Details of a Researcher - TSUCHIYA Takaaki

Papers - TSUCHIYA Takaaki

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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]

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

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]

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

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]

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 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]

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

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 2023.10

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 2023.07 [Domestic journal]

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

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 2023.03 [Domestic journal]

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

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 2023.03

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 2022.12 [International journal]

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

放射線照射7ヵ月後に非照射部の転移が縮小した悪性黒色腫の1例

佐々木洋, 加藤潤史, 執行遥香, 小林英理, 古舘和樹, 半田稔也, 細川夕菜, 佐藤さゆり, 堀本浩平, 宇原久, 土屋高旭, 染谷正則

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 132 ( 12 ) 2697 - 2697 2022.11

放射線照射7ヵ月後に非照射部の転移が縮小した悪性黒色腫の1例

佐々木洋, 加藤潤史, 執行遥香, 小林英理, 古舘和樹, 半田稔也, 細川夕菜, 佐藤さゆり, 堀本浩平, 宇原久, 土屋高旭, 染谷正則

日本皮膚科学会雑誌 ( (公社)日本皮膚科学会 ) 132 ( 12 ) 2697 - 2697 2022.11

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 2022.10

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 2022.09

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 2022.09

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

Delayed-onset abscopal effect after palliative radiotherapy for acral melanoma treated with anti-PD-1 therapy

Hiroshi Sasaki, Junji Kato, Kohei Horimoto, Sayuri Sato, Yuna Hosokawa, Toshiya Handa, Eri Kobayashi, Kazuki Furudate, Haruka Sigyo, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

JOURNAL OF DERMATOLOGY ( WILEY ) 49 ( 8 ) E255 - E256 2022.08

DOI

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 2022.05 [Domestic journal]

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

Complete Response Induced by Concurrent Chemoradiotherapy in a Patient with NUT Carcinoma: A Case Report

Joji Muramatsu, Kohichi Takada, Shintaro Sugita, Takaaki Tsuchiya, Keisuke Yamamoto, Masaru Takagi, Kazuyuki Murase, Saki Ameda, Yohei Arihara, Koji Miyanishi, Koh-Ichi Sakata, Junji Kato

Internal Medicine ( Japanese Society of Internal Medicine ) 2021.10 [Refereed] [Domestic journal]

An 18-year-old man presented with sudden vision loss in his left eye. Magnetic resonance imaging revealed a tumor that had invaded the left optic nerve, originating from the left posterior ethmoid sinus. Immunohistochemical analyses identified positive staining for NUT protein in the nuclei of tumor cells. We diagnosed locally advanced NUT carcinoma (NC) and initiated concurrent chemoradiotherapy (CCRT), consisting of chemotherapy with vincristine, doxorubicin, and cyclophosphamide, alternating with ifosphamide and etoposide, plus radiation therapy. The patient achieved a complete response. CCRT can be a useful treatment option for adolescent and young-adult patients with locally advanced unresectable NC.

DOI PubMed

Prediction of treatment response from the microenvironment of tumor immunity in cervical cancer patients treated with chemoradiotherapy.

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

Medical molecular morphology 54 ( 3 ) 245 - 252 2021.09 [Domestic journal]

To supplement clinical decision-making in the management of cervical cancer, various prognostic factors, including tumor immune microenvironments, were examined in patients with cervical cancer treated with definitive chemoradiotherapy. We retrospectively analyzed the expression of CD8, FoxP3, HLA-1, PD-L1, and XRCC4 in 100 cases of cervical cancer. The observed tumor immune microenvironments were also classified into three types: inflamed, excluded, and cold type. Less FoxP3+ T cells and cold-type tumor were found to be poor prognostic factors in addition to non-SCC, large pre-treatment tumor volume, and three or less cycles of concurrent chemotherapy based on multivariate analysis. Cold-type tumors had significantly worse prognoses than the other two types, whereas inflamed- and excluded-type tumors showed similar 5-year disease-specific survival (P < 0.001; 0% vs. 60.3% vs. 72.3%). Radiotherapy could overcome the inhibitory immune microenvironment that occurs in excluded type. Individualized combination therapy adapted to pre-treatment tumor immunity may be necessary to improve radiotherapy outcomes in cervical cancer.

