المؤلفون: Yusuke Ono, Ryohei Katayama, Noriko Yanagitani, Ken Uchibori, Makoto Nishio, Satoru Kitazono, Ryo Ariyasu, Ryohei Yoshida, Yusuke Mizukami, Mika Tsukahara, Takaaki Sasaki, Kazuma Kiyotani, Yuichi Ishikawa, Naoya Fujita, Hironori Ninomiya

المصدر: Cancer Science

مصطلحات موضوعية: 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Male, Cancer Research, Lung Neoplasms, T790M, Polymerase Chain Reaction, droplet digital PCR, GTP Phosphohydrolases, 0302 clinical medicine, Japan, Carcinoma, Non-Small-Cell Lung, Osimertinib, Digital polymerase chain reaction, Epidermal growth factor receptor, Trametinib, Aniline Compounds, biology, High-Throughput Nucleotide Sequencing, General Medicine, Middle Aged, ErbB Receptors, Oncology, 030220 oncology & carcinogenesis, osimertinib, Cohort, Disease Progression, Original Article, Female, Cell-Free Nucleic Acids, C797S, EGFR, resistance, 03 medical and health sciences, Clinical Research, Cell Line, Tumor, medicine, Humans, Lung cancer, Aged, Acrylamides, business.industry, Membrane Proteins, Original Articles, Sequence Analysis, DNA, medicine.disease, respiratory tract diseases, 030104 developmental biology, Drug Resistance, Neoplasm, Mutation, Cancer research, biology.protein, business

الوصف: Osimertinib is a third‐generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR‐TKI) that is effective in treating both naïve and T790M‐mutated EGFR‐TKI‐resistant non–small cell lung cancer patients. The EGFR C797S mutation is the major osimertinib resistance mechanism. The present study monitored the EGFR C797S mutation during osimertinib treatment in Japanese patients using droplet digital PCR (ddPCR). In our first cohort, C797S detection was validated with tumor specimens and/or plasma samples from 26 patients using ddPCR with custom‐designed probes detecting and discriminating T790M and C797S in cis and trans positions. In our second cohort, 18 patients with EGFR‐T790M who were going to start osimertinib were analyzed using ddPCR by collecting the plasma samples every month from the beginning of the course of osimertinib. In the first cohort, C797S was detected in 15.4% of patients. C797S and T790M in cis and trans positions were distinguished using ddPCR. In the second cohort, serial cfDNA evaluation revealed that the rate of EGFR mutation changes with disease state. Increases of EGFR mutation were detected, including C797S several months before the diagnosis of disease progression. As with the first cohort, C797S and T790M in cis and trans position were distinguished by ddPCR at disease progression. Coincidentally, in the first cohort, next generation sequencing detected NRAS Q61K mutation and the resistance with NRAS Q61K mutation was overcome by trametinib. In the second cohort, serial cfDNA analysis was useful for evaluating bone oligo‐progression and local radiation therapy.
In this study, we monitored osimertinib resistance mechanisms mainly using cfDNA in two cohorts: (i) tumor specimens and/or plasma samples from 26 patients with progressive disease during the osimertinib treatment after T790M confirmation were examined; and (ii) 18 patients with non–small cell lung cancer who were positive for EGFR‐T790M and who started osimertinib were analyzed by collecting plasma samples every month from the beginning of osimertinib treatment to disease progression or to 2 years after the osimertinib treatment. We found that C797S and T790M in cis and in trans positions can be detected by ddPCR after the disease progression and confirmed the usefulness of serial evaluation of EGFR mutation in the plasma cfDNA for detecting the emergence of tumor resistance 1‐2 months earlier than the diagnosis of disease progression and identifying the response to the radiation therapy for oligo‐progression.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a277e2cabf966445372f837b9fc33b98Test
http://europepmc.org/articles/PMC8177776Test

