ,Humans ,Pandemics ,IQR, interquartile range ,Aged ,Retrospective Studies ,Asthma ,Infection Control ,Clinical characteristics ,VOC, variant of concern ,SARS-CoV-2 ,business.industry ,COVID-19 ,Retrospective cohort study ,medicine.disease ,CI, confidence interval ,OR, odds ratio ,COPD, chronic obstructive pulmonary disease ,Medical crisis ,Osaka ,business - Abstract
Background The fourth wave of COVID-19 in Osaka Prefecture, Japan, caused a medical crisis. Here, we aim to identify the risk factors for COVID-19 severity and compare patients between the first–third waves and the fourth wave. Methods We performed an observational retrospective study of COVID-19 cases at the National Hospital Organization Kinki-Chuo Chest Medical Center. Results We identified 404 patients (median age: 71.0 years [interquartile range: 56.0–80.0]), of whom 199 (49.1%) had mild disease, 142 (35.2%) had moderate disease, and 63 (15.6%) had severe disease. The overall mortality rate was 5.4% (22/404). Based on multivariate logistic regression analysis, cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were independent risk factors for moderate to severe disease. For every 1 mg/dL increase in C-reactive protein, 10 IU/L increase in lactate dehydrogenase, and 100 ng/mL increase in ferritin, the risk for moderate to severe disease increased by 18.3%, 12.9%, and 8.9%, respectively. Overall disease severity in the fourth wave was higher than in the first–third waves. However, there was no significant difference in mortality. Because of a shortage of beds, four of the 28 severe patients (14.3%) in the fourth wave could not be transferred to the advanced hospital. Conclusions Cardiovascular disease, fever, dyspnea, and several inflammatory biomarkers were risk factors for moderate to severe COVID-19 in our cohort. During the fourth wave, COVID-19 severity worsened, increasing the number of patients who could not be transferred to beds for severe cases, resulting in a medical crisis in Osaka.
- Published
- 2021
14. Differential properties of KRAS transversion and transition mutations in non-small cell lung cancer: associations with environmental factors and clinical outcomes
- Author
-
Koichi, Sato, Hiroaki, Akamatsu, Yasuhiro, Koh, Koichi, Ogawa, Shun-Ichi, Isa, Masahiko, Ando, Akihiro, Tamiya, Akihito, Kubo, Chiyoe, Kitagawa, Tomoya, Kawaguchi, and Nobuyuki, Yamamoto
- Subjects
Proto-Oncogene Proteins p21(ras) ,Cohort Studies ,Cancer Research ,Lung Neoplasms ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Proto-Oncogene Proteins ,Mutation ,ras Proteins ,Genetics ,Humans ,Prospective Studies - Abstract
Background KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23–35% and 13–20% of all NSCLCs in white patients and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations and transition mutations, as well as their association with environmental factors and clinical outcome. Methods Dataset from the Japan Molecular Epidemiology Study, which is a prospective, multicenter, and molecular study epidemiology cohort study involving 957 NSCLC patients who underwent surgery, was used for this study. Questionnaire-based detailed information on clinical background and lifestyles was also used to assess their association with mutational subtypes. Somatic mutations in 72 cancer-related genes were analyzed by next-generation sequencing, and KRAS mutations were classified into three categories: transversions (G > C or G > T; G12A, G12C, G12R, G12V), transitions (G > A; G12D, G12S, G13D), and wild-type (WT). Clinical correlations between these subtypes have been investigated, and recurrence-free survival (RFS) and overall survival (OS) were evaluated. Results Of the 957 patients, KRAS mutations were detected in 80 (8.4%). Of these, 61 were transversions and 19 were transitions mutations. Both pack-years of smoking and smoking duration had significant positive correlation with the occurrence of transversion mutations (p = 0.03 and p = 0.01). Patients with KRAS transitions had the shortest RFS and OS compared to KRAS transversions and WT. Multivariate analysis revealed that KRAS transitions, along with age and stage, were significant predictors of shorter RFS and OS (HR 2.15, p = 0.01; and HR 2.84, p Conclusions Smoking exposure positively correlated with transversions occurrence in a dose-dependent manner. However, vegetable intake negatively correlated with transitions. Overall, KRAS transition mutations are significantly poor prognostic factors among resected NSCLC patients.
- Published
- 2022
15. Impact of prior immune checkpoint inhibitor and its tumor response on ramucirumab and docetaxel for advanced non-small cell lung cancer: a multicenter retrospective cohort study
- Author
-
Satoshi Tanizaki, Kinnosuke Matsumoto, Akihiro Tamiya, Yoshihiko Taniguchi, Yoshinobu Matsuda, Junji Uchida, Kiyonobu Ueno, Hayato Kawachi, Motohiro Tamiya, Takafumi Yanase, Hidekazu Suzuki, and Kyoichi Okishio
- Abstract
Purpose Ramucirumab (RAM) and docetaxel (DOC) are commonly used after first-line therapy including immune checkpoint inhibitor (ICI) for advanced non-small cell lung cancer (NSCLC). Therefore, it is important to evaluate sequential strategies of RAM and DOC following various type of treatments; however, those remain unknown. We aimed to elucidate the impact of front-line treatments including ICI, cytotoxic agent (CTx), bevacizumab (BEV), and tyrosine kinase inhibitor (TKI) on RAM and DOC efficacy. Methods We recruited patients with NSCLC who received RAM and DOC and compared the groups with and without prior ICI, CTx, BEV, and TKI, respectively. By tumor response to such treatments, the patients were further classified into “complete response (CR) + partial response (PR),” “stable disease.” and “progressive disease”groups, respectively. We compared RAM and DOC efficacy among these groups. Results 237 patients were registered. In the group with prior ICI, the objective response rate and disease control rate were significantly higher than those without prior ICI (p = 0.012 and 0.028, respectively), and the median progression-free survival (PFS) was also significantly longer (p = 0.027). There were no significant differences in PFS between the groups with and without CTx, BEV, and TKI. Multivariate analysis revealed that prior ICI was an independent factor associated with better PFS. Futheremore, the prior ICI group showing CR + PR significantly prolonged PFS compared to the group without prior ICI (p = 0.013). Conclusion RAM and DOC efficacy may be enhanced when ICIs are administered in the prior line and especially show good tumor response.
- Published
- 2022
16. A Retrospective, Multicenter, Observational Study to Evaluate Clinical Outcomes of Lorlatinib After Alectinib in Patients With ALK-Positive NSCLC in Japan
- Author
-
Yasushi Goto, Hirotsugu Kenmotsu, Motohiro Tamiya, Shuji Murakami, Takayasu Kurata, Noriko Yanagitani, Hirokazu Taniguchi, Shoichi Kuyama, Junichi Shimizu, Toshihide Yokoyama, Naoko Shimada, Tadashi Maeda, Akihiro Tamiya, Ayumi Uchiyama, Kazuyoshi Imaizumi, Takayuki Takahama, Terufumi Kato, Hidetoshi Hayashi, Naoko Shiraiwa, Shigeyuki Toyoizumi, Hironori Kikkawa, Despina Thomaidou, and Makoto Nishio
- Subjects
Pulmonary and Respiratory Medicine ,Oncology - Published
- 2023
17. Pembrolizumab plus chemotherapy-induced pneumonitis in chemo-naïve patients with non-squamous non-small cell lung cancer: A multicentre, retrospective cohort study
- Author
-
Toshihide Yokoyama, Takashi Yokoi, Satoru Miura, Shunsuke Teraoka, Shuji Murakami, Kazushige Wakuda, Yuko Oya, Motohiro Tamiya, Atsushi Nakamura, Takaaki Tokito, Keisuke Tomii, Kenichi Yoshimura, O. Yamaguchi, Nobuyuki Yamamoto, Satoshi Watanabe, Hiroshige Yoshioka, Tetsuhiko Asao, Shoichi Itoh, D. Fujimoto, Akihiro Tamiya, Hiroshi Yokouchi, and Koji Haratani
- Subjects
Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Time Factors ,Combination therapy ,Population ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Risk Assessment ,Gastroenterology ,03 medical and health sciences ,0302 clinical medicine ,Japan ,Risk Factors ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,education ,Lung cancer ,Immune Checkpoint Inhibitors ,Survival analysis ,Aged ,Retrospective Studies ,Pneumonitis ,education.field_of_study ,business.industry ,Incidence ,Retrospective cohort study ,Pneumonia ,Middle Aged ,medicine.disease ,Progression-Free Survival ,Treatment Outcome ,030104 developmental biology ,Pemetrexed ,Oncology ,030220 oncology & carcinogenesis ,Female ,business ,medicine.drug - Abstract
Introduction Despite the extensive use of the combination of cytotoxic chemotherapy and programmed cell death protein 1/programmed death-ligand 1 checkpoint inhibitors for cancer treatment, the incidence and characteristics of pneumonitis caused by this combination therapy have not been examined in clinical settings. Methods We conducted a 36-centre, retrospective cohort study in patients with chemo-naive advanced non-squamous non-small cell lung cancer who received a combination of platinum, pemetrexed and pembrolizumab between December 2018 and June 2019. Results The study comprised 299 patients. The most frequent grade ≥3 non-hematologic adverse event was pneumonitis. There were 37 patients (12.4%, 95% CI 8.9–16.7) with all-grade pneumonitis and 10 (3.3%, 95% CI 1.6–6.1) with grade ≥3 pneumonitis. Of these, 21 (7.0%, 95% CI 4.4–10.5) and 9 patients (3.0%, 95% CI 1.4–5.6) developed all-grade and grade ≥3 pneumonitis within 90 days after initiating the combination therapy, respectively. The median time to treatment failure and progression-free survival was 5.9 (95% CI 5.0–6.8) and 7.5 (95% CI 6.5–8.7) months, respectively. In the survival analysis after adjusting for immortal time bias, pneumonitis was independently associated with shorter progression-free survival (HR 1.99, 95% CI 1.07–3.69, P = 0.03) and overall survival (HR 3.03, 95% CI 1.12–8.20, P = 0.03). Conclusions Treatment-related pneumonitis occurred at a higher rate in the real-world population than that reported previously; it led to worse survival outcomes. Pneumonitis requires more attention. Additional studies are required to improve the safety of this combination therapy. Trial registration number UMIN000038084
- Published
- 2021
18. Prospective Observational Study of Treatment Resistance-related Gene Screening Using Plasma Circulating Tumor DNA in Third-generation EGFR-TKI Osimertinib Therapy (Elucidator)
- Author
-
Masahiko Ando, Yasuhiro Koh, Akihiro Tamiya, Shun-ichi Isa, Shinji Atagi, Yoshihiko Taniguchi, and Hideyuki Nakagawa
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Circulating Tumor DNA ,Cohort Studies ,03 medical and health sciences ,Egfr tki ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Osimertinib ,Prospective Studies ,Epidermal growth factor receptor ,Related gene ,Lung cancer ,Protein Kinase Inhibitors ,Acrylamides ,Aniline Compounds ,biology ,business.industry ,medicine.disease ,Third generation ,ErbB Receptors ,030104 developmental biology ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Observational study ,business - Abstract
Background Osimertinib is a third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) that potently and selectively inhibits EGFR activating and EGFR T790M resistance mutations. Osimertinib was found to be more effective than first-generation EGFR-TKIs in patients with previously untreated advanced non–small-cell lung cancer (NSCLC) harboring EGFR-positive mutations in a prior phase III trial. Osimertinib is, therefore, one of the most important standard therapies for EGFR mutation-positive patients. However, there are few reports about osimertinib resistance mechanisms in first-line EGFR-TKI therapy. Understanding first-line osimertinib resistance mechanisms is essential for future therapeutic strategies in patients with NSCLC with EGFR-positive mutations. To clarify the resistance mechanisms of first-line osimertinib, we proposed to analyze circulating tumor (ct) deoxyribonucleic acid (DNA) by the ultra-sensitive next-generation sequencing method. Patients and Methods We aim to collect ctDNA samples from patients with the following key inclusion criteria: histologically or cytologically proven NSCLC, activating EGFR mutation-positive, planned treatment with first-line osimertinib, and written informed consent. Patients with comorbidities, who are deemed unsuitable for participation by an attending physician, would be excluded. We plan to enroll 180 cases and estimate a final analysis of 120 cases following registration and 2-year observation. ctDNA samples are collected at osimertinib treatment initiation, 3 and 12 months later, and disease progression. The key primary endpoint is to clarify the incidence and ratio of osimertinib resistance. The key secondary endpoint is to examine how the quantity of osimertinib resistance-associated mutations detected in ctDNA at treatment initiation influences disease progression.