DOI PubMed

肛門管癌に対するS-1+MMCを用いた化学放射線療法

池内佑太郎, 福島悠希, 眞船翔, 小塚陽介, 土屋高旭, 長谷川智一, 堀正和, 染谷正則, 坂田耕一

北海道放射線医学雑誌 ( (NPO)メディカルイメージラボ ) 1 22 - 26 2021.03

本邦では、肛門管の原発性扁平上皮癌(SCC)は稀な疾患であり、治療方法及び治療成績に関する報告は少ない。現在、肛門管癌に対する化学放射線療法の標準治療は、5-FU+MMC+RTとされており、救済治療として手術が考えられている。5-FUは持続静注投与であり、入院加療が必要となり、そのため、経口剤であるS-1を用いたS-1+MMC+RTの方が、利便性が高いと考える。さらに、S-1は、5-FUのプロドラックであるテガフールと、ギメラシルが含まれている。ギメラシルは、5-FUの肝臓での分解を強力に抑え、結果としてフルオトウラシルを生体内で高濃度かつ長時間維持させる目的でS-1に含有されているが、他施設及び当科の基礎研究でギメラシルの放射線増感があることが示唆されており、それに期待してS-1を使用することとした。今回、当院で肛門管癌(StageI-IIIC(UICC8th))に対してS-1+MMC+RTを施行した9症例に対して検討した。(著者抄録)

Association between cancer immunity and treatment results in uterine cervical cancer patients treated with radiotherapy.

Masanori Someya, Takaaki Tsuchiya, Yuki Fukushima, Tomokazu Hasegawa, Yu Takada, Masakazu Hori, Katsutoshi Miura, Mio Kitagawa, Toshio Gocho, Yoshihiko Hirohashi, Toshihiko Torigoe, Masahiro Iwasaki, Motoki Matsuura, Tsuyoshi Saito, Koh-Ichi Sakata

Japanese journal of clinical oncology 50 ( 11 ) 1290 - 1297 2020.10 [International journal]

OBJECTIVE: To evaluate proteins related to tumor immune response and treatment outcome from radiotherapy for uterine cervical cancer patients. METHODS: We performed a retrospective immunohistochemical staining of 81 patients with uterine cervical cancer who underwent definitive radiotherapy. We examined the expression of programmed death ligand 1, human leukocyte antigen class I, tumor-infiltrating CD8+, and forkhead box P3+ (FoxP3+) T cells in tumor tissues. RESULTS: In biopsy specimen, patients with a higher number of CD8+ T cells and FoxP3+ T cells had a better disease-specific survival than patients with a lower number of CD8+ T cells and FoxP3+ cells (P = 0.018 and P = 0.009). Multivariate analysis showed that equivalent dose in 2 Gy fractions (EQD2) of the minimum dose to 90% of the high-risk clinical target volume, FoxP3+ T cells and expression of human leukocyte antigen class I were significant prognostic factors. When the EQD2 is 70 Gy or more, a higher local control rate is obtained regardless of the number of CD8- or FoxP3-positive cells. When EQD2 is <70 Gy, the number of CD8-positive cells has a significant impact on treatment outcome: the recurrence rate (local recurrence rate + distant metastasis rate) was 46.2% in the group with a CD8 value of 230 or higher, whereas the recurrence rate was 75.7% in the group with a CD8 value of less than 230. CONCLUSION: The combination of CD8 or FoxP3 with EQD2 can be potentially useful to predict the treatment results of radiotherapy for cervical cancer, leading to individualized optimal selection of treatment for cervical cancer.

DOI PubMed

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 ( INT INST ANTICANCER RESEARCH ) 34 ( 5 ) 2865 - 2872 2020.09

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

Association between radiotherapy-induced alteration of programmed death ligand 1 and survival in patients with uterine cervical cancer undergoing preoperative radiotherapy.

Takaaki Tsuchiya, Masanori Someya, Yu Takada, Tomokazu Hasegawa, Mio Kitagawa, Yuki Fukushima, Toshio Gocho, Masakazu Hori, Kensei Nakata, Yoshihiko Hirohashi, Toshihiko Torigoe, Tsuyoshi Saito, Koh-Ichi Sakata

Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] 196 ( 8 ) 725 - 735 2020.08 [International journal]