المؤلفون: Ryo Ariyasu, Hiroshi Yoshida, Hiroaki Sakamoto, Satoru Kitazono, Natsuki Takano, Makoto Nishio, Ryosuke Tsugitomi, Yoshiaki Amino, Ryo Manabe, Ken Uchibori, Shinsuke Ogusu, Noriko Yanagitani, Takehiro Tozuka

المصدر: Thoracic Cancer, Vol 12, Iss 6, Pp 906-913 (2021)
Thoracic Cancer

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Future studies, next‐generation sequencing (NGS), lcsh:RC254-282, Young Adult, 03 medical and health sciences, T790M, 0302 clinical medicine, Internal medicine, medicine, Humans, Osimertinib, In patient, Lung cancer, Protein Kinase Inhibitors, EGFR‐TKI, Aged, Aged, 80 and over, Diagnostic Tests, Routine, business.industry, Cancer, Original Articles, General Medicine, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, ErbB Receptors, Companion diagnostic (CDx), 030104 developmental biology, Egfr mutation, 030220 oncology & carcinogenesis, polymerase chain reaction (PCR), Original Article, Female, EGFR mutation, business, Companion diagnostic

الوصف: Background Several companion diagnostic (CDx) tests for epidermal growth factor receptor tyrosine kinase inhibitors (EGFR‐TKIs) have been approved. In our institute, the CDx test for EGFR‐TKIs was changed from the Therascreen test (Therascreen) to the Cobas EGFR v2 test (Cobas) because only Cobas was approved for the use of osimertinib in patients with EGFR‐mutated non‐small cell lung cancer (NSCLC) with T790M mutations. The clinical influence of switching the CDx test has not yet been examined comprehensively. Methods All serial patients with lung cancer tested for EGFR mutations with CDx tests between February 2014 and February 2016 at the Cancer Institute Hospital of the Japanese Foundation for Cancer Research (JFCR) were enrolled in this analysis. Results Therascreen was used as a CDx test for EGFR‐TKI therapy in 607 patients between February 2014 and January 2015, and Cobas was used in 621 patients between February 2015 and February 2016. EGFR mutations were detected in 218 patients (35.9%) and 244 patients (39.3%) tested with Therascreen and Cobas, respectively. At the initial diagnosis, 400 and 459 patients were tested with Therascreen and Cobas, respectively. EGFR mutation subtypes, including del19, L858R, and others, were detected in 13.0%, 17.0%, and 2.5% of patients using Therascreen and 17.4%, 14.4%, and 1.5% of patients using Cobas, respectively. Conclusions No significant impact of switching from Therascreen to Cobas as the CDx test for EGFR mutations in clinical practice was observed. However, the detection pattern of the EGFR mutation subtypes between the two CDx tests was slightly different. Key points Significant findings of the study We examined the influence of changing the EGFR test in 1228 patients in total. The detection rate of EGFR mutations was similar. However, the detection pattern for EGFR subtype mutations was slightly different between the two tests. What this study adds Switching CDx tests from target polymerase chain reaction (PCR)‐ to next‐generation sequencing (NGS)‐based methods may lead to obvious changes in clinical practice. When the CDx test is required to change, the investigation of this influence is warranted in future studies.
We examined the influence of changing the EGFR test among target PCR methods in 1228 patients in total. The detection rate of EGFR mutations was similar while the detection pattern for EGFR subtype mutations was slightly different between the two tests. In the future, switching companion diagnostic (CDx) tests from target PCR methods to NGS‐based methods may lead to obvious changes in clinical practice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::5b4b8e6ae7a1f05a33f62f905a01ce39Test
https://doi.org/10.1111/1759-7714.13797Test

المؤلفون: Shinsuke Ogusu, Makoto Nishio, Satoru Kitazono, Ryo Ariyasu, Hironori Ninomiya, Noriko Yanagitani, Takehiro Tozuka, Yoshiaki Amino, Kengo Takeuchi, Ryo Manabe, Hiroaki Sakamaoto, Ryosuke Tsugitomi, Ken Uchibori, Hiroshi Yoshida

المصدر: Thoracic Cancer
Thoracic Cancer, Vol 12, Iss 4, Pp 504-511 (2021)