- Published
- 2021
19. Impact of docetaxel plus ramucirumab on metastatic site in previously treated patients with non-small cell lung cancer: a multicenter retrospective study
- Author
-
Yoshihiko Taniguchi, Hidekazu Suzuki, Takafumi Yanase, Tomonori Hirashima, Akihiro Tamiya, Motohiro Tamiya, Satoshi Tanizaki, Kinnosuke Matsumoto, Kiyonobu Ueno, Hayato Kawachi, Junji Uchida, Yoshinobu Matsuda, and Shinji Atagi
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Performance status ,business.industry ,Hazard ratio ,medicine.disease ,Ramucirumab ,Metastasis ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,Docetaxel ,030220 oncology & carcinogenesis ,Internal medicine ,medicine ,Malignant pleural effusion ,Original Article ,Lung cancer ,business ,neoplasms ,medicine.drug ,Brain metastasis - Abstract
Background Docetaxel (DOC) plus ramucirumab (RAM) has been recommended as an optimal therapy for previously treated patients with non-small cell lung cancer (NSCLC). In a clinical setting, there are few reports about DOC plus RAM, therefore its effect on factors such as Eastern Cooperative Oncology Group (ECOG) performance status (PS) and metastatic sites is still unknown. Methods We recruited NSCLC patients who received DOC plus RAM in four medical facilities in Japan from June 2016 to March 2020. We retrospectively investigated the overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) of DOC plus RAM and conducted univariate and multivariate analyses using PFS as a dependent factor. Patients were followed up until June 30, 2020. Results A total of 237 patients were consecutively enrolled. For all patients, the ORR, DCR, and median PFS were 25.2%, 63.9%, and 4.5 months, respectively. The ORR and DCR for malignant pleural effusion (MPE), lung metastasis, and liver metastasis were 7.7% and 53.8%, 30.3% and 77.5%, and 48.6% and 71.4%, respectively. In the multivariate analysis, MPE, lung metastasis, and liver metastasis were not prognostic factors for poor PFS. However, ECOG-PS 2 or more [hazard ratio (HR): 1.66, 95% confidence interval (CI): 1.14-2.40, P=0.008] and brain metastasis (HR: 1.71, 95% CI: 1.23-2.37, P=0.001) were significant and independent factors associated with shorter PFS. Conclusions DOC plus RAM could be an optimal therapy for previous treated NSCLC patients with lung and liver metastasis, and furthermore, should be used carefully for patients with poor ECOG-PS or brain metastasis. Keywords Docetaxel and ramucirumab; non-small cell lung cancer (NSCLC); metastatic site; poor performance status.
- Published
- 2021
20. Prognostic impact of pretreatment T790M mutation on outcomes for patients with resected, EGFR-mutated, non-small cell lung cancer
- Author
-
Yoshiya, Matsumoto, Tomoya, Kawaguchi, Masaru, Watanabe, Shun-Ichi, Isa, Masahiko, Ando, Akihiro, Tamiya, Akihito, Kubo, Chiyoe, Kitagawa, Naoki, Yoshimoto, and Yasuhiro, Koh
- Subjects
ErbB Receptors ,Male ,Cancer Research ,Lung Neoplasms ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Genetics ,Humans ,Prognosis ,Protein Kinase Inhibitors ,Neoplasm Staging ,Retrospective Studies - Abstract
Background Many previous studies have demonstrated that minor-frequency pretreatment T790M mutation (preT790M) could be detected by ultrasensitive methods in a considerable number of treatment-naïve, epidermal growth factor receptor (EGFR)-mutated, non-small cell lung cancer (NSCLC) cases. However, the impact of preT790M in resected cases on prognosis remains unclear. Methods We previously reported that preT790M could be detected in 298 (79.9%) of 373 surgically resected, EGFR-mutated NSCLC patients. Therefore, we investigated the impact of preT790M on recurrence-free survival (RFS) and overall survival (OS) in this cohort by multivariate analysis. All patients were enrolled from July 2012 to December 2013, with follow-up until November 30, 2017. Results The median follow-up time was 48.6 months. Using a cutoff value of the median preT790M allele frequency, the high-preT790M group (n = 151) had significantly shorter RFS (hazard ratio [HR] = 1.51, 95% confidence interval [CI]: 1.01–2.25, P = 0.045) and a tendency for a shorter OS (HR = 1.87, 95% CI: 0.99–3.55, P = 0.055) than the low-preT790M group (n = 222). On multivariate analysis, higher preT790M was independently associated with shorter RFS (high vs low, HR = 1.56, 95% CI: 1.03–2.36, P = 0.035), irrespective of advanced stage, older age, and male sex, and was also associated with shorter OS (high vs low, HR = 2.16, 95% CI: 1.11–4.20, P = 0.024) irrespective of advanced stage, older age, EGFR mutation subtype, and history of adjuvant chemotherapy. Conclusions Minor-frequency, especially high-abundance of, preT790M was an independent factor associated with a poor prognosis in patients with surgically resected, EGFR-mutated NSCLC.
- Published
- 2022
21. Differential properties of KRAS transversion and transition mutations in non-small lung cancer: associations with environmental factors and clinical outcomes
- Author
-
Koichi Sato, Hiroaki Akamatsu, Yasuhiro Koh, Koichi Ogawa, Shun-ichi Isa, Masahiko Ando, Akihiro Tamiya, Akihito Kubo, Chiyoe Kitagawa, Tomoya Kawaguchi, and Nobuyuki Yamamoto
- Abstract
Background: KRAS-mutated non-small cell lung cancer (NSCLC) accounts for 23–35% and 13–20% of all NSCLCs in Caucasians and East Asians, respectively, and is therefore regarded as a major therapeutic target. However, its epidemiology and clinical characteristics have not been fully elucidated because of its wide variety of mutational subtypes. Here, we focused on two distinct base substitution types: transversion mutations (Tr) and transition mutations (Ts), as well as their association with environmental factors and clinical outcome. Methods: Dataset from the Japan Molecular Epidemiology Study, which is a prospective, multicenter, and molecular study epidemiology cohort study involving 957 NSCLC patients who underwent surgery, was used for this study. Questionnaire-based detailed information on clinical background and lifestyles was also used to assess their association with mutational subtypes. Somatic mutations in 72 cancer-related genes were analyzed by next-generation sequencing, and KRAS mutations were classified into three categories: Tr (G > C or G > T; G12A, G12C, G12R, G12V), Ts (G > A; G12D, G12S, G13D), and wild-type (WT). Clinical correlations between these subtypes have been investigated, and recurrence-free survival (RFS) and overall survival (OS) were evaluated. Results: Of the 957 patients, KRAS mutations were detected in 80 (8.4%). Of these, 61 were Tr and 19 were Ts mutations. Both pack-years of smoking and smoking duration had significant positive correlation with the occurrence of Tr (p = 0.03 and
- Published
- 2022
22. Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab‐paclitaxel for non‐squamous non‐small cell lung cancer with malignant pleural effusion
- Author
-
Tomonori Hirashima, Toru Kumagai, Kyoichi Okishio, Hidekazu Suzuki, Yoshihiko Taniguchi, Shojiro Minomo, Naoko Takeuchi, Norio Okamoto, Akihiro Tamiya, Yoshinobu Matsuda, Yujiro Naito, Shinji Atagi, Fumio Imamura, Keiko Nakao, Takayuki Shiroyama, Kanako Katayama, and Motohiro Tamiya
- Subjects
0301 basic medicine ,Oncology ,medicine.medical_specialty ,Bevacizumab ,medicine.medical_treatment ,Phases of clinical research ,Neutropenia ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Maintenance therapy ,Internal medicine ,medicine ,Malignant pleural effusion ,Pharmacology (medical) ,Lung cancer ,Pharmacology ,Chemotherapy ,business.industry ,medicine.disease ,Carboplatin ,030104 developmental biology ,chemistry ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Objectives Vascular endothelial growth factor plays an important role in the pathogenesis of malignant pleural effusion (MPE). We previously showed the efficacy of bevacizumab (Bev) plus carboplatin (CBDCA)/paclitaxel (PTX) in the treatment of non-small lung cell cancer (NSCLC) with MPE. However, the toxicities were a little severe, and the efficacy was not satisfied sufficiently. Therefore, we conducted a phase II study for NSCLC with MPE to evaluate the efficacy and safety of Bev plus CBDCA/nab-PTX, which is a new combination therapy. Methods Chemotherapy-naive non-squamous (SQ) NSCLC patients with MPE participated in the study. A single aspiration (not allowing chest tube drainage) was allowed before chemotherapy. Patients received a maximum of six cycles of Bev (15 mg/kg, day1) plus CBDCA (AUC 6, day1)/nab-PTX (100 mg/m2, day1, 8) every 3 weeks followed by Bev (15 mg/kg, day1) plus nab-PTX (100 mg/m2, day1, 8) every 3 weeks without disease progression or unacceptable severe toxicities. The primary endpoint was objective response rate (ORR). Results The study enrollment was ceased because of suspension of the registration period (as scheduled) after 12 of 20 planned patients were treated successfully between March 2014 and February 2018. The ORR was 58.3 % (95 % CI, 27.7–84.8 %), and the disease control rate was 100 % (95 % CI, 73.5–100 %). Eight patients received maintenance therapy. Median progression-free and overall survival times were 14.4 and 26.9 months, respectively. Most patients experienced hematological toxicities, including ≥ grade 3 neutropenia and anemia; none experienced severe bleeding events and grade 5 toxicities. Conclusion The combination of Bev plus CBDCA/nab-PTX, a novel combination, might have efficacy with acceptable toxicities in chemotherapy-naive non-SQ NSCLC patients with MPE. Trial Registration University Hospital Medical Information Network in Japan (UMIN) Clinical Trials Registry (No. UMIN000013329) registered on 4th March 2014.