PURPOSE: To evaluate radiotherapy-induced changes in the expression of programmed death ligand 1 (PD-L1), programmed death 1 (PD-1), and human leukocyte antigen class I (HLA-1) in patients with uterine cervical cancer, as well as infiltration of CD8+ and Forkhead box P3+ (FoxP3+) T lymphocytes into tumor tissue and the prognostic value of these parameters. MATERIALS AND METHODS: We performed immunohistochemical analysis of pre-radiotherapy biopsies and corresponding post-radiotherapy resected tissues in 104 uterine cervical cancer patients undergoing preoperative chemoradiotherapy or radiotherapy alone. We scored the expression of various proteins to distinguish positive from negative samples. RESULTS: PD-L1-expressing tumor cells (PD-L1 TC) increased significantly after chemoradiotherapy (p = 0.043). CD8+ T cell infiltration (p = 0.002) and FoxP3+ T cell infiltration (p = 0.003) decreased significantly after chemoradiotherapy. Expression of PD‑1, PD-L1-expressing immune cells (PD-L1 IC), and HLA‑1 did not change after chemoradiotherapy. In biopsy specimens obtained before chemoradiotherapy or radiotherapy, greater infiltration of CD8+ T cells (p = 0.001) and FoxP3+ T cells (p = 0.003) were significant predictors of better overall survival (OS). In surgical specimens obtained after chemoradiotherapy or radiotherapy, greater infiltration of PD-L1 TC was the only significant predictor of better OS (p < 0.001) and was related to a significantly lower probability of out-of-field recurrence (p = 0.005). CONCLUSION: Chemoradiotherapy induced an immunologic shift that increased PD-L1 TC. Chemoradiotherapy has immunological effects that can influence the results of treatment for uterine cervical cancer.

DOI PubMed

Evaluation of the urethral alpha/beta ratio and tissue repair half-time for iodine-125 prostate brachytherapy with or without supplemental external beam radiotherapy

Toshio Gocho, Masakazu Hori, Yuuki Fukushima, Masanori Someya, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Masato Hareyama, Masaru Takagi, Kohei Hashimoto, Naoya Masumori, Koh-ichi Sakata

BRACHYTHERAPY ( ELSEVIER SCIENCE INC ) 19 ( 3 ) 290 - 297 2020.05

PURPOSE: To assess the correlation between postimplant dosimetric quantifiers and the genitourinary (GU) toxicity of low-dose rate brachytherapy for prostate cancer.METHODS AND MATERIALS: The minimum urethral dose (UD10, 30, and 90) and the percent volume of the urethra receiving the prescription dose (V100, V150) were calculated from the post-implant dose-volume histograms of 182 patients. We then calculated various urethral biologically equivalent doses (uBEDs) using different values of the alpha/beta ratio and tissue repair half-time (t1/2) and examined the correlations with GU toxicity.RESULTS: Common dosimetric quantifiers, such as UD90 (brachytherapy) + UD50 (external beam radiotherapy), showed no correlation with Grade >= 2 GU toxicity. There was a significant correlation between Grade GU toxicity and uBED when the alpha/beta value was 0.5 or 1 Gy and t1/2 was 0.5-2.5 h. An uBED (alpha/beta = 1.0, t1/2 = 0.5) had the largest hazard ratio for GU toxicity, and it was also significantly correlated with Grade >= 2 GU toxicity according to multivariate analysis.CONCLUSIONS: We observed a significant correlation of uBED with GU toxicity when alpha/beta was 0.5 or 1.0 Gy and t1/2 was 0.5-2.5 h. As the simple formula we used has not been verified in basic experiments, more data are needed to validate our results. (C) 2020 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

DOI

Retrospective DVH analysis of point A based intracavitary brachytherapy for uterine cervical cancer.

Masanori Someya, Tomokazu Hasegawa, Takaaki Tsuchiya, Mio Kitagawa, Toshio Gocho, Yuuki Fukushima, Masakazu Hori, Katsutoshi Miura, Yu Takada, Kensei Nakata, Koh-Ichi Sakata

Journal of radiation research 61 ( 2 ) 265 - 274 2020.03 [International journal]

Combining external beam radiotherapy (EBRT) with intracavitary brachytherapy (ICBT) is important for definitive treatment of cervical cancer. In cervical cancer patients receiving radiotherapy, we evaluated treatment outcomes in relation to dose-volume histogram parameters, including the computed tomography (CT)-based high-risk clinical target volume (HR-CTV) for ICBT. Between 2010 and 2015, 89 consecutive cervical cancer patients were mostly treated with 40 Gy of EBRT in 20 fractions and 18 Gy of ICBT prescribed to point A in 3 fractions. CT scans were obtained during ICBT. The HR-CTV D90 was calculated and the total doses of ICBT and EBRT were converted to the equivalent dose in 2 Gy fractions (EQD2). When the patients were divided into four groups according to EQD2 of the HR-CTV D90, the 3-year local recurrence-free survival rates were 95.2, 78.4, 52.7 and 42.9% for patients receiving >80 , 70-80 , 60-70 and <60 Gy, respectively. There was a significant negative correlation between EQD2 of the HR-CTV D90 and the HR-CTV volume at first ICBT (r = -0.713). Local recurrence was more frequent when the HR-CTV volume was ≥22 cc and EQD2 of the HR-CTV D90 was <70 Gy. Multivariate analysis showed that EQD2 of the HR-CTV D90 and concurrent chemotherapy (≥4 cycles) were significant determinants of overall survival. HR-CTV D90 was an important prognostic indicator for local recurrence. HR-CTV D90 >70 Gy is required for the better local control, especially in patients with a larger HR-CTV (≥22 cc at initial ICBT).

