NCT01349322

Higher Per Daily Treatment-Dose Radiation Therapy or Standard Per Daily Treatment Radiation Therapy in Treating Patients With Early-Stage Breast Cancer That Was Removed by Surgery

Active, enrolled Phase 3 Results posted Last updated 5 March 2026

What this trial tests

Phase 3 trial testing Standard fractionation whole breast irradiation in Breast Cancer in 2,354 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

24 May 2011

Primary endpoint
25 January 2022

Quick facts

Lead sponsor	Radiation Therapy Oncology Group
Phase	Phase 3
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	2,354
Start date	24 May 2011
Primary completion	25 January 2022
Sites	415 locations across Hong Kong, Japan, Israel, South Korea, Canada, Switzerland, Singapore, United States

Drugs / interventions tested

• Standard fractionation whole breast irradiation
• Hypofractionated whole breast irradiation
• Concurrent boost
• Sequential boost

Conditions studied

• Breast Cancer — all drugs for Breast Cancer →

Sponsor

Radiation Therapy Oncology Group — full company profile →

Who can join

18 and older, female only, with Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With In-breast Recurrence (Local Failure) Primary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are reported here.

In-breast recurrence (IBR) is defined as any of the following: invasive local recurrence-ipsilateral breast (within treatment field); invasive local recurrence-ipsilateral breast (outside treatment field); non-invasive local recurrence-ipsilateral breast (within treatment field); or non-invasive local recurrence-ipsilateral breast (outside treatment field). Time to IBR is defined as time from randomization to the date of first IBR, last known follow-up (censored), or death without IBR (competing risk). IBR rates are estimated using the cumulative incidence method, while treatment effect compar

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	2.0	1.4 – 2.9
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	1.9	1.3 – 2.7

Percentage of Participants Alive Secondary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.

Failure is defined as death due to any cause. Failure time (overall survival time) is defined as the time from randomization to the date of death or last known follow-up (censored). Overall survival rates are estimated by the Kaplan-Meier method and distributions between the two arms are compared using the log-rank test. Five-year rates are provided here.

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	95.7	94.4 – 96.9
Hypofractionated Whole Breast Irradiation + Concurrent Boost	95.1	93.8 – 96.4

Percentage of Participants Alive Without Disease Secondary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.

Disease-free survival (DFS) time is defined as time from randomization to local-regional disease recurrence, distant metastases, second/new primary, death due to any cause or last known follow-up (censored). DFS rates are estimated by the Kaplan-Meier method and distributions between the two arms are compared using the log-rank test. Five-year rates are provided here.

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	90.2	88.5 – 92.0
Hypofractionated Whole Breast Irradiation + Concurrent Boost	88.5	86.7 – 90.4

Percentage of Participants Alive Without Distant Disease Secondary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are provided here.

Distant disease-free survival (DDFS) time is defined as time from randomization to distant metastases, second/new primary, death due to any cause or last known follow-up (censored). DDFS rates are estimated by the Kaplan-Meier method and distributions between the two arms are compared using the log-rank test. Five-year rates are provided here.

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	91.5	89.9 – 93.2
Hypofractionated Whole Breast Irradiation + Concurrent Boost	90.2	88.4 – 91.9

Number of Participants by Highest Grade Adverse Event Reported as Definitely, Probably, or Possibly Related to Protocol Treatment Secondary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years.

Common Terminology Criteria for Adverse Events (version 4.0) grades adverse event severity from 1=mild to 5=death. Summary data is provided in this outcome measure; see Adverse Events Module for specific adverse event data

Grade 1

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	427
Hypofractionated Whole Breast Irradiation + Concurrent Boost	554

Grade 2

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	379
Hypofractionated Whole Breast Irradiation + Concurrent Boost	290

Grade 3

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	34
Hypofractionated Whole Breast Irradiation + Concurrent Boost	35

Grade 4

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	2
Hypofractionated Whole Breast Irradiation + Concurrent Boost	4

Grade 5

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost	0
Hypofractionated Whole Breast Irradiation + Concurrent Boost	0

Change in Breast Cancer Treatment Outcome Scale (BCTOS) Cosmesis Subscale Score From Baseline to 3 Years Secondary · Baseline and 3 years

The BCTOS cosmesis subscale score measures perceived aesthetic (e.g., breast shape) status . Patients rated each item using a four-point scale evaluating the differences between the treated and the untreated breast (1=no difference, 2=slight difference, 3=moderate difference, 4=large difference) with higher scores indicating a worse outcome. The score for each subscale is the mean of the ratings over all items belonging to that specific subscale. Change was calculated as the value at 3 years minus the value at baseline. A positive change reflects a decline at 3 years and a negative change refl

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	0.16	0.08 – 0.24
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	0.18	0.11 – 0.25

Percentage of Participants With a Physician-reported Cosmetic Score of Excellent or Good at 3 Years Secondary · 3 years

Physicians rated cosmesis using a four point scale: * Excellent: When compared to the untreated breast or the original appearance of the breast, there is minimal/no difference in the size or shape of the treated breast. * Good: There is a slight difference in the size or shape of the treated breast as compared to the opposite breast or the original appearance of the treated breast. * Fair: Obvious differences in the size and shape of the treated breast. This change involves quarter or less of the breast. * Poor: Marked change in the appearance of the treated breast involving more than a quart

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	86	80 – 90
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	82	77 – 87

Percentage of Participants With In-breast Recurrence (Local Failure) by Race Secondary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are reported here.

