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Annual Report 2021

Department of Radiation Oncology

Hiroshi Igaki, Yuko Nakayama, Naoya Murakami, Kae Okuma, Tomoya Kaneda, Koji Inaba, Kana Takahashi, Tairo Kashihara, Ayaka Takahashi, Yuri Shimizu, Kanako Kojima

Introduction

 The role of our department is to provide state-of-the-art radiation therapy to all patients who need it, to educate and develop the expertise of radiation oncologists, radiation technologists, and medical physicists, and to lead new developments in radiation oncology in Japan as well as worldwide. All departmental activities are dedicated to cancer patients. A linear accelerator-based neutron irradiation system for boron neutron capture therapy (BNCT) has been installed in the hospital; an epithermal neutron beam was obtained and a clinical trial of BNCT for cutaneous melanoma and angiosarcoma is ongoing. Additionally, an MR-guided radiation therapy system, MRIdian®, has been introduced for the first time in Japan in our department. After strict acceptance and commissioning procedures, MRIdian is used mainly for on-line adaptive radiation therapy for abdominal or pelvic tumors.

The Team and What We Do

 Our department treats the largest number of radiation oncology patients in Japan. Four linear accelerators, CyberKnife, MRIdian, a brachytherapy system, four XCT-simulators, and 15 treatment planning computers are working together in online networks to provide state-of-the-art high-precision external beam radiation therapy. In addition to the conventional X-ray and electron therapies, stereotactic irradiations of brain and body tumors and intensity-modulated radiation therapy (IMRT) are routinely performed. Stereotactic brain irradiation is performed with CyberKnife in the treatment of metastatic as well as primary brain tumors. Stereotactic body radiation therapies are performed for lung and liver tumors under respiratory gating in linear accelerators or CyberKnife. All linear accelerators have on-board kilovoltage CT imagers, which help to precisely align patient and tumor coordinates. These image-guided radiation therapy (IGRT) facilities enable the precise delivery of IMRT in head and neck cancers, brain tumors, prostate cancers, postoperative cervical cancers, and other cancers. Gold marker fiducials have been implanted to improve the geometric precision of radiation field reproducibility. MRIdian, which is a fusion of MRI and a radiation therapy machine, is used mainly for pancreatic cancer and other upper abdominal cancers. Brachytherapy is also intensively performed to improve local control, and many patients are referred to us from all over Japan. For brachytherapy, the following modalities are being employed: an Ir-192 high dose rate (HDR) after-loading system including dedicated CT simulator and fluoroscopy; an I-125 seed implantation system, and other low dose rate (LDR) brachytherapy systems using Au-198 grains and Ru-106 eye plaques. The number of patients undergoing HDR brachytherapy continues to rise. HDR interstitial irradiation is performed mainly in gynecological, genitourinary, and head and neck tumors. Additionally, there are two beds in the shielded ward on Floor 13B. Ru-106 mold therapy is performed in collaboration with ophthalmologists to treat retinoblastomas and choroidal melanomas. LDR interstitial implants are carried out using Au-198 grains for the management of head and neck tumors and gynecological malignancies. The number of patients treated in our department is shown in Table 1.

Table 1.
Table 1.

Table 1.
Table 1.

Research activities

 Clinical research is an indispensable part of the daily activities of our department. The primary interests of the research activities of the department are as follows: (1) on-line adaptive radiation therapy using an MR-guided radiotherapy system; (2) clinical applications of accelerator-based boron neutron capture therapy for skin and other tumors; (3) image-guided brachytherapy for genitourinary and gynecologic cancers; (4) development of new medical devices for radiotherapy; (5) hypofractionated stereotactic irradiation of brain and body tumors; (6) an optimal fractionation regimen for pain palliation of bone metastasis.

Clinical trials

  • Many clinical trials are ongoing, as shown below.
  • JCOG studies for lung cancers, head and neck cancers, brain tumors, gynecological cancer, and esophageal cancers
  • International NRG studies for breast cancer and meningioma
  • International Study of Ophthalmic Radiation Therapy Toxicity
  • Phase I clinical trial of BNCT for melanoma and angiosarcoma of the skin
  • Development of an Adaptive Radiation Therapy System
  • Multi-institutional phase I/II trial of hybrid brachytherapy for cervical cancer
  • Many other multi- or single-institutional clinical trials are also ongoing or in preparation.

