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      An overview of the medical-physics-related verification system for radiotherapy multicenter clinical trials by the Medical Physics Working Group in the Japan Clinical Oncology Group–Radiation Therapy Study Group

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          Abstract

          The Japan Clinical Oncology Group Radiation Therapy Study Group (JCOG-RTSG) has initiated several multicenter clinical trials for high-precision radiotherapy, which are presently ongoing. When conducting multi-center clinical trials, a large difference in physical quantities, such as the absolute doses to the target and the organ at risk, as well as the irradiation localization accuracy, affects the treatment outcome. Therefore, the differences in the various physical quantities used in different institutions must be within an acceptable range for conducting multicenter clinical trials, and this must be verified with medical physics consideration. In 2011, Japan’s first Medical Physics Working Group (MPWG) in the JCOG-RTSG was established to perform this medical-physics-related verification for multicenter clinical trials. We have developed an auditing method to verify the accuracy of the absolute dose and the irradiation localization. Subsequently, we credentialed the participating institutions in the JCOG multicenter clinical trials that were using stereotactic body radiotherapy (SBRT) for lungs, intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) for several disease sites, and proton beam therapy (PT) for the liver. From the verification results, accuracies of the absolute dose and the irradiation localization among the participating institutions of the multicenter clinical trial were assured, and the JCOG clinical trials could be initiated.

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          Critical impact of radiotherapy protocol compliance and quality in the treatment of advanced head and neck cancer: results from TROG 02.02.

          To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center ( or = 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): -2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively. These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.
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            Prospective Trial of Stereotactic Body Radiation Therapy for Both Operable and Inoperable T1N0M0 Non-Small Cell Lung Cancer: Japan Clinical Oncology Group Study JCOG0403.

            To evaluate, in Japan Clinical Oncology Group study 0403, the safety and efficacy of stereotactic body radiation therapy (SBRT) in patients with T1N0M0 non-small cell lung cancer (NSCLC).
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              QA makes a clinical trial stronger: evidence-based medicine in radiation therapy.

              Quality assurance (QA) for radiation therapy (RT) in clinical trials is necessary to ensure treatment is safely and effectively administered. QA assurance requires however substantial human and financial resources, as it has become more comprehensive and labor intensive in recent RT trials. It is presumed that RT deviations decrease therapeutic effectiveness of the studied regimen. This study assesses the impact of RT protocol-deviations on patient's outcome in prospective phase II-III RT trials. PubMed, Medline and Embase identified nine prospective RT trials detailing QA RT violation and patient's outcome. Planned QA analysis was preformed retrospectively and prospectively in eight and one studies, respectively. Non-adherence to protocol-specified RT requirements in prospective trials is frequent: the observed major deviation rates range from 11.8% to 48.0% (mean, 28.1 ± 17.9%). QA RT deviations had a significant impact on the primary study end-point in a majority (62.5%) of studies. The number of patients accrued per center was a significant predictive factor for RT deviations in the largest series. These QA data stemming from prospective clinical trials show undisputedly that non adherence to protocol-specified RT requirements is associated with reduced survival, local control and potentially increased toxicity. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Contributors
                Journal
                J Radiat Res
                J Radiat Res
                jrr
                Journal of Radiation Research
                Oxford University Press
                0449-3060
                1349-9157
                November 2020
                29 September 2020
                29 September 2020
                : 61
                : 6
                : 999-1008
                Affiliations
                Department of Medical Physics , Graduate School of Medicine , Tokyo Women’s Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Division of Medical Physics , Department of Information Technology and Medical Engineering, Human He Sciences, Graduate School of Medicine , Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Medical Physics , National Cancer Center Hospital , 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045 Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiology , Tokyo Metropolitan Bokutoh Hospital , 4-23-15 Kotobashi, Sumida-ku, Tokyo 130-8575, Japan
                Department of Radiation Oncology , Tokyo Metropolitan Cancer and Infectious Disease Center Komagome Hospital , 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
                Division of Medical Physics , Department of Information Technology and Medical Engineering, Human He Sciences, Graduate School of Medicine , Kyoto University, 53 Shogoin-Kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Division of Medical Support and Partnership , Center for Cancer Control and Information Services , National Cancer Center, 5-1-1 Tsukiji, Chuo-ku, Tokyo 104-0045, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiation Oncology , Graduate School of Biomedical and Health Sciences , Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
                Hiroshima High-Precision Radiotherapy Cancer Center , 3-2-2, Futabanosato, Higashi-ku, Hiroshima 732-0057, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiation Oncology , Saitama Medical University International Medical Center , 1397-1 Yamane, Hidaka, Saitama 350-1298, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Faculty of Health Sciences , Hokkaido University , N-12 W-5 Kita-ku, Sapporo, 060-0812, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Division of Medical Physics , Tokyo Bay Advanced Imaging & Radiation Oncology Makuhari Clinic , 1-17 Toyosuna, Mihama-ku, Chiba, 261-0024, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiation Therapy , Tokyo Medical University Hospital , 6-7-1, Nishishinjuku, Shinjuku-ku, Tokyo 160-0023, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Radiation Therapy Section , Department of Clinical Support, Hiroshima University Hospital , 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiation Oncology , Aichi Cancer Center Hospital , 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Medical Physics , Hokkaido University Hospital , North-14, West-5, Kita-Ku, Sapporo, Hokkaido 060-8638, Japan
                Medical Physics Working Group (MPWG) in Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiology , Graduate School of Medical Sciences , Nagoya City University, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8601, Japan
                Radiotherapy Committee (RC) in Japan Clinical Oncology Group , Tokyo, Japan
                Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Department of Radiation Oncology , Kindai University Faculty of Medicine , 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan
                Japan Clinical Oncology Group - Radiation Therapy Study Group (JCOG-RTSG) , Tokyo, Japan
                Author notes
                Corresponding author. Department of Medical Physics, Graduate School of Medicine, Tokyo Women’s Medical University, 8-1, Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. Tel: +81-3-3353-8111; Fax: +81-3-5269-7040; Email: nishio.teiji@ 123456twmu.ac.jp
                Article
                rraa089
                10.1093/jrr/rraa089
                7674673
                32989445
                bcf4b96b-2210-45b1-87aa-b68ddc259cc3
                © The Author(s) 2020. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 21 July 2020
                : 25 August 2020
                : 26 August 2020
                Page count
                Pages: 10
                Funding
                Funded by: National Cancer Center Research and Development Fund;
                Award ID: 25-B-4
                Award ID: 28-A-14
                Award ID: 29-A-3
                Award ID: 2020-J-3
                Categories
                Miscellaneous
                AcademicSubjects/MED00870
                AcademicSubjects/SCI00960

                Oncology & Radiotherapy
                dosimetry audit,irradiation localization audit,credentialing,radiotherapy clinical trial

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