研究活動情報

• Correction: Post-radiation targeting of TIGIT and CD96 improved immunotherapy efficacy in head and neck squamous cell carcinoma.

  Mohammed Salah, Masafumi Saito, Hiroki Kawaguchi, Yasuyuki Shimizu, Yoshiko Fujita, Naritoshi Mukumoto, Joji Kotani, Hirotaka Shinomiya, Takeaki Ishihara, Daisuke Miyawaki, Nen-Ichi Nibu, Ryohei Sasaki

  2026年03月, Molecular medicine (Cambridge, Mass.), 32(1) (1), 英語, 国際誌


• Post-radiation targeting of TIGIT and CD96 improved immunotherapy efficacy in head and neck squamous cell carcinoma.

  Mohammed Salah, Masafumi Saito, Hiroki Kawaguchi, Yasuyuki Shimizu, Yoshiko Fujita, Naritoshi Mukumoto, Joji Kotani, Hirotaka Shinomiya, Takeaki Ishihara, Daisuke Miyawaki, Nen-Ichi Nibu, Ryohei Sasaki

  BACKGROUND: Immunotherapy is a promising treatment for drug-resistant cancers. However, its effectiveness against head and neck squamous cell carcinoma (HNSCC) is limited. This indicates the need to explore additional factors that can predict tumor response to new therapies and improve or supplement their effects. Therefore, we aimed to investigate whether the post-radiation usage of anti-TIGIT and/or anti-CD96 could enhance the antitumor response in HNSCC. METHODS: HNSCC tissues, as well as human and mouse cell lines, were examined to evaluate the effects of radiation on immune checkpoint receptors (TIGIT, CD96, and CD226) and tumor ligands (CD155, CD112, CD113, and CD111). Overall and disease-free survival, along with factors related to these immune checkpoint receptors and ligands, were detected. Moreover, we investigated the effects of radiation dose and exposure time on the expression of these receptors and ligands in vitro and in vivo. Tumor growth and survival rates were then evaluated using TIGIT and/or CD96 inhibitors injected intraperitoneally after exposure to radiation. Finally, various proliferative and immunological parameters of the tumor microenvironment were determined using immunohistochemistry and flow cytometry. Statistical analyses were performed using Student's t-test, one-way analysis of variance, or two-way analysis of variance. RESULTS: Elevated levels of TIGIT, CD96, CD155, CD112, CD113, and CD111 were observed in both HNSCC tissues and the cell lines. Radiation increased the expression of these inhibitory receptors and ligands. Thus, anti-TIGIT and anti-CD96 were used to target the upregulated expression of the receptors TIGIT and CD96, respectively. This treatment combination inhibited tumor growth by boosting apoptosis, reducing tumor cell proliferation, and restoring the cytotoxic functions of CD4+ and CD8+ T cells after radiation therapy. CONCLUSION: Our findings suggest that TIGIT and CD96 could be markers of the clinical stage and treatment response of HNSCC. Therefore, administering anti-TIGIT and anti-CD96 after radiotherapy may provide a novel approach for incorporating immunoradiotherapy into HNSCC treatment.

  2025年12月, Molecular medicine (Cambridge, Mass.), 32(1) (1), 5 - 5, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 鼻腔への放射線治療による鼻涙管閉塞および流涙に関する検討

  川口 弘毅, 妹尾 悟史, 石原 武明, 宮脇 大輔, 堀地 祐人, 由井 光子, 小山 泰司, 古川 竜也, 四宮 弘隆, 清田 尚臣, 丹生 健一, 佐々木 良平

  (一社)日本頭頸部癌学会, 2025年05月, 頭頸部癌, 51(2) (2), 178 - 178, 日本語


• Autologous Peripheral Blood Stem Cell Transplantation and Timing of Local Radiation Therapy in Patients With Malignant Lymphoma: Results of the Japanese Radiation Oncology Study Group Questionnaire Survey.

  Naoya Ishibashi, Yasuo Ejima, Toshinori Soejima, Hiroki Kawaguchi, Senzo Taguchi, Hitoshi Ito, Takuya Shimizuguchi, Kouichi Isobe, Masatoshi Hasegawa, Keisuke Sasai, Michiko Imai, Emiko Shimoda, Hisashi Kaizu, Naoko Okano, Toshiyuki Imagumbai, Tetsuo Akimoto

  BACKGROUND/AIM: Malignant lymphoma (ML) including Hodgkin's lymphoma and non-Hodgkin's lymphoma is often treated with local radiation therapy (RT) in combination with autologous hematopoietic stem cell transplantation (ASCT) to prevent relapse; however, the efficacy and optimal timing of this approach is unclear. In this study, a national survey conducted by the Japanese Radiation Oncology Study Group reviewed ML cases from 2011 to 2019 to determine whether RT should be added to ASCT, focusing on the use of autologous peripheral blood stem cell transplantation (auto-PBSCT), a predominant form of ASCT. PATIENTS AND METHODS: The survey encompassed 92 patients from 11 institutes, and assessed histological ML types, treatment regimens, timing of RT relative to auto-PBSCT, and associated adverse events. RESULTS: The results indicated no significant differences in adverse events, including myelosuppression, based on the timing of RT in relation to auto-PBSCT. However, anemia was more prevalent when RT was administered before auto-PBSCT, and there was a higher incidence of neutropenia recovery delay in patients receiving RT after auto-PBSCT. CONCLUSION: This study provides valuable insights into the variable practices of auto-PBSCT and local RT in ML treatment, emphasizing the need for optimized timing of these therapies to improve patient outcomes and reduce complications.

