Radiotherapy today is very different to the crude treatment first used more than 100 years ago – much more accurate and increasingly adjusted to an individual’s needs. One way it has become more sophisticated is the way the dose is prescribed. Rather than giving curative radiotherapy in a single, large dose, radiotherapy is split up, or fractionated, into many smaller doses over a number of days or weeks. This is usually the best way of causing the greatest damage to tumour tissue while limiting damage to surrounding healthy tissues.
Different tissues show different sensitivities to the total dose prescribed and also to the size of a daily fractions used to give this dose. For most cancers, total dose matters more than anything else, whereas many healthy tissues are also sensitive to the size of individual fractions. Giving many small fractions in order to safely deliver the highest total dose has generally been regarded as the best way of effectively treating cancers while sparing healthy tissue.
But a recent review published by scientists here at The Institute of Cancer Research in London argues that for breast cancer, a lower total dose is as effective when delivered in fewer, larger fractions, which can be given over a shorter period of time. These kinds of dosing schedule are known as ‘hypofractionated’ because of the smaller number of fractions they use. And they could benefit women with breast cancer, who often have to travel a long distance to receive radiotherapy, by reducing the number of times they have to travel to and from hospital.
Healthcare services could also benefit from hypofractionated radiotherapy regimens. By being able to provide fewer doses while maintaining the same clinical outcome, the NHS will save time and reduce the overall cost of radiotherapy for each patient.
The paper discusses a number of clinical trials which were run here at the ICR with our hospital partner The Royal Marsden, and assessed the role of hypofractionated radiotherapy for treating women with early breast cancer.
One such study is the FAST trial, which compared late side-effects – those appearing months or years after treatment – after hypofractionated radiotherapy with those that appeared after conventional radiotherapy. Women older than 50 years of age were split into three groups – two of which received a lower overall radiation dose given in five fractions over five weeks, and one of which, the control group, received a conventional dose in 25 fractions.
A crucial aspect of this trial is that while the total dose of the hypofractionated regimen was lower than the total dose of the conventional radiotherapy, patients received a much higher radiation dose with each fraction. It successfully showed that five larger fractions given as one fraction per week can be delivered, causing no more changes in the healthy tissues of the breast as the standard 25 small fractions over five weeks. The results of the FAST-Forward phase III trial, which assesses the safety and effectiveness of five fractions of radiotherapy given over one week in 4,000 UK women are expected in 2018–2019. The participants are highly motivated and regularly fill in detailed questionnaires that record their symptoms and daily activities.
Professor John Yarnold, who is corresponding author for the review article published in The Breast, is optimistic that hypofractionation of radiotherapy could become more common. He told me: “There is a real prospect that by the end of this decade, or in the 2020s, women with early breast cancer treated with radiotherapy will be offered a 1-week course of treatment to their whole breast or only part of their breast. This will greatly reduce time and travel commitments which these women must make to attend radiotherapy over the course of several weeks.”
The paper also discusses the START-A and START-B trials – trials which have resulted in hypofractionated radiotherapy becoming part of standard treatment for women with early breast cancer.
The results of the two START trials showed that 15 fractions given over three weeks were as safe and effective as 25 fractions given over five weeks, and since 2009, the UK standard of care for women with early breast cancer involves giving 15 fractions. In a UK-wide audit carried out in November 2011, 88% of all dose prescriptions for women prescribed breast radiotherapy used the 15-fraction schedule tested during the START-B trial.
Radiotherapy research continues to improve outcomes for patients – either treating cancer more effectively or sparing more healthy tissue from damage. Scientists and clinical researchers are still making new discoveries on how to shape a beam to fit a patient’s tumour, or how to track tumour movement in real time. Hypofractionation provides another example of progress in radiotherapy, offering benefit for patients with early breast cancer and the healthcare systems who treat them.
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