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      Validation of the clinical applicability of knowledge‐based planning models in single‐isocenter volumetric‐modulated arc therapy for multiple brain metastases

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          Abstract

          Purpose

          To validate the clinical applicability of knowledge‐based (KB) planning in single‐isocenter volumetric‐modulated arc therapy (VMAT) for multiple brain metastases using the k‐fold cross‐validation (CV) method.

          Methods

          This study comprised 60 consecutive patients with multiple brain metastases treated with single‐isocenter VMAT (28 Gy in five fractions). The patients were divided randomly into five groups (Groups 1–5). The data of Groups 1–4 were used as the training and validation dataset and those of Group 5 were used as the testing dataset. Four KB models were created from three of the training and validation datasets and then applied to the remaining Groups as the fourfold CV phase. As the testing phase, the final KB model was applied to Group 5 and the dose distributions were calculated with a single optimization process. The dose‐volume indices (DVIs), modified Ian Paddick Conformity Index (mIPCI), modulation complexity scores for VMAT plans (MCSv), and the total number of monitor units (MUs) of the final KB plan were compared to those of the clinical plan (CL) using a paired Wilcoxon signed‐rank test.

          Results

          In the fourfold CV phase, no significant differences were observed in the DVIs among the four KB plans (KBPs). In the testing phase, the final KB plan was statistically equivalent to the CL, except for planning target volumes (PTVs) D 2% and D 50%. The differences between the CL and KBP in terms of the PTV D 99.5%, normal brain, and D max to all organs at risk (OARs) were not significant. The KBP achieved a lower total number of MUs and higher MCSv than the CL with no significant difference.

          Conclusions

          We demonstrated that a KB model in a single‐isocenter VMAT for multiple brain metastases was equivalent in dose distribution, MCSv, and total number of MUs to a CL with a single optimization.

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          Most cited references23

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          Effect of Radiosurgery Alone vs Radiosurgery With Whole Brain Radiation Therapy on Cognitive Function in Patients With 1 to 3 Brain Metastases: A Randomized Clinical Trial.

          Whole brain radiotherapy (WBRT) significantly improves tumor control in the brain after stereotactic radiosurgery (SRS), yet because of its association with cognitive decline, its role in the treatment of patients with brain metastases remains controversial.
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            Neurocognition in patients with brain metastases treated with radiosurgery or radiosurgery plus whole-brain irradiation: a randomised controlled trial.

            It is unclear whether the benefit of adding whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) for the control of brain-tumours outweighs the potential neurocognitive risks. We proposed that the learning and memory functions of patients who undergo SRS plus WBRT are worse than those of patients who undergo SRS alone. We did a randomised controlled trial to test our prediction. Patients with one to three newly diagnosed brain metastases were randomly assigned using a standard permutated block algorithm with random block sizes to SRS plus WBRT or SRS alone from Jan 2, 2001, to Sept 14, 2007. Patients were stratified by recursive partitioning analysis class, number of brain metastases, and radioresistant histology. The randomisation sequence was masked until assignation, at which point both clinicians and patients were made aware of the treatment allocation. The primary endpoint was neurocognitive function: objectively measured as a significant deterioration (5-point drop compared with baseline) in Hopkins Verbal Learning Test-Revised (HVLT-R) total recall at 4 months. An independent data monitoring committee monitored the trial using Bayesian statistical methods. Analysis was by intention-to-treat. This trial is registered at www.ClinicalTrials.gov, number NCT00548756. After 58 patients were recruited (n=30 in the SRS alone group, n=28 in the SRS plus WBRT group), the trial was stopped by the data monitoring committee according to early stopping rules on the basis that there was a high probability (96%) that patients randomly assigned to receive SRS plus WBRT were significantly more likely to show a decline in learning and memory function (mean posterior probability of decline 52%) at 4 months than patients assigned to receive SRS alone (mean posterior probability of decline 24%). At 4 months there were four deaths (13%) in the group that received SRS alone, and eight deaths (29%) in the group that received SRS plus WBRT. 73% of patients in the SRS plus WBRT group were free from CNS recurrence at 1 year, compared with 27% of patients who received SRS alone (p=0.0003). In the SRS plus WBRT group, one case of grade 3 toxicity (seizures, motor neuropathy, depressed level of consciousness) was attributed to radiation treatment. In the group that received SRS, one case of grade 3 toxicity (aphasia) was attributed to radiation treatment. Two cases of grade 4 toxicity in the group that received SRS alone were diagnosed as radiation necrosis. Patients treated with SRS plus WBRT were at a greater risk of a significant decline in learning and memory function by 4 months compared with the group that received SRS alone. Initial treatment with a combination of SRS and close clinical monitoring is recommended as the preferred treatment strategy to better preserve learning and memory in patients with newly diagnosed brain metastases.
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              Stereotactic radiosurgery plus whole-brain radiation therapy vs stereotactic radiosurgery alone for treatment of brain metastases: a randomized controlled trial.

