The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial

Summary Background The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as...

Full description

Saved in:
Bibliographic Details
Published in:The lancet oncology 2008-04, Vol.9 (4), p.331-341
Main Authors: Bentzen, S M, Agrawal, R K, Aird, E G A, Barrett, J M, Barrett-Lee, P J, Bliss, J M, Brown, J, Dewar, J A, Dobbs, H J, Haviland, J S, Hoskin, P J, Hopwood, P, Lawton, P A, Magee, B J, Mills, J, Morgan, D A L, Owen, J R, Simmons, S, Sumo, G, Sydenham, M A, Venables, K, Yarnold, J R
Format: Article
Language:English
Subjects:
Adult
Age Factors
Aged
Aged, 80 and over
Breast Neoplasms - mortality
Breast Neoplasms - pathology
Breast Neoplasms - radiotherapy
Breast Neoplasms - surgery
Confidence Intervals
Dose Fractionation
Dose-Response Relationship, Radiation
Fast track
Female
Follow-Up Studies
Hematology, Oncology and Palliative Medicine
Humans
Kaplan-Meier Estimate
Mastectomy, Segmental - methods
Middle Aged
Neoplasm Staging
Pilot Projects
Proportional Hazards Models
Radiotherapy Dosage - standards
Radiotherapy, Adjuvant
Reference Values
Risk Assessment
Sex Factors
Survival Analysis
Treatment Outcome
United Kingdom
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Summary Background The international standard radiotherapy schedule for breast cancer treatment delivers a high total dose in 25 small daily doses (fractions). However, a lower total dose delivered in fewer, larger fractions (hypofractionation) is hypothesised to be at least as safe and effective as the standard treatment. We tested two dose levels of a 13-fraction schedule against the standard regimen with the aim of measuring the sensitivity of normal and malignant tissues to fraction size. Methods Between 1998 and 2002, 2236 women with early breast cancer (pT1-3a pN0-1 M0) at 17 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy versus 41·6 Gy or 39 Gy in 13 fractions of 3·2 Gy or 3·0 Gy over 5 weeks. Women were eligible if they were aged over 18 years, did not have an immediate surgical reconstruction, and were available for follow-up. Randomisation method was computer generated and was not blinded. The protocol-specified principal endpoints were local-regional tumour relapse, defined as reappearance of cancer at irradiated sites, late normal tissue effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN59368779. Findings 749 women were assigned to the 50 Gy group, 750 to the 41·6 Gy group, and 737 to the 39 Gy group. After a median follow up of 5·1 years (IQR 4·4–6·0) the rate of local-regional tumour relapse at 5 years was 3·6% (95% CI 2·2–5·1) after 50 Gy, 3·5% (95% CI 2·1–4·3) after 41·6 Gy, and 5·2% (95% CI 3·5–6·9) after 39 Gy. The estimated absolute differences in 5-year local-regional relapse rates compared with 50 Gy were 0·2% (95% CI −1·3% to 2·6%) after 41·6 Gy and 0·9% (95% CI −0·8% to 3·7%) after 39 Gy. Photographic and patient self-assessments suggested lower rates of late adverse effects after 39 Gy than with 50 Gy, with an HR for late change in breast appearance (photographic) of 0·69 (95% CI 0·52–0·91, p=0·01). From a planned meta-analysis with the pilot trial, the adjusted estimates of α/β value for tumour control was 4·6 Gy (95% CI 1·1–8·1) and for late change in breast appearance (photographic) was 3·4 Gy (95% CI 2·3–4·5). Interpretation The data are consistent with the hypothesis that breast cancer and the dose-limiting normal tissues respond similarly to change in radiotherapy fraction size. 41·6 Gy in 13 fractions was similar to the control regimen of 50 Gy in 25 fractio
ISSN:1470-2045
1474-5488
DOI:10.1016/S1470-2045(08)70077-9