ABSTRACT
Purpose: To report final results of a clinical trial of APBI using intensity modulated radiotherapy (IMRT) to deliver 27 Gy in 5 daily fractions following breast conserving surgery (BCS) prospectively designed to assess the efficacy and cosmetic outcomes of a oneweek, APBI regimen among women with early breast cancer. Material(s) and Method(s): Women >= 50 years, with lymph nodenegative, ER positive, HER-2 negative breast cancer or ductal carcinoma in situ (DCIS), <= 3cm diameter, following BCS with margins >= 2mm, and excellent or good baseline cosmesis received 27 Gy in 5 daily fractions to the seroma plus 1 cm CTV and 0.7 cm PTV margins. Clinical photographs, patient and provider cosmetic scores, breast fibrosis, telangiectasia and pain were collected prospectively, prior to RT and at 6 weeks, 1 and 2 years after RT. The primary endpoint was the proportion of women who retained Excellent or Good cosmesis at 2 years using the EORTC Cosmetic Rating System. Cosmetic failure was deterioration from Excellent or Good to Fair or Poor. A panel of 5 radiation oncologists independently assessed the cosmetic photographs. Secondary endpoints were rates and grades of breast fibrosis, telangiectasia, breast pain, ipsilateral breast tumour recurrence (IBRT), overall (OS), breast cancer-specific survival (BCSS) and subsequent mastectomy. Efficacy outcomes were assessed at clinic visits and by review of charts. ClinicalTrials.gov registration: NCT02681107. Result(s): A total of 298 patients were treated between April 25, 2016, and October 31, 2019. At a median follow-up of 48 months, the four-year OS was 98.5% (95% CI 96.1% - 99.5%) and BCSS was 99.7% (95% CI 97.6% - 99.9%). The four-year IBRT rate was 3.3% (95% CI 1.1% - 6.4%). There were 10 contralateral breast events for a four-year rate of 3.9% (95% CI 2.2% - 6.9%). There were 10 ipsilateral and six contralateral mastectomies. Two patients died of unrelated causes prior to two years;79 patients declined inclinic attendance due to COVID or competing comorbidities and 217 women had two-year cosmetic photographs and clinical assessments performed. Consensus of the photo-panel cosmesis at baseline was: Excellent: n=116 (53%), Good: n=102 (47%), Fair: n=1 (0.5%) and Poor: n=0. Consensus overall cosmesis at two years was: Excellent: n= 141 (65%), Good: n=78 (35%), Fair: n=0 and Poor: n=0. Most patients had either improved (n=168;77%) or no change (n=43;20%) in cosmesis at two years. No patient had cosmetic failure but 6 (3%) had a change from Excellent to Good at two years. Most patients reported either no (79%) or mild (21%) pain, with no moderate or severe pain. Two patients (0.9%) had Grade 2 fibrosis and five patients (2%) had visible telangiectasia that did not detract from overall cosmesis. Conclusion(s): APBI using 27 Gy in 5 fractions using a conformal IMRT technique, achieved excellent two-year cosmesis with minimal toxicity. The IBRT risk was comparable to the contralateral new breast cancer risk and to local recurrence rates of recently published early breast cancer trials. Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
ABSTRACT
Purpose: Breast-conserving surgery followed by several weeks of adjuvant radiotherapy is the current standard of care for low-risk breast cancer. A novel approach using single-fraction neoadjuvant radiotherapy is under study. We sought to investigate the rate of pathologic response, toxicities and cosmetic results related to this new treatment strategy. Material(s) and Method(s): Women 65 years of age or older with a new diagnosis of Stage I unifocal luminal A breast cancer were eligible for inclusion in this Phase I prospective trial. A single 20 Gy dose of radiotherapy to the breast tumour was given, followed by breast-conserving surgery three months later. The primary endpoint was the pathologic response rate assessed by microscopic evaluation using the Miller-Payne system. The secondary endpoints were the incidence of radiation toxicity and the cosmetic results, graded according to the Common Terminology Criteria for Adverse Events and the European Organisation for Research and Treatment of Cancer Cosmetic Rating System, respectively. Secondary outcomes were assessed at 6 weeks, 4 months and yearly after radiotherapy. Result(s): To date, 13 patients have been successfully treated with a median age of 71 years (range: 65-83 years). As previously reported, neoadjuvant radiotherapy resulted in a tumour pathologic response in 11 of 13 patients with a median residual cellularity of 1% (range: 0-10%). With an average follow-up of 31.9 months (range: 24.4- 39.2 months), no disease recurrences or deaths were recorded. Acute radiation toxicities were limited to Grade 1 dermatitis and breast pain. At the one-year follow-up, 11 patients had Grade 1 toxicities (dermatitis, fibrosis, breast pain and chest wall pain), one patient had a Grade 2 fatty necrosis, and two patients had Grade 3 toxicities (wound infection and hematoma). Only Grade 1 toxicities remained at the two-year follow-up. One-year cosmetic results were good or excellent in 46% of patients according to their self-assessment and in 54% of them according to the nurse's evaluation. Two-year cosmetic results were unavailable due to in-person visits cancellations during the COVID-19 pandemic. Conclusion(s): This study demonstrates that a single fraction of neoadjuvant radiotherapy preceding breast-conserving surgery is feasible, relatively well tolerated and leads to a high level of pathologic response for most patients. The Grade 3 toxicities and underwhelming cosmetic results may indicate that the 3-month interval after radiotherapy places surgery in a post-radiation inflammatory phase. Larger trials are needed to better assess the long-term toxicities as well as the optimal timing and fractionation of this novel technique in the management of early-stage breast cancer. Copyright © 2022 Elsevier Ireland Ltd. This is an open access article under the CC-BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).