CT 01 - Clinical Trials Session

LBA2 - FAST Phase III RCT of Radiotherapy Hypofractionation for Treatment of Early Breast Cancer: 10-Year Results (CRUKE/04/015)

Sunday, October 21
4:05 PM - 4:15 PM
Location: Stars at Night Ballroom

FAST Phase III RCT of Radiotherapy Hypofractionation for Treatment of Early Breast Cancer: 10-Year Results (CRUKE/04/015)
A. M. Brunt1, J. Haviland2, M. Sydenham2, H. Algurafi3, A. Alhasso4, P. Bliss5, D. Bloomfield6, M. Emson2, A. Goodman7, A. Harnett8, H. Passant9, Y. M. Tsang10, D. Wheatley11, J. Bliss2, and J. Yarnold12; 1Institute of Cancer Research, London, United Kingdom, 2The Institute of Cancer Research, Sutton, United Kingdom, 3Southend Hospital, Southend, United Kingdom, 4Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom, 5Torbay General Hospital, Torbay, United Kingdom, 6Royal Sussex County Hospital, Brighton, United Kingdom, 7Royal Devon and Exeter Hospital, Exeter, United Kingdom, 8Norfolk and Norwich University Hospital, Norwich, United Kingdom, 9Velindre Hospital, Cardiff, United Kingdom, 10Mount Vernon Cancer Centre, London, United Kingdom, 11Royal Cornwall Hospital, Truro, United Kingdom, 12Division of Radiotherapy and Imaging, the Institute of Cancer Research, London, United Kingdom

Purpose/Objective(s): The UK FAST trial tested 5 fractions (Fr) of 5.7 Gy and 6.0 Gy against 25 Fr of 2.0 Gy in women prescribed whole breast radiotherapy (no boost) after local excision of early breast cancer. Analysis of primary endpoint (normal tissue effects [by photograph]) showed that the 28.5 Gy/5 Fr regimen appeared similar to control (Radiother Oncol. 2011 Jul;100(1):93-100). Further follow-up now enables analysis of 10 year outcomes.

Materials/Methods: The FAST trial (ISRCTN62488883) randomised women aged ≥50 years with invasive breast carcinoma (pT1-2 pN0) to 3 whole breast radiotherapy schedules: 50 Gy in 25 Fr over 5 weeks (control), 30 Gy or 28.5 Gy in 5 Fr over 5 weeks (1:1:1). Exclusion criteria were planned lymphatic/breast boost radiotherapy or (neo)adjuvant cytotoxic therapy. Normal tissue effects (NTE) were assessed annually to 10 years by clinicians and photographs at 2 and 5 years compared with a pre-radiotherapy baseline. Breast tumour recurrence was a secondary endpoint.

Results: 915 women were recruited from 18 UK centres (2004-2007). Composite endpoint of any clinician-assessed breast NTE showed significantly higher levels at 5 and 10 years for 30 Gy compared with 50 Gy (Table). Prevalence of marked NTEs at 5 and 10 years were very low. Compared with 50Gy excess of moderate/marked effects for 30Gy were: 5 years +10.5%, 95%CI 4.9 to 16.1%; 10 years +9.4%, 95%CI 1.1 to 17.6% and for 28.5 Gy, were +2.4%, 95%CI -2.5 to 7.3% at 5 years and +5.5%, 95%CI -2.3 to 13.3% at 10 years. At 9.9 years median follow up, 10 local recurrences (50 Gy: 3, 30 Gy: 3, 28.5 Gy: 4) and 96 deaths (50 Gy: 33, 30 Gy: 33, 28.5 Gy: 30) have been reported.

Conclusion: Marked NTEs were rare for all schedules. Late moderate/marked NTE after 28.5Gy/5 Fr/5 weeks were similar to 50Gy/25 Fr/5 weeks, but higher after 30Gy/5 Fr/5 weeks. Local recurrence rates were very low at 10 years for all schedules. Further research of a 5-Fr regimen is warranted; the UK FAST-Forward trial is testing 5 Fr delivered in 1 week. 15 or 16-Fr schedules of adjuvant radiotherapy for early breast cancer have now been shown to be effective and safe but a once-weekly 5-Fr schedule may be considered for patients in whom a daily visit for 3 or 5 weeks is not acceptable however careful consideration of the dose per Fr is required.

Table: Clinician assessments of NTE at 5 and 10 years

Worst grade of any NTE in the breast1

50Gy/25Fr

(5 weeks)

n (%)

30Gy/5Fr

(5 weeks)

n (%)

28.5Gy/5Fr

(5 weeks)

n (%)

At 5 years:

None

Mild

Moderate

Marked

P-value2

N=254

160 (63.0)

75 (29.5)

15 (5.9)

4 (1.6)

-

N=267

152 (56.9)

67 (25.1)

40 (15.0)

8 (3.0)

0.008

N=253

155 (61.3)

73 (28.8)

24 (9.5)

1 (0.4)

0.475

At 10 years:

None

Mild

Moderate

Marked

P-value2

N=132

90 (68.2)

30 (22.7)

11 (8.3)

1 (0.8)

-

N=130

66 (50.8)

40 (30.8)

18 (13.8)

6 (4.6)

0.003

N=130

72 (55.4)

39 (30.0)

17 (13.1)

2 (1.5)

0.034

1 Shrinkage, induration, telangiectasia, oedema;

2 χ2 trend test (none, mild, moderate/marked); comparison with 50Gy/25Fr

Author Disclosure: A. Brunt: None. J. Haviland: None. A. Alhasso: None. D. Bloomfield: None.

Adrian Murray Brunt, MBBS, FRCR, FRCP

Disclosure:
No relationships to disclose.

Biography:
Murray Brunt is consultant clinical oncologist at The University Hospitals of North Midlands and a Honorary Professor at Keele University in the UK. he qualified from Westminster Medical School, London in 1983. As a consultant he specialises in breast and skin cancer with a particular interest in clinical research. Murray is the Chief Investigator of the FAST-Forward trial and has been closely involved with the UK series of breast radiotherapy trials over the last 30 years. He presented the primary endpoint FAST results to ESTRO in 2009 and is going to present the long term results in this meeting. Murray is the Cancer Research Lead for the West Midlands NIHR and has had many roles over the years in national breast cancer guidelines including the current (inaugural) RCR consensus guidelines for breast radiotherapy.

Presentation(s):

Send Email for Adrian Murray Brunt


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LBA2 - FAST Phase III RCT of Radiotherapy Hypofractionation for Treatment of Early Breast Cancer: 10-Year Results (CRUKE/04/015)

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