Hypofractionated volumetric modulated arc therapy in ductal carcinoma in situ: toxicity and cosmetic outcome from a prospective series.

BJR Received: 28 August 2017 © 2018 The Authors. Published by the British Institute of Radiology Revised: 29 December 2017 Accepted: 09 January 2018 https://doi.org/10.1259/bjr.20170634 Cite this article as: De Rose F, Fogliata A, Franceschini D, Iftode C, Torrisi R, Masci G, et al. Hypofractionated volumetric modulated arc therapy in ductal carcinoma in situ: toxicity and cosmetic outcome from a prospective series. Br J Radiol 2018; 91: 20170634. full paper Hypofractionated volumetric modulated arc therapy in ductal carcinoma in situ: toxicity and cosmetic outcome from a prospective series 1 Fiorenza De Rose, MD, 1Antonella Fogliata, MSc, 1Davide Franceschini, MD, 1Cristina Iftode, MD, Rosalba Torrisi, MD, 2Giovanna Masci, MD, 3Andrea Sagona, MD, 3Corrado Tinterri, MD, 3 Alberto Testori, MD, 3Wolfgang Gatzemeier, MD, 4Bethania Fernandes, MD, 4Daoud Rahal, MD, 1,5 Luca Cozzi, PhD, 2Armando Santoro, MD and 1,5Marta Scorsetti, MD 2 1 Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital and Cancer Center, Milan, Rozzano, Italy Department of Medical Oncology, Humanitas Research Hospital and Cancer Center, Milan, Rozzano, Italy Department of Breast Surgery, Humanitas Research Hospital and Cancer Center, Milan, Rozzano, Italy 4 Department of Pathology, Humanitas Research Hospital and Cancer Center, Milan, Rozzano, Italy 5 Department of Biomedical Sciences, Humanitas University, Milan, Rozzano, Italy 2 3 Address correspondence to: Dr Antonella Fogliata E-mail: Objective: Hypofractionated radiotherapy in early stage breast cancer is an effective adjuvant treatment, but there is a lack of randomized data for patients with ductal carcinoma in situ (DCIS). The aim of this study is the evaluation of skin toxicity and cosmesis, and early clinical outcome of DCIS patients enrolled in an institutional Phase II trial of hypofractionated breast irradiation. Methods: 137 DCIS patients were enrolled in the trial. All patients underwent volumetric modulated arc therapy (VMAT) to the whole breast with a total dose of 40.5 Gy in 15 fractions over 3 weeks, without tumour bed boost. Acute and late skin toxicities were recorded. Cosmetic outcomes were assessed as excellent/good or fair/poor. Early clinical outcome was reported. Results: Median age was 58 y.o. (range 30–86). The median follow-up time was 22 months (range 6–45). At the end of the radiotherapy, skin toxicity was grade G1 in 56% of the patients, G2 in 15%, no patients presented G3 toxicity. In the range of 3–9 months of follow-up, the skin toxicity was G1 in 28% of patients, no G2–G3 cases; cosmetic outcome was good/excellent in 95% of patients. In the follow-up interval of 9–24 months, the skin toxicity was G1 in 12% of patients, no G2-G3 toxicity; cosmetic outcome was good/excellent in 96% of patients. After an early evaluation of clinical outcomes, 5 patients (3.6%) presented an in-breast recurrence. Conclusion: Hypofractionated radiotherapy using VMAT is a viable option for DCIS. A longer follow-up is needed to assess clinical outcomes and late toxicity. Advances in knowledge: The use of hypofractionated VMAT is dosimetrically feasible for treating breast DCIS. Introduction Screening and advances in breast imaging led to a continuous increase of ductal carcinoma in situ (DCIS) diagnosis.1 Unfortunately, the management of this specific disease is still controversial regarding adjuvant therapy (radiation therapy and endocrine therapy) after the breast conserving surgery (BCS). Different authors reported analysis of small series, comparing standard radiotherapy with hypofractionated schedules,6–11 and all confirmed the equivalence in local control rates. Other investigators published toxicity, cosmetic and clinical outcomes of DCIS patients treated with hypofractionation,12–15 reporting encouraging results for the introduction of shorter schedules in the management of DCIS patients. Four randomized trials have shown a decrease of the local recurrence (LR) using adjuvant radiotherapy (from 28 to 13% at 10 years) with conventional fractionation (50 Gy in 25 fractions),2–5 but there is no prospective trial data about the use of hypofractionated regimens in patients with DCIS. In this context, the role of the radiotherapy boost is another debated issue. A retrospective analysis of a mono-institutional experience published by the Florence group showed the negative prognostic impact of surgical margins <1 mm De Rose et al BJR on LR rate, and the beneficial role of the radiation boost.16 A meta-analysis of observational studies17 confirmed a reduction of the risk for LR by adding the radiotherapy boost only in the presence of positive margins. Despite this results, a more recent retrospective analysis, using data from a large multi-institutional database, suggested that a radiotherapy boost for DCIS is associated with a small but statistically significant benefit in decreasing long-term LR, regardless the patient age and the endocrine therapy with tamoxifen.18 To better assess the use of the boost for DCIS patients, several prospective randomized trials are ongoing, but the results are expected in about 10 years.19 In the meantime, in the absence of robust evidence, the clinical management of DCIS patients varies, among different institutions, in the choice of the fractionation schemes, the use of an additional boost and the endocrine therapy. We previously reported on our Phase II trial on early stage breast irradiation with hypofractionated simultaneous integrated boost (SIB) and volumetric modulated arc therapy (VMAT) technique.20 Since 2013, with an amendment to the protocol, also patients presenting DCIS were considered eligible for receiving a hypofractionated treatment without SIB. The motivation of using an advanced technique as VMAT for breast radiotherapy in place of the most consolidated conventional tangential beams is supported, particularly for increased fraction doses, by the possibility to lower the doses to critical structures (mainly heart and lung) and reducing the target dose inhomogeneity (dose spillage). Patients could in principle benefit from such a dose distribution improvement, in terms of possible improved toxicity profile. In the present analysis, we reviewed the preliminary data for the DCIS subgroup, treated with hypofractionated VMAT according to our institutional protocol, in terms of cosmetic outcomes, toxicity and local control. Methods and materials From September 2013 to July 2016, 137 patients with DCIS after BCS received hypofractionated adjuvant radiotherapy with RapidArc technology (VMAT) at our institution. The study received the approval by the Ethical Review Committee, in compliance with the Helsinki declaration. Informed consent was obtained from all individual patients. The clinical target volume was the entire mammary gland. The planning target volume (PTV) was contoured by adding a 5 mm margin to the clinical target volume, limited to 4 mm within (...truncated)