- Published
- 2021
23. Mediastinal undifferentiated pleomorphic sarcoma with pleural effusion cytopathologically misdiagnosed as epithelial malignant pleural mesothelioma: An autopsy case report
- Author
-
Yoshihiko Taniguchi, Yuji Inagaki, Yukihiro Nakamura, Shinji Atagi, Akihiro Tamiya, Takahiko Kasai, Yoshinobu Matsuda, and Kinnosuke Matsumoto
- Subjects
0301 basic medicine ,Pulmonary and Respiratory Medicine ,Male ,Pathology ,medicine.medical_specialty ,Pleural effusion ,Case Report ,Case Reports ,lcsh:RC254-282 ,Undifferentiated Pleomorphic Sarcoma ,03 medical and health sciences ,0302 clinical medicine ,Biopsy ,medicine ,malignant pleural mesothelioma ,Humans ,Pathological ,Cell block ,medicine.diagnostic_test ,Pleural mesothelioma ,business.industry ,Soft tissue ,Mediastinum ,Sarcoma ,General Medicine ,respiratory system ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,cell block ,mediastinum ,respiratory tract diseases ,Pleural Effusion ,undifferentiated pleomorphic sarcoma ,030104 developmental biology ,medicine.anatomical_structure ,Oncology ,030220 oncology & carcinogenesis ,business - Abstract
Undifferentiated pleomorphic sarcoma (UPS) is a new disease in the World Health Organization's classification of tumors of soft tissue and bone published in 2013. Primary mediastinal UPS is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, which was initially misdiagnosed as epithelial malignant pleural mesothelioma (MPM). The cytopathological findings of the pleural effusion cell block often contribute to the diagnosis of various malignant tumors. However, these findings may lead to misdiagnosis of highly invasive mediastinal tumors such as UPS. A biopsy for primary mediastinal lesions should be performed because MPM rarely mimics mediastinal tumors with pleural effusion., Mediastinal undifferentiated pleomorphic sarcoma (UPS) is rare, especially with pleural effusion. Herein, we describe the pathological findings of pleural effusion followed by mediastinal UPS, cytopathologically mimicking epithelial malignant pleural mesothelioma.
- Published
- 2021
24. Durvalumab for patients with unresectable stage III non-small cell lung cancer and grade 1 radiation pneumonitis following concurrent chemoradiotherapy: a multicenter prospective cohort study
- Author
-
Akihiro Tamiya, Masaki Kanazu, Akito Hata, Takeya Sugimoto, Junji Uchida, Yuki Sato, Motohiro Tamiya, Shunichiro Iwasawa, Masaki Kokubo, Yasushi Fukuda, Katsuya Hirano, Satoshi Hara, Takashi Yokoi, Nobuyuki Yamamoto, and D. Fujimoto
- Subjects
Male ,0301 basic medicine ,medicine.medical_specialty ,Lung Neoplasms ,Durvalumab ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Pharmacology (medical) ,Stage (cooking) ,Adverse effect ,Prospective cohort study ,Immune Checkpoint Inhibitors ,Radiation Pneumonitis ,Aged ,Neoplasm Staging ,Pneumonitis ,Aged, 80 and over ,Pharmacology ,business.industry ,Antibodies, Monoclonal ,Chemoradiotherapy ,Middle Aged ,medicine.disease ,Concurrent chemoradiotherapy ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Introduction/Background Durvalumab demonstrated a good efficacy and safety in patients with unresectable stage III non-small cell lung cancer (NSCLC) after concurrent chemoradiotherapy (CCRT) in the PACIFIC trial. Although a history of radiation pneumonitis (RP) has been reported to increase the risk of pneumonitis associated with programmed death-1 inhibitors, the safety and efficacy of durvalumab in patients with baseline Grade 1 RP have not been assessed. Therefore, we carried out a multicenter prospective cohort study to evaluate the efficacy and safety of durvalumab in these patients. Patients and Methods This was a multicenter prospective cohort study of 35 patients with Grade 1 RP after CCRT and before durvalumab initiation. This study was a first prespecified analysis for the first 20 patients with the primary objective of assessing the short-term safety; it was assessed 3 months after durvalumab initiation. Results Twenty patients were enrolled in this study between March 1, 2019, and September 3, 2019. Three patients (15%) experienced drug-related Grade ≥3 adverse events, while three patients (15%) had Grade ≥2 pneumonitis/RP within 3 months after durvalumab initiation. Three months after durvalumab initiation, all the patients were alive and four patients (20%) experienced disease progression. Conclusion Durvalumab can be a feasible treatment option for patients with stage III NSCLC with baseline Grade 1 RP following CCRT.(Trial registration number: UMIN000036061. The registration period was between March 2019 and December 2019.).
- Published
- 2021
25. Prognostic Awareness and Discussions of Incurability in Patients with Pretreated Non-Small Cell Lung Cancer and Caregivers: A Prospective Cohort Study
- Author
-
Takaaki Hasegawa, Toru Okuyama, Takehiro Uemura, Yoshinobu Matsuda, Hiroyuki Otani, Junichi Shimizu, Yoshitsugu Horio, Naohiro Watanabe, Teppei Yamaguchi, Satoshi Fukuda, Tetsuya Oguri, Ken Maeno, Akihiro Tamiya, Kaname Nosaki, Kensuke Fukumitsu, and Tatsuo Akechi
- Subjects
Cancer Research ,Terminal Care ,Lung Neoplasms ,Oncology ,Caregivers ,Carcinoma, Non-Small-Cell Lung ,Neoplasms ,Humans ,Prospective Studies ,Neoplasm Recurrence, Local ,Prognosis - Abstract
Background Although patients with advanced cancer often have poor prognostic awareness, the most effective communication approach for improving prognostic awareness is unclear. In addition, the association between prognostic awareness and preferences for future medical treatment remains unexplored. Materials and Methods We performed a prospective observational study of consecutive patients with advanced or post-operative recurrent non-small cell lung cancer whose disease had progressed after first–line chemotherapy, and their caregivers. We evaluated patterns of clinical discussions about incurability, prognostic awareness, and preference for future medical treatment at baseline and 3 months later. Results We obtained 200 valid responses to the questionnaires at baseline and 147 valid responses 3 months later. In addition, 180 caregivers returned valid responses. A total of 54% of patients and 51% of caregivers had accurate awareness at baseline, and 52% of patients had accurate awareness 3 months later. Multiple logistic regression analysis revealed that patients who were informed about incurability in recent and past discussions were significantly more likely to have accurate awareness 3 months later, compared with those who were only informed recently (adjusted odds ratio 5.08; 95% CI, 1.31-19.78; P = .019). Accurate awareness at 3 months was significantly negatively associated with preference for life-prolonging treatment at 3 months after adjusting for covariates (adjusted odds ratio 0.39; 95% CI, 0.17-0.90; P = .028). Conclusion Patients with advanced cancer who had both recent and past discussions about incurability with their oncologists have more accurate prognostic awareness. Improving prognostic awareness could reduce the preference for life-prolonging treatment.
- Published
- 2022
26. A Multivariable Regression Model-based Nomogram for Estimating the Overall Survival of Patients Previously Treated With Nivolumab for Advanced Non-small-cell Lung Cancer
- Author
-
Yoshihiko Taniguchi, Takako Inoue, Hidekazu Suzuki, Toru Kumagai, Kenji Nakahama, Shun-ichi Isa, Akihiro Tamiya, Kei Kunimasa, Motohiro Tamiya, Fumio Imamura, Takayuki Shiroyama, Shinji Atagi, Kazumi Nishino, Ayumi Shintani, Hirofumi Go, and Tomonori Hirashima
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Antineoplastic Agents, Immunological ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Anaplastic lymphoma kinase ,Lung cancer ,Aged ,Retrospective Studies ,Aged, 80 and over ,Performance status ,Proportional hazards model ,business.industry ,Hazard ratio ,General Medicine ,Middle Aged ,Nomogram ,medicine.disease ,Survival Analysis ,Confidence interval ,Nivolumab ,Multivariate Analysis ,Mutation ,Regression Analysis ,Female ,business - Abstract
Aim Although nivolumab improves progression-free (PFS) and overall (OS) survival of patients previously treated for metastatic non-small-cell lung cancer (NSCLC), approximately 50% of treated patients experience disease progression within 3 months. As predictive biomarkers of response are not yet established, development of biomarkers to predict longer PFS and OS of patients treated with nivolumab is crucial. Therefore, we analyzed the impact of predictive markers of response to nivolumab and quantified the impact of each factor using nomograms. Patients and methods Clinical data at nivolumab commencement were retrospectively collected from 201 patients treated with nivolumab between December 2015 and July 2016. Immunohistochemistry for programmed cell death ligand 1 (PD-L1) was performed using two assay systems (22C3 and 28-8). OS was calculated from nivolumab treatment initiation. Multivariate Cox regression analysis was conducted to identify independent predictors of OS. A nomogram was constructed to estimate OS. Results The median patient age was 68 years (135 males). Thirty-nine patients had driver mutations (epidermal growth factor receptor mutations and anaplastic lymphoma kinase rearrangement). In 22C3 and 28-8 immunostaining assays, 36.3% and 36.8% patients had PD-L1-negative cells, 17.4% and 14.4% had 1-49% PD-L1-positive cells, 11.9% and 14.9% had ≥50% PD-L1-positive cells, and 34.3% and 33.8% had unknown PD-L1 status, respectively. Kendall's rank correlation coefficient between the staining assays was 0.8414. The median OS of the whole patient cohort was 12.27 months [95% confidence interval (CI)=10.87-15.6]. Performance status ≥2 [hazard ratio (HR)=2.15, 95% CI=1.35-3.42, p=0.001) and high baseline lactate dehydrogenase (HR=1.15, 95% CI=1.05-1.26, p=0.004] were independent predictors of shorter OS. There was no significant correlation between PD-L1 status and OS. We constructed a nomogram to estimate the OS of patients previously treated with nivolumab. Conclusion The multivariate analysis-based nomogram might be useful to estimate the OS of patients previously treated with nivolumab for advanced NSCLC.