  2024年07月, Anticancer research, 44(7) (7), 3033 - 3041, 英語, 国際誌

  研究論文（学術雑誌）


• Respiratory motion tracking of spine stereotactic radiotherapy in prone position.

  Kazufusa Mizonobe, Hiroaki Akasaka, Kazuyuki Uehara, Yuya Oki, Masao Nakayama, Shuhei Tamura, Yoshiki Munetomo, Katsumaro Kubo, Hiroki Kawaguchi, Aya Harada, Hiroshi Mayahara

  PURPOSE: The CyberKnife system is a specialized device for non-coplanar irradiation; however, it possesses the geometric restriction that the beam cannot be irradiated from under the treatment couch. Prone positioning is expected to reduce the dose to normal lung tissue in spinal stereotactic body radiotherapy (SBRT) owing to the efficiency of beam arrangement; however, respiratory motion occurs. Therefore, the Xsight spine prone tracking (XSPT) system is used to reduce the effects of respiratory motion. The purpose of this study was to evaluate the motion-tracking error of the spine in the prone position. MATERIALS AND METHODS: Data from all 25 patients who underwent spinal SBRT at our institution between April 2020 and February 2022 using CyberKnife (VSI, version 11.1.0) with the XSPT tracking system were retrospectively analyzed using log files. The tumor motion, correlation, and prediction errors for each patient were examined. Furthermore, to assess the potential relationships between the parameters, the relationships between the tumor-motion amplitudes and correlation or prediction errors were investigated using linear regression. RESULTS: The tumor-motion amplitudes in each direction were as follows: superior-inferior (SI), 0.51 ± 0.39 mm; left-right (LR), 0.37 ± 0.29 mm; and anterior-posterior (AP), 3.43 ± 1.63 mm. The overall mean correlation and prediction errors were 0.66 ± 0.48 mm and 0.06 ± 0.07 mm, respectively. The prediction errors were strongly correlated with the tumor-motion amplitudes, whereas the correlation errors were not. CONCLUSIONS: This study demonstrated that the correlation error of spinal SBRT in the prone position is sufficiently small to be independent of the tumor-motion amplitude. Furthermore, the prediction error is small, contributing only slightly to the tracking error. These findings will improve the understanding of how to compensate for respiratory-motion uncertainty in the prone position.

  2023年05月, Journal of applied clinical medical physics, 24(5) (5), e13910, 英語, 国際誌

  研究論文（学術雑誌）


• 嗅神経芽細胞腫に対する術後放射線治療を施行した1例

  高林 畑銘, 小林 加奈, 岩下 和真, 妹尾 悟史, 窪田 光, 川口 弘毅, 石原 武明, 宮脇 大輔, 佐々木 良平

  (公社)日本医学放射線学会, 2023年02月, Japanese Journal of Radiology, 41(Suppl.) (Suppl.), 33 - 33, 日本語


• Fiducial marker position affects target volume in stereotactic lung irradiation.

  Hiroaki Akasaka, Kazufusa Mizonobe, Yuya Oki, Kazuyuki Uehara, Masao Nakayama, Shuhei Tamura, Yoshiki Munetomo, Haruna Kawaguchi, Jun Ishida, Aya Harada, Takeaki Ishihara, Hikaru Kubota, Hiroki Kawaguchi, Ryohei Sasaki, Hiroshi Mayahara

  PURPOSE: Real-time tracking systems of moving respiratory targets such as CyberKnife, Radixact, or Vero4DRT are an advanced robotic radiotherapy device used to deliver stereotactic body radiotherapy (SBRT). The internal target volume (ITV) of lung tumors is assessed through a fiducial marker fusion using four-dimensional computed tomography (CT). It is important to minimize the ITV to protect normal lung tissue from exposure to radiation and the associated side effects post SBRT. However, the ITV may alter if there is a change in the position of the fiducial marker with respect to the tumor. This study investigated the relationship between fiducial marker position and the ITV in order to prevent radiation exposure of normal lung tissue, and correct target coverage. MATERIALS AND METHODS: This study retrospectively reviewed 230 lung cancer patients who received a fiducial marker for SBRT between April 2015 and September 2021. The distance of the fiducial marker to the gross tumor volume (GTV) in the expiratory (dex ) and inspiratory (din ) CT, and the ratio of the ITV/V(GTVex ), were investigated. RESULTS: Upon comparing each lobe, although there was no significant difference in the ddiff and the ITV/V(GTVex ) between all lobes for dex  < 10 mm, there was significant difference in the ddiff and the ITV/V(GTVex ) between the lower and upper lobes for dex ≥ 10 mm (p < 0.05). Moreover, there was significant difference in the ddiff and the ITV/V(GTVex ) between dex ≥10 mm and dex  < 10 mm in all lung regions (p < 0.05). CONCLUSION: The ITV that had no margin from GTVs increased when dex was ≥10 mm for all lung regions (p < 0.05). Furthermore, the increase in ITV tended to be greater in the lower lung lobe. These findings can help decrease the possibility of adverse events post SBRT, and correct target coverage.

  2022年06月, Journal of applied clinical medical physics, 23(6) (6), e13596, 英語, 国際誌

  研究論文（学術雑誌）


• Reactive oxygen species-inducing titanium peroxide nanoparticles as promising radiosensitizers for eliminating pancreatic cancer stem cells.

