Research Experience 【 display / non-display 】

Research Experience 【 display / non-display 】

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  Sapporo Medical University   放射線医学講座   助教

  博士

Professional Memberships 【 display / non-display 】

Professional Memberships 【 display / non-display 】

• 2013.10

  -

  Now

  日本放射線腫瘍学会

• 2011.04

  -

  Now

  日本医学放射線学会

Research Areas 【 display / non-display 】

Research Areas 【 display / non-display 】

• Life sciences   Radiology   放射線腫瘍学

Affiliation 【 display / non-display 】

Affiliation 【 display / non-display 】

• Sapporo Medical University   Department of Radiology   Assistant Professor  

Research Interests 【 display / non-display 】

Research Interests 【 display / non-display 】

• 腫瘍免疫と放射線治療

• リキッドバイオプシー

• 放射線腫瘍学

Papers 【 display / non-display 】

Papers 【 display / non-display 】

• 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

  Anticancer research   44 ( 7 ) 3077 - 3086  2024.07  [International journal]

  　View Summary

  BACKGROUND/AIM: This study evaluated the association between programmed cell death-ligand 1 (PD-L1) and prognosis in patients with cervical cancer treated with postoperative radiation and the impact of neoadjuvant chemotherapy (NAC) on this association. PATIENTS AND METHODS: Immunohistochemical analysis was performed on biopsy specimens from 42 patients who did not receive NAC and from paired samples before (biopsies) and after (resected tissues) chemotherapy from 46 patients who received NAC to determine the association of PD-L1 with radiotherapy outcomes. RESULTS: In the non-NAC group, patients with ≥10% PD-L1-expressing tumor cells prior to treatment had better recurrence-free survival (RFS) than those with <10% PD-L1-expressing tumor cells (p=0.001). In the NAC group, RFS was significantly lower (p=0.005) in the group with a ≥5% reduction of PD-L1 expression in tumor cells after chemotherapy than in those with <5% reduction. In multivariate analysis, only PD-L1 expression (non-NAC group) and the change in PD-L1 expression (NAC group) were associated with RFS. CONCLUSION: Low PD-L1 expression in a cervical tumor prior to treatment was identified as a risk factor for a poor outcome after postoperative radiotherapy. Furthermore, NAC induces an immunological shift that reduces PD-L1 levels in tumor cells, thereby negatively impacting treatment outcomes.

  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  [International journal]

  　View Summary

  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  [International journal]

  　View Summary

  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  2023.11  [International journal]

  　View Summary

  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

• 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  2023.11

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Misc 【 display / non-display 】

Misc 【 display / non-display 】

• 当院において根治的放射線治療を行った食道癌症例の検討

  大黒敦矢, 眞船翔, 戸島有香, 芦名彩斗, 上山凌央, 後町俊夫, 土屋高旭, 北川未央, 長谷川智一, 染谷正則

  北海道医学雑誌   99 ( 2 )  2024

  J-GLOBAL

• 動注化学放射線療法と外科手術を行った口腔癌の免疫組織学的評価

  染谷正則, 池内佑太郎, 眞船翔, 長谷川智一, 土屋高旭, 北川未央, 後町俊夫, 坂田耕一

  日本免疫治療学会学術集会プログラム・抄録集   21st  2024

  J-GLOBAL

• 化学放射線療法+免疫療法を行った3期切除不能非小細胞肺癌における,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, 眞船翔, 後町俊夫, 池内佑太郎, 金関貴幸, 鳥越俊彦, 坂田耕一

  日本免疫治療学会学術集会プログラム・抄録集   20th  2023

  J-GLOBAL

• 血中エクソソーム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, 池内佑太郎, 眞船翔, 小塚陽, 北川未央, 後町俊夫, 坂田耕一

  日本免疫治療学会学術集会プログラム・抄録集   19th  2022

  J-GLOBAL

• 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(Web)   60th  2022

  J-GLOBAL

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Research Projects 【 display / non-display 】

Research Projects 【 display / non-display 】

• 腫瘍免疫のリアルタイムモニタリングによる個別化放射線治療の確立

  基盤研究(C)

  Project Year :

  2023.04

  -

  2026.03

   

  土屋 高旭

• Analysis of biological factors involved in tumor immunity and its application to personalized radiotherapy.

