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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 (A) and Nelson-Aalen cumulative hazard plot (B) of local-regional tumour relapse in 2215 patients
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fig2: Kaplan-Meier plot (A) and Nelson-Aalen cumulative hazard plot (B) of local-regional tumour relapse in 2215 patients

Mentions: At the time of analysis, 65 (2·9%) patients had experienced a local-regional relapse. The hazard ratio for local-regional relapse after 40 Gy compared with 50 Gy was 0·79 (95% CI 0·48–1·29; table 2). The estimated absolute difference in local-regional relapse rates for 40 Gy compared with 50 Gy at 5 years was −0·7% (−1·7% to 0·9%), which indicates that the absolute difference between schedules is likely to be at worst 0·9% higher and at best 1·7% lower after 40 Gy in 15 fractions than after 50 Gy in 25 fractions. Since the main concern over hypofractionation is an excess risk rather than a possible benefit, a more precise estimate of the potential excess risk of local-regional relapse is obtained from the upper limit of the one-sided 95% CI for the absolute difference in 5-year local-regional relapse rates. This calculation indicated an upper limit of 0·6% excess risk associated with the 15-fraction schedule. The Kaplan-Meier and cumulative hazard rate plots for local-regional relapse according to fractionation schedule (figure 2) illustrate the low event rate in both randomised groups.


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 (A) and Nelson-Aalen cumulative hazard plot (B) of local-regional tumour relapse in 2215 patients
© Copyright Policy
Related In: Results  -  Collection

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

fig2: Kaplan-Meier plot (A) and Nelson-Aalen cumulative hazard plot (B) of local-regional tumour relapse in 2215 patients
Mentions: At the time of analysis, 65 (2·9%) patients had experienced a local-regional relapse. The hazard ratio for local-regional relapse after 40 Gy compared with 50 Gy was 0·79 (95% CI 0·48–1·29; table 2). The estimated absolute difference in local-regional relapse rates for 40 Gy compared with 50 Gy at 5 years was −0·7% (−1·7% to 0·9%), which indicates that the absolute difference between schedules is likely to be at worst 0·9% higher and at best 1·7% lower after 40 Gy in 15 fractions than after 50 Gy in 25 fractions. Since the main concern over hypofractionation is an excess risk rather than a possible benefit, a more precise estimate of the potential excess risk of local-regional relapse is obtained from the upper limit of the one-sided 95% CI for the absolute difference in 5-year local-regional relapse rates. This calculation indicated an upper limit of 0·6% excess risk associated with the 15-fraction schedule. The Kaplan-Meier and cumulative hazard rate plots for local-regional relapse according to fractionation schedule (figure 2) illustrate the low event rate in both randomised groups.

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