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      Hybrid volumetric-modulated arc therapy for postoperative breast cancer including regional lymph nodes: the advantage of dosimetric data and safety of toxicities

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          ABSTRACT

          To improve the homogeneity and conformity of the irradiation dose for postoperative breast cancer including regional lymph nodes, we planned Hybrid volumetric-modulated arc therapy (VMAT), which combines conventional tangential field mainly for the chest area and VMAT mainly for the supraclavicular area and marginal zone. In this study, we compared the dosimetric impact between traditional 3D conformal radiotherapy (3DCRT) and Hybrid VMAT and observed toxicities following Hybrid VMAT. A total of 70 patients indicated between October 2016 and December 2017 were included. The prescribed dose was 50 Gy/25 fractions. For the dosimetric impact, 3DCRT and Hybrid VMAT plans were compared in each patient with respect to the dosimetric parameters. Toxicities were followed using the Common Terminology Criteria for Adverse Events version 4.0. The median follow-up duration was 319 days. For the dosimetric impact, the homogeneity index (HI) and conformity index (CI) of PTV were significantly improved in the Hybrid VMAT plan compared with that in the 3DCRT plan (HI, 0.15 ± 0.07 in Hybrid VMAT vs 0.41 ± 0.19 in 3DCRT, P < 0.001; CI, 1.61 ± 0.44 in Hybrid VMAT vs 2.10 ± 0.56 in 3DCRT, P < 0.001). The mean irradiated ipsilateral lung dose was not significantly different in both plans (12.0 ± 2.4 Gy in Hybrid VMAT vs 11.8 ± 2.8 Gy in 3DCRT, P < 0.533). Regarding toxicity, there were no patients who developed ≥grade 3 acute toxicity and ≥grade 2 pneumonitis during the follow-up. Hybrid VMAT for postoperative breast cancer including regional lymph nodes was a reasonable technique that improved the homogeneity and conformity of the irradiation dose to the planning target volume while keeping the irradiation dose to organs at risk to a minimum.

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          Postoperative radiotherapy in high-risk postmenopausal breast-cancer patients given adjuvant tamoxifen: Danish Breast Cancer Cooperative Group DBCG 82c randomised trial.

          M. Overgaard, M. B. Jensen, J Overgaard … (1999)
          Postmastectomy radiotherapy is associated with a lower locoregional recurrence rate and improved disease-free and overall survival when combined with chemotherapy in premenopausal high-risk breast-cancer patients. However, whether the same benefits apply also in postmenopausal women treated with adjuvant tamoxifen for similar high-risk cancer is unclear. In a randomised trial among postmenopausal women who had undergone mastectomy, we compared adjuvant tamoxifen alone with tamoxifen plus postoperative radiotherapy. Between 1982 and 1990, postmenopausal women with high-risk breast cancer (stage II or III) were randomly assigned adjuvant tamoxifen (30 mg daily for 1 year) alone (689) or with postoperative radiotherapy to the chest wall and regional lymph nodes (686). Median follow-up was 123 months. The endpoints were first site of recurrence (locoregional recurrence, distant metastases, or both), and disease-free and overall survival. Locoregional recurrence occurred in 52 (8%) of the radiotherapy plus tamoxifen group and 242 (35%) of the tamoxifen only group (p<0.001). In total there were 321 (47%) and 411 (60%) recurrences, respectively. Disease-free survival was 36% in the radiotherapy plus tamoxifen group and 24% in the tamoxifen alone group (p<0.001). Overall survival was also higher in the radiotherapy group (385 vs 434 deaths; survival 45 vs 36% at 10 years, p=0.03). Postoperative radiotherapy decreased the risk of locoregional recurrence and was associated with improved survival in high-risk postmenopausal breast-cancer patients after mastectomy and limited axillary dissection, with 1 year of adjuvant tamoxifen treatment. Improved survival in high-risk breast cancer can best be achieved by a strategy of both locoregional and systemic tumour control.
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            Locoregional radiation therapy in patients with high-risk breast cancer receiving adjuvant chemotherapy: 20-year results of the British Columbia randomized trial.