Education

 Seven residents have been trained in all fields of radiation oncology. Seminars on biology, physics, and clinical radiation oncology are regularly held during the evening.

Future Prospects

 With the expanding indications of radiation therapy, additional manpower will be required and research perspectives will be considerably broadened. Radiation oncology is one of the most promising disciplines in oncology.

List of papers published in 2021

Journal

1. Nakamura S, Murakami N, Suzuki S, Ito K, Takemori M, Nakayama H, Kaga K, Chiba T, Iijima K, Takahashi K, Goka T, Itami J, Okamoto H, Igaki H. Monte Carlo simulation of tilted contact plaque brachytherapy placement for juxtapapillary retinoblastoma. Radiation oncology (London, England), 17:16, 2022

2. Kashihara T, Ishiki H, Kato K. Definitive Chemoradiotherapy for Older Patients With Esophageal Cancer. JAMA oncology, 8:304-305, 2022

3. Imamichi S, Chen L, Ito T, Tong Y, Onodera T, Sasaki Y, Nakamura S, Mauri P, Sanada Y, Igaki H, Murakami Y, Suzuki M, Itami J, Masunaga S, Masutani M. Extracellular Release of HMGB1 as an Early Potential Biomarker for the Therapeutic Response in a Xenograft Model of Boron Neutron Capture Therapy. Biology, 11:2022

4. Igaki H, Murakami N, Nakamura S, Yamazaki N, Kashihara T, Takahashi A, Namikawa K, Takemori M, Okamoto H, Iijima K, Chiba T, Nakayama H, Takahashi A, Kaneda T, Takahashi K, Inaba K, Okuma K, Nakayama Y, Shimada K, Nakagama H, Itami J. Scalp angiosarcoma treated with linear accelerator-based boron neutron capture therapy: A report of two patients. Clinical and translational radiation oncology, 33:128-133, 2022

5. Murakami N, Okuma K, Okamoto H, Nakamura S, Kashihara T, Kaneda T, Takahashi K, Inaba K, Igaki H, Masui K, Yoshida K, Kato T, Itami J. Bevacizumab increases late toxicity in re-irradiation with image-guided high-dose-rate brachytherapy for gynecologic malignancies. Journal of contemporary brachytherapy, 14:52-59, 2022

6. Murakami N, Kuno I, Yoshida H, Shiraishi K, Kato T, Igaki H. How should we appropriately classify low-risk uterine cervical cancer patients suitable for de-intensified treatment? Journal of radiation research, 63:312-313, 2022

7. Akiyama H, Yoshida K, Takenaka T, Kotsuma T, Masui K, Monzen H, Sumida I, Tsujimoto Y, Miyao M, Okumura H, Shimbo T, Takegawa H, Murakami N, Inaba K, Kashihara T, Takácsi-Nagy Z, Tselis N, Yamazaki H, Tanaka E, Nihei K, Ariji Y . Effect of a lead block on alveolar bone protection in image-guided high-dose-rate interstitial brachytherapy for tongue cancer: using model-based dose calculation algorithms to correct for inhomogeneity. Journal of contemporary brachytherapy, 14:87-95, 2022

8. Murakami N, Ohno T, Toita T, Ando K, Ii N, Okamoto H, Kojima T, Tsujino K, Masui K, Yoshida K, Ikushima H. Japanese Society for Radiation Oncology Consensus Guidelines of combined intracavitary and interstitial brachytherapy for gynecological cancers. Journal of radiation research, 63:402-411, 2022

9. Murakami N, Ando K, Murata M, Murata K, Ohno T, Aoshika T, Kato S, Okonogi N, Saito AI, Kim JY, Yoshioka Y, Sekii S, Tsujino K, Lowanichkiattikul C, Pattaranutaporn P, Kaneyasu Y, Nakagawa T, Watanabe M, Uno T, Umezawa R, Jingu K, Kanemoto A, Wakatsuki M, Shirai K, Igaki H, Itami J. An Asian multi-national multi-institutional retrospective study comparing intracavitary versus the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical carcinoma. Journal of radiation research, 63:412-427, 2022