  Mohammed Salah, Hiroaki Akasaka, Yasuyuki Shimizu, Kenta Morita, Yuya Nishimura, Hikaru Kubota, Hiroki Kawaguchi, Tomomi Sogawa, Naritoshi Mukumoto, Chiaki Ogino, Ryohei Sasaki

  BACKGROUND: Despite recent advances in radiotherapy, radioresistance in patients with pancreatic cancer remains a crucial dilemma for clinical treatment. Cancer stem cells (CSCs) represent a major factor in radioresistance. Developing a potent radiosensitizer may be a novel candidate for the eradication of pancreatic CSCs. METHODS: CSCs were isolated from MIA PaCa-2 and PANC1 human pancreatic cancer cell lines. Titanium peroxide nanoparticles (TiOxNPs) were synthesized from titanium dioxide nanoparticles (TiO2NPs) and utilized as radiosensitizers when added one hour prior to radiation exposure. The antitumor activity of this novel therapeutic strategy was evaluated against well-established pancreatic CSCs model both in vitro and in vivo. RESULTS: It is shown that TiOxNPs combined with ionizing radiation exhibit anti-cancer effects on radioresistant CSCs both in vitro and in vivo. TiOxNPs exhibited a synergistic effect with radiation on pancreatic CSC-enriched spheres by downregulating self-renewal regulatory factors and CSC surface markers. Moreover, combined treatment suppressed epithelial-mesenchymal transition, migration, and invasion properties in primary and aggressive pancreatic cancer cells by reducing the expression of proteins relevant to these processes. Notably, radiosensitizing TiOxNPs suppressed the growth of pancreatic xenografts following primary or dissociating sphere MIA PaCa-2 cell implantation. It is inferred that synergy is formed by generating intolerable levels of reactive oxygen species (ROS) and inactivating the AKT signaling pathway. CONCLUSIONS: Our data suggested the use of TiOxNPs in combination with radiation may be considered an attractive therapeutic strategy to eliminate pancreatic CSCs.

  2022年04月, Journal of experimental & clinical cancer research : CR, 41(1) (1), 146 - 146, 英語, 国際誌

  研究論文（学術雑誌）


• cT3N0M0声門癌に対する根治的放射線治療の成績

  岩下 和真, 石原 武明, 妹尾 悟史, 窪田 光, 川口 弘毅, 小林 加奈, 宮脇 大輔, 佐々木 良平, 手島 直則, 丹生 健一, 今村 善宣, 清田 尚臣

  (公社)日本医学放射線学会, 2022年02月, Japanese Journal of Radiology, 40(Suppl.) (Suppl.), 36 - 36, 日本語


• 当院における中・高リスク前立腺癌に対する外照射併用小線源治療に関する検討

  川口 弘毅, 宮脇 大輔, 石原 武明, 小林 加奈, 椋本 成俊, 赤坂 浩亮, 佐々木 良平, 吉田 賢史, 原 琢人, 古川 順也, 藤澤 正人, 西谷 隆治

  (公社)日本医学放射線学会, 2022年02月, Japanese Journal of Radiology, 40(Suppl.) (Suppl.), 36 - 36, 日本語


• cT3N0M0声門癌に対する根治的放射線治療の成績

  岩下 和真, 石原 武明, 妹尾 悟史, 窪田 光, 川口 弘毅, 小林 加奈, 宮脇 大輔, 佐々木 良平, 手島 直則, 丹生 健一, 今村 善宣, 清田 尚臣

  (公社)日本医学放射線学会, 2022年02月, Japanese Journal of Radiology, 40(Suppl.) (Suppl.), 36 - 36, 日本語


• Predicting factors of symptomatic radiation pneumonitis induced by durvalumab following concurrent chemoradiotherapy in locally advanced non-small cell lung cancer.

  Hiroshi Mayahara, Kazuyuki Uehara, Aya Harada, Keiji Kitatani, Tomonori Yabuuchi, Shuichirou Miyazaki, Takeaki Ishihara, Hiroki Kawaguchi, Hikaru Kubota, Hideaki Okada, Taira Ninomaru, Chihiro Shindo, Akito Hata

  BACKGROUND: Concurrent chemoradiotherapy (CCRT) followed by durvalumab is the standard of care for unresectable locally-advanced non-small cell carcinoma (LA-NSCLC). However, a major concern about administration of durvalumab after CCRT is whether the incidence of symptomatic radiation pneumonitis (RP) may increase or not. In the present analysis, we report the initial results of CCRT followed by durvalumab in patients with LA-NSCLC in a real-world setting with focus on predicting factors for symptomatic RP. METHODS: Patients who were pathologically diagnosed as NSCLC and initiated treatment with CCRT followed by durvalumab between July 2018 to December 2019 were eligible for this study. Patients were included if they completed the planned CRT course and administered at least one course of durvalumab. We retrospectively investigated the preliminary survival outcome and incidence and predicting factors for symptomatic RP. RESULTS: Of the 67 patients who planned CCRT, 63 patients completed the entire CCRT course. Of these, 56 patients proceeded to consolidation with durvalumab. The median time to eternal discontinuation of durvalumab was 9.7 months. The cumulative proportion of the patients who exhibited symptomatic RP was 30, 40 and 44% at 3, 6 and 12 months, respectively. In multivariate analyses, pulmonary fibrosis score and lung V40 were significant predictive factors for symptomatic RP (p < 0.001, HR: 7.83, 95% CI: 3.38-18.13, and p = 0.034, HR: 3.17, 95% CI: 1.09-9.19, respectively). CONCLUSIONS: Pulmonary fibrosis sore and lung V40 were significant predictive factors for symptomatic RP. We should be cautious about the administration of durvalumab for patients having subclinical pulmonary fibrosis. To our best knowledge, this is one of the first report showing the predictive value of high dose volumes to the lung in patients with LA-NSCLC who received CCRT followed by durvalumab.

