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

Abstract

SummaryBackgroundThe international standard radiotherapy schedule for early breast cancer delivers 50 Gy in 25 fractions of 2·0 Gy over 5 weeks, but there is a long history of non-standard regimens delivering a lower total dose using fewer, larger fractions (hypofractionation). We aimed to test the benefits of radiotherapy schedules using fraction sizes larger than 2·0 Gy in terms of local-regional tumour control, normal tissue responses, quality of life, and economic consequences in women prescribed post-operative radiotherapy.MethodsBetween 1999 and 2001, 2215 women with early breast cancer (pT1-3a pN0-1 M0) at 23 centres in the UK were randomly assigned after primary surgery to receive 50 Gy in 25 fractions of 2·0 Gy over 5 weeks or 40 Gy in 15 fractions of 2·67 Gy over 3 weeks. Women were eligible for the trial if they were aged over 18 years, did not have an immediate 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.Findings1105 women were assigned to the 50 Gy group and 1110 to the 40 Gy group. After a median follow up of 6·0 years (IQR 5·0–6·2) the rate of local-regional tumour relapse at 5 years was 2·2% (95% CI 1·3–3·1) in the 40 Gy group and 3·3% (95% CI 2·2 to 4·5) in the 50 Gy group, representing an absolute difference of −0·7% (95% CI −1·7% to 0·9%)—ie, the absolute difference in local-regional relapse could be up to 1·7% better and at most 1% worse after 40 Gy than after 50 Gy. Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy.InterpretationA radiation schedule delivering 40 Gy in 15 fractions seems to offer rates of local-regional tumour relapse and late adverse effects at least as favourable as the standard schedule of 50 Gy in 25 fractions.

Hypofractionated Radiotherapy as Adjuvant Treatment in Early Breast Cancer. A Review and Meta-Analysis of Randomized Controlled Trials

“…The search resulted in 21 hits. Considering only trials that had already published efficacy data and sufficient follow-up (> 5 years) yielded 4 trials [16,17,18,19,20,21,22,23] relevant for this review and meta-analysis of efficacy. These 4 randomized controlled trials tested different schedules of hypofractionated radiotherapy against conventionally fractionated radiotherapy (50 Gy in 25 fractions in 3-5 weeks).…”

Breast cancer

“…The international standard radiotherapy schedule administers 50 Gray in 25 fractions, but a recent trial investigated different radiotherapy schedules, concluding that 40 Gray in 15 fractions offered similar loco-regional control without increased toxicity. 6 Other trials are in progress, investigating novel radiotherapy techniques and partial breast radiation.…”

Adjuvante hypofraktionierte Strahlentherapie beim frühen Mammakarzinom. Übersicht und Meta-Analyse randomisierter kontrollierter Studien

“…Die Suche ergab 21 Treffer. Nach Eingrenzung auf Untersuchungen, zu denen bereits veröffentlichte Wirksamkeitsdaten vorlagen und die bereits eine ausreichende Nachbeobachtungszeit (> 5 Jahre) aufwiesen, verblieben 4 Studien [16,17,18,19,20,21,22,23], die für die vorliegende Übersicht und Meta-Analyse der Wirksamkeit relevant waren. In diesen 4 randomisierten kontrollierten Studien wurden unterschiedliche Schemata der hypofraktionierten Strahlentherapie im Vergleich zu konventionell fraktionierter Strahlentherapie (50 Gy in 25 Fraktionen über 3-5 Wochen) untersucht.…”

“…Die erwarteten Auswirkungen der verschiedenen Strahlentherapie-Schemata auf gesundes und Tumorgewebe gemäß Vorhersage des strahlenbiologischen linear-quadratischen Modells sind in Abbildung 1 dargestellt. Die Studien START Pilot [17,18] und START A [22] verglichen die konventionell fraktionierte Strahlentherapie mit jeweils 2 verschiedenen 5-wöchigen Schemata hypofraktionierter Strahlentherapie im 1:1:1-Design, während in der Ontario-Studie [19,20] und der START-B-Studie [23] 3-wöchige hypofraktionierte Strahlentherapie-Schemata mit konventioneller Fraktionierung im 1:1-Design verglichen wurden. Eine konsekutive konventionell fraktionierte Booster-Bestrahlung des Tumorbetts wurde in der Ontario-Studie bei keiner Patientin und in den anderen Studien bei 43-75% der Patientinnen angewandt.…”