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, real‐world analysis, Carcinoma, Non-Small-Cell Lung, Internal medicine, Biopsy, medicine, Humans, Biopsy procedure, turnaround time, Aged, Aged, 80 and over, medicine.diagnostic_test, business.industry, High-Throughput Nucleotide Sequencing, Original Articles, General Medicine, Middle Aged, Surgical procedures, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Cobas EGFR mutation test, Clinical trial, Sample quality, Clinical Practice, ALK‐immunohistochemistry, 030104 developmental biology, Egfr mutation, 030220 oncology & carcinogenesis, Female, Original Article, Non small cell, business, Oncomine Dx Target test

الوصف: Background The usefulness of the Oncomine Dx Target test (Oncomine Dx), a next‐generation sequencing (NGS) test, has already been proven in clinical trials. However, NGS requires high‐quality tumor samples and takes a long time to generate results. The feasibility of NGS for use in advanced non‐small cell lung cancer (NSCLC) patients in clinical practice has not yet been determined. Methods Patients serially diagnosed with advanced NSCLC were evaluated in our hospital. The Oncomine Dx, Cobas EGFR mutation test (Cobas EGFR), and ALK‐IHC were performed. The patients were divided into four sets: the full analysis set (FAS) that referred to patients diagnosed with NSCLC, the intent to perform companion diagnostics (CDx) set (IPS) that referred to patients in which CDx had been ordered regardless of sample quality, the per‐performed CDx set (PPS) that referred to patients who could undergo CDx regardless of the results, and the per‐completed CDx set (CCS) that referred to patients in which informative results were received from the CDx. Results The total number of patients analyzed in the study was 167. The IPS/FAS of Oncomine Dx (80.2%) was lower than that of the ALK‐IHC (85.0%) and Cobas EGFR (92.8%). The CCS/FAS of Oncomine Dx (65.9%) was lower than that of the ALK‐IHC (82.0%) and Cobas EGFR (92.2%). PPS/IPS and CCS/PPS of the Oncomine Dx with nonsurgical biopsy ranged between 78.6% and 90.9%, which was lower than those patients who underwent surgical resection (95.0% and 100%). Conclusions The feasibility of Oncomine Dx in clinical practice was lower than the other CDx. The feasibility of Oncomine Dx will increase by improving the biopsy procedure. Key points Significant study findings The usefulness of a next‐generation sequencing (NGS) test has been proven in clinical trials.The feasibility of NGS is lower than other diagnostics in clinical practice especially with regard to nonsurgical biopsy. What this study adds It is necessary to improve the feasibility of NGS in clinical practice.To improve NGS feasibility, turnaround time must be shortened, and larger samples must be obtained during surgical procedures.
The feasibility of Oncomine Dx in clinical practice is relatively low compared with that of the ALK‐IHC and Cobas EGFR.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d028c4cf5d1a05a14610be4783d3204Test
https://doi.org/10.1111/1759-7714.13786Test

المؤلفون: Ryo Ariyasu, Noriko Yanagitani, Fumiyoshi Ohyanagi, Ken Uchibori, Tsukasa Hasegawa, Makoto Nishio, Keita Kudo, Shingo Nishikawa, Yuichi Tambo, Atsushi Horiike, Satoru Kitazono

المصدر: International Journal of Clinical Oncology. 26:507-514

مصطلحات موضوعية: 0301 basic medicine, medicine.medical_specialty, Bevacizumab, business.industry, Phases of clinical research, Combination chemotherapy, Hematology, General Medicine, medicine.disease, Chemotherapy regimen, Gastroenterology, 03 medical and health sciences, Regimen, 030104 developmental biology, 0302 clinical medicine, Oncology, 030220 oncology & carcinogenesis, Internal medicine, medicine, Mucositis, Surgery, business, Adverse effect, Lung cancer, medicine.drug