  2022年01月, Radiation oncology (London, England), 17(1) (1), 7 - 7, 英語, 国際誌

  研究論文（学術雑誌）


• A treatment planning study comparison between supine and prone position for different lung tumour locations using CyberKnife TPS

  Hiroaki Akasaka, Kazufusa Mizonobe, Yuya Oki, Kazuyuki Uehara, Aya Harada, Shuichiro Miyazaki, Keiji Kitatani, Tomonori Yabuuchi, Takeaki Ishihara, Daisuke Miyawaki, Masao Nakayama, Naritoshi Mukumoto, Ryuichi Yada, Ai Nakaoka, Hikaru Kubota, Hiroki Kawaguchi, Satoshi Seno, Ryohei Sasaki, Hiroshi Mayahara

  Abstract Aim: CyberKnife is the most advanced form of stereotactic body radiotherapy (SBRT) system that uses a robotic arm to deliver highly focused beams of radiation; however, a limitation is that it only irradiates from ceiling to floor direction. In patients with posterior lungs tumour who are positioned supine, normal lung tissue may suffer undesirable radiation injuries. This study compares the treatment planning between the prone set-up and the supine set-up for lung cancer in CyberKnife SBRT to decrease normal lung dose to avoid radiation side effects. Materials and methods: A human phantom was used to generate 108 plans (54 for prone and 54 for supine) using the CyberKnife planning platform. The supine and prone plans were compared in terms of the dosimetric characteristics, delivery efficiency and plan efficiency. Results: For posterior targets, the area of low-dose exposure to normal lungs was smaller in the prone set-up than in the supine set-up. V10 of the lungs was 7·53% and 10·47% (p < 0·001) in the anterior region, and 10·78% and 8·03% (p < 0·001) in the posterior region in the supine and prone set-up plans, respectively. Conclusions: The comparison between the prone set-up and the supine set-up was investigated with regard to target coverage and dose to organs at risk. Our results may be deployed in CyberKnife treatment planning to monitor normal tissue dose by considering patient positioning. This may assist in the design of better treatment plans and prevention of symptomatic radiation pneumonitis in lung cancer patients.

  Cambridge University Press (CUP), 2021年05月, Journal of Radiotherapy in Practice, 21(3) (3), 309 - 314

  研究論文（学術雑誌）


• T3N0M0声門癌に対する根治的放射線治療の成績

  岩下 和真, 石原 武明, 妹尾 悟史, 窪田 光, 川口 弘毅, 小林 加奈, 宮脇 大輔, 佐々木 良平, 蓼原 瞬, 手島 直則, 四宮 弘隆, 丹生 健一, 今村 善宣, 清田 尚臣

  (一社)日本頭頸部癌学会, 2021年05月, 頭頸部癌, 47(2) (2), 239 - 239, 日本語


• Efficacy of Spacers in Radiation Therapy for Locally Advanced Pancreatic Cancer: A Planning Study.

  Hiroki Kawaguchi, Yusuke Demizu, Naritoshi Mukumoto, Takeaki Ishihara, Daisuke Miyawaki, Shohei Komatsu, Hiroaki Akasaka, Makoto Shinoto, Yoshiyuki Shioyama, Katsumasa Nakamura, Takumi Fukumoto, Ryohei Sasaki

  BACKGROUND/AIM: We aimed to investigate the dosimetric effects of a spacer placed between the pancreas and surrounding gastrointestinal structures in intensity-modulated radiation therapy (IMRT) planning to provide more effective radiation therapy for locally advanced pancreatic cancer (LAPC). PATIENTS AND METHODS: Treatment planning was performed for six patients with LAPC based on computed tomography images without spacers and with 5-mm or 10-mm spacers virtually inserted under the supervision of a hepatobiliary pancreatic surgeon. The prescription dose was 63 Gy in 28 fractions. RESULTS: With the exception of one case of pancreatic head cancer, planning target volume receiving ≥95% of the prescribed dose (PTV V95) was achieved by 90% or more by inserting a spacer, and by 95% or more in all 3 cases of pancreatic body and tail cancer by inserting a 10-mm spacer. CONCLUSION: IMRT with appropriate spacer placement may help provide high-dose treatment for LAPC and improve associated patient outcomes.

  2021年01月, Anticancer research, 41(1) (1), 503 - 508, 英語, 国際誌

  研究論文（学術雑誌）


• 小児・若年の上咽頭癌3例の治療経験

  宮脇 大輔, 妹尾 悟史, 窪田 光, 川口 弘毅, 石原 武明, 植村 優, 山本 暢之, 今村 善宣, 清田 尚臣, 丹生 健一, 佐々木 良平

  (一社)日本頭頸部癌学会, 2020年07月, 頭頸部癌, 46(2) (2), 168 - 168, 日本語


• Oncogenic miRNAs Identified in Tear Exosomes From Metastatic Breast Cancer Patients.

