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.

• Authors: Simona F Shaitelman, Pamela J Schlembach, Isidora Arzu, Matthew Ballo, Elizabeth S Bloom, Daniel Buchholz, Gregory M Chronowski, Tomas Dvorak, Emily Grade, Karen E Hoffman, Patrick Kelly, Michelle Ludwig, George H Perkins, Valerie Reed, Shalin Shah, Michael C Stauder, Eric A Strom, Welela Tereffe, Wendy A Woodward, Joe Ensor, Donald Baumann, Alastair M Thompson, Diana Amaya, Tanisha Davis, William Guerra, Lois Hamblin, Gabriel Hortobagyi, Kelly K Hunt, Thomas A Buchholz, Benjamin D Smith
• Journal: JAMA oncology (JAMA Oncol) Vol. 1 Issue 7 Pg. 931-41 (Oct 2015) ISSN: 2374-2445 [Electronic] United States
• PMID: 26247543 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Topics

• Academic Medical Centers
• Breast Neoplasms (pathology, radiotherapy, surgery)
• Carcinoma, Ductal, Breast (pathology, radiotherapy, surgery)
• Carcinoma, Intraductal, Noninfiltrating (pathology, radiotherapy, surgery)
• Chi-Square Distribution
• Dose Fractionation, Radiation
• Female
• Humans
• Logistic Models
• Mastectomy, Segmental
• Multivariate Analysis
• Neoplasm Staging
• Odds Ratio
• Quality of Life
• Radiation Dose Hypofractionation
• Radiation Injuries (diagnosis, etiology, prevention & control)
• Radiotherapy, Adjuvant (adverse effects)
• Risk Factors
• Severity of Illness Index
• Surveys and Questionnaires
• Time Factors
• Treatment Outcome
• United States