الوصف: We assessed the efficacy and safety of bevacizumab and S-1 chemotherapy for patients with previously treated advanced non-squamous non-small-cell lung cancer (NSCLC). This was a prospective single-arm study, including patients with non-squamous NSCLC who had received at least one chemotherapy regimen along with a platinum-based regimen. Bevacizumab 15 mg/kg was intravenously administered every 3 weeks, and S-1 40 mg/m2 was orally administered twice daily from day 1 (evening) through day 15 (morning). The treatment continued for 3 weeks/cycle until disease progression or until unacceptable toxicities occurred. During the lead-in part, six patients were evaluated for dose-limiting toxicity (DLT) rate. In phase II, the primary endpoint was objective response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety. In the lead-in part, we evaluated the safety in the first six patients and observed no DLT. In phase II, a total of 46 patients were enrolled from September 2012 to December 2018. The median follow-up duration was 13.7 months [95% confidence interval (CI) 1.4–72.0]. The ORR was 28.3%. The median PFS and OS were 4.3 (95% CI 2.9–5.9) and 15.0 months (95% CI 9.8–30.3), respectively. The most common adverse events were hypertension (65.2%), diarrhea (47.8%), mucositis oral (45.7%), and proteinuria (43.5%), and the most common grade 3 adverse events were hypertension (23.9%) and proteinuria (6.5%). Grade 4/5 adverse events were not observed. Bevacizumab and S-1 combination chemotherapy showed high activity and were well tolerated in patients with previously treated advanced non-squamous NSCLC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::6d6f784915f0cfcebc80ffafd4cfc39dTest
https://doi.org/10.1007/s10147-020-01822-7Test

المؤلفون: Tsukasa Hasegawa, Ryo Ariyasu, Masahiro Seike, Makoto Nishio, Takeshi Horai, Hiroshi Yoshida, Noriko Yanagitani, Akihiko Gemma, Ken Uchibori, Takehiro Tozuka, Satoru Kitazono, Yoshiaki Amino, Takahiro Yoshizawa, Hiroaki Sakamoto, Shinya Uematsu

المصدر: Thoracic Cancer
Thoracic Cancer, Vol 11, Iss 9, Pp 2465-2472 (2020)

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Lung Neoplasms, medicine.medical_treatment, immune checkpoint inhibitor, B7-H1 Antigen, central nervous system metastases, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, brain metastases, Programmed cell death 1, Medicine, Aged, 80 and over, biology, Brain Neoplasms, digestive, oral, and skin physiology, General Medicine, Middle Aged, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, 030220 oncology & carcinogenesis, Female, Original Article, Non small cell, medicine.symptom, Antibody, Adult, Pulmonary and Respiratory Medicine, medicine.medical_specialty, education, lcsh:RC254-282, Anti PD‐1/PD‐L1 antibody, Asymptomatic, 03 medical and health sciences, Internal medicine, Humans, Poor performance status, Lung cancer, Aged, Retrospective Studies, business.industry, Retrospective cohort study, Original Articles, Immunotherapy, medicine.disease, stomatognathic diseases, 030104 developmental biology, biology.protein, business

الوصف: Background The efficacy of anti‐programmed cell death‐1/ligand 1 antibody monotherapy (anti‐PD‐1/PD‐L1 monotherapy) in patients with active brain metastases (BMs) is not established. Here, we aimed to evaluate the efficacy of anti‐PD‐1/PD‐L1 monotherapy in non‐small cell lung cancer (NSCLC) patients with active BMs. Methods This retrospective study included NSCLC patients treated with second‐line or later‐line anti‐PD‐1/PD‐L1 monotherapy between December 2015 and August 2019. Patients were classified into those with or without active BMs, including symptomatic BMs requiring systemic steroids and untreated BMs. The progression‐free survival (PFS) and overall survival (OS) of the patients with and without active BMs were compared. Intracranial and extracranial tumor responses were evaluated in patients with active BMs. Results We analyzed 197 patients who had received anti‐PD‐1/PD‐L1 monotherapy. Among them, 24 had active BMs. Among those without active BMs, 145 had no BMs and 28 had treated asymptomatic BMs. The PFS and OS of patients with active BMs were significantly shorter than those of patients without active BMs (1.3 vs. 2.7 months; P
The present study showed that anti‐PD‐1/PD‐L1antibody monotherapy was not effective for non‐small cell lung cancer patients with active brain metastases. Intracranial and extracranial response rates were 13.3% and 26.7% respectively. Further studies on immunotherapy are needed for patients with active BMs.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b8f1ff75d1a1081b9e457351f91678f9Test
https://doi.org/10.1111/1759-7714.13557Test

