研究者詳細 - 長谷川　智一

論文 - 長谷川　智一

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Prediction of Results of Radiotherapy With Ku70 Expression and an Artificial Neural Network

TOMOKAZU HASEGAWA, MASANORI SOMEYA, MASAKAZU HORI, TAKAAKI TSUCHIYA, YUUKI FUKUSHIMA, YOSHIHISA MATSUMOTO, KOH-ICHI SAKATA

In Vivo ( Anticancer Research USA Inc. ) 34 ( 5 ) 2865 - 2872 2020年09月

Background/Aim: Accurate prediction of radiotherapy results is indispensable for the individualized selection of treatment modalities of cancer. We examined the application of the artificial neural network (ANN) model in predicting radiotherapy results using clinical factors and immunohistochemical staining of Ku70 as inputs. Patients and Methods: We analyzed 79 prostate cancer patients with localized adenocarcinoma treated with radiotherapy between August 2001 and October 2010. We also analyzed 46 hypopharyngeal cancer patients with squamous cell carcinoma treated with radiotherapy between March 2002 and December 2009. The properly trained ANN analysis using a standard feedforward, back-propagation neural network was used to predict the radiotherapy treatment results. Results: The areas under the receiver-operating characteristic curve (AUC) were 0.939 for patients treated with intensity modulated radiotherapy (IMRT)+androgen deprivation therapy (ADT), 0.803 for IMRT alone, and 0.960 for 3D-conformal radiotherapy (CRT) alone in prostate cancer. Sensitivity and specificity were 85.7% and 90.4% for IMRT+ADT, 75.0% and 88.5% for IMRT alone, and 92.3% and 100% for 3D-CRT alone. The AUC was 0.901 for hypopharyngeal cancer. Sensitivity and specificity were 66.7% and 88.2%, respectively. Conclusion: We demonstrated a possibility to predict the radiotherapy treatment results in prostate and hypopharyngeal cancer using ANN in combination with Ku70 expression and clinical factors as inputs.

DOI

Expression of Ku70 predicts results of radiotherapy in prostate cancer.

Tomokazu Hasegawa, Masanori Someya, Masakazu Hori, Yoshihisa Matsumoto, Kensei Nakata, Masanori Nojima, Mio Kitagawa, Takaaki Tsuchiya, Naoya Masumori, Tadashi Hasegawa, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 193 ( 1 ) 29 - 37 2017年01月 [国際誌]

BACKGROUND AND PURPOSE: Therapeutic strategy for prostate cancer is decided according to T stage, Gleason score, and prostate-specific antigen (PSA) level. These clinical factors are not accurate enough to predict individual risk of local failure of prostate cancer after radiotherapy. Parameters involved with radiosensitivity are required to improve the predictive capability for local relapse. PATIENTS AND METHODS: We analyzed 58 patients with localized adenocarcinoma of the prostate between August 2007 and October 2010 treated with 76 Gy of intensity-modulated radiotherapy (IMRT) as a discovery cohort and 42 patients between March 2001 and May 2007 treated with three-dimensional conformal radiotherapy (3D-CRT) as a validation cohort. Immunohistochemical examination for proteins involved in nonhomologous end-joining was performed using biopsy specimens. RESULTS: Ku70 expression was not correlated with various clinical parameters, such as the Gleason score and D'amico risk classification, indicating that Ku70 expression was an independent prognostic factor. The predictive value for PSA relapse was markedly improved after the combination of Gleason score and Ku70 expression, as compared with Gleason score alone. In patients treated with radiotherapy and androgen deprivation therapy (ADT), no relapses were observed in patients with Gleason score ≤7 or low Ku70 expression. In contrast, patients with Gleason score ≥8 and high Ku70 expression had high PSA relapse rates. In the validation cohort, similar results were obtained. CONCLUSION: Treatment with 76 Gy and ADT can be effective for patients with Gleason score ≤7 or low Ku70 expression, but is not enough for patients with Gleason score ≥8 and high Ku70 expression and, thus, require other treatment approaches.

DOI PubMed

[RPT Doi Award: Virtual clinical trial based on outcome modeling with iteratively redistributed extrapolation data].