  Sachiko Inubushi, Hiroki Kawaguchi, Sachiko Mizumoto, Tomonari Kunihisa, Motoi Baba, Yukiya Kitayama, Toshifumi Takeuchi, Robert M Hoffman, Hirokazu Tanino, Ryohei Sasaki

  BACKGROUND/AIM: Exosomes are produced by normal and cancer cells. Exosomes are found in the serum of cancer patients and have been used for diagnosis and prognosis. Recently tears from non-cancer patients have been found to contain exosomes. In the present report we describe tears from advanced breast-cancer patients. MATERIALS AND METHODS: We found oncogenic miRNAs in the exosomes isolated from tear fluids obtained from five patients with metastatic breast cancer and compared them with tear exosomes form eight healthy volunteers. RESULTS: Tear exosomes had a significantly higher quantity of exosome markers than serum exosomes (CD9, CD63). Tear exosomes were subjected to quantitative reverse-transcription polymerase reaction (qRT-PCR), and western blot analysis to elucidate the status of miRNAs, previously reported in serum from patients with metastatic breast cancer. qRT-PCR and western-blot analysis revealed that breast-cancer-specific miR-21 and miR-200c were highly expressed in tear exosomes from metastatic breast cancer patients in contrast to tear exosomes from healthy volunteers. CONCLUSION: Tear exosomes can be a potential source of diagnostic and prognostic biomarkers for metastatic breast cancer, and possibly other cancers or diseases.

  2020年06月, Anticancer research, 40(6) (6), 3091 - 3096, 英語, 国際誌

  研究論文（学術雑誌）


• National survey on total-body irradiation prior to reduced-intensity stem cell transplantation in Japan: The Japanese Radiation Oncology Study Group.

  Hiroki Kawaguchi, Toshinori Soejima, Naoya Ishibashi, Takeshi Akiba, Masatoshi Hasegawa, Kouichi Isobe, Hitoshi Ito, Michiko Imai, Yasuo Ejima, Masaharu Hata, Keisuke Sasai, Emiko Shimoda, Masahiko Oguchi, Tetsuo Akimoto

  Reduced-intensity stem cell transplantation (RIST) minimizes the adverse effects of traditional hematopoietic stem cell transplantation, and low-dose total-body irradiation (TBI) is administered over a short period prior to RIST (TBI-RIST). Different institutes adopt different approaches for the administration of TBI-RIST, and since no study had previously investigated this issue, a survey of the TBI schedules in Japan was conducted. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of TBI-RIST procedures conducted between 2010 and 2014. Of 186 institutions performing TBI, 90 (48%) responded to the survey, 78 of which performed TBI-RIST. Of 2488 patients who underwent TBI for malignant disease at these institutions, 1412 (56.8%) patients were treated for leukemia, 477 (19.2%) for malignant lymphoma, 453 (18.2) for myelodysplastic syndrome, 44 (1.8%) for multiple myeloma, and 102 (4.1%) for other malignant diseases. Further, 206 (52.0%) of 396 patients (a high proportion of patients) who underwent TBI for benign disease had aplastic anemia. The TBI-RIST equipment and treatment methods were similar to those used for myeloablative regimens. Routinely shielded organs included the lungs (43.6%), eyes (50.0%) and kidneys (10.2%). The ovaries (14.1%), thyroid (6.4%) and testicles (16.7%) were also frequently shielded, possibly reflecting an emphasis on shielding reproductive organs in children. TBI-RIST was performed more frequently than myeloablative conditioning in patients with benign disease. Genital and thyroid shielding were applied more frequently in patients treated with TBI-RIST than in patients treated with myeloablative conditioning. In conclusion, this study indicates the status of TBI-RIST in Japan and can assist future efforts to standardize TBI-RIST treatment methods and to design a future multicenter collaborative research study.

  2019年10月, Journal of radiation research, 60(5) (5), 579 - 585, 英語, 国際誌

  研究論文（学術雑誌）


• Patient preference study comparing hypofractionated versus conventionally fractionated whole-breast irradiation after breast-conserving surgery.

  Hiroki Kawaguchi, Kayoko Tsujino, Mayuko Miki, Yoko Matsumoto, Yosuke Ota, Koichi Hirokaga, Shintaro Takao, Toshinori Soejima, Ryohei Sasaki

  OBJECTIVE: To compare patient preferences and acute adverse events of hypofractionated (HF) and conventionally fractionated (CF) whole-breast irradiation (WBI) after breast-conserving surgery in our institution. METHODS: We conducted a patient preference study comparing CF-WBI (50 Gy/25 fractions) and HF-WBI (41.6 Gy/16 fractions) after breast-conserving surgery. Eligible patients selected either type of fractionation following an explanation from the radiation oncologist. In this report, we analyzed the selection rate and acute toxicities. RESULTS: Between June 2009 and December 2013, 348 patients (349 breasts) were identified as eligible for the study. Among them, 259 patients (260 breasts [74.5%]) selected CF-WBI and 89 patients (89 breasts [25.5%]) selected HF-WBI. Factors significantly associated with the selection of HF-WBI were older age (P = 0.028) and no adjuvant chemotherapy (P = 0.041). Regarding acute adverse events, Grade 2 (G2) or higher radiation dermatitis was less frequently observed in HF-WBI than in CF-WBI (13.8% vs. 29.4%; P = 0.004). In addition, G2 or higher breast pain was only observed in the CF-WBI group (6.9%; P = 0.012). There were no significant differences in the presence of fatigue, wound pain or radiation pneumonitis of G2 or higher between the groups. CONCLUSIONS: In this study, in which patients themselves selected the irradiation method, more patients tended to select CF-WBI. The frequency of G2 or higher dermatitis and breast pain was significantly lower in the HF-WBI group than in the CF-WBI group. Our results support the evidence for recommending HF-WBI after breast-conserving surgery while presenting aspects of patient preferences.