- Published
- 2020
27. Impact of somatic mutations on prognosis in resected non‐small‐cell lung cancer: The Japan Molecular Epidemiology for lung cancer study
- Author
-
Yukiyasu Takeuchi, Mitsuhiro Takenoyama, Yasuhiro Koh, Katsuya Watanabe, Hideo Saka, Kazuhiko Kataoka, Tsutomu Tagawa, Tomoya Kawaguchi, Osamu Kawashima, Akihito Kubo, Motohiro Yamashita, Shun-ichi Isa, Akihiro Tamiya, Sadanori Takeo, Naoki Yoshimoto, Masahiko Ando, Hirofumi Adachi, and Akihide Matsumura
- Subjects
Male ,0301 basic medicine ,Cancer Research ,Lung Neoplasms ,Multivariate analysis ,next‐generation sequencing ,recurrence free survival ,Gene mutation ,medicine.disease_cause ,Gastroenterology ,0302 clinical medicine ,Japan ,Carcinoma, Non-Small-Cell Lung ,somatic mutation ,Prospective Studies ,Stage (cooking) ,Pneumonectomy ,Original Research ,Aged, 80 and over ,Molecular Epidemiology ,Middle Aged ,Prognosis ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Survival Rate ,Oncology ,030220 oncology & carcinogenesis ,Female ,KRAS ,Adult ,non‐small cell lung cancer ,medicine.medical_specialty ,overall survival ,lcsh:RC254-282 ,Young Adult ,03 medical and health sciences ,Germline mutation ,Internal medicine ,Biomarkers, Tumor ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Lung cancer ,Pathological ,Aged ,Proportional hazards model ,business.industry ,Clinical Cancer Research ,medicine.disease ,030104 developmental biology ,Mutation ,business ,Follow-Up Studies - Abstract
Background To report the follow up data and clinical outcomes of the JME study (UMIN 000008177), a prospective, multicenter, molecular epidemiology examination of 876 surgically resected non‐small‐cell lung cancer (NSCLC) cases, and the impact of somatic mutations (72 cancer‐associated genes) on recurrence‐free survival (RFS) and overall survival (OS). Methods Patients were enrolled between July 2012 and December 2013, with follow up to 30th November 2017. A Cox proportional hazards model was used to assess the impact of gene mutations on RFS and OS, considering sex, smoking history, age, stage, histology, EGFR, KRAS, TP53, and number of coexisting mutations. Results Of 876 patients, 172 had ≥2 somatic mutations. Median follow‐up was 48.4 months. On multivariate analysis, number of coexisting mutations (≥2 vs 0 or 1, HR = 2.012, 95% CI: 1.488‐2.695), age (≥70 vs, A prospective, multi‐center, molecular epidemiology study of 876 surgically resected non‐small cell lung cancer cases, and the impact of somatic mutations (72 cancer‐associated genes) on recurrence‐free survival and overall survival (OS). A smaller number of co‐existing mutations, earlier stage, and younger age were associated with longer recurrence free survival and OS, while epidermal growth factor receptor mutations were significantly associated with improved OS.
- Published
- 2020
28. Predictive factors for progression‐free survival in non‐small cell lung cancer patients receiving nivolumab based on performance status
- Author
-
Akihiro Tamiya, Yuichi Adachi, Kyoichi Okishio, Takatoshi Enomoto, Shunichi Kouno, Nobuhiko Saijo, Yuji Inagaki, Kouji Azuma, Yoshihiko Taniguchi, and Shinji Atagi
- Subjects
Male ,0301 basic medicine ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Pleural effusion ,Severity of Illness Index ,Gastroenterology ,lcsh:RC254-282 ,Metastasis ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Risk Factors ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Humans ,Medicine ,performance status ,Radiology, Nuclear Medicine and imaging ,Progression-free survival ,Lung cancer ,Glucocorticoids ,non-small cell lung cancer ,Original Research ,Aged ,Proportional Hazards Models ,Retrospective Studies ,nivolumab ,Performance status ,business.industry ,Liver Neoplasms ,Smoking ,Hazard ratio ,Clinical Cancer Research ,Middle Aged ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Progression-Free Survival ,Confidence interval ,Pleural Effusion, Malignant ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,immunotherapy ,prognosis ,Nivolumab ,business - Abstract
Background Nivolumab has promising efficacy for the treatment of non‐small cell lung cancer (NSCLC). Various predictive factors for nivolumab response in those with NSCLC have been reported, including performance status (PS). The objective of this retrospective study was to determine the predictive factors for nivolumab response in those with NSCLC with good PS and those with poor PS. Methods We retrospectively collected pretreatment clinical data of 296 consecutive patients with NSCLC treated with nivolumab. We investigated the relationship between progression‐free survival (PFS) and patient characteristics and analyzed predictive factors associated with good PS (PS 0‐1) or poor PS (PS 2‐4). Results The median age of patients was 70 years; 206 patients were male, and 224 were classified as having good PS (PS 0‐1). The median PFS was 3.0 months, 3.7 months, and 1.2 months for all patients, patients with good PS, and patients with poor PS respectively. Multivariate analysis showed that never smoking (hazard ratio [HR], 1.77; 95% confidence interval [CI], 1.15‐2.75), high C‐reactive protein (CRP) (HR, 1.39; 95% CI, 1.00‐1.93), liver metastasis (HR, 1.95; 95% CI, 1.24‐3.07), pleural effusion (HR, 1.45; 95% CI, 1.06‐2.00), and steroid use (HR, 2.85; 95% CI, 1.65‐4.94) were associated with significantly shorter PFS in patients with good PS. A high advanced lung cancer inflammation index (ALI) was significantly associated with longer PFS in patients with poor PS (HR, 0.24; 95% CI, 0.08‐0.79). Conclusions In patients with NSCLC treated with nivolumab, the factors found to be predictive of shorter PFS in patients with good PS were never smoking, high CRP, liver metastasis, pleural effusion, and steroid administration, whereas high ALI was predictive of longer PFS in patients with poor PS., PS was associated with PFS in patients with NSCLC receiving nivolumab treatment. Never smoking, high CRP, liver metastasis, pleural effusion, and steroid use at the commencement of nivolumab treatment were predictive of worse PFS in patients with NSCLC who received nivolumab treatment with good PS, and a high ALI was predictive of better PFS in patients with poor PS.
- Published
- 2020
29. Population pharmacokinetics of afatinib and exposure-safety relationships in Japanese patients with EGFR mutation-positive non-small cell lung cancer
- Author
-
Kimie Imai, Shun-ichi Isa, Shuhei Marutani, Toshiyuki Sakaeda, Shinji Atagi, Keiko Nakao, Kyoichi Okishio, Ayano Iwazaki, Akihiro Tamiya, Motohiro Tamiya, Masaki Kanazu, Shinji Kobuchi, and Tomonori Hirashima
- Subjects
Male ,0301 basic medicine ,Oncology ,Lung Neoplasms ,Afatinib ,Datasets as Topic ,lcsh:Medicine ,Severity of Illness Index ,0302 clinical medicine ,Japan ,Carcinoma, Non-Small-Cell Lung ,Epidermal growth factor receptor ,lcsh:Science ,Aged, 80 and over ,education.field_of_study ,Multidisciplinary ,biology ,Middle Aged ,ErbB Receptors ,Dose–response relationship ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,medicine.medical_specialty ,Drug-Related Side Effects and Adverse Reactions ,Population ,Renal function ,Drug development ,Models, Biological ,Article ,03 medical and health sciences ,Targeted therapies ,Internal medicine ,medicine ,Carcinoma ,Humans ,Computer Simulation ,Lung cancer ,education ,Adverse effect ,Aged ,Dose-Response Relationship, Drug ,business.industry ,lcsh:R ,medicine.disease ,030104 developmental biology ,Biological Variation, Population ,Mutation ,biology.protein ,lcsh:Q ,business - Abstract
To investigate the exposure–safety relationships of afatinib in Japanese population, we performed population pharmacokinetics (PK) analysis of afatinib in Japanese advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutation. Plasma samples were collected at 0.5–1, 2–3, 8–12, and 24 h after oral afatinib (40 mg) administration on day 1 and day 8. Plasma afatinib concentrations were determined using high-performance liquid chromatography. Data was analyzed following the population approach and using the software Phoenix® NLMETM Version 7.0 software (Certara USA, Inc., Princeton, NJ, USA). From 34 patients, a total of 354 afatinib plasma concentration values were available for the population PK analysis. Significant covariates in the population PK model included aspartate aminotransferase and creatinine clearance on CL/F, and age and body mass index on V/F. Results of simulation based on final PK model indicated that hepatic impairment had a significant effect on afatinib levels in plasma after multiple dosing. Afatinib trough plasma concentrations on day 8 were higher in patients with adverse events of grade 3 or higher. The population PK analysis showed that hepatic impairment affected afatinib PK parameters and contributed to the high inter-patient variability and high plasma concentrations of afatinib following multiple treatments.
- Published
- 2019
30. Association between metastatic sites and first-line pembrolizumab treatment outcome for advanced non–small cell lung cancer with high PD-L1 expression: a retrospective multicenter cohort study
- Author
-
Akihiro Tamiya, Tomonori Hirashima, Nobuhiko Sawa, Ryota Kominami, Toshihide Yokoyama, Hidekazu Suzuki, Daichi Fujimoto, Junji Uchida, Masaki Kanazu, Satoshi Hara, Hirotaka Matsumoto, Kazutaka Hosoya, Mitsunori Morita, Hayato Kawachi, Yasushi Fukuda, Motohiro Tamiya, Takeshi Makio, Toru Kumagai, Katsuya Hirano, and Seigo Ishii
- Subjects
Adult ,Male ,0301 basic medicine ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Pembrolizumab ,Adenocarcinoma ,Antibodies, Monoclonal, Humanized ,B7-H1 Antigen ,Metastasis ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Biomarkers, Tumor ,Humans ,Medicine ,Malignant pleural effusion ,Pharmacology (medical) ,Lung cancer ,Response Evaluation Criteria in Solid Tumors ,Aged ,Retrospective Studies ,Aged, 80 and over ,Pharmacology ,business.industry ,Hazard ratio ,Bone metastasis ,Retrospective cohort study ,Middle Aged ,Prognosis ,medicine.disease ,Survival Rate ,030104 developmental biology ,030220 oncology & carcinogenesis ,Carcinoma, Squamous Cell ,Female ,business ,Follow-Up Studies - Abstract
Associations between treatment outcomes of immune checkpoint inhibitors and metastatic sites in advanced non-small cell lung cancer (NSCLC) are not well known. Therefore, this multicenter retrospective study aimed to investigate the predictive factors of metastatic sites after first-line pembrolizumab treatment for advanced NSCLC with a PD-L1 tumor proportion score (TPS) ≥50%. We retrospectively analyzed advanced NSCLC patients with a PD-L1 TPS ≥50% who underwent first-line pembrolizumab therapy at 11 institutions between February 2017 and April 2018. Clinical data collected from medical records included metastatic sites at the time of pembrolizumab treatment. Treatment outcomes of pembrolizumab were assessed according to the Response Evaluation Criteria in Solid Tumors, version 1.1. In total, 213 patients were included in the study. The median age was 71 years (range 39-91 years). Of the 213 patients, 176 (83%) were men and 172 (81%) had an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 0-1. The most common metastases were thoracic lymph node metastasis (77%), intrapulmonary metastasis (31%), bone metastasis (28%), and malignant pleural effusion (26%). On multivariate analysis, a poor ECOG-PS score (hazard ratio: 1.95, 95.0% confidence interval: 1.25-3.04; P = 0.003) and malignant pleural effusion (hazard ratio: 1.52, 95.0% confidence interval: 1.01-2.29; P = 0.043) were independent predictors of shorter progression-free survival in patients treated with pembrolizumab. For NSCLC patients with malignant pleural effusion, pembrolizumab monotherapy is not a suitable first-line treatment because of its insufficient effectiveness, even though their PD-L1 TPS was high.