Kohei Oguma, Taiki Magome, Masanori Someya, Tomokazu Hasegawa, Koh-Ichi Sakata

Igaku butsuri : Nihon Igaku Butsuri Gakkai kikanshi = Japanese journal of medical physics : an official journal of Japan Society of Medical Physics 44 ( 3 ) 52 - 52 2024年 [国内誌]

DOI PubMed

Identification and Quantification of Radiotherapy-related Protein Expression in Cancer Tissues Using the Qupath Software and Prediction of Treatment Response.

Tomokazu Hasegawa, Masanori Someya, Takaaki Tsuchiya, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Shoh Mafune, Ryuu Okuda, Juno Kaguchi, Atsuya Ohguro, Ryo Kamiyama, Ayato Ashina, Yuka Toshima, Yoshihiko Hirohashi, Toshihiko Torigoe, Koh-Ichi Sakata

In vivo (Athens, Greece) 38 ( 3 ) 1470 - 1476 2024年 [国際誌]

BACKGROUND/AIM: Automated measurement of immunostained samples can enable more convenient and objective prediction of treatment outcome from radiotherapy. We aimed to validate the performance of the QuPath image analysis software in immune cell markers detection by comparing QuPath cell counting results with those of physician manual cell counting. PATIENTS AND METHODS: CD8- and FoxP3-stained cervical, CD8-stained oropharyngeal, and Ku70-stained prostate cancer tumor sections were analyzed in 104 cervical, 92 oropharyngeal, and 58 prostate cancer patients undergoing radiotherapy at our Institution. RESULTS: QuPath and manual counts were highly correlated. When divided into two groups using ROC curves, the agreement between QuPath and manual counts was 89.4% for CD8 and 88.5% for FoxP3 in cervical cancer, 87.0% for CD8 in oropharyngeal cancer and 80.7% for Ku70 in prostate cancer. In cervical cancer, the high CD8 group based on QuPath counts had a better prognosis and the low CD8 group had a significantly worse prognosis [p=0.0003; 5-year overall survival (OS), 65.9% vs. 34.7%]. QuPath counts were more predictive than manual counts. Similar results were observed for FoxP3 in cervical cancer (p=0.002; 5-year OS, 62.1% vs. 33.6%) and CD8 in oropharyngeal cancer (p=0.013; 5-year OS, 80.2% vs. 47.2%). In prostate cancer, high Ku70 group had worse and low group significantly better outcome [p=0.007; 10-year progression-free survival (PFS), 56.0% vs. 93.8%]. CONCLUSION: QuPath showed a strong correlation with manual counting, confirming its utility and accuracy and potential applicability in clinical practice.

DOI PubMed

Prediction of Treatment Response Based on Nutritional Status and Tumor Immunity in Oropharyngeal Cancer Patients Treated With Chemoradiotherapy.

Mio Kitagawa, Juno Kaguchi, Masanori Someya, Yuki Fukushima, Tomokazu Hasegawa, Takaaki Tsuchiya, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Ryu Okuda, Atsuya Ohguro, Ryo Kamiyama, Ayato Ashina, Yuka Toshima, Yoshihiko Hirohashi, Toshihiko Torigoe, Koh-Ichi Sakata

Cancer diagnosis & prognosis 4 ( 6 ) 789 - 796 2024年 [国際誌]

BACKGROUND/AIM: Radiotherapy (RT) for advanced oropharyngeal cancer (OPC) is effective, especially when combined with chemotherapy (CRT). However, its success can vary depending on factors, such as tumor stage, HPV infection (p16 status), and the patient's nutritional and immune status. This study examined the controlling nutritional status (CONUT) score and tumor immunity as predictive factors for treatment outcomes in OPC, aiming to develop a personalized risk score. PATIENTS AND METHODS: A retrospective analysis was conducted on 84 patients with OPC treated with definitive RT or CRT, and survival outcomes were compared based on various factors, including BMI, CONUT score, CD8 expression, and HLA class II expression. RESULTS: We observed better overall survival (OS) rates in CD8-positive patients and those with higher HLA class II expression. The univariate analysis identified stage, p16 status, BMI, CONUT score, and CD8 expression as significantly associated with OS. In multivariate analysis, stage, BMI, and CONUT score remained significant predictors of OS. A risk scoring system was developed based on stage, p16 status, BMI, CONUT score, and CD8 expression. Patients were categorized into low-risk and high-risk groups, with significantly better survival in the low-risk group. CONCLUSION: A combined risk score incorporating clinical, nutritional, and immune factors can improve the prediction of treatment outcomes for OPC patients. This risk stratification may enable personalized treatment plans and improve ΟS rates.

