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Showing content from https://pubmed.ncbi.nlm.nih.gov/18356109/ below:

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

Randomized Controlled Trial

doi: 10.1016/S1470-2045(08)70077-9. Epub 2008 Mar 19. The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial S M Bentzen, R K Agrawal, E G A Aird, J M Barrett, P J Barrett-Lee, J M Bliss, J Brown, J A Dewar, H J Dobbs, J S Haviland, P J Hoskin, P Hopwood, P A Lawton, B J Magee, J Mills, D A L Morgan, J R Owen, S Simmons, G Sumo, M A Sydenham, K Venables, J R Yarnold

Collaborators

START Trialists' Group: W P Abram, J Clarke, J J A McAleer, J D Graham, P Riddle, S Goodman, M Tomlinson, K Benstead, R Counsell, S A G Elyan, J R Owen, B Lavery, E Sugden, J Dobbs, S Whittaker, C Brammer, M Churn, D J A Adamson, J A Dewar, D A L Morgan, J M Barrett, C D A Charlton, P Bliss, A Goodman, A Holmes, A Hong, A Neal, G Ross, A Rostom, D Tait, J R Yarnold, G Ross, M Illsley, R Laing, A Neal, C Topham, C Topham, S Whittaker, C Trask, P Bliss, A G Goodman, P J Barrett-Lee, T D L Crosby, C C Gaffney, T W O Tilsley, A Barrett, M Armitage, S M Bentzen, U Chetty, P Mayles, L Walker, H Lucraft, M Parmar, I Turesson, M Carling, J Pritchard, M King, E Parkin, K Law, S Perkins, U Wells

PMID: 18356109
PMCID: PMC2323709
DOI: 10.1016/S1470-2045(08)70077-9

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Randomized Controlled Trial

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

START Trialists' Group et al. Lancet Oncol. 2008 Apr.

doi: 10.1016/S1470-2045(08)70077-9. Epub 2008 Mar 19. Authors START Trialists' Group; S M Bentzen, R K Agrawal, E G A Aird, J M Barrett, P J Barrett-Lee, J M Bliss, J Brown, J A Dewar, H J Dobbs, J S Haviland, P J Hoskin, P Hopwood, P A Lawton, B J Magee, J Mills, D A L Morgan, J R Owen, S Simmons, G Sumo, M A Sydenham, K Venables, J R Yarnold Collaborators

START Trialists' Group: W P Abram, J Clarke, J J A McAleer, J D Graham, P Riddle, S Goodman, M Tomlinson, K Benstead, R Counsell, S A G Elyan, J R Owen, B Lavery, E Sugden, J Dobbs, S Whittaker, C Brammer, M Churn, D J A Adamson, J A Dewar, D A L Morgan, J M Barrett, C D A Charlton, P Bliss, A Goodman, A Holmes, A Hong, A Neal, G Ross, A Rostom, D Tait, J R Yarnold, G Ross, M Illsley, R Laing, A Neal, C Topham, C Topham, S Whittaker, C Trask, P Bliss, A G Goodman, P J Barrett-Lee, T D L Crosby, C C Gaffney, T W O Tilsley, A Barrett, M Armitage, S M Bentzen, U Chetty, P Mayles, L Walker, H Lucraft, M Parmar, I Turesson, M Carling, J Pritchard, M King, E Parkin, K Law, S Perkins, U Wells

PMID: 18356109
PMCID: PMC2323709
DOI: 10.1016/S1470-2045(08)70077-9

Item in Clipboard

Abstract

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 alpha/beta 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 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.

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Figures
Figure 1

Trial profile for START Trial…

Figure 1

Trial profile for START Trial A *Only major treatment deviations listed. Minor deviations…

Figure 1

Trial profile for START Trial A *Only major treatment deviations listed. Minor deviations due to public holidays, machine service days, and machine breakdowns not included.

Figure 2

Kaplan-Meier plot (A) and Nelson-Aalen…

Figure 2

Kaplan-Meier plot (A) and Nelson-Aalen cumulative hazard plot (B) of local-regional tumour relapse…

Figure 2

Kaplan-Meier plot (A) and Nelson-Aalen cumulative hazard plot (B) of local-regional tumour relapse in 2236 patients

Figure 3

Kaplan-Meier plot of mild/marked change…

Figure 3

Kaplan-Meier plot of mild/marked change in breast appearance (photographic) in 1055 patients with…

Figure 3

Kaplan-Meier plot of mild/marked change in breast appearance (photographic) in 1055 patients with breast conserving surgery

Figure 4

Forest plot of late normal…

Figure 4

Forest plot of late normal tissue effects assessed as moderate/marked by patients and…

Figure 4

Forest plot of late normal tissue effects assessed as moderate/marked by patients and mild/marked from photographs