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      Acral cutaneous malignant melanoma treated with linear accelerator-based boron neutron capture therapy system: a case report of first patient

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          Abstract

          This study reports the first patient treatment for cutaneous malignant melanoma using a linear accelerator-based boron neutron capture therapy (BNCT) system. A single-center open-label phase I clinical trial had been conducted using the system since November 2019. A patient with a localized node-negative acral malignant melanoma and the largest diameter of the tumor ≤ 15 cm who refused primary surgery and chemotherapy was enrolled. After administering boronophenylalanine (BPA), a single treatment of BNCT with the maximum dose of 18 Gy-Eq delivered to the skin was performed. The safety and efficacy of the accelerator-based BNCT system for treating localized cutaneous malignant melanoma were evaluated. The first patient with cutaneous malignant melanoma in situ on the second finger of the left hand did not develop dose-limiting toxicity in the clinical trial. After BNCT, the treatment efficacy was gradually observed, and the patient achieved PR within 6 months and CR within 12 months. Moreover, during the follow-up period of 12 months after BNCT, the patient did not exhibit a recurrence without any treatment-related grade 2 or higher adverse events. Although grade 1 adverse events of dermatitis, dry skin, skin hyperpigmentation, edema, nausea, and aching pain were noted in the patient, those adverse events were relieved without any treatment. This case report shows that the accelerator-based BNCT may become a promising treatment modality for cutaneous malignant melanoma. We expect further clinical trials to reveal the efficacy and safety of the accelerator-based BNCT for cutaneous malignant melanoma.

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          Most cited references18

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          Features of Particle and Heavy Ion Transport code System (PHITS) version 3.02

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            ICRP publication 118: ICRP statement on tissue reactions and early and late effects of radiation in normal tissues and organs--threshold doses for tissue reactions in a radiation protection context.

            This report provides a review of early and late effects of radiation in normal tissues and organs with respect to radiation protection. It was instigated following a recommendation in Publication 103 (ICRP, 2007), and it provides updated estimates of 'practical' threshold doses for tissue injury defined at the level of 1% incidence. Estimates are given for morbidity and mortality endpoints in all organ systems following acute, fractionated, or chronic exposure. The organ systems comprise the haematopoietic, immune, reproductive, circulatory, respiratory, musculoskeletal, endocrine, and nervous systems; the digestive and urinary tracts; the skin; and the eye. Particular attention is paid to circulatory disease and cataracts because of recent evidence of higher incidences of injury than expected after lower doses; hence, threshold doses appear to be lower than previously considered. This is largely because of the increasing incidences with increasing times after exposure. In the context of protection, it is the threshold doses for very long follow-up times that are the most relevant for workers and the public; for example, the atomic bomb survivors with 40-50years of follow-up. Radiotherapy data generally apply for shorter follow-up times because of competing causes of death in cancer patients, and hence the risks of radiation-induced circulatory disease at those earlier times are lower. A variety of biological response modifiers have been used to help reduce late reactions in many tissues. These include antioxidants, radical scavengers, inhibitors of apoptosis, anti-inflammatory drugs, angiotensin-converting enzyme inhibitors, growth factors, and cytokines. In many cases, these give dose modification factors of 1.1-1.2, and in a few cases 1.5-2, indicating the potential for increasing threshold doses in known exposure cases. In contrast, there are agents that enhance radiation responses, notably other cytotoxic agents such as antimetabolites, alkylating agents, anti-angiogenic drugs, and antibiotics, as well as genetic and comorbidity factors. Most tissues show a sparing effect of dose fractionation, so that total doses for a given endpoint are higher if the dose is fractionated rather than when given as a single dose. However, for reactions manifesting very late after low total doses, particularly for cataracts and circulatory disease, it appears that the rate of dose delivery does not modify the low incidence. This implies that the injury in these cases and at these low dose levels is caused by single-hit irreparable-type events. For these two tissues, a threshold dose of 0.5Gy is proposed herein for practical purposes, irrespective of the rate of dose delivery, and future studies may elucidate this judgement further. Copyright © 2012. Published by Elsevier Ltd.
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              Boron neutron capture therapy using cyclotron-based epithermal neutron source and borofalan (10B) for recurrent or locally advanced head and neck cancer (JHN002): An open-label phase II trial

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                Author and article information

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                Journal
                Front Oncol
                Front Oncol
                Front. Oncol.
                Frontiers in Oncology
                Frontiers Media S.A.
                2234-943X
                13 October 2023
                2023
                : 13
                : 1272507
                Affiliations
                [1] 1 Department of Radiation Oncology, National Cancer Center Hospital , Tokyo, Japan
                [2] 2 Division of Research and Development for Boron Neutron Capture Therapy, National Cancer Center Exploratory Oncology Research & Clinical Trial Center , Tokyo, Japan
                [3] 3 Division of Radiation Safety and Quality Assurance, National Cancer Center Hospital , Tokyo, Japan
                [4] 4 Medical Physics Laboratory, Division of Health Science, Graduate School of Medicine, Osaka University , Suita, Osaka, Japan
                [5] 5 Department of Dermatologic Oncology, National Cancer Center Hospital , Tokyo, Japan
                [6] 6 Department of Radiation Oncology, Jutendo University School of Medicine , Tokyo, Japan
                [7] 7 Department of Radiological Science, Graduate School of Human Health Sciences, Tokyo Metropolitan University , Tokyo, Japan
                [8] 8 National Cancer Center Hospital , Tokyo, Japan
                [9] 9 Shin-Matsudo Accuracy Radiation Therapy Center, Shin-Matsudo Central General Hospital , Chiba, Japan
                Author notes

                Edited by: Minoru Suzuki, Kyoto University, Japan

                Reviewed by: Koichi Yasuda, Hokkaido University, Japan; Shintaro Shiba, Shonan Kamakura General Hospital, Japan

                *Correspondence: Satoshi Nakamura, satonaka@ 123456ncc.go.jp
                Article
                10.3389/fonc.2023.1272507
                10613025
                37901311
                64e4ea8f-2c85-4180-ae41-67c11b0fa2ae
                Copyright © 2023 Igaki, Nakamura, Yamazaki, Kaneda, Takemori, Kashihara, Murakami, Namikawa, Nakaichi, Okamoto, Iijima, Chiba, Nakayama, Nagao, Sakuramachi, Takahashi, Inaba, Okuma, Nakayama, Shimada, Nakagama and Itami

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 August 2023
                : 26 September 2023
                Page count
                Figures: 2, Tables: 2, Equations: 0, References: 19, Pages: 6, Words: 2401
                Funding
                The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by a JSPS Grant-in-Aid for Young Scientists (Grant Number 19K17218) and a JSPS Grant-in-Aid for Young Scientists (B) (Grant Number 26860410), and partially supported by a JSPS Grant-in-Aid for Scientific Research (B) and (C) (Grant Number 19H03611 and 16K10410) and by Japanese Agency for Medical Research and Development (23mk0121267h0001).
                Categories
                Oncology
                Case Report
                Custom metadata
                Radiation Oncology

                Oncology & Radiotherapy
                boron neutron capture therapy (bnct),malignant melanoma,linear accelerator-based bnct system,solid-state li target,acral malignant melanoma,first treatment

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