  2019年06月, Japanese journal of clinical oncology, 49(6) (6), 545 - 553, 英語, 国際誌

  研究論文（学術雑誌）


• 頭頸部癌に対する放射線治療後の放射線性顎骨壊死に関する検討

  窪田 光, 宮脇 大輔, 佐々木 香織, 妹尾 悟史, 井上 由子, 川口 弘毅, 西川 遼, 石原 武明, 吉田 賢史, 岸本 恵美, 明石 昌也, 佐々木 良平

  (一社)日本頭頸部癌学会, 2019年05月, 頭頸部癌, 45(2) (2), 244 - 244, 日本語


• National survey of myeloablative total body irradiation prior to hematopoietic stem cell transplantation in Japan: survey of the Japanese Radiation Oncology Study Group (JROSG).

  Naoya Ishibashi, Toshinori Soejima, Hiroki Kawaguchi, Takeshi Akiba, Masatoshi Hasegawa, Kouichi Isobe, Hitoshi Ito, Michiko Imai, Yasuo Ejima, Masaharu Hata, Keisuke Sasai, Emiko Shimoda, Toshiya Maebayashi, Masahiko Oguchi, Tetsuo Akimoto

  A myeloablative regimen that includes total-body irradiation (TBI) before hematopoietic stem cell transplantation results in higher patient survival rates than achieved with regimens without TBI. The TBI protocol, however, varies between institutions. In October 2015, the Japanese Radiation Oncology Study Group initiated a national survey of myeloablative TBI (covering 2010-2014). Among the 186 Japanese institutions performing TBI, 90 (48%) responded. The 82 institutions that had performed myeloablative TBI during this period treated 2698 patients with malignant disease [leukemia (2082 patients, 77.2%), malignant lymphoma (378, 14%)] and 37 with non-malignant disease [severe aplastic anemia (20, 54%), inborn errors of metabolism (5, 14%)]. A linear accelerator was used at all institutions. The institutions were divided into 41 large and 41 small institutions based on the median number of patients. The long source-surface distance technique was the method of choice in the 34 institutions (82.9%) and the moving-couch technique in the 7 (17.1%) in the large institutions. The schedules most routinely used by the participating institutions consisted of 12 Gy/6 fractions/3 days (26 institutions, 63.5%) in the large institutions. The dose rate varied from 5 to 26 cGy/min. The lungs and lenses were routinely shielded in 23 large institutions (56.1%), and only the lungs in 9 large institutions (21.9%). At lung-shielding institutions, the most frequent maximum acceptable total dose for the lungs was 8 Gy (19 institutions, 27.5%). Our results reveal considerable differences in the TBI methods used by Japanese institutions and thus the challenges in designing multicenter randomized trials based on TBI.

  2018年07月, Journal of radiation research, 59(4) (4), 477 - 483, 英語, 国際誌

  研究論文（学術雑誌）


• Additional chemotherapy improved local control and overall survival after stereotactic body radiation therapy for patients with oligo-recurrence.

  Masaki Nakamura, Naoki Hashimoto, Hiroshi Mayahara, Haruka Uezono, Aya Harada, Ryo Nishikawa, Yoshiro Matsuo, Hiroki Kawaguchi, Hideki Nishimura

  BACKGROUND: Oligo-recurrence has been considered to confer improved prognosis than other oligometastatic conditions, and stereotactic body radiation therapy (SBRT) is considered as an option of local therapy for lung or liver metastases. The purpose of this study was to investigate the efficacy and safety of SBRT for lung and liver oligo-recurrent lesions and evaluate predictive factors for local control and prognosis. METHODS: This retrospective study included patients who presented with 1-3 matachronous lung or liver metastases, and treated with SBRT between May 2013 and March 2016 at a single institution. All patients harbored a controlled primary lesion. Patients with < 6 months of follow-up were excluded. Local control, progression free survival, and overall survival rates were analyzed according to the Kaplan-Meier product limit method. Univariable log-rank and multivariable Cox regression analyses were performed to clarify predictive factors for local control and prognosis. Toxicity was graded according to the Common Terminology Criteria for Adverse Events, version 4.0. RESULTS: Seventy-six patients with a total of 70 and 44 lung and liver lesions were included. The median follow-up period was 21 (range, 7-43) months. The 1-year local control, progression-free survival and overall survival rates were 89, 38 and 96%, respectively. Smaller gross tumor volume and additional chemotherapy after SBRT were significant predictive factors for better local control (p = 0.005 and p = 0.047), and the presence of a single metastatic lesion was a significant factor of good progression free survival (p = 0.008). Additional chemotherapy after SBRT was not a significant predictive factor but conferred to better overall survival (p = 0.078). Among colorectal cancer patients, post SBRT chemotherapy was significantly associated with better OS (p = 0.025). Over grade 3 adverse event was seen in only one patient. CONCLUSION: SBRT is a safe and effective treatment for patients with lung and liver oligo-recurrence. Additional chemotherapy after SBRT improved local control, and single metastatic lesion was a significant predictive factor of better PFS in this study. Among colorectal cancer patients, additional chemotherapy after SBRT significantly associated better OS.

  2018年04月, Radiation oncology (London, England), 13(1) (1), 75 - 75, 英語, 国際誌

  研究論文（学術雑誌）


• High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images: relationship with increasing cumulative dose of a gadolinium-based contrast material.