            Joseph Ragaz, Ivo A Olivotto, John Spinelli … (2005)
            The British Columbia randomized radiation trial was designed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy. Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy (37.5 Gy in 16 fractions). Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance. We report the analysis of data from the 20-year follow-up. Survival was analyzed by the Kaplan-Meier method. Relative risk estimates were calculated by the Wald test from the proportional hazards regression model. All statistical tests were two-sided. At the 20 year follow up (median follow up for live patients: 249 months) chemotherapy and radiation therapy, compared with chemotherapy alone, were associated with a statistically significant improvement in all end points analyzed, including survival free of isolated locoregional recurrences (74% versus 90%, respectively; relative risk [RR] = 0.36, 95% confidence interval [CI] = 0.18 to 0.71; P = .002), systemic relapse-free survival (31% versus 48%; RR = 0.66, 95% CI = 0.49 to 0.88; P = .004), breast cancer-free survival (48% versus 30%; RR = 0.63, 95% CI = 0.47 to 0.83; P = .001), event-free survival (35% versus 25%; RR = 0.70, 95% CI = 0.54 to 0.92; P = .009), breast cancer-specific survival (53% versus 38%; RR = 0.67, 95% CI = 0.49 to 0.90; P = .008), and, in contrast to the 15-year follow-up results, overall survival (47% versus 37%; RR = 0.73, 95% CI = 0.55 to 0.98; P = .03). Long-term toxicities, including cardiac deaths (1.8% versus 0.6%), were minimal for both arms. For patients with high-risk breast cancer treated with modified radical mastectomy, treatment with radiation therapy (schedule of 16 fractions) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone, and it is well tolerated, with acceptable long-term toxicity.
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              Study of failure pattern among high-risk breast cancer patients with or without postmastectomy radiotherapy in addition to adjuvant systemic therapy: long-term results from the Danish Breast Cancer Cooperative Group DBCG 82 b and c randomized studies.

              Florian C. Grau, Jens Overgaard, Per Nielsen … (2006)
              Postmastectomy radiotherapy (RT) in high-risk breast cancer patients can reduce locoregional recurrences (LRRs) and improve disease-free and overall survival. The aim of this analysis was to examine the overall disease recurrence pattern among patients randomly assigned to receive treatment with or without RT. A long-term follow-up was performed among the 3,083 patients from the Danish Breast Cancer Cooperative Group 82 b and c trials, except in those already recorded with distant metastases (DM) or contralateral breast cancer (CBC). The end points were LRR, DM, and CBC, and the follow-up continued until DM, CBC, emigration, or death. Information was selected from medical records, general practitioners, and the National Causes of Death Registry. The median potential follow-up time was 18 years. The 18-year probability of any first breast cancer event was 73% and 59% (P < .001) after no RT and RT, respectively (relative risk [RR], 0.68; 95% CI, 0.63 to 0.75). The 18-year probability of LRR (with or without DM) was 49% and 14% (P < .001) after no RT and RT, respectively (RR, 0.23; 95% CI, 0.19 to 0.27). The 18-year probability of DM subsequent to LRR was 35% and 6% (P < .001) after no RT and RT, respectively (RR, 0.15; 95% CI, 0.11 to 0.20), whereas the probability of any DM was 64% and 53% (P < .001) after no RT versus RT, respectively (RR, 0.78; 95% CI, 0.71 to 0.86). Postmastectomy RT changes the disease recurrence pattern in high-risk breast cancer patients; fewer patients have LRR as first site of recurrence, and overall fewer patients have DM.
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                Author and article information

                Journal
                Journal ID (nlm-ta): J Radiat Res
                Journal ID (iso-abbrev): J. Radiat. Res
                Journal ID (publisher-id): jrr
                Title: Journal of Radiation Research
                Publisher: Oxford University Press
                ISSN (Print): 0449-3060
                ISSN (Electronic): 1349-9157
                Publication date Collection: September 2020
                Publication date (Electronic): 12 August 2020
                Publication date PMC-release: 12 August 2020
                Volume: 61
                Issue: 5
                Pages: 747-754
                Affiliations
                [1 ] Hiroshima High-Precision Radiotherapy Cancer Center , 3-2-2, Futabanosato, Higashi-ku, Hiroshima-shi, Hiroshima, 732-0057, Japan
                [2 ] Department of Radiation Oncology , Institute of Biomedical & Health Sciences, Hiroshima University, 3-2-2, Futabanosato, Higashi-ku, Hiroshima-shi, Hiroshima, 732-0057, Japan
                Author notes
                Corresponding author. Hiroshima High-Precision Radiotherapy Cancer Center, 3-2-2, Futabanosato, Higashi-ku, Hiroshima-shi, Hiroshima, 732-0057, Japan. Tel: +81-82-263-1330; Fax: +81-82-263-1331; Email: doi@ 123456hiprac.jp
                Article
                Publisher ID: rraa057
                DOI: 10.1093/jrr/rraa057
                PMC ID: 7482153
                PubMed ID: 32785596
                SO-VID: e548d316-4868-44e0-92da-3cef06bb89bb
                Copyright © © The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.
                License:

                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
                Date received : 17 February 2020
                Date revision received : 27 May 2020
                Date revision requested : 29 June 2020
                Page count
                Pages: 8
                Categories
                Subject: AcademicSubjects/MED00870
                Subject: AcademicSubjects/SCI00960
                Subject: Regular Paper

                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: postoperative breast cancer,regional lymph nodes,hybrid volumetric-modulated arc therapy,homogeneity and conformity,lung irradiation dose
                Data availability:
                ScienceOpen disciplines: Oncology & Radiotherapy
                Keywords: postoperative breast cancer, regional lymph nodes, hybrid volumetric-modulated arc therapy, homogeneity and conformity, lung irradiation dose

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