المؤلفون: Mika Tsukahara, Koutaroh Okada, Ryohei Katayama, Noriko Yanagitani, Makoto Nishio, Kenichi Okubo, Ken Uchibori, Ken Takahashi, Yosuke Seto, Naoya Fujita, Shinya Uematsu, Tomoko Oh-hara

المصدر: Thoracic Cancer, Vol 11, Iss 3, Pp 581-587 (2020)
Thoracic Cancer

مصطلحات موضوعية: 0301 basic medicine, Alectinib, Lung Neoplasms, Apoptosis, next‐generation sequence, 0302 clinical medicine, Piperidines, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, Tumor Cells, Cultured, Anaplastic lymphoma kinase, Medicine, Anaplastic Lymphoma Kinase, Sulfones, ALK compound mutation, Sanger sequencing, General Medicine, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Oncology, 030220 oncology & carcinogenesis, symbols, Original Article, Female, medicine.drug, Pulmonary and Respiratory Medicine, non‐small cell lung cancer, Brigatinib, Carbazoles, lcsh:RC254-282, 03 medical and health sciences, symbols.namesake, Organophosphorus Compounds, Crizotinib, Humans, Lung cancer, Protein Kinase Inhibitors, Aged, Cell Proliferation, Ceritinib, business.industry, Original Articles, medicine.disease, Lorlatinib, 030104 developmental biology, Pyrimidines, Drug Resistance, Neoplasm, Mutation, Cancer research, business

الوصف: Background Anaplastic lymphoma kinase (ALK) fusion genes are found in 3%-5% of non-small cell lung cancers (NSCLCs). ALK inhibitors show a very high response rate to ALK-positive NSCLCs. However, the emergence of acquired resistance is inevitable. In this study, we investigated the drugs for overcoming resistance especially compound mutations after sequential treatment with crizotinib, alectinib, and lorlatinib. Method Next-generation sequencing (NGS) and Sanger sequencing were performed on a liver biopsy tissue obtained from a clinical case. Ba/F3 cells in which mutant EML4-ALK were overexpressed were prepared, and cell viability assay and immunoblotting were performed to check the sensitivity of five independent ALK inhibitors. Results I1171S + G1269A double mutation was identified by NGS and Sanger sequencing on a liver biopsy tissue from a patient who relapsed on lorlatinib treatment. Ceritinib and brigatinib-but not other ALK inhibitors-were active against the compound mutations in the cell line model. Conclusions With the sequential ALK inhibitors treatment, cancer cells accumulate new mutations in addition to mutations acquired previously. The identified compound mutation (I1171S + G1269A) was found to be sensitive to ceritinib and brigatinib, and indeed the patient's tumor partially responded to ceritinib. Key points ALK compound mutation was found in a clinical sample that was resistant to lorlatinib after sequential ALK-tyrosine kinase inhibitor (TKI) treatment. Ceritinib and brigatinib are potential overcoming drugs against ALK I1171S + G1269A double mutation.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::435113d9a070a711eacc79dd3055f9b4Test
https://doaj.org/article/8eb722c532b94cce883b69c0048498a1Test

المؤلفون: Ryohei Katayama, Noriko Yanagitani, Fumiyoshi Ohyanagi, Mika Tsukahara, Makoto Nishio, Naoya Fujita, Yuichi Tambo, Sumie Koike, Atsushi Horiike, Satoru Kitazono, Takahiro Yoshizawa, Shingo Nishikawa, Ken Uchibori

