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

Abstract

SummaryBackgroundThe 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.MethodsBetween 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.Findings749 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).InterpretationThe 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 fractions in terms of local-regional tumour control and late normal tissue effects, a result consistent with the result of START Trial B. A lower total dose in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50 Gy in 25 fractions.

The photon dose calculation algorithm used in breast radiotherapy has significant impact on the parameters of radiobiological models

“…This validates the assumption to consider the PBC‐Hom dose distribution as the reference dose distribution with known clinical outcome for T1‐T2 breast tumors, and to use it for the determination of the TCP parameters of the PBC‐MB, the AAA, the Acuros‐M, and the Acuros‐W algorithms (Table 4). $\alpha /\beta =4.6\hspace{0.17em}\text{Gy}$ (23) was kept fixed.…”

“…For each patient, five TCPs were calculated: 1) of the dose distribution calculated with PBC‐MB (${\text{TCP}}_{\text{PBC}-\text{MB}}$), 2) of the dose distribution calculated with AAA (${\text{TCP}}_{\text{AAA}}$), 3) of the dose distribution calculated with Acuros‐M (${\text{TCP}}_{\text{Acuros}-\mathrm{normalM}}$), 4) of the dose distribution calculated with Acuros‐W (${\text{TCP}}_{\text{Acuros}-\mathrm{normalW}}$), and 5) of the dose distribution calculated with PBC‐Hom (${\text{TCP}}_{\text{PBC}-\text{Hom}}$). First, each homogeneous dose level of the dDVH was converted to a total dose delivered in 2 Gy fractions with the biological effective dose (BED) method, (22) with $\alpha /\beta =4.6\hspace{0.17em}\text{Gy}$ (23) . Next, the TCP was calculated using the Poisson model for an inhomogeneous dose distribution (24) using Eq.…”

An accelerated hypofractionated radiotherapy regimen in patients after organ-sparing surgery for stages I–IIA breast cancer

“…Поздние лучевые повреждения нормальных тканей при применении ЛТ РОД 2,66 (26,2 %) и 3 Гр (30 %) возникали статистически достоверно реже, чем при стандартной ЛТ (31,2 и 34,2 % в исследованиях START В и START А) и не приводили к повышению ри-ска кардиологических и легочных побочных эффектов. Применение гипофракционированного ускоренного режима -РОД 2,66 Гр, СОД 40 Гр -привело к увели-чению безрецидивной выживаемости по сравнению со стандартной ЛТ [5][6][7][8][9][10][11][12][13]. В целом исследования пока-зали эффективность гипофракционированных и уско-ренных режимов.…”

“…Будущие исследо-вания помогут разработать индивидуальный подход к параметрам облучения, основанный на клинических, fractionated radiotherapy regimen were also significantly higher than in those who had the standard radiotherapy regimen: 97. 9 Характеристика пациенток представлена в табл. 1.…”

Low‐cost Kinect Version 2 imaging system for breath hold monitoring and gating: Proof of concept study for breast cancer VMAT radiotherapy

“…Surgery followed by radiotherapy improves local control and survival such that rates of local tumor relapse in the breast are now approximately 3% at 5 yr 2, 3. However, breast radiotherapy is also associated with a 1% increase in nonbreast‐cancer‐related deaths at 15 yr, 90% of which are cardiovascular in origin 4, 5.…”