Hypofractionated Postmastectomy Radiation Therapy Is Safe and Effective: First Results From a Prospective Phase II Trial

Abstract

Purpose Conventionally fractionated postmastectomy radiation therapy (PMRT) takes approximately 5 to 6 weeks. Data supporting hypofractionated PMRT is limited. We prospectively evaluated a short course of hypofractionated PMRT, in which therapy was completed in 15 treatment days. Patients and Methods We delivered PMRT at a dose of 36.63 Gy in 11 fractions of 3.33 Gy over 11 days to the chest wall and the draining regional lymph nodes, followed by an optional mastectomy scar boost of four fractions of 3.33 Gy. Our primary end point was freedom from any grade 3 or higher toxicities. We incorporated early stopping criteria on the basis of predefined toxicity thresholds. Results We enrolled 69 women with stage II to IIIa breast cancer, of whom 67 were eligible for analysis. After a median follow-up of 32 months, there were no grade 3 toxicities. There were 29 reported grade 2 toxicities, with grade 2 skin toxicities being the most frequent (16 of 67; 24%). There were two patients with isolated ipsilateral chest wall tumor recurrences (2 of 67; crude rate, 3%). Three-year estimated local recurrence-free survival was 89.2% (95% CI, 0.748 to 0.956). The 3-year estimated distant recurrence-free survival was 90.3% (95% CI, 0.797 to 0.956). Forty-one patients had chest wall reconstructions; three had expanders removed for infection before radiation therapy. The total rate of implant loss or failure was 24% (9 of 38), and the unplanned surgical correction rate was 8% (3 of 38), for a total complication rate of 32%. Conclusion To our knowledge, our phase II prospective study offers one of the shortest courses of PMRT reported, delivered in 11 fractions to the chest wall and nodes and 15 fractions inclusive of a boost. We demonstrated low toxicity and high local control with this schedule. On the basis of our data, we have designed a cooperative group phase III prospective, randomized trial of conventional versus hypofractionated PMRT that will activate soon.

Trends and Patterns of Utilization of Hypofractionated Postmastectomy Radiotherapy: A National Cancer Database Analysis

“…9,14 More recently, results from a Phase II trial of 69 patients treated with hypofractionated PMRT in the US demonstrated that hypofractionated PMRT may be safe and effective. 15 The favorable results from this trial have provided the impetus for the development of a Phase III randomized trial – Alliance A221505 – which seeks to compare outcomes following hypofractionated PMRT versus standard fractionation PMRT in a large cohort of women.…”

Recent Developments in Radiation Oncology: An Overview of Individualised Treatment Strategies in Breast Cancer

“…In the START A/B trials, 491 patients had a mastectomy and received hypofractionated postmastectomy radiotherapy (HF-PMRT). The first prospective phase II study on HF-PMRT was recently published in May 2017 [10] showing promising results. The same group is carrying out the Alliance A221505 study, a phase III randomized trial of HF-PMRT following breast reconstruction.…”

Postmastectomy Hypo Fractionated Radiotherapy: May be a Breakthrough in Breast Cancer Management

“…In most recent study conducted by Khan et al and published in journal of clinical oncology, which was a phase II prospective study offered one of the shortest courses of post mastectomy hypo fractionated radiotherapy delivered in eleven fractions to the chest wall and regional nodes with fifteen fractions inclusive of a boost, they demonstrated low toxicity and high local control with this regimen but they finally reported that these are more robustly tested and described in breast cancer than in any other human malignancy and still, they do not believe these shorter schedules should be used routinely off study, particularly among women with breast reconstruction [16].…”

“…AllianceA221505, a randomized phase III trial of post mastectomy hypo fractionated radiotherapy in which it will test the safety of a shorter course schedule (42.56 Gy in 16 fractions) compared to conventional fractionation, all women in this trial will have breast reconstruction or intent for ultimate reconstruction. The primary end point of this trial is reconstruction complication rate and secondary end points will include lymph edema, toxicities including brachial plexopathy, recurrence-free survival, and end points for health costs/economics [16].…”