title: Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial.
abstract: OBJECTIVE
  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).
  
  
  METHODS
  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.
  
  
  METHODS
  Administration of CF-WBI or HF-WBI.
  
  
  METHODS
  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
  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.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01266642.
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Simona F
authors.initials: SF
authors.lastname: Shaitelman
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Schlembach
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Isidora
authors.initials: I
authors.lastname: Arzu
authors.affiliation: Department of Radiation Oncology, The University of Tennessee Health Science Center, Memphis.
authors.forename: Matthew
authors.initials: M
authors.lastname: Ballo
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Bloom
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Orlando Health, Orlando.
authors.forename: Daniel
authors.initials: D
authors.lastname: Buchholz
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Chronowski
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Orlando Health, Orlando.
authors.forename: Tomas
authors.initials: T
authors.lastname: Dvorak
authors.affiliation: Department of Radiation Oncology, Banner MD Anderson Cancer Center, Gilbert, Arizona.
authors.forename: Emily
authors.initials: E
authors.lastname: Grade
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Hoffman
authors.affiliation: Department of Radiation Oncology, University of Florida Health Cancer Center, Orlando Health, Orlando.
authors.forename: Patrick
authors.initials: P
authors.lastname: Kelly
authors.affiliation: Department of Radiation Oncology, Baylor College of Medicine, Houston, Texas.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ludwig
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: George H
authors.initials: GH
authors.lastname: Perkins
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Valerie
authors.initials: V
authors.lastname: Reed
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Shalin
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authors.lastname: Shah
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Stauder
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Strom
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Welela
authors.initials: W
authors.lastname: Tereffe
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Wendy A
authors.initials: WA
authors.lastname: Woodward
authors.affiliation: Houston Methodist Research Institute, The Methodist Hospital, Houston, Texas.
authors.forename: Joe
authors.initials: J
authors.lastname: Ensor
authors.affiliation: Department of Plastic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Donald
authors.initials: D
authors.lastname: Baumann
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Alastair M
authors.initials: AM
authors.lastname: Thompson
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Diana
authors.initials: D
authors.lastname: Amaya
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Tanisha
authors.initials: T
authors.lastname: Davis
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: William
authors.initials: W
authors.lastname: Guerra
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Lois
authors.initials: L
authors.lastname: Hamblin
authors.affiliation: Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Hortobagyi
authors.affiliation: Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Kelly K
authors.initials: KK
authors.lastname: Hunt
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchholz
authors.affiliation: Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston.
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mesh_terms: D000046:Academic Medical Centers; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D018270:Carcinoma, Ductal, Breast / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D016009:Chi-Square Distribution; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D016015:Logistic Models; D015412:Mastectomy, Segmental; D015999:Multivariate Analysis; D009367:Neoplasm Staging; D016017:Odds Ratio; D011788:Quality of Life; D000069473:Radiation Dose Hypofractionation; D011832:Radiation Injuries / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D012307:Risk Factors; D012720:Severity of Illness Index; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States