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

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

doi:10.1001/jamaoncol.2015.2666

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

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 EnsorDonald Baumann, Alastair M Thompson, Diana Amaya, Tanisha Davis, William Guerra, Lois Hamblin, Gabriel Hortobagyi, Kelly K Hunt, Thomas A Buchholz, Benjamin D Smith

Research output: Contribution to journal › Article › peer-review

172 Scopus citations

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.

Original language	English (US)
Pages (from-to)	931-41
Number of pages	11
Journal	JAMA oncology
Volume	1
Issue number	7
DOIs	https://doi.org/10.1001/jamaoncol.2015.2666
State	Published - Oct 2015

Keywords

Academic Medical Centers
Breast Neoplasms
Carcinoma, Ductal, Breast
Carcinoma, Intraductal, Noninfiltrating
Chi-Square Distribution
Dose Fractionation
Dose Hypofractionation
Female
Humans
Logistic Models
Mastectomy, Segmental
Multivariate Analysis
Neoplasm Staging
Odds Ratio
Quality of Life
Radiation Injuries
Radiotherapy, Adjuvant
Risk Factors
Severity of Illness Index
Surveys and Questionnaires
Time Factors
Treatment Outcome
United States
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Access to Document

10.1001/jamaoncol.2015.2666

Cite this

Shaitelman, S. F., Schlembach, P. J., Arzu, I., Ballo, M., Bloom, E. S., Buchholz, D., Chronowski, G. M., Dvorak, T., Grade, E., Hoffman, K. E., Kelly, P., Ludwig, M., Perkins, G. H., Reed, V., Shah, S., Stauder, M. C., Strom, E. A., Tereffe, W., Woodward, W. A., ... Smith, B. D. (2015). Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial. JAMA oncology, 1(7), 931-41. https://doi.org/10.1001/jamaoncol.2015.2666

Shaitelman, SF, Schlembach, PJ, Arzu, I, Ballo, M, Bloom, ES, Buchholz, D, Chronowski, GM, Dvorak, T, Grade, E, Hoffman, KE, Kelly, P, Ludwig, M, Perkins, GH, Reed, V, Shah, S, Stauder, MC, Strom, EA, Tereffe, W, Woodward, WA, Ensor, J, Baumann, D, Thompson, AM, Amaya, D, Davis, T, Guerra, W, Hamblin, L, Hortobagyi, G, Hunt, KK, Buchholz, TA & Smith, BD 2015, 'Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation: A Randomized Clinical Trial', JAMA oncology, vol. 1, no. 7, pp. 931-41. https://doi.org/10.1001/jamaoncol.2015.2666

@article{960b61d8772942cabf36cd5f1ec27978,

title = "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.",

keywords = "Academic Medical Centers, Breast Neoplasms, Carcinoma, Ductal, Breast, Carcinoma, Intraductal, Noninfiltrating, Chi-Square Distribution, Dose Fractionation, Dose Hypofractionation, Female, Humans, Logistic Models, Mastectomy, Segmental, Multivariate Analysis, Neoplasm Staging, Odds Ratio, Quality of Life, Radiation Injuries, Radiotherapy, Adjuvant, Risk Factors, Severity of Illness Index, Surveys and Questionnaires, Time Factors, Treatment Outcome, United States, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't",

author = "Shaitelman, {Simona F} and Schlembach, {Pamela J} and Isidora Arzu and Matthew Ballo and Bloom, {Elizabeth S} and Daniel Buchholz and Chronowski, {Gregory M} and Tomas Dvorak and Emily Grade and Hoffman, {Karen E} and Patrick Kelly and Michelle Ludwig and Perkins, {George H} and Valerie Reed and Shalin Shah and Stauder, {Michael C} and Strom, {Eric A} and Welela Tereffe and Woodward, {Wendy A} and Joe Ensor and Donald Baumann and Thompson, {Alastair M} and Diana Amaya and Tanisha Davis and William Guerra and Lois Hamblin and Gabriel Hortobagyi and Hunt, {Kelly K} and Buchholz, {Thomas A} and Smith, {Benjamin D}",

year = "2015",

month = oct,

doi = "10.1001/jamaoncol.2015.2666",

language = "English (US)",

volume = "1",

pages = "931--41",

journal = "JAMA oncology",

issn = "2374-2437",

publisher = "American Medical Association",

number = "7",

}

TY - JOUR

T1 - Acute and Short-term Toxic Effects of Conventionally Fractionated vs Hypofractionated Whole-Breast Irradiation

T2 - A Randomized Clinical Trial

AU - Shaitelman, Simona F

AU - Schlembach, Pamela J

AU - Arzu, Isidora

AU - Ballo, Matthew

AU - Bloom, Elizabeth S

AU - Buchholz, Daniel

AU - Chronowski, Gregory M

AU - Dvorak, Tomas

AU - Grade, Emily

AU - Hoffman, Karen E

AU - Kelly, Patrick

AU - Ludwig, Michelle

AU - Perkins, George H

AU - Reed, Valerie

AU - Shah, Shalin

AU - Stauder, Michael C

AU - Strom, Eric A

AU - Tereffe, Welela

AU - Woodward, Wendy A

AU - Ensor, Joe

AU - Baumann, Donald

AU - Thompson, Alastair M

AU - Amaya, Diana

AU - Davis, Tanisha

AU - Guerra, William

AU - Hamblin, Lois

AU - Hortobagyi, Gabriel

AU - Hunt, Kelly K

AU - Buchholz, Thomas A

AU - Smith, Benjamin D

PY - 2015/10

Y1 - 2015/10

N2 - 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.

AB - 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.

KW - Academic Medical Centers

KW - Breast Neoplasms

KW - Carcinoma, Ductal, Breast

KW - Carcinoma, Intraductal, Noninfiltrating

KW - Chi-Square Distribution

KW - Dose Fractionation

KW - Dose Hypofractionation

KW - Female

KW - Humans

KW - Logistic Models

KW - Mastectomy, Segmental

KW - Multivariate Analysis

KW - Neoplasm Staging

KW - Odds Ratio

KW - Quality of Life

KW - Radiation Injuries

KW - Radiotherapy, Adjuvant

KW - Risk Factors

KW - Severity of Illness Index

KW - Surveys and Questionnaires

KW - Time Factors

KW - Treatment Outcome

KW - United States

KW - Journal Article

KW - Multicenter Study

KW - Randomized Controlled Trial

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1001/jamaoncol.2015.2666

DO - 10.1001/jamaoncol.2015.2666

M3 - Article

C2 - 26247543

VL - 1

SP - 931

EP - 941

JO - JAMA oncology

JF - JAMA oncology

SN - 2374-2437

IS - 7

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this