المصدر: Cancer Science

مصطلحات موضوعية: 0301 basic medicine, Alectinib, Cancer Research, Lung Neoplasms, Lactams, Lactams, Macrocyclic, Carbazoles, Aminopyridines, Drug resistance, 03 medical and health sciences, tyrosine kinase inhibitor, 0302 clinical medicine, Asian People, Crizotinib, Piperidines, Clinical Research, Carcinoma, Non-Small-Cell Lung, hemic and lymphatic diseases, medicine, Humans, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, Sulfones, Progression-free survival, Lung cancer, Protein Kinase Inhibitors, Ceritinib, business.industry, progression‐free survival, Original Articles, General Medicine, medicine.disease, Lorlatinib, Recombinant Proteins, respiratory tract diseases, Pyrimidines, 030104 developmental biology, Oncology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, Cancer research, Pyrazoles, Original Article, business, resistance mechanism, medicine.drug

الوصف: The treatment for anaplastic lymphoma kinase (ALK)‐positive lung cancer has been rapidly evolving since the introduction of several ALK tyrosine kinase inhibitors (ALK‐TKI) in clinical practice. However, the acquired resistance to these drugs has become an important issue. In this study, we collected a total of 112 serial biopsy samples from 32 patients with ALK‐positive lung cancer during multiple ALK‐TKI treatments to reveal the resistance mechanisms to ALK‐TKI. Among 32 patients, 24 patients received more than two ALK‐TKI. Secondary mutations were observed in 8 of 12 specimens after crizotinib failure (G1202R, G1269A, I1171T, L1196M, C1156Y and F1245V). After alectinib failure, G1202R and I1171N mutations were detected in 7 of 15 specimens. G1202R, F1174V and G1202R, and P‐gp overexpression were observed in 3 of 7 samples after ceritinib treatment. L1196M + G1202R, a compound mutation, was detected in 1 specimen after lorlatinib treatment. ALK‐TKI treatment duration was longer in the on‐target treatment group than that in the off‐target group (13.0 vs 1.2 months). In conclusion, resistance to ALK‐TKI based on secondary mutation in this study was similar to that in previous reports, except for crizotinib resistance. Understanding the appropriate treatment matching resistance mechanisms contributes to the efficacy of multiple ALK‐TKI treatment strategies.
Anaplastic lymphoma kinase (ALK)‐positive lung cancer accounts for 3%–5% of all non–small cell lung cancer cases. The use of ALK tyrosine kinase inhibitors (ALK‐TKI) is highly effective and four ALK‐TKI have been approved in Japan. However, ALK‐TKI lose their efficacy because of acquired resistance. In this study, we analyzed “real world” resistance mechanisms using serial tumor biopsies during sequential treatment with ALK‐TKI in Japanese patients with ALK‐positive lung cancer and revealed the sequential transition of resistance mechanisms. The identification of resistance mechanisms revealed that the precise utilization of ALK‐TKI based on resistance mechanisms will have potential benefits in patients with ALK‐positive lung cancer in clinical settings.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2b2406885a5cd0179f5722a930abe6adTest
https://doi.org/10.1111/cas.14314Test

المؤلفون: Takahiro Yoshizawa, Tsukasa Hasegawa, Kazuo Kasahara, Shinya Uematsu, Takeshi Horai, Makoto Nishio, Satoru Kitazono, Ken Uchibori, Noriko Yanagitani, Atsushi Horiike, Yoshiaki Amino

المصدر: International Journal of Clinical Oncology. 25:67-73

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Programmed Cell Death 1 Receptor, Locally advanced, 03 medical and health sciences, Antineoplastic Agents, Immunological, 0302 clinical medicine, Surgical oncology, Carcinoma, Non-Small-Cell Lung, Internal medicine, medicine, Humans, Adverse effect, Aged, Retrospective Studies, Pneumonitis, Chemotherapy, business.industry, Standard treatment, Anti pd 1, Chemoradiotherapy, Hematology, General Medicine, Middle Aged, medicine.disease, Survival Analysis, Treatment Outcome, 030104 developmental biology, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Female, Surgery, Neoplasm Recurrence, Local, business