  Grant-in-Aid for Early-Career Scientists

  Project Year :

  2020.04

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  2023.03

   

  土屋 高旭

  　View Summary

  本研究では腫瘍免疫関連タンパクの発現と放射線治療成績の相関を解明し、臨床応用に結びつけることを目的とする。 具体的には、(A) 治療開始前の生検検体および術後摘出標本を用いた、腫瘍免疫関連タンパクの免疫組織染色による放射線治療効果予測、(B)血中のPD-L1(Programmed death ligand-1)測定による腫瘍免疫応答の解析、(C)腫瘍免疫の制御に関わる血中マイクロRNAの同定を行い、癌細胞の腫瘍免疫関連タンパクを用いた放射線感受性予測法の臨床応用と個別化放射線治療の実用化を目指す。 2020年度は当施設で根治的放射線治療を行った子宮頸癌症例において、腫瘍組織へのCD8陽性T細胞の浸潤形式を調べ、その微小腫瘍環境と臨床因子とOutcomeとの関連を調べた。

• Development of a practical radiosensitivity prediction method for clinical applications

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2018.04

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  2021.03

   

  Sakata Koh-ichi

  　View Summary

  Using biopsy and surgical specimens of breast and cervical cancers, we analyzed the correlation between various protein expressions and radiotherapy outcomes. Radiotherapy of cervical cancer increased the expression of PD-L1 in tumor cells, and there was a strong correlation between the expression of PD-L1 in tumor cells after radiotherapy and overall survival. This suggests that irradiation-induced immunological changes may affect the radiotherapy effect. In patients with early-stage breast cancer treated with postoperative radiotherapy, XRCC4 expression rates in tumor cells were significantly correlated with intra-breast recurrence. By type of recurrence, there was a correlation with XRCC4 expression in True recurrence. True recurrence may be due to the low radiosensitivity of tumor cells.

• Analysis of tumor immunity and radiotherapy using liquid biopsy

  Grant-in-Aid for Early-Career Scientists

  Project Year :

  2018.04

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  2020.03

   

  Tsuchiya Takaaki

  　View Summary

  In the present study, we evaluated the changes in tumor immune-related protein expression caused by radiotherapy in patients with cervical cancer and examined the association between these proteins and prognosis. In 104 patients with uterine cervical cancer treated with preoperative radiotherapy, we evaluated tumor immune-related proteins by immunohistochemistry using biopsy specimens before radiotherapy and surgical specimens after radiotherapy. The results show that radiotherapy causes immunological changes in tumors, and that these changes affect the outcome of radiotherapy.

• Development of methods predicting radiosensitivity that can be clinically applied

  Grant-in-Aid for Scientific Research (C)

  Project Year :

  2015.04

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  2018.03

   

  Sakata Koh-ichi

  　View Summary

  We developed a practical method for predicting radiosensitivity to realize individualized radiotherapy according to the biological characteristics of cancer cells. In uterine cervical cancer and prostate cancer, the correlation between expression proteins involved in repair of DNA double-strand breaks of tumor cells by biopsy specimens and radiotherapy results is analyzed, which is a predictive factor of therapeutic effect. In uterine cervical cancer, the expression rates of Ku 86 and XRCC 4 were predictors of the radiotherapeutic effect on cervical cancer. In prostate cancer, the expression of Ku70 in prostate cancer cells is a prognostic factor independent of clinical factors, and it has been shown that in addition to the prognostic factors presently used in clinical practice, recurrence after radiation treatment can be predicted with high accuracy.