  Tomonori Kanda, Kazunari Ishii, Hiroki Kawaguchi, Kazuhiro Kitajima, Daisuke Takenaka

  PURPOSE: To explore any correlation between the number of previous gadolinium-based contrast material administrations and high signal intensity (SI) in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance (MR) images. MATERIALS AND METHODS: The institutional review board approved this study, waiving the requirement to obtain written informed consent. A group of 381 consecutive patients who had undergone brain MR imaging was identified for cross-sectional analysis. For longitudinal analysis, 19 patients who had undergone at least six contrast-enhanced examinations were compared with 16 patients who had undergone at least six unenhanced examinations. The mean SIs of the dentate nucleus, pons, globus pallidus, and thalamus were measured on unenhanced T1-weighted images. The dentate nucleus-to-pons SI ratio was calculated by dividing the SI in the dentate nucleus by that in the pons, and the globus pallidus-to-thalamus SI ratio was calculated by dividing the SI in the globus pallidus by that in the thalamus. Stepwise regression analysis was undertaken in the consecutive patient group to detect any relationship between the dentate nucleus-to-pons or globus pallidus-to-thalamus SI ratio and previous gadolinium-based contrast material administration or other factors. A random coefficient model was used to evaluate for longitudinal analysis. RESULTS: The dentate nucleus-to-pons SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.010; 95% confidence interval [CI]: 0.009, 0.011; standardized regression coefficient, 0.695). The globus pallidus-to-thalamus SI ratio showed a significant correlation with the number of previous gadolinium-based contrast material administrations (P < .001; regression coefficient, 0.004; 95% CI: 0.002, 0.006; standardized regression coefficient, 0.288), radiation therapy (P = .009; regression coefficient, -0.014; 95% CI: -0.025, -0.004; standardized regression coefficient, -0.151), and liver function (P = .031; regression coefficient, 0.023; 95% CI: 0.002, 0.044; standardized regression coefficient, 0.107). The dentate nucleus-to-pons and globus pallidus-to-thalamus SI ratios in patients who had undergone contrast-enhanced examinations were significantly greater than those of patients who had undergone unenhanced examinations (P < .001 for both). CONCLUSION: High SI in the dentate nucleus and globus pallidus on unenhanced T1-weighted images may be a consequence of the number of previous gadolinium-based contrast material administrations.

  2014年03月, Radiology, 270(3) (3), 834 - 41, 英語, 国際誌

  研究論文（学術雑誌）

• Combatting pancreatic cancer stem cells by novel titanium peroxides nanoparticles combined with X-ray radiation

  Mohammed Salah, Hiroki Kawaguchi, Hiroaki Akasaka, Yasuyuki Shimizu, Kenta Morita, Yuya Nishimura, Hikaru Kubota, Tomomi Sogawa, Naritoshi Mukumoto, Chiaki Ogino, Ryohei Sasaki

  2023年04月01日, CANCER RESEARCH, 83(7) (7), 英語

  研究発表ペーパー・要旨（国際会議）


• Oncogenic miRNAs Identified in Tear Exosomes From Metastatic Breast Cancer Patients (vol 40, pg 3091, 2020)

  Sachiko Inubushi, Hiroki Kawaguchi, Sachiko Mizumoto, Tomonari Kunihisa, Motoi Baba, Yukiya Kitayama, Toshifumi Takeuchi, Robert M. Hoffman, Hirokazu Tanino, Ryohei Sasaki