الوصف: Chemoradiotherapy (CRT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Recently, anti-PD-1 antibody therapy became a key treatment for stage IV NSCLC as the combination of immune checkpoint inhibitors (ICIs) and platinum doublet chemotherapy. However, the efficacy and toxicity of anti-PD-1 therapy for recurrence after CRT in stage III NSCLC are not well examined. Patients who received anti-PD-1 therapy for recurrence after CRT were identified in our clinical database. The safety and efficacy of anti-PD-1 therapy were retrospectively analyzed. From March 1, 2013 to April 30, 2018, there were 20 patients who received anti-PD-1 therapy for recurrence after CRT. The median duration from CRT to initial anti-PD-1 therapy was 9.3 months. 12 patients (60%) were alive and 7 patients (35%) were still receiving anti-PD-1 therapy at the data cutoff point (median follow-up, 13.5 months). The ORR for anti-PD-1 therapy was 45.0%. Median progression-free survival (PFS) and overall survival (OS) from initiation of anti-PD-1 therapy was 8.4 months and 26.2 months, respectively. PFS in patients who had a short interval from last CRT to initial anti-PD-1 therapy seemed to have better outcomes (duration from last CRT to initial anti-PD-1 therapy

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e3bfafdc96519c9dac691a5390e3448cTest
https://doi.org/10.1007/s10147-019-01537-4Test

المؤلفون: Atsushi Horiike, Noriko Yanagitani, Takahiro Yoshizawa, Shingo Nishikawa, Ryo Ariyasu, Junji Koyama, Ken Uchibori, Tomoaki Sonoda, Makoto Nishio, Hironori Ninomiya, Yosuke Dotsu, Masafumi Saiki, Yuichi Ishikawa, Satoru Kitazono

المصدر: Journal of Thoracic Disease. 11:1919-1928

مصطلحات موضوعية: Pulmonary and Respiratory Medicine, Oncology, endocrine system, medicine.medical_specialty, business.industry, Thyroid Transcription Factor 1, Thyroid, non-small cell lung cancer (NSCLC), Pembrolizumab, Odds ratio, respiratory system, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Internal medicine, medicine, Original Article, Nivolumab, business, Lung cancer, 030215 immunology, Hormone

الوصف: Background: Recent studies have suggested a correlation between immune-related thyroid dysfunction (irTD) and the superior efficacy of anti-programmed cell death protein-1 (anti-PD-1) treatment in non-small cell lung cancer (NSCLC). Embryologically, the lung and thyroid are similar in origin, and thyroid transcription factor-1 (TTF-1) expresses in both organs, including NSCLC. We explored our hypothesis that TTF-1 expression in NSCLC might correlate with irTD incidence and anti-PD-1 treatment efficacy. Methods: We identified 132 patients with NSCLC treated with anti-PD-1 antibody at our hospital between December 2015 and June 2017. We evaluated TTF-1 expression in tumor by immunohistochemistry using a mouse monoclonal antibody (clone 8G7G3/1, 1:100, Dako). IrTD was defined as two or more successive abnormal levels of thyroid-stimulating hormone (TSH) during anti-PD-1 treatment. We retrospectively assessed correlations between TTF-1 expression in tumor, irTD incidence, and anti-PD-1 treatment efficacy. Results: Of 132 patients, 67 (51%) and 65 (49%) were positive and negative for TTF-1, respectively. We observed irTD in 19 patients (6 positives and 13 negatives for TTF-1). The incidence of irTD was 9% and 20% in TTF-1-positive and TTF-1-negative NSCLCs, respectively (P=0.086). Particularly, in non-squamous (NSQ) cell carcinomas, the irTD incidence was significantly higher in patients negative for TTF-1 (30%) than in those positive for TTF-1 (9%; P=0.010), and TTF-1 expression was identified as a significant risk factor for irTD on multivariate logistic regression analysis [odds ratio (OR), 0.18; 95% confidence interval (CI), 0.05–0.59; P=0.005]. Furthermore, longer median progression-free survival (10.3 months) was observed in patients with TTF-1-negative NSCLC with irTD compared to those with TTF-1-positive NSCLC with irTD, TTF-1-positive NSCLC without irTD, and TTF-1-negative NSCLC without irTD (4.2, 1.4, and 2.4 months, respectively). Conclusions: TTF-1 expression in NSCLC might correlate with irTD and anti-PD-1 treatment efficacy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fd1ce2a8bb1c0340835f56148a7dcd60Test
https://doi.org/10.21037/jtd.2019.04.102Test

