Ten-year results from the FAST study show that there are no significant differences in normal tissue effects (NTE) rates after 28.5 Gy/5 fractions (fr) compared with 50 Gy/25 fr in patients with early breast cancer; however, NTE were higher with 30 Gy/5 fr, according to a study published in the Journal of Clinical Oncology. In an interview with i3 Health, Murray Brunt, MBBS, FRCP, FRCR, lead study author, provides insights on the significance of these results and how treatment will evolve in the future.
Can you comment on the significance of your study results?
Murray Brunt, MBBS, FRCP, FRCR: The FAST trial was conceived in the early 2000s when 25 fractions in 5 weeks as standard was being compared with 15 fractions (START trial in UK) and 16 fractions (Ontario trial in Canada) in 3 weeks. FAST aimed to establish the feasibility of a 5-fraction treatment. To keep time constant, we treated once per week over 5 weeks. An older low-risk breast cancer patient group was deliberately used with the main end point being the effects on normal tissue. We had two test doses so that if one of them was not equivalent, we would still be able to calculate an equivalent. The 10-year results are significant because the 28.5 Gy in 5 fractions is equivalent to the old standard of 25 fractions in 5 weeks. The main significance is that it confirms that 5 treatments are possible. This once-a-week treatment is useful for a minority (approximately 5% or less) of patients who struggle to attend daily for radiotherapy due to medical frailty.
How does using 5-fraction whole-breast radiotherapy affect survival outcomes of patients with early breast cancer?
Dr. Brunt: The survival is equivalent. This trial had a low risk group of patients and after 10 years only 1.3% had a recurrence in the treated breast. It was not statistically powered to measure this as an outcome.
What are the unmet needs that still exist in this patient population?
Dr. Brunt: The FAST trial helped to inform the FAST-Forward trial which is 5 fractions in a week. This trial reported the 5-year results in The Lancet published just under 3 months ago. This is a trial of over 4,000 patients from the UK. This trial compared 15 fractions over 3 weeks (the current standard) with 5 fractions a week and found that it is not inferior (statistical aim) in effectiveness and similar in side effects with one of the two test arms. The 5 fractions in a week is now standard to the breast in many departments the UK and likely to be confirmed as the national standard later this year. We await information from the FAST-Forward lymph node radiotherapy substudy for patients requiring radiotherapy to breast and lymph nodes.
How do you see the treatment landscape evolving in the coming years?
Dr. Brunt: I see 5-fractions in a week becoming an international standard. Coincidentally, the regimen has been widely used around the globe because it is safer during the COVID-19 pandemic. The reduced patient footfall to hospital is safer. This will mean that many radiotherapy departments have used the regimen where under normal circumstances a major change often takes a long time to become standard.
Any final thoughts on the current treatment paradigm?
Dr. Brunt: The radiobiology helped us to plan the trials and has supported the paradigm. Five fractions offers a significant benefit to patients. The benefit to health care is that the resources can be focused on delivering what is an ever more accurate and therefore complex treatment. In a publicly funded system such as here in the UK there is also a financial benefit. The aim has always been primarily medical and for the patients.
About Dr. Brunt
Murray Brunt, MBBS, FRCP, FRCR is a Professor in The School of Medicine, University of Keele and until recently a Consultant Clinical Oncologist at University Hospitals of North Midlands for almost 30 years. Professor Brunt is Chief Investigator of the FAST-Forward trial.
For More Information
Brunt AM, Haviland JS, Sydenham M, et al (2020). Ten-year results of FAST: a randomized controlled trial of 5-fraction whole-breast radiotherapy for early breast cancer. J Clin Oncol. [Epub ahead of print] DOI:10.1200/JCO.19.02750
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.