DOI PubMed

Prediction of late adverse events in pelvic cancer patients receiving definitive radiotherapy using radiation-induced gamma-H2AX foci assay.

Masanori Someya, Tomokazu Hasegawa, Asako J Nakamura, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Sho Mafune, Yutaro Ikeuchi, Hiroshi Tauchi, Koh-Ichi Sakata

Journal of radiation research 64 ( 6 ) 948 - 953 2023年11月 [国際誌]

Radiation can induce DNA double-stranded breaks, which are typically detected by the fluorescence of phosphorylated histone H2AX. In this study, we examined the usefulness of the dynamics of radiation-induced gamma-H2AX foci of peripheral blood lymphocytes (PBLs), as a marker of DNA repair ability, in predicting late adverse events from radiotherapy. A total of 46 patients with cervical, vaginal and anal canal cancers treated with radical radiotherapy between 2014 and 2019 were included in this analysis. Concurrent chemotherapy was administered in 36 cases (78.3%). Peripheral blood was obtained before treatment, and then irradiated ex vivo with 1 Gy X-ray. The ratio of radiation-induced gamma-H2AX foci in PBLs measured at 30 min and at 4 h was defined as the foci decay ratio (FDR). With a median follow-up of 54 months, 9 patients (19.6%) were observed to have late genitourinary or gastrointestinal (GU/GI) toxicity. The FDR ranged from 0.51 to 0.74 (median 0.59), with a significantly higher incidence of Grade 1 or higher late adverse events in the FDR ≥ 0.59 group. In multivariate analysis, FDR ≥ 0.59 and hypertension also emerged as significant factors associated with the development of late toxicities. Overall, our results suggest that measurement of radiation-induced gamma-H2AX foci in PBLs may predict the risk of late GU/GI toxicities from chemoradiotherapy, which can enable tailoring the radiation dose to minimize adverse effects.

DOI PubMed

Analysis of treatment response with proteins related to tumor immunity in postoperative irradiated cervical cancer patients

Shoh Mafune, Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Ryu Okuda, Masahiro Iwasaki, Motoki Matsuura, Terufumi Kubo, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-ichi Sakata

2023年11月

DOI

放射線感受性の個人差に基づく次世代の放射線治療と放射線防護腫瘍および正常組織の放射線感受性予測に基づいた個別化放射線治療の実践(Personalized radiotherapy based on the prediction of radiosensitivity of tumors and normal tissues)

Someya Masanori, Hasegawa Tomokazu, Tsuchiya Takaaki, Kitagawa Mio, Gocho Toshio, Mafune Shoh, Sakata Koh-ichi

日本放射線影響学会大会講演要旨集 ( (一社)日本放射線影響学会 ) 66回 12 - 12 2023年11月

化学放射線+免疫療法を行った3期NSCLCにおける、末梢血リンパ細胞のTCRレパトア解析

染谷正則, 長谷川智一, 北川未央, 土屋高旭, 後町俊夫, 眞船翔, 金関貴幸, 蒔田芹奈, 鳥越俊彦, 坂田耕一

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 61回 O46 - 3 2023年10月

Immunohistological evaluation of patients treated with intra-arterial chemoradiotherapy and surgery for oral cancer.

Yutaro Ikeuchi, Masanori Someya, Tomokazu Hasegawa, Masato Saito, Shoh Mafune, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Hironari Dehari, Kazuhiro Ogi, Takanori Sasaki, Yoshihiko Hirohashi, Toshihiko Torigoe, Naoki Hirokawa, Akihiro Miyazaki, Koh-Ichi Sakata

Medical molecular morphology 2023年07月 [国内誌]