10. Murakami N, Watanabe M, Uno T, Sekii S, Tsujino K, Kasamatsu T, Machitori Y, Aoshika T, Kato S, Hirowatari H, Kaneyasu Y, Nakagawa T, Ikushima H, Ando K, Murata M, Yoshida K, Yoshioka H, Murata K, Ohno T, Okonogi N, Saito A, Ichikawa M, Okuda T, Tsuchida K, Sakurai H, Yoshimura R, Yoshioka Y, Yorozu A, Okamoto H, Inaba K, Kato T, Igaki H, Itami J. Large volume was associated with increased risk of acute non-hematologic adverse events in the hybrid of intracavitary and interstitial brachytherapy for locally advanced uterine cervical cancer: preliminary results of prospective phase I/II clinical trial. Japanese journal of clinical oncology, 2022

11. Okamoto H, Okuma K, Nakayama H, Nakamura S, Iijima K, Chiba T, Takemori M, Fujii K, Mikasa S, Nakaichi T, Aikawa A, Katsuta S, Igaki H. In vivo dosimetry for testicular and scalp shielding in total skin electron therapy using a radiophotoluminescence glass dosimeter. Journal of radiation research, 63:51-54, 2022

12. Okamoto H, Iijima K, Chiba T, Takemori M, Nakayama H, Fujii K, Kon M, Mikasa S, Nakaichi T, Urago Y, Aikawa A, Katsuta S, Nakamura S, Igaki H. Technical note: Analysis of brachytherapy source movement by high-speed camera. Medical physics, 2022

13. Tamura Y, Demachi K, Igaki H, Okamoto H, Nakano M. A Real-Time Four-Dimensional Reconstruction Algorithm of Cine-Magnetic Resonance Imaging (Cine-MRI) Using Deep Learning. Cureus, 14:e22826, 2022

14. Kashihara T, Igaki H, Ogata D, Nakayama H, Nakamura S, Okuma K, Mori T, Yamakawa K, Takahashi A, Namikawa K, Takahashi A, Takahashi K, Kaneda T, Inaba K, Murakami N, Nakayama Y, Okamoto H, Yamazaki N, Itami J. Prognostic factor analysis of definitive radiotherapy using intensity-modulated radiation therapy and volumetric modulated arc therapy with boluses for scalp angiosarcomas. Scientific reports, 12:4355, 2022

15. Kobayashi R, Murakami N, Chiba T, Okuma K, Inaba K, Takahashi K, Kaneda T, Kashihara T, Takahashi A, Shimizu Y, Nakayama Y, Kato T, Ito Y, Igaki H . Effect of Hyaluronate Acid Injection on Dose-Volume Parameters in Brachytherapy for Cervical Cancer. Advances in radiation oncology, 7:100918, 2022

16. Yonezawa H, Ohno M, Igaki H, Miyakita Y, Takahashi M, Tamura Y, Shima S, Matsushita Y, Ichimura K, Narita Y. Outcomes of salvage fractionated re-irradiation combined with bevacizumab for recurrent high-grade gliomas that progressed after bevacizumab treatment*. Japanese journal of clinical oncology, 51:1028-1035, 2021

17. Kashihara T, Nakamura S, Murakami N, Ito K, Matsumoto Y, Kobayashi K, Omura G, Mori T, Honma Y, Kubo Y, Okamoto H, Takahashi K, Inaba K, Okuma K, Igaki H, Nakayama Y, Kato K, Matsumoto F, Yoshimoto S, Itami J. Initial Experience of Intentional Internal High-Dose Policy Volumetric Modulated Arc Therapy of Neck Lymph Node Metastases ≥ 2 cm in Patients With Head and Neck Squamous Cell Carcinoma. Frontiers in oncology, 11:651409, 2021

18. Inaba K, Tsuchida K, Kashihara T, Umezawa R, Takahashi K, Okuma K, Murakami N, Ito Y, Igaki H, Sumi M, Nakayama Y, Shinoda Y, Hara T, Matsui Y, Komiyama M, Fujimoto H, Itami J. Treatment results of radiotherapy to both the prostate and metastatic sites in patients with bone metastatic prostate cancer. Journal of radiation research, 62:511-516, 2021

19. Murakami N, Asami Y, Yoshida H, Takayanagi D, Hirose S, Kuno I, Takahashi K, Matsuda M, Shimada Y, Yamano S, Sunami K, Honda T, Nakahara T, Watanabe T, Okuma K, Kuroda T, Kohno T, Kato T, Shiraishi K, Itami J. Distribution of genetic alterations in high-risk early-stage cervical cancer patients treated with postoperative radiation therapy. Scientific reports, 11:10567, 2021

