“Fewer doses of radiation still beat cancer” reads the headline in The Independent . Findings from two trials carried out over 10 years and involving 4,500 women may lead to ”a revolution in radiotherapy treatment for breast cancer,” the newspaper says.
The story is based on results from two clinical trials which found that reducing the total radiation dose by 20% and the number of sessions of radiotherapy by 40% reduced the side effects associated with the treatment without any increase in cancer recurrence. The radiation dose at each session was higher than that given with standard radiation. After five years, there were no differences between women who had received the standard regimen and those on the new regimen in terms of cancer recurrence. However, side effects of treatment, such as breast-tissue hardening, were fewer in the women who had received the new regimen.
The research suggests that a schedule of lower total dose radiotherapy in fewer, higher doses seems to be as safe and effective as the current regimen. It is not saying that the current regimen is any less effective or causes a greater risk of harmful effects. This is one of many carefully controlled and monitored clinical trials that are continually carried out for different cancer treatments to see whether current standards can be improved to produce better outcomes for patients. Further research with longer-term follow up will need to be carried out before any changes are made to current practice.
Where did the story come from?
The research was carried out in two parts by members of the UK Standardisation of Radiotherapy (START) Trialists’ Group from various healthcare trusts across the UK. The study was funded by Cancer Research UK, the UK Medical Research Council and the Department of Health. The separate parts were published in peer-reviewed medical journals The Lancet and The Lancet Oncology .
What kind of scientific study was this?
These were two randomised controlled trials in women with early invasive breast cancer. Standard treatment is to give 50Gy of radiation in 25 sessions over five weeks (i.e. 2Gy at each session). The two trials investigated the effects of a lower total dose of radiation using two different methods.
The START A trial looked at giving a lower total dose of radiation over the standard treatment period (five weeks). The START B trial investigated using a shorter treatment period (three to five weeks) with fewer total radiation doses but with a higher dose of radiation at each treatment (a process called hypofractionation). The trials aimed to investigate whether hypofractionation, with its convenience of fewer radiotherapy visits for patients, produced any difference in the recurrence of cancer or the side effects compared with the current regimen. Both trials were unblinded, i.e. both the patient and the treatment provider were aware of the treatment schedule that was being given.
START A was carried out in 17 medical centres across the UK between 1998 and 2002. The trial involved 2,236 women with early, stage one to three breast cancer (where the cancer was confined to the breast tissue and had not invaded muscle, skin, lymph nodes or other parts of the body). After surgery to remove the primary cancer (either removal of the lump or mastectomy), the participants were randomised into three equally sized treatment groups. One group received standard radiotherapy. The second group received a five-week treatment schedule of 13 sessions with a dose of 3Gy, giving a total radiation dose of 39. The third group also received treatment over five weeks, but with a dose of 3.2Gy at each session giving a total radiation dose of 41.6Gy.
All women were aged over 18 years and were not planned for immediate breast reconstruction surgery. Use of additional treatments, such as tamoxifen and chemotherapy, was balanced between the groups. The women were followed over five years to look at rates of local tumour relapse, effects upon breast tissue, quality of life (which was self assessed and included questions on breast change), disease-free survival and occurrence of cancer at any secondary sites.
Photographs of breast appearance were taken after surgery and before radiotherapy, and then at two and five years post-radiotherapy for comparison. The observers who looked at the photos were blind to the treatment received by the patient. The results of all women were analysed in the groups that they were originally assigned to by randomisation, regardless of whether their treatment regimen was changed or they dropped out of treatment.
START B was carried out in 23 medical centres in the UK between 1999 and 2001. This trial involved 2,215 women with the same stage of breast cancer as START A. However, in this trial, women were assigned to receive either the standard regimen over five weeks, or to a total of 40Gy in 15 sessions of 2.67Gy at each, given over the shorter period of three weeks. Other trial conditions and follow up were the same as for START A but the average follow up period of six years was slightly longer.
What were the results of the study?
In START A the researchers found that the rates of tumour relapse at five years were 3.6% in the standard group, 5.2% in the 39Gy group and 3.5% in the 41.6Gy group. There was no significant difference among the rates in any group. Photographic change in breast appearance (assessed in about half of the total trial members) and self-reported change in skin appearance occurred less frequently in the 39Gy group compared with the standard 50Gy group, but there was no difference between the standard and 41.6Gy group. There were no differences among the groups in any other side effects measured, including breast swelling, shrinkage, hardness or change in skin appearance.
In START B the researchers found that the rates of tumour relapse at five years were 3.3% in the standard group and 2.2% in the 40Gy group. There was no significant difference between the rates in either group. Change in skin appearance after radiotherapy occurred less frequently in the 40Gy group compared with the standard 50Gy group. There was a trend towards reduced risk of other side effects (e.g. photographic change, swelling, shrinkage, hardness) in the 40Gy group, but there were no significant differences in rates between the two. There were also some significant differences in rates of secondary breast cancer outcomes in this study (i.e. not ones that the authors were principally looking at): those in the 40Gy group had a reduced risk of any side effects, distant cancer spread or death from any cause.
What interpretations did the researchers draw from these results?
The START group concluded that giving 41.6Gy in 13 sessions “was similar to the control regimen of 50Gy in 25 sessions” in terms of the effects on normal breast tissue and tumour control. Likewise, giving 40Gy in 15 fractions over three weeks was as safe and effective as the standard regimen. They say that “the combined trials present mounting evidence that hypofractionation is a safe and effective approach to breast cancer radiotherapy”.
What does the NHS Knowledge Service make of this study?
These two well-conducted trials have suggested that giving radiotherapy to women with early stage breast cancer (following surgery) in a hypofractionation schedule of a lower total dose given in fewer, higher dose fractions seems to be as safe and effective as the current regimen. It is important to note that the trials have not found the current regimen to be any less effective or to cause any greater risk of harmful effects.
These trials do have some limitations, including relatively short follow up periods. Furthermore, the analysis has not accounted for factors that may have an effect upon breast cancer prognosis and outcome, such as oestrogen receptor status. Further research is needed before any changes are made to standard practice, and longer-term follow up will be of benefit to see whether there are any effects upon other body tissues, such as the heart. The current studies have only investigated hypofractionation in women with this particular stage of breast cancer and results cannot be generalised outside of this population.
Sir Muir Gray adds...
All treatments do harm as well as good; any study that shows how harm can be reduced while maintaining benefit is very, very welcome.