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

The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial
The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial
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% Cl -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% Cl 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.
331-341
Bentzen, S.M.
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Agrawal, R.K.
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Aird, E.G.A.
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Barrett, J.M.
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Barrett-Lee, P.J
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Bliss, J.M.
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Brown, J.
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Dewar, J.A.
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Dobbs, H.J.
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Haviland, J.S.
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Hoskin, P.J.
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Hopwood, P.
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Lawton, P.A.
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Magee, B.J.
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Mills, J.
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Morgan, D.A.
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Owen, J.R.
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Simmons, S.
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Sumo, G.
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Sydenham, M.A.
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Venables, K.
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Yarnold, J.R.
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Bentzen, S.M.
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Agrawal, R.K.
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Aird, E.G.A.
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Barrett, J.M.
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Barrett-Lee, P.J
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Bliss, J.M.
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Brown, J.
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Dewar, J.A.
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Dobbs, H.J.
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Hopwood, P.
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Lawton, P.A.
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Magee, B.J.
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Mills, J.
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Morgan, D.A.
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Owen, J.R.
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Simmons, S.
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Sumo, G.
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Sydenham, M.A.
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Venables, K.
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Yarnold, J.R.
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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., Owen, J.R., Simmons, S., Sumo, G., Sydenham, M.A., Venables, K. and Yarnold, J.R. (2008) The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial. Lancet Oncology, 9 (4), 331-341. (doi:10.1016/S1470-2045(08)70077-9). (PMID:18356109)

Record type: Article

Abstract

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% Cl -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% Cl 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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Published date: April 2008
Organisations: Faculty of Medicine

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Local EPrints ID: 354524
URI: https://eprints.soton.ac.uk/id/eprint/354524
PURE UUID: 4892ba32-857f-40b0-85a3-be58a1de39f4

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Date deposited: 12 Jul 2013 11:56
Last modified: 11 Nov 2019 20:56

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Contributors

Author: S.M. Bentzen
Author: R.K. Agrawal
Author: E.G.A. Aird
Author: J.M. Barrett
Author: P.J Barrett-Lee
Author: J.M. Bliss
Author: J. Brown
Author: J.A. Dewar
Author: H.J. Dobbs
Author: J.S. Haviland
Author: P.J. Hoskin
Author: P. Hopwood
Author: P.A. Lawton
Author: B.J. Magee
Author: J. Mills
Author: D.A. Morgan
Author: J.R. Owen
Author: S. Simmons
Author: G. Sumo
Author: M.A. Sydenham
Author: K. Venables
Author: J.R. Yarnold

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