- Published
- 2019
31. Efficacy and safety of ramucirumab and docetaxel in previously treated patients with squamous cell lung cancer: a multicenter retrospective cohort study
- Author
-
Hayato Kawachi, Motohiro Tamiya, Kinnosuke Matsumoto, Akihiro Tamiya, Takafumi Yanase, Satoshi Tanizaki, and Toru Kumagai
- Subjects
Pharmacology ,Lung Neoplasms ,Treatment Outcome ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Carcinoma, Squamous Cell ,Humans ,Pharmacology (medical) ,Epithelial Cells ,Docetaxel ,Antibodies, Monoclonal, Humanized ,Retrospective Studies - Abstract
Objective: Ramucirumab plus docetaxel therapy (RAM/DOC) is currently the standard for previously treated advanced non-small cell lung cancer (NSCLC), irrespective of histology. However, the safety data of anti-angiogenic agents for squamous cell NSCLC (Sq) is lacking, with a higher reported rate of severe hemoptysis in a clinical trial setting. We conducted a multicenter retrospective cohort study to confirm the efficacy and safety of RAM/DOC for Sq in real-world settings.Methods: We retrospectively analyzed previously treated patients with advanced NSCLC who underwent RAM/DOC at four institutions. Clinical data on the initiation of RAM/DOC were collected from medical records. Treatment outcomes of RAM/DOC were assessed according to the Response Evaluation Criteria in Solid Tumors version 1.1. Incidence of pulmonary hemorrhage was assessed according to the Common Terminology Criteria for Adverse Events version 5.0.Results: Overall, 237 patients with NSCLC were included and 38 (16%) had squamous cell carcinoma. There were no significant differences in median progression-free survival and overall survival between Sq and non-Sq patients (5.8 months vs. 4.3 months, P=0.0937; 15.2 months vs. 13.4 months, P=0.714, respectively). Of all patients, 13 (5%) developed pulmonary hemorrhage. According to histology, there was no significant difference in pulmonary hemorrhage proportion between Sq and non-Sq cohorts (2/38 vs. 11/199, respectively, P=0.947).Conclusion: For previously treated patients with Sq, efficacy and safety data of RAM/DOC were confirmed in a real-world setting and were similar to non-Sq. Ramucirumab is the only vascular endothelial growth factor-blocker available for Sq.
- Published
- 2021
32. Histologic transformation of epidermal growth factor receptor-mutated lung cancer
- Author
-
Daichi Fujimoto, Hiroaki Akamatsu, Takeshi Morimoto, Kazushige Wakuda, Yuki Sato, Yoshitaka Kawa, Toshihide Yokoyama, Motohiro Tamiya, Ryota Hiraoka, Naoki Shingu, Hideki Ikeda, Akihiro Tamiya, Masaki Kanazu, Eisaku Miyauchi, Satoru Miura, Masaaki Yanai, Makiko Yomota, Ryotaro Morinaga, Takashi Yokoi, Akito Hata, Hidekazu Suzuki, Hirotaka Matsumoto, Shinya Sakata, Naoki Furuya, Yuhei Harutani, Ichiro Nakachi, Ayumu Otsuki, Shinya Uematsu, Satoshi Hara, Keiki Yokoo, Takeya Sugimoto, and Nobuyuki Yamamoto
- Subjects
ErbB Receptors ,Cancer Research ,Lung Neoplasms ,Oncology ,Carcinoma, Non-Small-Cell Lung ,Mutation ,Humans ,Immune Checkpoint Inhibitors ,Protein Kinase Inhibitors ,Retrospective Studies - Abstract
This study aimed to determine the incidence and clinical course of epidermal growth factor receptor (EGFR)-mutated lung cancer with histologic transformation (HT).We conducted a multicentre, retrospective, cohort study of patients with advanced EGFR-mutated lung cancer who received EGFR-tyrosine kinase inhibitors (TKIs) between 2012 and 2019. The primary outcome was the incidence of HT. The secondary outcome was treatment efficacy in patients with HT.In total, 6356 patients were enrolled. In 2624 patients, the histological type was proven by rebiopsy after acquiring resistance to EGFR-TKIs. Among them, 74 patients had HT (incidence rate: 2.8% [95% confidence interval: 2.3%-3.5%]). The median progression-free survival after EGFR-TKIs and first-line therapy after confirming HT was 10.4 and 4.4 months, respectively, which was not significantly different between patients with transformation to high-grade neuroendocrine carcinoma and those with transformation to another subtype of non-small cell lung cancer. Overall survival after confirming HT was 12.2 months. Twenty-seven patients received immune checkpoint inhibitors: 6 and 21 received immune checkpoint inhibitors before and after confirming HT, respectively. No patients achieved 1-year progression-free survival. The median progression-free survival after immune checkpoint inhibitor therapy after confirming HT was 1.6 months.HT occurred in approximately 3% of EGFR-mutated patients who developed resistance to EGFR-TKIs. Cytotoxic agents are likely to be effective in patients with HT. However, the therapeutic effectiveness of immune checkpoint inhibitors was limited in these patients. Given the rarity of HT and absence of prospective trials, our findings are important to inform the treatment of these patients.
- Published
- 2021
33. Classification and regression tree for estimating predictive markers to detect T790M mutations after acquired resistance to first line EGFR-TKI: HOPE-002
- Author
-
Toru Kumagai, Mitsunori Morita, Go Saito, Kazutaka Hosoya, Akihiro Tamiya, Yuki Saito, Motohiro Tamiya, Hidekazu Suzuki, T. Hirashima, Takuji Suzuki, Satoshi Teramukai, Junji Uchida, D. Fujimoto, Kei Fujikawa, Takeshi Uenami, Masashi Kanazu, Yasushi Fukuda, Toshihide Yokoyama, and Kiyonobu Ueno
- Subjects
Pharmacology ,Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Epidermal Growth Factor ,First line ,Decision tree ,Biology ,Afatinib ,respiratory tract diseases ,ErbB Receptors ,T790M ,Egfr tki ,Acquired resistance ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Mutation ,medicine ,Humans ,Pharmacology (medical) ,Protein Kinase Inhibitors - Abstract
Background and objective: Osimertinib as first-line treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor (EGFR) mutations remains controversial. Sequential EGFR-tyrosine kinase inhibitor (TKI) might be superior to the first line osimertinib in patients at risk of developing acquired T790M mutations.Methods: We enrolled consecutive patients with EGFR-mutated (deletion 19 or L858R) advanced NSCLC treated with first-line drugs and evaluated predictive markers using classification and regression tree (CART) for the detection of T790M mutations based on patient backgrounds prior to initial treatment.Results: Patients without acquired T790M mutations had worse outcomes than those with T790M mutations (median OS: 798 days vs. not reached; HR: 2.70; P
- Published
- 2021
34. Efficacy and safety of ramucirumab plus docetaxel in older patients with advanced non-small cell lung cancer: A multicenter retrospective cohort study
- Author
-
Hidekazu Suzuki, Yoshihiko Taniguchi, Akihiro Tamiya, Hayato Kawachi, Yoshinobu Matsuda, Satoshi Tanizaki, Kinnosuke Matsumoto, Kiyonobu Ueno, Takafumi Yanase, Junji Uchida, Shinji Atagi, Motohiro Tamiya, and Yuji Inagaki
- Subjects
Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Docetaxel ,Antibodies, Monoclonal, Humanized ,Ramucirumab ,Older patients ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Lung cancer ,Severe toxicity ,Aged ,Retrospective Studies ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Treatment Outcome ,Dose reduction ,Non small cell ,Geriatrics and Gerontology ,business ,medicine.drug - Abstract
Ramucirumab (RAM) plus Docetaxel (DOC) is one of the standard treatments after first-line treatment failure in patients with advanced non-small cell lung cancer (NSCLC). However, little is known about the efficacy and safety of RAM plus DOC in older patients. We aimed to clarify these and elucidate the prognostic factors.In this multicenter retrospective study, conducted at four medical facilities in Japan, we evaluated the efficacy and safety data for two groups (65 and ≥ 65 years). Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and log-rank test. Multivariate analysis was performed to reveal the prognostic factors for better PFS and OS. Patient characteristics and adverse events (AEs) in both groups were compared using the Mann-Whitney's U and Fisher's exact tests for categorical variables.A total of 237 patients were included, of whom 43% (n = 103), and 57% (n = 134) were aged65, and ≥ 65 years. Median OS was 12.2 (95% CI: 9.4-15.0), and 14.8 months (95% CI: 10.8-18.8), respectively, and there were no significant differences between the groups (p = 0.534). Multivariate analysis identified DOC dose reduction (none vs performed, HR: 2.66, 95% CI: 1.62-4.35, p0.001) as an independent prognostic factor for OS in older patients, and a similar result was shown for the PFS. Grade ≥ 3 all AEs were identified in 42.7% and 56.7% of younger and older patients, respectively, and there was a significant difference between the groups (p = 0.033); however, the difference between the groups disappeared with primary DOC dose reduction (p = 0.526).The efficacy of RAM plus DOC administration in older, pretreated patients with advanced NSCLC was comparable to those of younger patients, whereas RAM plus DOC should be cautiously administered to older patients because of severe toxicity. Moreover, appropriate DOC dose reduction may be recommended for increased survival benefit and safety in such patients.
- Published
- 2021
35. The ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd generation EGFR-TKI-refractory NSCLC
- Author
-
Fumio Imamura, Kazumi Nishino, Toru Kumagai, Shinji Atagi, Hidekazu Suzuki, Tomonori Hirashima, Norio Okamoto, Yoshihiko Taniguchi, Akihiro Tamiya, and Motohiro Tamiya
- Subjects
Oncology ,Adult ,Male ,medicine.medical_specialty ,Lung Neoplasms ,Afatinib ,Science ,Antineoplastic Agents ,medicine.disease_cause ,Article ,T790M ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Medicine ,Humans ,Osimertinib ,Epidermal growth factor receptor ,Protein Kinase Inhibitors ,Cancer ,Aged ,Aged, 80 and over ,Mutation ,Acrylamides ,Multidisciplinary ,Aniline Compounds ,biology ,Epidermal Growth Factor ,business.industry ,Point mutation ,Middle Aged ,medicine.disease ,respiratory tract diseases ,Treatment Outcome ,biology.protein ,Female ,EGFR Activating Mutation ,business ,medicine.drug - Abstract
The most frequent mechanism of resistance after 1st/2nd-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) is secondary point mutation Thr790Met (T790M) in EGFR. Afatinib followed by osimertinib (Afa group) may provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-G EGFR-TKI followed by osimertinib (1st-G group). We studied 111 consecutive NSCLC patients with T790M mutation treated with osimertinib after progression following 1st/2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed the ratio of T790M to EGFR-activating mutation (T790M ratio) in post EGFR-TKI resistance re-biopsy tissue using droplet digital polymerase chain reaction. And investigated whether afatinib purified the T790M mutation more than 1st-G EGFR-TKI. Among 60 patients with preserved re-biopsy tissue, we analyzed 38 having adequate DNA content. The response rate in Afa group was 81.8% (n = 11) and 1st-G group was 85.2% (n = 27). The mean T790M ratio in total population was 0.3643. The ratio in those with response to osimertinib was significantly higher than in the non-responders (0.395, 0.202; p = 0.0231) and was similar in Afa and 1st-G group (0.371, 0.362; p = 0.9693). T790M ratio significantly correlated with osimertinib response and was similar between the 1st/2nd-G EGFR-TKIs in 1st/2nd-G EGFR-TKI-refractory tumors.
