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 & 10 others Donald 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 journalArticle

75 Citations (Scopus)

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 [10.00-14.00Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56Gy/16 fractions + boost [10.00-12.50Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287women 40 years or older with stage0 to II breast cancer forwhomWBI without addition of a third fieldwas recommended; 76%of study participants (n = 217)were overweight or obese. Patientswere 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 ?2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149were randomized to CF-WBI and 138 to HF-WBI. Treatment armswerewell 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 effectswas 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 ofHF-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.

Original languageEnglish (US)
Pages (from-to)931-941
Number of pages11
JournalJAMA Oncology
Volume1
Issue number7
DOIs
StatePublished - Oct 1 2015

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Poisons
Breast
Randomized Controlled Trials
Fatigue
Quality of Life
Physicians
Odds Ratio
Mastodynia
Dose Fractionation
Breast Neoplasms
Hyperpigmentation
Intention to Treat Analysis
Segmental Mastectomy
National Cancer Institute (U.S.)
Dermatitis
Pruritus
Neoplasms
Decision Making
Radiotherapy
Therapeutics

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Acute and short-term toxic effects of conventionally fractionated vs hypofractionated whole-breast irradiation : A randomized clinical trial. / Shaitelman, Simona F.; Schlembach, Pamela J.; Arzu, Isidora; Ballo, Matthew; Bloom, Elizabeth S.; Buchholz, Daniel; Chronowski, Gregory M.; Dvorak, Tomas; Grade, Emily; Hoffman, Karen E.; Kelly, Patrick; Ludwig, Michelle; Perkins, George H.; Reed, Valerie; Shah, Shalin; Stauder, Michael C.; Strom, Eric A.; Tereffe, Welela; Woodward, Wendy A.; Ensor, Joe; Baumann, Donald; Thompson, Alastair M.; Amaya, Diana; Davis, Tanisha; Guerra, William; Hamblin, Lois; Hortobagyi, Gabriel; Hunt, Kelly K.; Buchholz, Thomas A.; Smith, Benjamin D.

In: JAMA Oncology, Vol. 1, No. 7, 01.10.2015, p. 931-941.

Research output: Contribution to journalArticle

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. 931-941. https://doi.org/10.1001/jamaoncol.2015.2666
Shaitelman, Simona F. ; Schlembach, Pamela J. ; Arzu, Isidora ; Ballo, Matthew ; Bloom, Elizabeth S. ; Buchholz, Daniel ; Chronowski, Gregory M. ; Dvorak, Tomas ; Grade, Emily ; Hoffman, Karen E. ; Kelly, Patrick ; Ludwig, Michelle ; Perkins, George H. ; Reed, Valerie ; Shah, Shalin ; Stauder, Michael C. ; Strom, Eric A. ; Tereffe, Welela ; Woodward, Wendy A. ; Ensor, Joe ; Baumann, Donald ; Thompson, Alastair M. ; Amaya, Diana ; Davis, Tanisha ; Guerra, William ; Hamblin, Lois ; Hortobagyi, Gabriel ; Hunt, Kelly K. ; Buchholz, Thomas A. ; Smith, Benjamin D. / Acute and short-term toxic effects of conventionally fractionated vs hypofractionated whole-breast irradiation : A randomized clinical trial. In: JAMA Oncology. 2015 ; Vol. 1, No. 7. pp. 931-941.
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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 [10.00-14.00Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56Gy/16 fractions + boost [10.00-12.50Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287women 40 years or older with stage0 to II breast cancer forwhomWBI without addition of a third fieldwas recommended; 76{\%}of study participants (n = 217)were overweight or obese. Patientswere 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 ?2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149were randomized to CF-WBI and 138 to HF-WBI. Treatment armswerewell 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 effectswas 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 ofHF-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.",
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.}",
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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 - 2015/10/1

Y1 - 2015/10/1

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 [10.00-14.00Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56Gy/16 fractions + boost [10.00-12.50Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287women 40 years or older with stage0 to II breast cancer forwhomWBI without addition of a third fieldwas recommended; 76%of study participants (n = 217)were overweight or obese. Patientswere 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 ?2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149were randomized to CF-WBI and 138 to HF-WBI. Treatment armswerewell 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 effectswas 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 ofHF-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.

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 [10.00-14.00Gy/5-7 fractions]) vs HF-WBI (n = 138; 42.56Gy/16 fractions + boost [10.00-12.50Gy/4-5 fractions]) following breast-conserving surgery administered in community-based and academic cancer centers to 287women 40 years or older with stage0 to II breast cancer forwhomWBI without addition of a third fieldwas recommended; 76%of study participants (n = 217)were overweight or obese. Patientswere 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 ?2 test, Cochran-Armitage test, and ordinal logistic regression. RESULTS Of 287 participants, 149were randomized to CF-WBI and 138 to HF-WBI. Treatment armswerewell 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 effectswas 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 ofHF-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.

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