Preoperative intra-arterial chemoradiotherapy (IACRT) can improve the outcome and reduce the extent of surgery in patients with advanced oral cancer. However, the response to this regimen varies among patients, which may be related to the immune status of the tumor. We investigated the effects of proteins involved in tumor immunity on the outcomes of combined IACRT and surgery for oral cancer. We examined CD8 + and FoxP3 + tumor-infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) expression on immune cells and tumor cells in pretreatment biopsy samples from 69 patients diagnosed with oral cancer treated with IACRT at our institution during 2000-2020. Patients with abundant CD8 + TILs had significantly better 5-year disease-specific survival (DSS) compared to that of patients with less infiltration of these cells (P = 0.016). Patients with higher FoxP3 + T-cells invasion had significantly better DSS compared to that of less FoxP3 (P = 0.005). Patients with high PD-L1 expression in tumor cells and immune cells had significantly better DSS than that of patients with low PD-L1 expression in these cells (P = 0.009 and P = 0.025, respectively). Collectively, these results suggest that the tumor immune microenvironment could affect outcomes of IACRT treatment in oral cancer.

DOI PubMed

Virtual clinical trial based on outcome modeling with iteratively redistributed extrapolation data.

Kohei Oguma, Taiki Magome, Masanori Someya, Tomokazu Hasegawa, Koh-Ichi Sakata

Radiological physics and technology 2023年03月 [国内誌]

Virtual clinical trials (VCTs) can potentially simulate clinical trials on a computer, but their application with a limited number of past clinical cases is challenging due to the biased estimation of the statistical population. In this study, we developed ExMixup, a novel training technique based on machine learning, using iteratively redistributed extrapolated data. Information obtained from 100 patients with prostate cancer and 385 patients with oropharyngeal cancer was used to predict the recurrence after radiotherapy. Model performance was evaluated by developing outcome prediction models based on three types of training methods: training with original data (baseline), interpolation data (Mixup), and interpolation + extrapolation data (ExMixup). Two types of VCTs were conducted to predict the treatment response of patients with distinct characteristics compared to the training data obtained from patient cohorts categorized under risk classification or cancer stage. The prediction models developed with ExMixup yielded concordance indices (95% confidence intervals) of 0.751 (0.719-0.818) and 0.752 (0.734-0.785) for VCTs on the prostate and oropharyngeal cancer datasets, respectively, which significantly outperformed the baseline and Mixup models (P < 0.01). The proposed approach could enhance the ability of VCTs to predict treatment results in patients excluded from past clinical trials.

DOI PubMed

末梢血リンパ球TCRレパトア解析を用いたNSCLCの治療効果予測(Prediction of Treatment Response in NSCLC using Peripheral Blood Lymphocyte TCR Repertoire Analysis)

Someya Masanori, Hasegawa Tomokazu, Kitagawa Mio, Tsuchiya Takaaki, Fukushima Yuki, Gocho Toshio, Mafune Shou, Kanaseki Takayuki, Tokita Serina, Sakata Koh-ichi

日本医学放射線学会学術集会抄録集 ( (公社)日本医学放射線学会 ) 82回 S173 - S173 2023年03月

Combined chemoradiotherapy and programmed cell death-ligand 1 blockade leads to changes in the circulating T-cell receptor repertoire of patients with non-small-cell lung cancer.

Masanori Someya, Serina Tokita, Takayuki Kanaseki, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yoh Kozuka, Shoh Mafune, Yutaro Ikeuchi, Mamoru Takahashi, Keigo Moniwa, Kazuhiko Matsuo, Tadashi Hasegawa, Toshihiko Torigoe, Koh-Ichi Sakata

Cancer science 113 ( 12 ) 4394 - 4400 2022年12月 [国際誌]

Combined chemoradiotherapy (CRT) and programmed cell death-ligand 1 (PD-L1) blockade is a new care standard for unresectable stage III non-small-cell lung cancer (NSCLC). Although this consolidation therapy has improved the overall survival of patients with NSCLC, the synergistic action mechanisms of CRT and immunotherapy on T cells remain unclear. In addition, there is a paucity of reliable biomarkers to predict clinical responses to therapy. In this study, we analyzed T-cell receptor (TCR) sequences in the peripheral blood of five patients with NSCLC. T-cell receptor analysis was undertaken before treatment, after CRT, and after PD-L1 blockade. Notably, we observed the expansion and alteration of the dominant T-cell clonotypes in all cases with a complete response. In contrast, neither expansion nor alteration of the TCR repertoire was observed in cases with progressive disease. T cell expansion was initiated after CRT and was further enhanced after PD-L1 blockade. Our findings suggest the systemic effect of CRT on circulating T cells in addition to the curative effect on limited tumor sites. Dynamic changes in circulating T-cell clonotypes could have a prognostic significance for combined CRT and PD-L1 blockade.

