Intensity-Modulated Radiotherapy with Concomitant Boost After Breast Conserving Surgery: A Phase I–II Trial

Abstract

Purpose

A concomitant boost (CB) in patients treated with postoperative radiotherapy after conservative surgery of invasive breast cancer (BC) has been suggested for treatment time reduction and therapy intensification. The aim of this analysis was to assess long-term tolerability of a CB in patients treated with postoperative intensity Modulated Accelerated RAdiotherapy (MARA).

Patients and Methods

In this phase I–II trial, 321 patients with intermediate-high risk BC (pT1-4 with at least one of the following characteristics: pre or perimenopausal status, pN2-3, positive or close margins) were enrolled. Patients were treated with forward-planned intensity modulated radiotherapy (IMRT) and CB. A total dose of 50 Gy (2 Gy/fraction) and 60 Gy (2.4 Gy/fraction) was prescribed to the whole breast and the tumor bed, respectively. The potential impact of hypertension, diabetes, smoking habit, alcohol consumption, chemotherapy, and hormone therapy on both skin and subcutaneous late toxicity-free survival (LTFS) was evaluated. Survival curves were calculated using the Kaplan–Meier method.

Results

Median follow-up was 52 months (range: 3–115). Regional node irradiation, adjuvant chemotherapy and hormonal therapy were prescribed to 29.3%, 65.4% and 81.0% of patients, respectively. Five-year G2 and G3 skin LTFS were 95.6% and 100.0%, respectively. Five-year G2 and G3 subcutaneous LTFS were 80.0% and 98.6%, respectively. Only diabetes showed a significant correlation with worse G3 subcutaneous LTFS (p: 0.024). Five-year loco-regional control, metastasis-free survival, disease-free survival, and overall survival were 98.0%, 91.8%, 89.7% and 96.3%, respectively.

Conclusion

IMRT combined with CB was associated with a low risk of > G2 late toxicities (0.0% and 1.4% for skin and subcutaneous tissue, respectively). The cumulative actuarial incidence of local recurrences was 2.0% despite the exclusion of low-risk patients. Our results suggest that CB is safe and effective in patients with intermediate-high risk BC.

Trial Registration

ClinicalTrials.gov: NCT03471741.

Keywords:

• breast cancer
• adjuvant radiotherapy
• concomitant boost
• IMRT
• toxicity

Data Sharing Statement

The data sets used and/or analyzed during the current study (de-identified patients characteristics and outcomes) are available from the corresponding author after publication and for the duration of 5 years on reasonable request. No other documents will be made available.

Disclosure

Claudio Zamagni reports grants, personal fees, and non-financial support from Roche, Novartis, AstraZeneca, and Pfizer, grants from Eisai, PharmaMar, Celgene, lilly, Amgen, Pierre Fabre, Takeda, TEVA, Medivation, Array BioPharma, Abbvie, Morphotek, Synthon, Seattle Genetics, Daiichi and Sankyo, grants and personal fees from Tesaro, personal fees from QuintilesIMS, and travel accommodation and research funding from Istituto Gentili, outside the submitted work.

Alessio G. Morganti reports grants from Elekta, Beyer, and IGEA and personal fees from Astellas and Alfa-Sigma, outside the submitted work.

The authors report no other potential conflicts of interest in this work.