  2020年08月, ANTICANCER RESEARCH, 40(8) (8), 4805 - 4805, 英語

  その他


• 非小細胞肺癌の転移性脳腫瘍に対する定位照射に関する検討

  川口 弘毅, 馬屋原 博, 石原 武明, 佐々木 良平

  (NPO)日本肺癌学会, 2018年10月, 肺癌, 58(6) (6), 567 - 567, 日本語


• 胃癌切除術後の孤発性腹部リンパ節再発に対する強度変調放射線治療(IMRT)の初期経験

  馬屋原 博, 原田 文, 西村 英輝, 上薗 玄, 橋本 直樹, 川口 弘毅, 石原 武明, 西川 遼, 中山 雅央, 佐々木 良平, 藤井 正彦

  (一社)日本癌治療学会, 2017年10月, 日本癌治療学会学術集会抄録集, 55回, P169 - 6, 日本語

• JASTRO NEWSLETTER153号（特集）

  分担執筆, ホジキンリンパ腫の放射線治療における心毒性低減, 公益社団法人日本放射線腫瘍学会, 2024年09月


• がん・放射線療法

  大西, 洋 (医学), 唐澤, 久美子, 西尾, 禎治, 石川, 仁

  分担執筆, 7-77 造血器腫瘍:皮膚悪性リンパ腫・菌状息肉症, Gakken, 2023年10月, 日本語, ISBN: 9784055200493

• 呼気凝縮液由来エクソソームを利用した頭頸部がんの革新的な治療効果予測法の開発

  宮脇 大輔, 佐々木 良平, 川口 弘毅, 椋本 成俊, 清水 康之

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2025年04月01日 - 2028年03月31日


• 超高線量率X線による革新的がん治療法のメカニズム解明

  佐々木 良平, 椋本 成俊, 城 鮎美, 川口 弘毅, 中山 雅央, 福本 毅

  日本学術振興会, 科学研究費助成事業, 国際共同研究加速基金(海外連携研究), 神戸大学, 2024年09月09日 - 2028年03月31日


• パンデミック下での前立腺癌の放射線治療休止に直面した際の克服手段に関する提案

  川口 弘毅

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2023年04月01日 - 2026年03月31日

  2023年8月に日本放射線腫瘍学機構（JROSG）の部位別委員会ミーティングが開催され、本研究の概要を提案し、JROSGを通じた、新型コロナウイルス罹患によって休止を余儀なくされた症例の状況に関する探索に関して議論を行った。当初前立腺癌を中心に、悪性リンパ腫や早期食道癌等も対象に含めることを検討していたが、前立腺癌と、それ以外に関して必要とする線量が異なることから、問題となる課題にも差異があり、対象疾患としては限定的とならざるを得ない点、また症例抽出の手法についても系統的な探索が困難であることから、組織を通じた調査を立案することが困難であることが考えられた。このことからまずは代表研究者が所属する神戸大学病院を中心とした関連病院に関して、前立腺癌症例について調査を行ったうえで、フォローアップの状況を観察することとした。関連病院において該当する症例については経過観察が継続されている。 また基礎研究に関しては、まずマウスにヒト前立腺癌細胞を埋植する方法を用いてモデルを作製することを予定している。手法としてはすでに膵癌細胞・大腸癌細胞を用いてマウスの腹腔内に埋植させることによって生着させることを試験的に実施しており、これをもとに次年度より具体的な計画立案を実施のうえ、実験を進めていく予定としている。また、並行してX線照射について、当院所属研究者の指導・助言を受けたうえで手技の確立に努め、本研究での手法を検討していく。


• 金属ナノ粒子を応用した新規・免疫放射線増感療法の開発

  岡本 欣晃, 赤坂 浩亮, 佐々木 良平, 宮脇 大輔, 妹尾 悟史, 川口 弘毅, 窪田 光

  日本学術振興会, 科学研究費助成事業, 基盤研究(C), 神戸大学, 2020年04月01日 - 2024年03月31日

  過酸化チタンナノ粒子は、X 線照射でROS を発生し殺細胞効果を示す。腫瘍局所では腫瘍浸潤リンパ球（TIL）やPDL1発現の増加し免疫チェックポイント阻害剤の併用で更なる局所抗腫瘍効果を得た。過酸化チタンナノ粒子は、マウス悪性黒色腫モデルで優れた腫瘍増殖抑制効果を示し、非照射部位にも増殖抑制効果を示すアブスコパル効果も得た。機序は放射線照射で免疫原性細胞死が起こり、がん抗原放出と樹状細胞からTILへの抗原提示が行われ、大量のTILが腫瘍へと浸潤し免疫サイクルが加速した。小胞体ストレスを誘導しMHC class I の発現の増強し圧倒的な免疫原性を獲得に成功し、成果は国際特許申請に至った。


• 超低侵襲を可能にする新規の体液診断マーカーを併用した放射線治療の開発

  川口 弘毅

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 2019年04月01日 - 2022年03月31日

  エクソソームは血液をはじめとする体液中に存在する。これは正常細胞にもがん細胞にも存在し、両者に存在するエクソソームの違いを検出することでがん診断のツールとして用いる試みが行われている。我々は涙液に注目し、これを診断のツールとして用いることができれば低侵襲ながん診断のツールとして用いることができると考えた。本研究では乳がん患者において涙液ががん診断および予後予測に用いることができる可能性を見出した。


• 超・高線量率マイクロスリットX線照射を用いた多発肺転移の新規治療戦略

  川口 弘毅

  日本学術振興会, 科学研究費助成事業, 研究活動スタート支援, 神戸大学, 2016年08月26日 - 2018年03月31日

  超・高線量率マイクロスリットX線照射を用いた多発肺転移の新規治療戦略を構築することを目的とする。近年、次世代の高精度放射線治療として、VMAT，Rapid Arcなど線量率を可変させながら照射し、総線量を積算する治療法が開発されつつあるが、積算線量のみで生物学的効果を判断してよいか否かは慎重に検証すべき課題である。低線量率の生体反応に関してはこれまで諸家の報告が多々あるが、超・高線量率に関しては照射法を工夫しなければ生体内（In vivo）の反応を検討することは難しい。そこで、高輝度放射光設備(SPring-8)から供給される指向性の高いX線ビームを用いて、超・高線量率（11,000cGy/ sec）X線照射を用いた多発肺転移の新規治療戦略を検討した。方法として超・高線量率X線のスリットビームを用いて、動物実験にてその生体反応（正常組織、腫瘍）を解析し、正常組織の反応を中心に研究し、移植腫瘍に対する治療法を検討した。マウスの正常組織（片肺、全肺、心臓）を対象とし、格子幅、総線量を変化させて、分子病理学的評価及び、生存率からその毒性を解析する。腫瘍に関しては多発肺転移マウスモデルを用いてブロードビーム、スリットビーム、格子状ビームの増殖抑制効果に関して解析を行った。同時に、スリットビーム、格子状照射における正確な線量分布を評価するため、専用のファントムを作成し、ガフクロミックフィルムを用いて各格子幅での物理学的特性、線量プロファイルの作成を行った。 多発肺モデルの検討では、スリットビーム照射を用いた片肺照射においてにおいて有意な肺転移数の減少を確認でき、急性期毒性を反映すると思われるマウスの致死率増加は認められなかった。これらの結果より、これまで放射線を用いた有用な治療方法がないとされてきた多発肺転移に対しても本治療方法は有効な一手段となることが示された。