20. Chen L, Imamichi S, Tong Y, Sasaki Y, Onodera T, Nakamura S, Igaki H, Itami J, Masutani M. A Combination of GM-CSF and Released Factors from Gamma-Irradiated Tumor Cells Enhances the Differentiation of Macrophages from Bone Marrow Cells and Their Antigen-Presenting Function and Polarization to Type 1. Medicines (Basel, Switzerland), 8:2021

21. Itami J, Murakami N, Watanabe M, Sekii S, Kasamatsu T, Kato S, Hirowatari H, Ikushima H, Ando K, Ohno T, Okamoto H, Okuma K, Igaki H. Combined Interstitial and Intracavitary High-Dose Rate Brachytherapy of Cervical Cancer. Frontiers in oncology, 11:809825, 2021

22. Murakami N, Nakamura S, Kashihara T, Inaba K, Kaneda T, Takahashi K, Okuma K, Igaki H, Itami J. Increased number of prostate cancer patients selecting high dose-rate interstitial brachytherapy during the COVID-19 pandemic. Radiotherapy and oncology: journal of the European Society for Therapeutic Radiology and Oncology, 154:274-275, 2021

23. Murakami N, Omura G, Yatsuoka W, Okamoto H, Yoshimoto S, Ueno T, Itami J. Hybrid Intracavitary-Interstitial brachytherapy in a case of nasal vestibule cancer penetrating the hard palate. BJR case reports, 7:20200178, 2021

24. Yokoyama K, Murakami N, Takahashi A, Kobayashi K, Igaki H, Itami J. Radiotherapy-Induced Autoeczematization. Pract Radiat Oncol, 11:E447-E448, 2021

25. Umezawa R, Wakita A, Katsuta Y, Ito Y, Nakamura S, Okamoto H, Kadoya N, Takahashi K, Inaba K, Murakami N, Igaki H, Jingu K, Itami J. A Pilot Study of Synchronization of Respiration-Induced Motions in the Duodenum and Stomach for the Primary Tumor in Radiation Therapy for Pancreatic Cancer Using 4-Dimensional Computed Tomography. Advances in radiation oncology, 6:100730, 2021

26.  Murakami N, Ando K, Murata M, Murata K, Ohno T, Aoshika T, Kato S, Okonogi N, Saito AI, Kim JY, Kumai Y, Yoshioka Y, Sekii S, Tsujino K, Lowanichkiattikul C, Pattaranutaporn P, Kaneyasu Y, Nakagawa T, Watanabe M, Uno T, Umezawa R, Jingu K, Kanemoto A, Wakatsuki M, Shirai K, Igaki H, Itami J. Why not de-intensification for uterine cervical cancer? Gynecologic oncology, 163:105-109, 2021

27. Murakami N, Honma Y, Yoshimoto S, Shima S, Kashihara T, Takahashi K, Kaneda T, Inaba K, Okuma K, Masui K, Yoshida K, Igaki H, Itami J. Gel spacer to protect carotid artery and reconstructed jejunum in image-guided interstitial brachytherapy for recurrent hypopharyngeal cancer: a technical report. Journal of contemporary brachytherapy, 13:583-587, 2021

28. Kuno I, Takayanagi D, Asami Y, Murakami N, Matsuda M, Shimada Y, Hirose S, Kato MK, Komatsu M, Hamamoto R, Okuma K, Kohno T, Itami J, Yoshida H, Shiraishi K, Kato T. TP53 mutants and non-HPV16/18 genotypes are poor prognostic factors for concurrent chemoradiotherapy in locally advanced cervical cancer. Scientific reports, 11:19261, 2021

29. Nakamura S, Igaki H, Ito M, Imamichi S, Kashihara T, Okamoto H, Nishioka S, Iijima K, Chiba T, Nakayama H, Takemori M, Abe Y, Kaneda T, Takahashi K, Inaba K, Okuma K, Murakami N, Nakayama Y, Masutani M, Nishio T, Itami J. Neutron flux evaluation model provided in the accelerator-based boron neutron capture therapy system employing a solid-state lithium target. Scientific reports, 11:8090, 2021

30. Takada M, Nunomiya T, Masuda A, Matsumoto T, Tanaka H, Nakamura S, Endo S, Nakamura M, Aoyama K, Ueda O, Narita M, Nakamura T. Development of a real-time neutron beam detector for boron neutron capture therapy using a thin silicon sensor. Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine, 176:109856, 2021

