NRG Oncology–Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence

Abstract

Purpose NRG Oncology RTOG 1014 is a prospective phase II trial of 3D-CRT PBrI following repeat lumpectomy for in-breast recurrence following previous whole breast irradiation (WBI). The primary goal of the trial was to determine the associated toxicity, tolerance and safety of PBrI. Materials and Methods Eligibility criteria included in-breast recurrence occurring >1 year following WBI, <3cm, unifocal and resected with negative margins. PBrI was targeted to surgical cavity + 1.5 cm; prescription dose of 45 Gy in 1.5Gy BID for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable, 86% power, 1-sided α=0.07. Results Between 2010 and 2013, 65 patients were accrued and the first 55 eligible and with 1 year follow-up were analyzed. Median age is 68 years. 22 patients had DCIS and 33 invasive disease; 19 ≤1cm, 13 >1 to ≤2cm and 1 >2cm. All patients were clinically node-negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume (TV) contouring and TV dose volume analysis (DVA). Only 4 (7%) scored unacceptable for organs at risk (OAR) contouring and OAR DVA. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64%, grade 2 in 7% with only 1 (<2%) grade ≥3 and identified as grade 3 fibrosis of deep connective tissue. Conclusion PBrI with 3D-CRT following second lumpectomy for patients experiencing in-breast failures after WBI is safe and feasible with acceptable treatment quality achieved. Skin, fibrosis and breast pain toxicity was acceptable and grade 3 toxicity was rare.

Proton beam therapy reirradiation for breast cancer: Multi‐institutional prospective PCG registry analysis

“…As such, it is not surprising that these variables were associated with the development of severe toxicity. Lastly, our cumulative median dose of 110.6 Gy is higher than most other studies (Table ) . These differences make a direct comparison between studies a challenging prospect and should be considered when comparing toxicities.…”

“…The risk of toxicity with reRT has prevented widespread use of radiation for breast cancer recurrences. Notwithstanding, several small studies have published their results on the use of reRT for recurrent breast cancer, employing techniques such as brachytherapy, partial breast irradiation (PBI), hyperthermia, concurrent chemotherapy, or twice‐daily fractionation …”

Increased Mortality with Repeat Lumpectomy Alone After Ipsilateral Breast Tumor Recurrence

“…It is commonly accepted that a second full-dose course of whole breast radiotherapy therapy after repeat lumpectomy cannot be tolerated by the tissues and would lead to unacceptable levels of toxicities and poor cosmetic result [6]. However, several published articles demonstrate that accelerated partial breast irradiation after repeat lumpectomy is safe and feasible and can achieve acceptable skin, fibrosis, and breast pain toxicity, as well as satisfactory cosmetic results [18,24,25]. Despite the importance and safety of RT for IBTR, we were surprised that the majority of patients (75.3%) did not receive RT after repeat lumpectomy in our real-world observational study.…”

Local recurrence of breast cancer: Salvage lumpectomy as an option for local treatment

“…The toxicity of external beam re‐irradiation was carefully evaluated by Arthur et al, in the NRG oncology‐radiation therapy group study 1014. This study included IBTR occurring at least one year after whole breast irradiation, with uni‐focal disease of less than 3 cm, resected with negative margins.…”