              In patients with brain metastases, it is unclear whether adding up-front whole-brain radiation therapy (WBRT) to stereotactic radiosurgery (SRS) has beneficial effects on mortality or neurologic function compared with SRS alone. To determine if WBRT combined with SRS results in improvements in survival, brain tumor control, functional preservation rate, and frequency of neurologic death. Randomized controlled trial of 132 patients with 1 to 4 brain metastases, each less than 3 cm in diameter, enrolled at 11 hospitals in Japan between October 1999 and December 2003. Patients were randomly assigned to receive WBRT plus SRS (65 patients) or SRS alone (67 patients). The primary end point was overall survival; secondary end points were brain tumor recurrence, salvage brain treatment, functional preservation, toxic effects of radiation, and cause of death. The median survival time and the 1-year actuarial survival rate were 7.5 months and 38.5% (95% confidence interval, 26.7%-50.3%) in the WBRT + SRS group and 8.0 months and 28.4% (95% confidence interval, 17.6%-39.2%) for SRS alone (P = .42). The 12-month brain tumor recurrence rate was 46.8% in the WBRT + SRS group and 76.4% for SRS alone group (P<.001). Salvage brain treatment was less frequently required in the WBRT + SRS group (n = 10) than with SRS alone (n = 29) (P<.001). Death was attributed to neurologic causes in 22.8% of patients in the WBRT + SRS group and in 19.3% of those treated with SRS alone (P = .64). There were no significant differences in systemic and neurologic functional preservation and toxic effects of radiation. Compared with SRS alone, the use of WBRT plus SRS did not improve survival for patients with 1 to 4 brain metastases, but intracranial relapse occurred considerably more frequently in those who did not receive WBRT. Consequently, salvage treatment is frequently required when up-front WBRT is not used. umin.ac.jp/ctr Identifier: C000000412.
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                Author and article information

                Contributors
                m_nkmr@kuhp.kyoto-u.ac.jp
                Journal
                J Appl Clin Med Phys
                J Appl Clin Med Phys
                10.1002/(ISSN)1526-9914
                ACM2
                Journal of Applied Clinical Medical Physics
                John Wiley and Sons Inc. (Hoboken )
                1526-9914
                19 September 2020
                October 2020
                : 21
                : 10 ( doiID: 10.1002/acm2.v21.10 )
                : 141-150
                Affiliations
                [ 1 ] Department of Radiation Oncology and Image‐Applied Therapy Graduate School of Medicine Kyoto University Kyoto Japan
                [ 2 ] Department of Information Technology and Medical Engineering Division of Medical Physics Graduate School of Medicine Human Health Sciences Kyoto University Kyoto Japan
                Author notes
                [*] [* ] Author to whom correspondence should be addressed. Mitsuhiro Nakamura

                E‐mail: ( m_nkmr@ 123456kuhp.kyoto-u.ac.jp ); Telephone: +81‐75‐751‐4176, Fax: +81‐75‐771‐9749

                Article
                ACM213022
                10.1002/acm2.13022
                7592973
                32951337
                0ac7acbc-aace-4a62-a409-5770ba0e37c5
                © 2020 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of American Association of Physicists in Medicine.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 November 2019
                : 01 June 2020
                : 07 August 2020
                Page count
                Figures: 6, Tables: 3, Pages: 10, Words: 5854
                Funding
                Funded by: JSPS KAKENHI
                Award ID: 18H02766
                Award ID: 18K07700
                Award ID: 19K21271
                Categories
                Radiation Oncology Physics
                Radiation Oncology Physics
                Custom metadata
                2.0
                October 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:28.10.2020

                k‐fold cross‐validation,knowledge‐based planning,multiple brain metastases,single‐isocenter vmat

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