DOI PubMed

Predictive value of an exosomal microRNA-based signature for tumor immunity in cervical cancer patients treated with chemoradiotherapy.

Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Masashi Idogawa, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Medical molecular morphology 56 ( 1 ) 38 - 45 2022年11月 [国内誌]

Resistance of cervical cancer to radiotherapy with concurrent chemotherapy (CCRT) results in a poor prognosis. To identify new biomarkers for predicting the treatment response and prognosis, we explored exosomal microRNA (miRNA) expression signatures associated with the outcome of cervical cancer patients treated with CCRT. Exosomes were isolated from the plasma of 45 patients prior to CCRT during 2014-2020, and miRNA analysis was performed by next-generation sequencing. At a median follow-up of 38 months, 26 patients were recurrence free, 15 patients had died of the disease, and 4 patients received salvage chemotherapy due to distant metastasis. Of the 2522 miRNAs detected, 9 (miR-148a-5p, 1915-3p, 3960, 183-5p, 196b-5p, 200c-3p, 182-5p, 374a-5p, and 431-5p) showed differential expression between the recurrence-free and recurrence groups. Patients were divided into high- and low-risk groups according to the cutoff of the miRNAs-based risk score calculated from respective expression levels. The high-risk group had significantly worse disease-specific survival than the low-risk group (p < 0.001). In addition, miR-374a-5p and miR-431-5p expression showed a weak inverse correlation with tumor-infiltrating CD8+ and FOXP3+ T cells, suggesting a potential inhibitory effect on CCRT by suppressing tumor immunity. This miRNA signature could improve non-invasive monitoring and personalized treatment for cervical cancer.

DOI PubMed

血中エクソソーム由来miRNAを用いた子宮頸癌の治療効果予測

染谷正則, 土屋高旭, 福島悠希, 長谷川智一, 井戸川雅史, 松浦基樹, 岩崎雅宏, 廣橋良彦, 鳥越俊彦, 齋藤豪, 坂田耕一

日本癌治療学会学術集会抄録集 ( (一社)日本癌治療学会 ) 60回 P102 - 2 2022年10月

食道癌化学放射線療法症例における放射線胃炎のリスク因子の検討

佐藤昌則, 大沼啓之, 早坂尚貴, 伊藤亮, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 55 - 55 2022年09月

食道癌化学放射線療法症例における放射線胃炎のリスク因子の検討

佐藤昌則, 大沼啓之, 早坂尚貴, 伊藤亮, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

表在型食道癌ESD後のMM-SM癌における追加化学放射線療法の長期成績

伊藤亮, 大沼啓之, 早坂尚貴, 佐藤昌則, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集 ( 日本消化器病学会-北海道支部 ) 131回・125回 56 - 56 2022年09月

表在型食道癌ESD後のMM-SM癌における追加化学放射線療法の長期成績

伊藤亮, 大沼啓之, 早坂尚貴, 佐藤昌則, 村瀬和幸, 高田弘一, 福島悠希, 長谷川智一, 土屋高旭, 染谷正則, 宮西浩嗣, 坂田耕一, 加藤淳二

Radiotherapy for HPV-related cancers: prediction of therapeutic effects based on the mechanism of tumor immunity and the application of immunoradiotherapy.

Masanori Someya, Yuki Fukushima, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Shoh Mafune, Yutaro Ikeuchi, Yoh Kozuka, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Japanese journal of radiology 40 ( 5 ) 458 - 465 2022年05月 [国内誌]

Human papillomavirus (HPV)-related cancer is one of the diseases entities for which the applications of radiotherapy have been increasing. Recently, the process of carcinogenesis from HPV infection and the mechanism of tumor immunity that develops during disease progression have been elucidated. In this review, we will describe the mechanism of tumor immunity and how chemoradiotherapy may overcome and improve the efficacy of tumor immunity. We will also discuss the usefulness of proteins involved with tumor immunity as a predictive marker of radiotherapy response, and present an overview of ongoing clinical trials of combinations of immune checkpoint inhibitors and radiotherapy to demonstrate the promising combination therapy that has been currently emerging.

DOI PubMed

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