31.  Urago Y, Okamoto H, Kaneda T, Murakami N, Kashihara T, Takemori M, Nakayama H, Iijima K, Chiba T, Kuwahara J, Katsuta S, Nakamura S, Chang W, Saitoh H, Igaki H. Evaluation of auto-segmentation accuracy of cloud-based artificial intelligence and atlas-based models. Radiation oncology (London, England), 16:175, 2021

32. Nakayama H, Nakamura S, Iijima K, Chiba T, Takemori M, Kashihara T, Okuma K, Igaki H, Saitoh H, Chang W, Okamoto H. Efficacy of tangential irradiation with volumetric modulated arc therapy on scalp angiosarcoma using medical linac. Physica medica: PM: an international journal devoted to the applications of physics to medicine and biology: official journal of the Italian Association of Biomedical Physics (AIFB), 91:105-116, 2021

33. Iijima K, Okamoto H, Nishioka S, Sakasai T, Nakamura S, Chiba T, Kaga K, Takemori M, Nakayama H, Miura Y, Fujiyama D, Tsunoda Y, Igaki H, Katsuta S, Itami J. Performance of a newly designed end-to-end phantom compatible with magnetic resonance-guided radiotherapy systems. Medical physics, 48:7541-7551, 2021

34. Ishiyama H, Tsumura H, Nagano H, Watanabe M, Mizuno E, Taka M, Kobayashi H, Eriguchi T, Imada H, Inaba K, Nakamura K. Multi-institutional retrospective analysis of ultrahypofractionated radiotherapy for Japanese prostate cancer patients. Scientific reports, 11:13194, 2021

35. Kitaguchi M, Yamashita H, Takenaka R, Okuma K, Nawa K, Nakagawa K. Helical Skin Radiation Therapy Including Total Skin Radiation Therapy Using Tomotherapy for Primary Cutaneous Lymphoma With Bone Marrow Suppression as a Related Adverse Event. Practical radiation oncology, 11:e308-e321, 2021

36. Shimizu Y, Murakami N, Chiba T, Kaneda T, Okamoto H, Nakamura S, Takahashi A, Kashihara T, Takahashi K, Inaba K, Okuma K, Nakayama Y, Itami J, Igaki H. High-Dose-Rate Interstitial Brachytherapy for Deeply Situated Gynecologic Tumors Guided by Combination of Transrectal and Transabdominal Ultrasonography: A Technical Note. Frontiers in oncology, 11:808721, 2021

37. Kashihara T, Kashihara K. Radiotherapy with genomic-adjusted radiation dose. The Lancet. Oncology, 22:e468, 2021

38. Kashihara T, Kashihara K. Lutetium-177-PSMA-617 for Prostate Cancer. The New England journal of medicine, 385:2494-2495, 2021

39. Murakami N, Mori T, Machida R, Kodaira T, Ito Y, Shikama N, Konishi K, Matsumoto Y, Murakami Y, Nakamura N, Yamashita H, Yorozu A, Yoshimura M, Inoue K, Nozaki M, Ishikura S, Itami J, Nishimura Y, Kagami Y. Prognostic Value of Epithelial Cell Adhesion Molecules in T1-2N0M0 Glottic Cancer. The Laryngoscope, 131:1522-1527, 2021

40. Kobayashi K, Murakami N, Takahashi K, Inaba K, Igaki H, Hamamoto R, Itami J. Tensor Regression-based Model to Investigate Heterogeneous Spatial Radiosensitivity After I-125 Seed Implantation for Prostate Cancer. In vivo (Athens, Greece), 35:489-497, 2021

41. Takayanagi D, Hirose S, Kuno I, Asami Y, Murakami N, Matsuda M, Shimada Y, Sunami K, Komatsu M, Hamamoto R, Kato MK, Matsumoto K, Kohno T, Kato T, Shiraishi K, Yoshida H. Comparative Analysis of Genetic Alterations, HPV-Status, and PD-L1 Expression in Neuroendocrine Carcinomas of the Cervix. Cancers, 13:2021

42.  Watase C, Shiino S, Shimoi T, Noguchi E, Kaneda T, Yamamoto Y, Yonemori K, Takayama S, Suto A. Breast Cancer Brain Metastasis-Overview of Disease State, Treatment Options and Future Perspectives. Cancers, 13:2021