- Published
- 2021
36. Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study
- Author
-
Toru Kumagai, Junji Uchida, Yoshihiko Taniguchi, Satoshi Tanaka, Mitsunori Morita, Akihiro Tamiya, D. Fujimoto, Masaki Kanazu, Takeshi Morimoto, Keisuke Tomii, Masahide Mori, Katsuya Hirano, Ryota Kominami, Hirotaka Matsumoto, Toshihide Yokoyama, Kazutaka Hosoya, Tomonori Hirashima, Motohiro Tamiya, Tadashi Ishida, Ikue Fukuda, Hidekazu Suzuki, and Kenji Nagata
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Oligoprogression ,Lung Neoplasms ,medicine.medical_treatment ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,lcsh:RC254-282 ,PD-L1 Positive ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Non-small cell lung cancer ,Surgical oncology ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Genetics ,medicine ,Humans ,Lung cancer ,Aged ,Retrospective Studies ,business.industry ,Bone metastasis ,Immunotherapy ,medicine.disease ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Treatment Outcome ,Response Evaluation Criteria in Solid Tumors ,030220 oncology & carcinogenesis ,Female ,Acquired resistance ,business ,Cohort study ,Research Article - Abstract
Background Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved. Methods We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions. Results Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR. Conclusions Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.
- Published
- 2021
37. Cytopathological Features of SMARCA4-Deficient Thoracic Sarcoma: Report of 2 Cases and Review of the Literature
- Author
-
Nobuhiko Saijo, Yoko Tani, Shigeki Shimizu, Chiho Ohbayashi, Maiko Takeda, Takahiko Kasai, Keiko Nakao, Shinji Atagi, Kenji Otsuka, Kyoichi Okishio, Yoshihiko Taniguchi, and Akihiro Tamiya
- Subjects
Pathology ,medicine.medical_specialty ,biology ,business.industry ,CD99 ,CD34 ,medicine.disease ,Pathology and Forensic Medicine ,Cytokeratin ,SALL4 ,medicine ,Synaptophysin ,biology.protein ,Surgery ,Sarcoma ,Anatomy ,Differential diagnosis ,business ,Epithelioid cell - Abstract
SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity of thoracic sarcomas with an undifferentiated rhabdoid morphology and SMARCA4 inactivation. Regardless of some reports about the histopathological findings so far, there have been only a few reports about the cytological features. In this article, we present the pathological features of 2 SMARCA4-DTS cases, including the cytological findings. Histopathologically, the tumor cells showed atypical loosely cohesive large epithelioid cells focally with geographic necrosis. Some cells were characterized by rhabdoid cells. Both patients showed intrathoracic masses with a history of smoking, and loss of SMARCA4 expression was confirmed with histopathological specimens. Immunohistochemically, tumor cells of both cases were at least focally positive for cytokeratin, CD34, CD99, synaptophysin, SOX2, and SALL4. In addition, tumor cells demonstrated significantly reduced expression of BRG1/SMARCA4 and SMARCA2. In conclusion, SMARCA4-DTS should be taken into consideration in the differential diagnosis of tumors with undifferentiated rhabdoid morphology involving the thoracic region.
- Published
- 2019
38. Efficacy and safety of pembrolizumab as first-line therapy in advanced non-small cell lung cancer with at least 50% PD-L1 positivity: a multicenter retrospective cohort study (HOPE-001)
- Author
-
Toru Kumagai, Masaki Kanazu, Daichi Fujimoto, Akihiro Tamiya, Hirotaka Matsumoto, Toshihide Yokoyama, Junji Uchida, Satoshi Hara, Mitsunori Morita, Yoshihiko Taniguchi, Motohiro Tamiya, Nobuhiko Sawa, Ryota Kominami, Kazutaka Hosoya, Yoshinori Kinoshita, Katsuya Hirano, Hidekazu Suzuki, Tomonori Hirashima, and Yasushi Fukuda
- Subjects
Adult ,Male ,0301 basic medicine ,medicine.medical_specialty ,Lung Neoplasms ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,Gastroenterology ,B7-H1 Antigen ,03 medical and health sciences ,Antineoplastic Agents, Immunological ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Carcinoma ,Humans ,Pharmacology (medical) ,Progression-free survival ,Lung cancer ,Adverse effect ,Aged ,Pneumonitis ,Aged, 80 and over ,Pharmacology ,Predictive marker ,business.industry ,Retrospective cohort study ,Middle Aged ,medicine.disease ,Treatment Outcome ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Female ,business - Abstract
Objectives As first line therapy, pembrolizumab provides longer progression free survival (PFS) and overall survival (OS) than platinum doublets in programmed death ligand 1 (PD-L1)-positive non-small cell lung cancer (NSCLC) with tumor propensity scores (TPS) ≥50%. However, clinical trials do not represent real-world patients. Materials and Methods This multicenter retrospective study conducted across 11 medical centers in Japan analyzed clinical data from patients receiving first-line pembrolizumab for NSCLC between February 1, 2017 and April 30, 2018. The efficacy, safety, and suitability of pembrolizumab monotherapy were evaluated. Results The median age of the 213 enrolled patients was 71 (range: 39–91) years. Among them, 176 (82.6%) were male, 20 (9.4%) were never smokers (median Brinkman index: 900), 172 (80.8%) had an ECOG PS of 0–1, 55 (25.8%) had squamous-cell carcinoma (SQ). PD-L1 TPS were 50–74%, 75–89%, and 90–100% in 97 (45.5%), 47 (22.1%), and 69 (32.4%) patients, respectively. Adverse events (AEs) of grades ≥3 were observed in 39 (18.3%) patients. Pneumonitis was the most common severe AE, occurring in 10 patients (4.7%) including 1 with grade 4 toxicity; no severe AE-related deaths occurred. The overall response rate, median PFS, and median OS was 51.2%, 8.3 months, and 17.8 months, respectively. On multivariate analysis, ECOG PS (0–1 vs. ≥2: HR: 1.69, 95.0% CI: 1.05–2.72; p = 0.03138), CRP/Alb (
- Published
- 2019
39. Which Is Better EGFR-TKI Followed by Osimertinib: Afatinib or Gefitinib/Erlotinib?
- Author
-
Tomonori Hirashima, Fumio Imamura, Yoshihiko Taniguchi, Akihiro Tamiya, Kei Kunimasa, Hidekazu Suzuki, Toru Kumagai, Madoka Kimura, Motohiro Tamiya, Kenji Nakahama, Kazumi Nishino, Takako Inoue, Kazunori Moriizumi, Hanako Kuhara, and Shinji Atagi
- Subjects
Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Afatinib ,Antineoplastic Agents ,Piperazines ,Erlotinib Hydrochloride ,03 medical and health sciences ,T790M ,0302 clinical medicine ,Gefitinib ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Humans ,Osimertinib ,Protein Kinase Inhibitors ,Aged ,Aged, 80 and over ,Acrylamides ,Aniline Compounds ,Performance status ,business.industry ,Retrospective cohort study ,General Medicine ,Middle Aged ,respiratory tract diseases ,ErbB Receptors ,Treatment Outcome ,Egfr mutation ,030220 oncology & carcinogenesis ,Female ,Erlotinib ,business ,medicine.drug - Abstract
Background/aim Treatment with EGFR-tyrosine kinase inhibitor (TKI) shows a durable response against NSCLC harboring EGFR mutation; however, treatment resistance occurs within 1-1.5 years following first-line EGFR-TKIs [first- and second-generation (G) TKIs]. When resistant NSCLC exhibits T790M mutations, osimertinib is the standard therapy. However, intratumoral heterogeneity and clonal evolution may occur in NSCLC. Afatinib may overcome tumor heterogeneity, leading to T790M colonal purity. We aimed to determine whether NSCLC treatment with afatinib followed by osimertinib (afatinib group) provides higher therapeutic efficacy than other 1st-G EFGR-TKIs followed by osimertinib (1st-G group). Materials and methods This multicenter retrospective study evaluated outcomes between afatinib group and 1st-G group. We analyzed clinical data from NSCLC patients receiving osimertinib after progression following 1st- or 2nd-G EGFR-TKIs between March 28, 2016 and March 31, 2018. Patients with performance status (PS) 0-2 were enrolled to reduce bias of patients' conditions. Results We enrolled 111 patients treated with osimertinib. The median age was 69 (range: 39-88) years. Out of 111 patients, 33 (29.7%) were men, 100 (90%) had PS 0-1, and 35 (31.5%) were in the afatinib group. The objective RR and DCR were significantly higher in the afatinib group than in the 1st-G group [82.9% vs. 53.9% (p=0.0065); 91.4% vs. 71.1% (p=0.032)]. The median PFS tended higher in the afatinib group than in the 1st-G group (15.6 vs. 8.9 months, p=0.195). Conclusion Afatinib followed by osimertinib may provide better outcomes for T790M-positive NSCLC than 1st-G EGFR-TKIs. Afatinib followed by osimertinib may be a therapeutic option for NSCLC harboring EGFR mutation.
- Published
- 2019
40. The Japanese Lung Cancer Society Guideline for non-small cell lung cancer, stage IV
- Author
-
Takaaki Sasaki, Yuji Minegishi, Kiichiro Ninomiya, Takashi Seto, Takashi Sone, Yoshihiro Hattori, Satoru Miura, Yasushi Goto, Takeharu Yamanaka, Shigeki Umemura, Hidenori Mizugaki, Shinsuke Amano, Yusuke Okuma, Makoto Maemondo, Hiroshige Yoshioka, Chiyo K. Imamura, Yuki Katsuya, Nobuyuki Yamamoto, Kentaro Tanaka, Reiko Matsui, Setsuko Sakamoto, Masahiro Morise, Kazuko Nakajima, Akihiro Tamiya, Satoshi Morita, Toshiyuki Kozuki, Haruko Daga, Hiroaki Akamatsu, Hirotsugu Kenmotsu, Kazuo Hasegawa, Yukari Tsubata, Shunsuke Teraoka, and Kaname Nosaki
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Lung Neoplasms ,Guideline ,Medical Oncology ,Patient advocacy ,Special Article ,03 medical and health sciences ,0302 clinical medicine ,Non-small cell lung cancer ,Japan ,Surgical oncology ,Carcinoma, Non-Small-Cell Lung ,medicine ,Lung cancer stage iv ,Chemotherapy ,Humans ,Intensive care medicine ,Lung cancer ,Grading (tumors) ,Societies, Medical ,Kinase inhibitor ,Programed death-ligand 1 inhibitor ,business.industry ,Hematology ,General Medicine ,medicine.disease ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,English version ,Programed cell death-1 inhibitor ,Surgery ,Non small cell ,Neoplasm Grading ,business - Abstract
According to rapid development of chemotherapy in advanced non-small cell lung cancer (NSCLC), the Japan Lung Cancer Society has been updated its own guideline annually since 2010. In this latest version, all of the procedure was carried out in accordance with grading of recommendations assessment, development and evaluation (GRADE) system. It includes comprehensive literature search, systematic review, and determination of the recommendation by multidisciplinary expert panel which consisted of medical doctors, pharmacists, nurses, statisticians, and patients from patient advocacy group. Recently, we have had various types of chemotherapeutic drugs like kinase inhibitors or immune-checkpoint inhibitors. Thus, the guideline proposes to categorize patients into three entities: (1) driver oncogene-positive, (2) PD-L1 ≥ 50%, and (3) others. Based on this subgroup, 31 clinical questions were described. We believe that this attempt enables clinicians to choose appropriate treatment easier. Here, we report an English version of the Japan Lung Cancer Society Guidelines 2018 for NSCLC, stages IV.