DOI PubMed

放射線治療を施行した進行子宮頸癌患者における腫瘍免疫と生存の関連性(Association between tumor Immunity and survival in patients with advanced uterine cervical cancer treated with raiotherapy)

Someya Masanori, Hasegawa Tomokazu, Tsuchiya Takaaki, Fukushima Yuuki, Kitagawa Mio, Hori Masakazu, Sakata Koh-ichi, Takada Yu, Nakata Kensei, Miura Katsutoshi

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 ) 79回 S176 - S176 2020.02

Efficacy of combined radiotherapy and anti-programmed death 1 therapy in acral and mucosal melanoma.

Junji Kato, Tokimasa Hida, Masanori Someya, Sayuri Sato, Masahide Sawada, Kohei Horimoto, Mao Fujioka, Tomoyuki Minowa, Yoshiyuki Matsui, Takaaki Tsuchiya, Mio Kitagawa, Kensei Nakata, Koh-Ichi Sakata, Toshihiko Torigoe, Hisashi Uhara

The Journal of dermatology 46 ( 4 ) 328 - 333 2019.04 [International journal]

Some studies showed that clinical response to immune check point inhibitors is lower in acral and mucosal melanoma than in cutaneous melanoma. Although the synergistic effect of radiotherapy (RT) and ipilimumab has been reported in patients with brain metastasis, the efficacy of combined RT and anti-programmed death 1 (PD-1) therapy for acral and mucosal melanoma is unclear. The present study aimed to evaluate the efficacy of combined RT and anti-PD-1 therapy for acral and mucosal melanoma. We retrospectively analyzed patients with acral or mucosal melanoma who were treated with anti-PD-1 and RT at Sapporo Medical University Hospital. In 10 patients (acral, 3; mucosal, 7), the response rate (RR) and the disease control rate (DCR) were 40% and 60%, respectively. As regards mucosal melanoma, four of the seven patients had achieved complete response + partial response, and three had progressive disease (RR = 57.1%). Meanwhile, two of the three patients with acral melanoma had stable disease and one had progressive disease (RR and DCR were 0% and 66.6%, respectively). Except for the patients treated with palliative RT for bone metastasis in the present study, the RR was 50% (4/8 patients), and the DCR was 75% (6/8 patients). Vitiligo developed after RT in five (50%) patients at a median duration of 2 months after RT. The clinical response and the high occurrence of vitiligo suggest that the combination of RT and anti-PD-1 therapy could be effective in some patients with mucosal melanoma.

DOI PubMed

Successful rechallenge with nivolumab therapy after radiotherapy in mucosal melanoma.

Junji Kato, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Keiju Kobayashi, Masahide Sawada, Mao Fujioka, Takaaki Tsuchiya, Masanori Someya, Hisashi Uhara

The Journal of dermatology 46 ( 2 ) e72-e73 2019.02 [International journal]

DOI PubMed

Influence of PD-L1 expression in immune cells on the response to radiation therapy in patients with oropharyngeal squamous cell carcinoma.

Yuki Fukushima, Masanori Someya, Kensei Nakata, Masakazu Hori, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Toshio Gocho, Hikaru Ikeda, Yoshihiko Hirohashi, Toshihiko Torigoe, Shintaro Sugita, Tadashi Hasegawa, Tetsuo Himi, Koh-Ichi Sakata

Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 129 ( 2 ) 409 - 414 2018.11 [International journal]