NIH-required analysis. In-breast recurrence (IBR) is defined as any of the following: invasive local recurrence-ipsilateral breast (within treatment field); invasive local recurrence-ipsilateral breast (outside treatment field); non-invasive local recurrence-ipsilateral breast (within treatment field); or non-invasive local recurrence-ipsilateral breast (outside treatment field). Time to IBR is defined as time from randomization to the date of first IBR, last known follow-up (censored), or death without IBR (competing risk). IBR rates are estimated using the cumulative incidence method, while

American Indian or Alaska Native

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	14.3	1.1 – 43.4
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	0	NA – NA

Asian

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	0	NA – NA
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	7.1	2.8 – 14.2

Native Hawaiian or Other Pacific Islander

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	33.3	0.7 – 78.2
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	0	NA – NA

Black or African American

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	1.5	0.4 – 4.2
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	1.6	0.4 – 4.4

White

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	1.9	1.2 – 2.8
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	1.6	1.0 – 2.4

More than one race

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	0	NA – NA
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	0	NA – NA

Unknown or Not Reported

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	8.7	2.0 – 21.6
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	5.3	0.6 – 18.6

Percentage of Participants With In-breast Recurrence (Local Failure) by Ethnicity Secondary · From randomization to last follow-up. Evaluated weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years. Five-year rates are reported here.

NIH-required analysis. In-breast recurrence (IBR) is defined as any of the following: invasive local recurrence-ipsilateral breast (within treatment field); invasive local recurrence-ipsilateral breast (outside treatment field); non-invasive local recurrence-ipsilateral breast (within treatment field); or non-invasive local recurrence-ipsilateral breast (outside treatment field). Time to IBR is defined as time from randomization to the date of first IBR, last known follow-up (censored), or death without IBR (competing risk). IBR rates are estimated using the cumulative incidence method, while

Hispanic or Latino

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	7.2	2.8 – 14.4
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	4.3	1.4 – 9.7

Not Hispanic or Latino

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	1.8	1.2 – 2.6
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	1.8	1.2 – 2.6

Unknown or Not Reported

Group	Value	95% CI
Whole Breast Irradiation + Sequential Boost (Arm 1)	0	NA – NA
Hypofractionated Whole Breast Irradiation + Concurrent Boost (Arm 2)	0	NA – NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Weekly during radiation therapy (RT), last day of RT, 1, 6, and 12 months after RT completion, then annually. Maximum follow-up at time of analysis was 10.1 years.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Whole Breast Irradiation + Sequential Boost

Serious: 18/1100 (2%)

Deaths: 87/1124

Hypofractionated Whole Breast Irradiation + Concurrent Boost

Serious: 20/1123 (2%)

Deaths: 86/1138

Serious adverse events (42 terms)

Reaction	System	Whole Breast Irradiation +…	Hypofractionated Whole Bre…
Dermatitis radiation	Injury, poisoning and procedural complications	—	—
Breast pain	Reproductive system and breast disorders	—	—
Fatigue	General disorders and administration site conditions	—	—
Localized edema	General disorders and administration site conditions	—	—
Breast infection	Infections and infestations	—	—
Lung infection	Infections and infestations	—	—
Seroma	Injury, poisoning and procedural complications	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Treatment related secondary malignancy	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—
Pneumonitis	Respiratory, thoracic and mediastinal disorders	—	—
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	—	—
Hypertension	Vascular disorders	—	—
Lymphedema	Vascular disorders	—	—
Cardiac disorders - Other, specify	Cardiac disorders	—	—
Left ventricular systolic dysfunction	Cardiac disorders	—	—
Sinus bradycardia	Cardiac disorders	—	—
Endocrine disorders - Other, specify	Endocrine disorders	—	—
Colitis	Gastrointestinal disorders	—	—
Colonic obstruction	Gastrointestinal disorders	—	—
Colonic perforation	Gastrointestinal disorders	—	—
Chills	General disorders and administration site conditions	—	—
Flu like symptoms	General disorders and administration site conditions	—	—
General disorders and administration site conditions - Other, specify	General disorders and administration site conditions	—	—
Pain	General disorders and administration site conditions	—	—
Appendicitis	Infections and infestations	—	—