- Published
- 2019
41. A High PD-L1 Expression in Pulmonary Pleomorphic Carcinoma Correlates with Parietal-pleural Invasion and Might Predict a Poor Prognosis
- Author
-
Maiko Naito, Akihiro Tamiya, Maiko Takeda, Yoshihiko Taniguchi, Akihide Matsumura, Kyoichi Okishio, Takahiko Kasai, Shinji Atagi, Nobuhiko Saijo, Yoko Naoki, and Hyung-Eun Yoon
- Subjects
Adult ,Male ,programmed death-ligand 1 ,Poor prognosis ,medicine.medical_specialty ,Lung Neoplasms ,parietal-pleural invasion ,Clone (cell biology) ,Adenocarcinoma ,030204 cardiovascular system & hematology ,Pleomorphic carcinoma ,Gastroenterology ,B7-H1 Antigen ,Disease-Free Survival ,pleomorphic carcinoma ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Biomarkers, Tumor ,Internal Medicine ,medicine ,Humans ,Neoplasm Invasiveness ,Risk factor ,Pathological ,Aged ,Neoplasm Staging ,Aged, 80 and over ,Tumor size ,business.industry ,General Medicine ,Middle Aged ,Prognosis ,Immunohistochemistry ,Neoplasm Proteins ,Lymphatic Metastasis ,Pleura ,Original Article ,Female ,030211 gastroenterology & hepatology ,Pd l1 expression ,Neoplasm Recurrence, Local ,business - Abstract
Objective Pleomorphic carcinoma (PC) is a rare pulmonary epithelial malignant tumor with a poor prognosis. The objective of the present study was to investigate the programmed death-ligand 1 (PD-L1) expression in PC and its correlation between the clinicopathological factors and prognosis. Methods Clinical and pathological data of 35 patients with surgically resected PC encountered from 2002 to 2016 at our institution were collected. The PD-L1 expression on tumor cells was evaluated via immunohistochemistry (clone 22C3). We examined the correlation between the PD-L1 expression and patients' clinicopathological factors and their prognosis. Results A high PD-L1 expression (≥50%) was seen in 21 (60%) patients, and parietal-pleural invasion was significantly correlated with a high PD-L1 expression (p=0.012). The 5-year overall survival and relapse-free survival were 68.2% and 43.2%, respectively. Tumor size ≥50 mm (p=0.021), lymph node metastasis (p=0.023), and a high PD-L1 expression (p=0.047) were correlated with a short relapse-free survival. Since lymph node metastasis was an independent risk factor of a poor overall survival (p=0.012), patients with a high PD-L1 expression also tended to have a worse overall survival than those with low levels (p=0.081). Conclusion A high PD-L1 expression is frequently seen in PC. The PD-L1 expression is associated with parietal-pleural invasion and might indicate a poor prognosis.
- Published
- 2019
42. Improvement of Mycobacterium abscessus Pulmonary Disease after Nivolumab Administration in a Patient with Advanced Non-small Cell Lung Cancer
- Author
-
Yoshihiko Taniguchi, Yuko Abe, Katsuhiro Suzuki, Shun-ichi Isa, Kazunari Tsuyuguchi, Seigo Ishii, Tsunehiro Tanaka, Shinji Atagi, and Akihiro Tamiya
- Subjects
Oncology ,medicine.medical_specialty ,Bevacizumab ,medicine.medical_treatment ,Mycobacterium abscessus ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Internal medicine ,Internal Medicine ,medicine ,Lung cancer ,Chemotherapy ,Lung ,biology ,business.industry ,General Medicine ,medicine.disease ,biology.organism_classification ,Carboplatin ,medicine.anatomical_structure ,030228 respiratory system ,chemistry ,030220 oncology & carcinogenesis ,Sputum ,medicine.symptom ,Nivolumab ,business ,medicine.drug - Abstract
Nivolumab has become the standard second-line chemotherapy for non-small cell lung cancer. A 73-year-old man with stage IV non-small cell lung cancer received 6 cycles of chemotherapy with nab-paclitaxel/carboplatin/bevacizumab followed by 11 cycles of nab-paclitaxel/bevacizumab; however, treatment was stopped due to pneumothorax. One year after therapy started, a nodule appeared in the left upper lung and increased in size. Mycobacterium abscessus subsp. massiliense disease was diagnosed by a sputum analysis. After short antibiotic treatment, nivolumab was administered. Two months after nivolumab treatment, the nodule improved along with a good tumour response. The effectiveness of nivolumab for chronic infectious diseases, such as M. abscessus disease, should be investigated.
- Published
- 2018
43. Ratio of T790M to EGFR-activating mutation predicts response of osimertinib in 1st or 2nd - generation EGFR-TKI-refractory NSCLC
- Author
-
Motohiro Tamiya, Akihiro Tamiya, Norio Okamoto, Yoshihiko Taniguchi, Kazumi Nishino, Shinji Atagi, Tomonori Hirashima, Fumio Imamura, Toru Kumagai, and Hidekazu Suzuki
- Subjects
respiratory tract diseases - Abstract
Background: Afatinib followed by osimertinib (Afa group) may reportedly provide better outcomes for T790M-positive non-small cell lung cancer (NSCLC) than 1st-generation (G) epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) (1st-G group). Methods: We studied 111 consecutive patients with T790M mutation-positive NSCLC who were treated with osimertinib after progression following 1st- or 2nd-G EGFR-TKI between March 28, 2016 and March 31, 2018. We analyzed T790M ratio with the re-biopsy tissue, obtained after EGFR-TKI resistance using droplet digital polymerase chain reaction, and investigate whether afatinib prifies the T790M mutation more than 1st-G EGFR-TKI.Results: Among the 60 patients with preserved re-biopsy tissues, we analyzed 38 patients whose re-biopsy tissue had adequate DNA content. Eleven patients in the Afa group had 81.8% of response rate, and 27 patients in the 1st-G group had 85.2% with RR. The mean T790M ratio was 0.3643. The T790M ratio in those with response of the osimertinib group was significantly higher than in those with non-response group (p=0.0272) and was similar in the Afa and 1st-G group (p=0.9693).Conclusion: T790M ratio significantly correlated with osimertinib response and T790M ratio was similar between the 1st and 2nd -G EGFR-TKIs in 1st or 2nd -G EGFR-TKI-refractory tumors.
- Published
- 2021
44. Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab-paclitaxel for non-squamous non-small cell lung cancer with malignant pleural effusion
- Author
-
Motohiro, Tamiya, Akihiro, Tamiya, Hidekazu, Suzuki, Yoshihiko, Taniguchi, Kanako, Katayama, Shojiro, Minomo, Keiko, Nakao, Naoko, Takeuchi, Yoshinobu, Matsuda, Yujiro, Naito, Takayuki, Shiroyama, Norio, Okamoto, Kyoichi, Okishio, Toru, Kumagai, Shinji, Atagi, Fumio, Imamura, and Tomonori, Hirashima
- Subjects
Male ,Lung Neoplasms ,Paclitaxel ,Middle Aged ,Progression-Free Survival ,Carboplatin ,Pleural Effusion, Malignant ,Bevacizumab ,Survival Rate ,Albumins ,Carcinoma, Non-Small-Cell Lung ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Female ,Prospective Studies ,Aged - Abstract
Objectives Vascular endothelial growth factor plays an important role in the pathogenesis of malignant pleural effusion (MPE). We previously showed the efficacy of bevacizumab (Bev) plus carboplatin (CBDCA)/paclitaxel (PTX) in the treatment of non-small lung cell cancer (NSCLC) with MPE. However, the toxicities were a little severe, and the efficacy was not satisfied sufficiently. Therefore, we conducted a phase II study for NSCLC with MPE to evaluate the efficacy and safety of Bev plus CBDCA/nab-PTX, which is a new combination therapy. Methods Chemotherapy-naive non-squamous (SQ) NSCLC patients with MPE participated in the study. A single aspiration (not allowing chest tube drainage) was allowed before chemotherapy. Patients received a maximum of six cycles of Bev (15 mg/kg, day1) plus CBDCA (AUC 6, day1)/nab-PTX (100 mg/m
- Published
- 2021
45. Japanese Lung Cancer Society Guidelines for Stage IV NSCLC With EGFR Mutations
- Author
-
Junko Tanizaki, Haruko Daga, Masahiro Morise, Hideaki Mizutani, Tomohiro Sakamoto, Takaaki Sasaki, Chiyo K. Imamura, Keiju Aokage, Shunsuke Teraoka, Yuko Oya, Satoshi Morita, Kenichi Suzuki, Yukiko Nakamura, Takeharu Yamanaka, Kiichiro Ninomiya, Toshiyuki Kozuki, Kaname Nosaki, Yuichi Takiguchi, Toyoaki Hida, Hitomi Nishimoto, Satoru Miura, Satoshi Oizumi, Shinsuke Amano, Yoshitaka Zenke, Hisashi Tanaka, Yasushi Goto, Yusuke Okuma, Kentaro Tanaka, Noriyuki Ebi, Katsuyuki Hotta, Eisaku Miyauchi, Kazuo Hasegawa, O. Yamaguchi, Kazuko Nakajima, Akihiro Tamiya, and Hirotsugu Kenmotsu
- Subjects
Pulmonary and Respiratory Medicine ,Oncology ,medicine.medical_specialty ,medicine.medical_treatment ,Review Article ,Guidelines ,lcsh:RC254-282 ,Internal medicine ,Medicine ,Non–small cell lung cancer ,Osimertinib ,Epidermal growth factor receptor ,Lung cancer ,Grading (tumors) ,Chemotherapy ,biology ,business.industry ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,respiratory tract diseases ,Systematic review ,Egfr mutation ,biology.protein ,business ,Stage iv - 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.