BACKGROUND AND PURPOSE: To investigate influences of proteins involved with tumor immunity on outcomes of radiotherapy for oropharyngeal squamous cell carcinoma (OPSCC). MATERIAL AND METHODS: We performed immunohistochemical staining to examine expressions of p16 and proteins involved with tumor immunity in 92 OPSCC patients treated with radiotherapy. RESULTS: Patients with abundant infiltrating CD8-positive cells had the significantly better overall survival (OS) rate than patients with fewer CD8-positive cells (p = 0.026). Patients with higher PD-L1 expression in tumor cells (TC 1-3) had a better outcome than those with low PD-L1 expression in tumor cells (TC 0) for both OS (p = 0.019) and progression-free survival (PFS) rate (p = 0.032). Patients with high PD-L1 expression in infiltrating immune cells (IC 3) showed significantly better OS (p = 0.009) and PFS (p = 0.011) than those with low PD-L1 expression (IC 0-2). Patients with p16-negative and IC 3 showed similar OS to patients with p16-positive and IC 0-2. P16-positive tumors had a significantly higher CD8-positive cell infiltration and PD-L1 expression in tumor cells than p16-negative tumors. CONCLUSIONS: In addition to tumor p16 expression, PD-L1 expression in TC and IC can be useful for predicting the response of OPSCC to radiotherapy.

DOI PubMed

Prediction of acute gastrointestinal and genitourinary radiation toxicity in prostate cancer patients using lymphocyte microRNA.

Masanori Someya, Masakazu Hori, Toshio Gocho, Kensei Nakata, Takaaki Tsuchiya, Mio Kitagawa, Tomokazu Hasegawa, Yuuki Fukushima, Koh-Ichi Sakata

Japanese journal of clinical oncology 48 ( 2 ) 167 - 174 2018.02 [International journal]

BACKGROUND: To search for novel biomarkers that can predict acute radiation toxicity, we conducted microRNA expression analysis of peripheral blood lymphocytes (PBLs). METHODS: The discovery cohort was 69 patients with localized adenocarcinoma of the prostate who received intensity-modulated radiation therapy between October 2007 and October 2010. The validation cohort was 72 patients treated with low-dose-rate brachytherapy between May 2008 and March 2014. After13 microRNAs were selected by TaqMan® Array analysis in a preliminary experiment, expression of these microRNAs in all samples was analyzed by RT-PCR. RESULTS: In the discovery cohort, the average prostate volume, the rectal volume receiving 70 Gy, and expression of miR-410 and miR-221 were significant risk factors for Grade 1-2 gastrointestinal toxicity. Receiver operating characteristic analysis showed that the area under the curve (AUC) was 0.807. The maximum dose to the urinary bladder, prostate volume, pretreatment urinary function score, and miR-99a and miR-221 expression were risk factors for Grade 2 genitourinary toxicity. The corresponding AUC was 0.796. In the validation cohort, reproducibility of these markers was confirmed for gastrointestinal toxicity, but not for genitourinary toxicity. CONCLUSION: Combining radiation dose parameters with microRNA expression in PBLs may be useful for predicting acute gastrointestinal toxicity of radiation therapy, thus contributing to personalized treatment of prostate cancer.

DOI PubMed

食道癌生検標本における抗PD-L1抗体の発現

堀正和, 染谷正則, 中田健生, 北川未央, 土屋高旭, 長谷川智一, 福島悠希, 後町俊夫, 松本健一, 坂田耕一

北海道医学雑誌 ( 北海道医学会 ) 92 ( 2 ) 115 - 115 2017.11

Influence of XRCC4 expression in esophageal cancer cells on the response to radiotherapy.

Masakazu Hori, Masanori Someya, Yoshihisa Matsumoto, Kensei Nakata, Mio Kitagawa, Tomokazu Hasegawa, Takaaki Tsuchiya, Yuki Fukushima, Toshio Gocho, Yasushi Sato, Hiroyuki Ohnuma, Junji Kato, Shintaro Sugita, Tadashi Hasegawa, Koh-Ichi Sakata

Medical molecular morphology 50 ( 1 ) 25 - 33 2017.03 [Domestic journal]