Other adverse events (26 terms — click to expand)

Reaction	System	Whole Breast Irradiation +…	Hypofractionated Whole Bre…
Skin hyperpigmentation	Skin and subcutaneous tissue disorders	—	—
Fatigue	General disorders and administration site conditions	—	—
Dermatitis radiation	Injury, poisoning and procedural complications	—	—
Breast pain	Reproductive system and breast disorders	—	—
Hot flashes	Vascular disorders	—	—
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	—	—
Pain	General disorders and administration site conditions	—	—
Pruritus	Skin and subcutaneous tissue disorders	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—
Localized edema	General disorders and administration site conditions	—	—
Superficial soft tissue fibrosis	Musculoskeletal and connective tissue disorders	—	—
Reproductive system and breast disorders - Other, specify	Reproductive system and breast disorders	—	—
Skin induration	Skin and subcutaneous tissue disorders	—	—
Peripheral sensory neuropathy	Nervous system disorders	—	—
Hypertension	Vascular disorders	—	—
Lymphedema	Vascular disorders	—	—
Erythema multiforme	Skin and subcutaneous tissue disorders	—	—
Musculoskeletal and connective tissue disorder - Other, specify	Musculoskeletal and connective tissue disorders	—	—
Insomnia	Psychiatric disorders	—	—
Dry skin	Skin and subcutaneous tissue disorders	—	—
Fibrosis deep connective tissue	Musculoskeletal and connective tissue disorders	—	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—	—
Breast atrophy	Reproductive system and breast disorders	—	—
Nausea	Gastrointestinal disorders	—	—
Headache	Nervous system disorders	—	—
Depression	Psychiatric disorders	—	—

Most-reported serious reactions: Dermatitis radiation, Breast pain, Fatigue, Localized edema, Breast infection, Lung infection, Seroma, Pain in extremity.

Data from ClinicalTrials.gov NCT01349322 adverse events section.

Sponsor's own description

RATIONALE: It is not yet know whether higher per daily radiation therapy is equally as effective as standard per daily radiation therapy in treating breast cancer.

PURPOSE: This randomized phase III trial studies how well an accelerated course of higher per daily radiation therapy with concomitant boost works compared to standard per daily radiation therapy with a sequential boost in treating patients with early-stage breast cancer that was removed by surgery.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Moderate hypofractionation remains the standard of care for whole-breast radiotherapy in breast cancer: Considerations regarding FAST and FAST-Forward.
   Krug D, Baumann R, Combs SE, Duma MN, et al · · 2021 · cited 44× · PMID 33507331 · DOI 10.1007/s00066-020-01744-3
2. Fraction size in radiation therapy for breast conservation in early breast cancer.
   Hickey BE, James ML, Lehman M, Hider PN, et al · · 2016 · cited 40× · PMID 27425588 · DOI 10.1002/14651858.cd003860.pub4
3. Journey to hypofractionation in radiotherapy for breast cancer: critical reviews for recent updates.
   Kim N, Kim YB. · · 2022 · cited 14× · PMID 36606299 · DOI 10.3857/roj.2022.00577
4. Feasibility of feature-based indexing, clustering, and search of clinical trials. A case study of breast cancer trials from ClinicalTrials.gov.
   Boland MR, Miotto R, Gao J, Weng C. · · 2013 · cited 14× · PMID 23666475 · DOI 10.3414/me12-01-0092
5. Hypofractionation with simultaneous integrated boost after breast-conserving surgery: Long term results of two phase-II trials.
   Pfaffendorf C, Vonthein R, Krockenberger-Ziegler K, Dellas K, et al · · 2022 · cited 13× · PMID 35691249 · DOI 10.1016/j.breast.2022.05.008
6. Plan quality assessment of modern radiotherapy delivery techniques in left-sided breast cancer: an analysis stratified by target delineation guidelines.
   Ahmad I, Chufal KS, Bhatt CP, Miller AA, et al · · 2020 · cited 7× · PMID 33330831 · DOI 10.1259/bjro.20200007
7. Patterns of Failure Observed in the 2-Step Institution Credentialing Process for NRG Oncology/Radiation Therapy Oncology Group 1005 (NCT01349322) and Lessons Learned.
   Li XA, Moughan J, White JR, Freedman GM, et al · · 2020 · cited 5× · PMID 31790823 · DOI 10.1016/j.prro.2019.11.007
8. Cardiac markers in left-sided breast cancer patients receiving adjuvant radiotherapy: a prospective study.
   Chufal K, Ahmad I, Prakash A, Miller A, et al · · 2024 · cited 4× · PMID 38589947 · DOI 10.1186/s40959-024-00225-1