- Published
- 2020
46. Can smoking duration alone replace pack-years to predict the risk of smoking-related oncogenic mutations in non-small cell lung cancer? A cross-sectional study in Japan
- Author
-
Tomoya Kawaguchi, Motohiro Izumi, Yoshiya Matsumoto, Akihiro Tamiya, Shun-ichi Isa, Naoki Yoshimoto, Akihide Matsumura, Kenji Sawa, Hiroyasu Kaneda, Yasuhiro Koh, Masahiko Ando, Mitsuru Fukui, Hideo Saka, Yoshihiko Taniguchi, Akihito Kubo, and Koichi Ogawa
- Subjects
Oncology ,medicine.medical_specialty ,Lung Neoplasms ,Cross-sectional study ,Gene mutation ,medicine.disease_cause ,Logistic regression ,Proto-Oncogene Proteins p21(ras) ,Japan ,Internal medicine ,Recall bias ,Carcinoma, Non-Small-Cell Lung ,Epidemiology ,medicine ,Humans ,Lung cancer ,Smoking and Tobacco ,Receiver operating characteristic ,respiratory tract tumours ,business.industry ,Smoking ,General Medicine ,medicine.disease ,ErbB Receptors ,Cross-Sectional Studies ,molecular aspects ,Mutation ,Medicine ,epidemiology ,KRAS ,business - Abstract
ObjectiveTo investigate whether smoking duration alone can replace pack-years to predict the risk of oncogenic mutations in non-small cell lung cancer (NSCLC).DesignA cross-sectional study using the baseline dataset from the Japan Molecular Epidemiology for Lung Cancer Study.SettingForty-three medical institutions nationwide in Japan.ParticipantsFrom July 2012 to December 2013, 957 patients with newly diagnosed stage I–IIIB NSCLC who underwent surgery were enrolled, and molecular analyses were performed on 876 samples (from 441 ever-smokers and 435 never-smokers).Main outcomes measuredWe calculated the area under the receiver operating characteristic curve (AUC) values using logistic regression to compare between the predictive values of smoking duration and pack-years for mutational frequencies in the v-Ki-ras2 Kirsten rat sarcoma (KRAS), tumour suppressor p53 (TP53), and epidermal growth factor receptor (EGFR) genes and for cytosine-to-adenine base substitution (C>A).ResultsFor predicting KRAS mutations, the AUC values for smoking duration and pack-years were 0.746 (95% CI 0.682 to 0.800) and 0.759 (95% CI 0.700 to 0.810), respectively (p=0.058). For predicting KRAS mutations in smokers, the AUC values for smoking duration and pack-years were 0.772 (95% CI 0.697 to 0.833) and 0.787 (95% CI 0.714 to 0.845), respectively (p=0.036). There were no significant differences between the AUC values for smoking duration and pack-years in terms of predicting TP53 and EGFR mutations and C>A. Pack-years was a significantly better predictor of KRAS mutations than smoking duration.ConclusionSmoking duration was not significantly different from pack-years in predicting the likelihood of smoking-related gene mutations. Given the recall bias in obtaining smoking information, smoking duration alone should be considered for further investigation as a simpler alternative to pack-years.
- Published
- 2020
47. Opioids impair Nivolumab outcomes: a retrospective propensity score analysis in non-small-cell lung cancer
- Author
-
Shinji Atagi, Akihiro Tokoro, Akihiro Tamiya, Yoshinobu Matsuda, Yoshihiko Taniguchi, Takatoshi Enomoto, Yuichi Adachi, Shunichi Kouno, and Kouji Azuma
- Subjects
medicine.medical_specialty ,Lung ,Oncology (nursing) ,business.industry ,Medical record ,Medicine (miscellaneous) ,Retrospective cohort study ,General Medicine ,medicine.disease ,03 medical and health sciences ,Medical–Surgical Nursing ,0302 clinical medicine ,medicine.anatomical_structure ,Opioid ,030220 oncology & carcinogenesis ,Internal medicine ,Propensity score matching ,medicine ,030212 general & internal medicine ,Non small cell ,Nivolumab ,business ,Lung cancer ,medicine.drug - Abstract
ObjectivesOpioids are often administered for cancer-related pain relief. However, few reports have evaluated the association between opioids and immune checkpoint inhibitor treatment for patients with non-small-cell lung cancer (NSCLC). The aim of this retrospective study was to reveal the effect of opioids on the prognosis of patients harbouring NSCLC treated with nivolumab.MethodsThe medical records of consecutive patients with NSCLC receiving nivolumab at our institution were retrospectively reviewed. We collected clinical data at the time of nivolumab treatment initiation. Propensity score matching (PSM) was performed to minimise potential selection bias. We compared clinical outcomes with and without baseline opioid use.ResultsOf the 296 patients identified in the study, after PSM, 38 cases with opioid use and matched 38 cases without opioid use were selected. The overall response rate was significantly lower in patients with opioid use than in those without (2.63%, 95% CI 0.47% to 13.49%, vs 21.05%, 95% CI 11.07% to 36.35%; p=0.0284). The median progression-free survival in patients with opioid use was significantly shorter than that in patients without (1.17, 95% CI 0.93 to 1.73 months, vs 2.07 95% CI 1.23 to 4.73 months; p=0.002). The median overall survival in patients with opioid use was significantly shorter than that in patients without (4.20, 95% CI 2.53 to 6.20 months, vs 9.57, 95% CI 2.23 to not reached months; p=0.018).ConclusionsPatients with NSCLC receiving regular opioid administration at nivolumab treatment initiation had a worse nivolumab treatment outcome than patients without opioid use.
- Published
- 2020
48. Nivolumab treatment beyond progressive disease in advanced non-small cell lung cancer
- Author
-
Kinnosuke Matsumoto, Akihiro Tamiya, S. Kouno, K. Azuma, Yuji Inagaki, Yuichi Adachi, Takatoshi Enomoto, N. Saijo, Kyoichi Okishio, Y. Taniguchi, and Shinji Atagi
- Subjects
0301 basic medicine ,Oncology ,Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.medical_treatment ,Antineoplastic Agents ,Kaplan-Meier Estimate ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Medicine ,Humans ,Lung cancer ,Adverse effect ,Immune Checkpoint Inhibitors ,Response Evaluation Criteria in Solid Tumors ,Aged ,Retrospective Studies ,Aged, 80 and over ,business.industry ,Drug Substitution ,Medical record ,General Medicine ,Immunotherapy ,Middle Aged ,medicine.disease ,Discontinuation ,030104 developmental biology ,Cross-Sectional Studies ,Nivolumab ,030220 oncology & carcinogenesis ,Disease Progression ,Regression Analysis ,Female ,business ,Progressive disease - Abstract
This study evaluated the efficacy and safety of nivolumab treatment beyond progressive disease (PD) in non-small cell lung cancer (NSCLC). Medical records of consecutive patients with advanced NSCLC who received nivolumab between December 2015 and December 2018 were reviewed. Clinical outcomes of three groups of eligible patients who received nivolumab as a second-line treatment after PD were compared based on Response Evaluation Criteria in Solid Tumors v1.1. We conducted subgroup analyses in patients with and without new lesions at first PD. Twenty-eight patients continued nivolumab treatment beyond PD (TBP). Post PD, 46 patients switched to other anti-cancer treatment (OAT), and 21 received no further anti-cancer treatment (NAT). There were no significant differences in overall survival (OS) or survival post progression (SPP) between TBP and OAT groups (OS: 15.6 vs. 13.4 months, P = .40, SPP: 12.2 vs. 9.3 months, P = .42). Subgroup analyses indicated that among patients without new lesions at first PD, SPP was longer in the TBP than in the OAT groups (12.6 vs. 9.3 months, P = .22, HR: 0.64; 95% CI 0.31‒1.31). The frequency of immune-related adverse events leading to discontinuation during nivolumab beyond PD was equivalent to that for pre-PD (10.7 vs. 12.6%). No significant benefits were associated with continuation of nivolumab for advanced NSCLC patients. Continuation of nivolumab beyond PD could be a more useful option in patients without new lesions at first PD. Treatment-related toxicities require attention during nivolumab treatment not only before PD but also beyond PD.
- Published
- 2020
49. Prediction of patients with a tumor proportion score > 50% who do not respond to first-line monotherapy with pembrolizumab
- Author
-
Junji Uchida, Mitsunori Morita, Hiromi Tomioka, Yasushi Fukuda, Hidekazu Suzuki, Masaki Kanazu, Toshihide Yokoyama, Daichi Fujimoto, Ryota Kominami, Satoshi Hara, Akihiro Tamiya, Motohiro Tamiya, Shuji Yamashita, and Katsuya Hirano
- Subjects
Male ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,Efficacy ,Population ,Pembrolizumab ,Antibodies, Monoclonal, Humanized ,lcsh:RC254-282 ,Gastroenterology ,B7-H1 Antigen ,03 medical and health sciences ,0302 clinical medicine ,Antineoplastic Agents, Immunological ,Non-small cell lung cancer ,Internal medicine ,Carcinoma, Non-Small-Cell Lung ,Genetics ,Medicine ,Malignant pleural effusion ,Humans ,030212 general & internal medicine ,Neoplasm Metastasis ,education ,Aged ,Neoplasm Staging ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,Univariate analysis ,Performance status ,business.industry ,Odds ratio ,Middle Aged ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Confidence interval ,Programmed death ligand-1 ,Treatment Outcome ,Oncology ,030220 oncology & carcinogenesis ,First-line therapy ,Female ,business ,Progressive disease ,Research Article - Abstract
Background Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50% [1]. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) > 50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N = 52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥ 2 (p = 0.0832), stage IV disease or recurrence (p = 0.0487), PD-L1 TPS 50–89% (p = 0.0657), use of steroids prior to the administration of pembrolizumab (p = 0.0243), malignant pleural effusion (p = 0.0032), and baseline C-reactive protein (CRP) levels > 1.0 mg/dL (p = 0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p = 0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p = 0.0228), and baseline CRP > 1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p = 0.0402) were significantly associated with non-response to treatment. Conclusion In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels > 1.0 mg/dL reduced the response of first-line monotherapy with pembrolizumab.
- Published
- 2020
50. Prediction of patients with a tumor proportion score >50% who do not respond to first-line monotherapy with pembrolizumab
- Author
-
Mitsunori Morita, Motohiro Tamiya, Daichi Fujimoto, Akihiro Tamiya, Hidekazu Suzuki, Katsuya Hirano, Yasushi Fukuda, Toshihide Yokoyama, Ryota Kominami, Masaki Kanazu, Junji Uchida, Satoshi Hara, Shuji Yamashita, and Hiromi Tomioka
- Abstract
Background: Pembrolizumab is effective as first-line therapy against advanced non-small cell lung cancer (NSCLC) in patients with programmed death ligand-1 (PD-L1) expression levels ≥50%. However, it is not effective in all patients, and the factors predicting responses among this population remain unknown. Methods: We retrospectively analyzed patients with NSCLC and a PD-L1 tumor proportion score (TPS) >50%, who received first-line monotherapy with pembrolizumab from February 1, 2017 to April 30, 2018. The study included 11 hospitals, which participated in the Hanshin Oncology clinical Problem Evaluation group (HOPE). We analyzed the differences between responders and non-responders in terms of age, sex, performance status score, degree of progression, histological type, smoking history, expression of PD-L1, use of steroids prior to treatment, metastasis site, and laboratory data. Results: A total of 205 patients were included in this study. Of those, 108 patients exhibiting complete or partial response were defined as responders. Those exhibiting progressive disease (N=52) were defined as non-responders. In the univariate analysis, Eastern Cooperative Oncology Group performance status score ≥2 (p=0.0832), stage IV disease or recurrence (p=0.0487), PD-L1 TPS 50–89% (p=0.0657), use of steroids prior to the administration of pembrolizumab (p=0.0243), malignant pleural effusion (p=0.0032), and baseline C-reactive protein (CRP) levels >1.0 mg/dL (p=0.0390) were significantly associated with non-response to treatment. In the multivariate analysis, use of steroids prior to the administration of pembrolizumab (odds ratio [OR]: 5.86; 95% confidence interval [CI]: 1.32–31.8; p=0.0200), malignant pleural effusion (OR: 2.68; 95% CI: 1.15–6.35; p=0.0228), and baseline CRP >1.0 mg/dL (OR: 2.17; 95% CI: 1.03–4.68; p=0.0402) were significantly associated with non-response to treatment. Conclusion: In real-world patients with NSCLC and a PD-L1 TPS ≥50%, use of steroids prior to treatment, malignant pleural effusion, and baseline CRP levels >1.0mg/dL reduced the effectiveness of first-line monotherapy with pembrolizumab.
- Published
- 2019
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.