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

START Trialists' GroupBentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR - Lancet (2008)

Bottom Line: Analysis was by intention to treat.Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy.A 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.

View Article: PubMed Central - PubMed

ABSTRACT

Background: The 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.

Methods: Between 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.

Findings: 1105 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.

Interpretation: A 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.

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Related in: MedlinePlus

Kaplan-Meier plot of mild/marked change in breast appearance (photographic) in 923 patients with breast conserving surgery
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fig4: Kaplan-Meier plot of mild/marked change in breast appearance (photographic) in 923 patients with breast conserving surgery

Mentions: Change in breast appearance (photographic) was assessed on a 3-point graded scale (none, mild, marked) in 923 patients with a baseline and at least one follow-up image (461 for 50 Gy and 462 for 40 Gy). Not all patients had photographs available at both 2 and 5 years, for reasons including the 5-year assessment not yet being done at the time of scoring and analysis, patient refusal, and withdrawal from the photographic study due to relapse. There were no associations between score for change in breast appearance (photographic) at 2 years or patient demographic or treatment characteristics and whether or not the patient had a 5-year assessment (data not shown). Mild change was graded for 284 (30·8%) patients and marked change for 28 (3·0%) patients, by 5 years. Change in breast appearance (photographic) was less likely after 40 Gy than after 50 Gy, with a hazard ratio of 0·83 (95% CI 0·66–1·04, p=0·06; figures 4 and 5). Adjusting for breast size and surgical deficit made little difference to these results. Figure 4 shows that the treatment differences were evident at the first time point of 2 years, and persisted to 5 years.


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

START Trialists' GroupBentzen SM, Agrawal RK, Aird EG, Barrett JM, Barrett-Lee PJ, Bentzen SM, Bliss JM, Brown J, Dewar JA, Dobbs HJ, Haviland JS, Hoskin PJ, Hopwood P, Lawton PA, Magee BJ, Mills J, Morgan DA, Owen JR, Simmons S, Sumo G, Sydenham MA, Venables K, Yarnold JR - Lancet (2008)

Kaplan-Meier plot of mild/marked change in breast appearance (photographic) in 923 patients with breast conserving surgery
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2277488&req=5

fig4: Kaplan-Meier plot of mild/marked change in breast appearance (photographic) in 923 patients with breast conserving surgery
Mentions: Change in breast appearance (photographic) was assessed on a 3-point graded scale (none, mild, marked) in 923 patients with a baseline and at least one follow-up image (461 for 50 Gy and 462 for 40 Gy). Not all patients had photographs available at both 2 and 5 years, for reasons including the 5-year assessment not yet being done at the time of scoring and analysis, patient refusal, and withdrawal from the photographic study due to relapse. There were no associations between score for change in breast appearance (photographic) at 2 years or patient demographic or treatment characteristics and whether or not the patient had a 5-year assessment (data not shown). Mild change was graded for 284 (30·8%) patients and marked change for 28 (3·0%) patients, by 5 years. Change in breast appearance (photographic) was less likely after 40 Gy than after 50 Gy, with a hazard ratio of 0·83 (95% CI 0·66–1·04, p=0·06; figures 4 and 5). Adjusting for breast size and surgical deficit made little difference to these results. Figure 4 shows that the treatment differences were evident at the first time point of 2 years, and persisted to 5 years.

Bottom Line: Analysis was by intention to treat.Photographic and patient self-assessments indicated lower rates of late adverse effects after 40 Gy than after 50 Gy.A 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.

View Article: PubMed Central - PubMed

ABSTRACT

Background: The 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.

Methods: Between 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.

Findings: 1105 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.

Interpretation: A 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.

Show MeSH
Related in: MedlinePlus