المؤلفون: Miyako Satouchi, Ken Uchibori, Motoko Tachihara, Chiyuki Kokan, Yoshiko Urata, Keisuke Aoe, Kazuyuki Kobayashi, Kentaro Iwanaga, Akemi Sato, Naoko Sueoka-Aragane, Satoshi Morita, Tomonori Hirashima, Nobuyuki Katakami, Shunichi Negoro, Takako Inoue, Fumio Imamura, Masahide Mori

المصدر: Lung Cancer. 124:65-70

مصطلحات موضوعية: Male, 0301 basic medicine, Pulmonary and Respiratory Medicine, Oncology, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Pemetrexed, Gene mutation, 03 medical and health sciences, T790M, 0302 clinical medicine, Gefitinib, Carcinoma, Non-Small-Cell Lung, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Osimertinib, Epidermal growth factor receptor, Lung cancer, Aged, Neoplasm Staging, Aged, 80 and over, biology, business.industry, Middle Aged, medicine.disease, Progression-Free Survival, respiratory tract diseases, ErbB Receptors, 030104 developmental biology, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Mutation, biology.protein, Female, Neoplasm Recurrence, Local, business, Progressive disease, medicine.drug

الوصف: Objectives Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (i.e., EGFR-TKIs) improve the survival of lung cancer patients harboring EGFR mutations. Despite the initial efficacy of EGFR-TKIs, the disease progression caused by acquired resistance to these inhibitors is inevitable. T790M mutations represent a major resistance mechanism to EGFR-TKIs but can be overcome using osimertinib. The IMPRESS trial revealed that the continuation of EGFR-TKI beyond progressive disease (PD) concurrent with platinum-doublet chemotherapy was not beneficial. However, various clinical trials have suggested that EGFR-TKI beyond PD plus single-agent chemotherapy may be a possible treatment strategy. Materials and Methods This study was a single-arm phase II trial. Patients with EGFR-activating mutations (del19 and L858R) that progressed using first-line gefitinib treatment were enrolled and treated with gefitinib beyond PD plus pemetrexed 500 mg/m2 q3w. The primary endpoint was progression-free survival (PFS). Mutation-biased polymerase chain reaction quenching probe, which is the original method for detecting T790M mutations in cell-free plasma DNA, was used prior to treatment. Results Thirty-six patients were enrolled between May 1, 2013, and March 31, 2016. One patient was excluded before starting the treatment. Among the 35 patients, 15 patients had del19 mutations, and 20 patients had L858R mutations; 33 patients were evaluable for response by using radiographic findings. The median PFS was 6.7 months (95% confidence interval: 4.4–7.7 months). Nineteen patients were T790M positive. No significant difference in PFS was found in a subgroup analysis of EGFR mutation status and T790M positivity. All toxicities were tolerable. Conclusion Gefitinib plus pemetrexed treatment following relapse using gefitinib in patients with Non-small cell lung cancer harboring EGFR mutations demonstrated preferable PFS with mild toxicity. This combination therapy may be considered for platinum-unfit patients without T790M with disease progression using first-line gefitinib. (This clinical trial was registered in UMIN-CTGR as UMIN000010709).

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4104cdcde8f376c37e0e4f1a5a4da861Test
https://doi.org/10.1016/j.lungcan.2018.07.031Test