Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial

Abstract

Importance: The most appropriate dose fractionation for whole-breast irradiation (WBI) remains uncertain.

Objective: To assess acute and 6-month toxic effects and quality of life (QOL) with conventionally fractionated WBI (CF-WBI) vs hypofractionated WBI (HF-WBI).

Design, setting, and participants: Unblinded randomized trial of CF-WBI (n = 149; 50.00 Gy/25 fractions + boost [10.00-14.00 Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56 Gy/16 fractions + boost [10.00-12.50 Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287 women 40 years or older with stage 0 to II breast cancer for whom WBI without addition of a third field was recommended; 76% of study participants (n = 217) were overweight or obese. Patients were enrolled from February 2011 through February 2014 and observed for a minimum of 6 months.

Interventions: Administration of CF-WBI or HF-WBI.

Main outcomes and measures: Physician-reported acute and 6-month toxic effects using National Cancer Institute Common Toxicity Criteria, and patient-reported QOL using the Functional Assessment of Cancer Therapy for Patients with Breast Cancer (FACT-B). All analyses were intention to treat, with outcomes compared using the χ2 test, Cochran-Armitage test, and ordinal logistic regression.

Results: Of 287 participants, 149 were randomized to CF-WBI and 138 to HF-WBI. Treatment arms were well matched for baseline characteristics, including FACT-B total score (HF-WBI, 120.1 vs CF-WBI, 118.8; P = .46) and individual QOL items such as somewhat or more lack of energy (HF-WBI, 38% vs CF-WBI, 39%; P = .86) and somewhat or more trouble meeting family needs (HF-WBI, 10% vs CF-WBI, 14%; P = .54). Maximum physician-reported acute dermatitis (36% vs 69%; P < .001), pruritus (54% vs 81%; P < .001), breast pain (55% vs 74%; P = .001), hyperpigmentation (9% vs 20%; P = .002), and fatigue (9% vs 17%; P = .02) during irradiation were lower in patients randomized to HF-WBI. The rate of overall grade 2 or higher acute toxic effects was less with HF-WBI than with CF-WBI (47% vs 78%; P < .001). Six months after irradiation, physicians reported less fatigue in patients randomized to HF-WBI (0% vs 6%; P = .01), and patients randomized to HF-WBI reported less lack of energy (23% vs 39%; P < .001) and less trouble meeting family needs (3% vs 9%; P = .01). Multivariable regression confirmed the superiority of HF-WBI in terms of patient-reported lack of energy (odds ratio [OR], 0.39; 95% CI, 0.24-0.63) and trouble meeting family needs (OR, 0.34; 95% CI, 0.16-0.75).

Conclusions and relevance: Treatment with HF-WBI appears to yield lower rates of acute toxic effects than CF-WBI as well as less fatigue and less trouble meeting family needs 6 months after completing radiation therapy. These findings should be communicated to patients as part of shared decision making.

Trial registration: clinicaltrials.gov Identifier: NCT01266642.

Conflict of interest statement

Conflict of Interest Disclosures: SFS: Grant from Elekta; Consultation for MD Anderson Physicians’ Network; BDS: Grant from Varian Medical Systems. MCS: Consultation for MD Anderson Physicians’ Network; None of this funding was used to support the research contained herein. DB: Honorarium from Genomic Health Advisory Panel. GNH: served as a Scientific/Advisory Committee member for Antigen Express, Bayer Healthcare Pharmaceuticals, Galena Biopharma, Metastat, Novartis Pharmaceuticals Corp., Oncimmune, Pfizer, Inc., and Rockpointe and served as consultant to AstraZeneca Pharmaceuticals, Celgene, Genentech Inc., Peregrine Pharmaceuticals, Inc (none of the disclosure from GNH are relevant to the current manuscript).

Figures

Figure 1. Consort diagram

Abbreviations: CF (conventional fractionation), HF (hypofractionation), WBI (whole breast irradiation)