DNA double-strand break (DSB) is one of the most serious forms of damage induced by ionizing irradiation and is mainly repaired by the non-homologous end joining (NHEJ) repair. Immunohistochemical analysis of proteins involved in NHEJ, such as XRCC4 (X-ray repair cross-complementing protein 4), Ku86 and DNA-PKcs (DNA-dependent protein kinase, catalytic subunits), may be useful for predicting tumor radiosensitivity. We examined 92 patients with esophageal squamous cell carcinoma (ECSS) who were treated by radiotherapy between 1999 and 2008. Immunohistochemical examination of tumor tissue for Ki-67 and DSB-related proteins, including XRCC4, Ku86, and DNA-PKcs, was performed using pretreatment biopsy specimens. Low expression of XRCC4 was detected in 31 of 92 examined samples (33.7 %). The 5-year overall survival (OS) rate was 67.7 % in the low expression group and 31.0 % in the high expression group (P = 0.00). Multivariate analysis confirmed that advanced T-stage (HR 3.24, P = 0.01), radiation dose less than 66 Gy (HR 2.23, P = 0.02), absence of systemic chemotherapy (HR 2.59, P = 0.05), and high expression of XRCC4 (HR 12.0, P = 0.02) were independent prognostic factors for predicting poor OS. Other DSB-related proteins and Ki-67 were not predictive factors. XRCC4 expression might have an influence on results of radiotherapy for patients with ESCC.

DOI PubMed

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 2017.01 [International journal]

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

孤立性心筋炎に心筋虚血を合併した一剖検例

鈴木悠也, 渡邊智, 鳥羽浩輔, 吉田敬, 杉本美夕, 前川夏穂, 村上里奈, 清水淳也, 土屋高旭, 水尾圭祐, 岡崎俊一郎, 兵頭秀樹

法医学の実際と研究 ( 法医学談話会 ) ( 59 ) 171 - 174 2016.11

Stage IIIB非小細胞肺癌に対する呼吸同期放射線治療

藤田紘弥, 境英承, 藤田茂雄, 前田昌直, 相澤一宏, 石田祥之, 土屋高旭, 池田光

市立札幌病院医誌 ( 市立札幌病院 ) 75 ( 1 ) 47 - 52 2015.10

近年、放射線治療装置やシステムの進歩により、高精度放射線治療が様々な場所で行われるようになった。当院でも放射線治療システムが更新され、高精度放射線治療の一つである呼吸同期放射線治療が開始された。呼吸同期放射線治療は、呼吸相に合わせて照射を行う方法であり、照射中の誤差の減少と照射野の縮小が可能である。今までは、肺のように呼吸性移動が大きな臓器ではマージンを広くし照射を行う必要があったが、呼吸同期放射線治療を行うことで腫瘍周囲の正常組織への線量の減少と腫瘍への正確な照射ができ、線量の増加が可能となる。そのため、呼吸同期放射線治療により有害事象発生率の低下と高い局所制御率につがると考えられる。2015年1月にStage IIIBの非小細胞肺癌の患者に対して化学療法併用呼吸同期放射線治療を施行した。10MV-X線を使用し、処方線量は60Gy/30Frとした。4D-CTから腫瘍の呼吸性移動による三次元的な移動長は18mmであり、10mm以上の照射野縮小が可能となった。軽度の放射線肺臓炎はあったが、その他特記すべき有害事象なく治療完遂した。照射後3ヵ月で腫瘍は51mmから30mmへ縮小し、PET-CTにて縦隔リンパ節への集積は消失した。(著者抄録)

当院における頭頸部癌に対するセツキシマブ併用放射線治療

土屋高旭, 池田光, 高田優

市立札幌病院医誌 ( 市立札幌病院 ) 74 ( 2 ) 185 - 188 2015.03

2013年3月〜2014年9月にセツキシマブ(商品名:アービタックス)を併用した根治的分子標的薬併用放射線治療を施行した頭頸部癌10例について、一次効果と有害事象について検討した。一次効果はCRが9例、PRが1例で良好な成績であった。一方で皮膚炎・粘膜炎・ざ瘡様皮疹の有害事象を認め、皮膚炎はGrade 3が60.0%、粘膜炎はGrade 3が70.0%と高度な有害事象の割合は高いものであった。有害事象の増悪時には栄養介入やセツキシマブ投与中止など、適宜介入が必要と考える。(著者抄録)

PVEとTAEにて切除可能となった肝IPNBの1例

齊藤正人, 廣川直樹, 宇佐見陽子, 土屋高旭, 後町俊夫, 坂田耕一

IVR: Interventional Radiology ( (一社)日本インターベンショナルラジオロジー学会 ) 29 ( 4 ) 429 - 429 2014.12

食道癌におけるドセタキセル併用化学放射線治療

堀正和, 染谷正則, 中田健生, 北川未央, 土屋高旭, 長谷川智一, 小野寺耕一, 坂田耕一, 佐藤康史, 大沼啓之, 加藤淳二

北海道外科雑誌 ( 北海道外科学会 ) 59 ( 2 ) 205 - 205 2014.12

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