Breast cancer: Shorter Radiotherapy

19 Mar 2008

For ECMS by Freelance Reporter Stephen Pinn

New radiotherapy regimens proposed for early breast cancer - but are the START data too good to be true?

Doubts have been cast about the validity of new data showing that radiotherapy for breast cancer patients can be delivered as a lower overall dose in fewer, larger doses, giving similar tumour control and fewer adverse side effects than current best practice (Lancet).

The international standard radiotherapy schedule for early breast cancer delivers 50Gy of radiation in 25 fractions of 2.0Gy over five weeks. However, cancer specialists in the UK have long believed that a lower total dose delivered in fewer, larger fractions can be at least as safe and effective as the standard.

START (Standardisation of Breast Radiotherapy Trial) was jointly funded by Cancer Research UK, the UK Medical Research Council, and the UK Department of Health, and involved researchers from 35 UK cancer centres.

In Start A, 2236 women were randomly assigned after primary surgery to receive 50Gy in 25 fractions of 2.0Gy (749 women) versus 41.6Gy in 13 fractions of 3.2Gy (750 women) or 39Gy in 13 fractions of 3.0Gy (737 women).

Professor John Yarnold (Institute of Cancer Research and Royal Marsden Hospital) and his fellow UK researchers found that the rate of tumour relapse at 5 years was 3.6% after 50Gy, 3.5% after 41.6Gy, and 5.2% after 39Gy. Neither late adverse effects nor local tumour relapse after 41.6 Gy were different compared to 50Gy.

They concluded: "A lower total dose (41.6Gy) in a smaller number of fractions could offer similar rates of tumour control and normal tissue damage as the international standard fractionation schedule of 50Gy in 25 fractions."

In Start B, 2215 were randomly assigned after primary surgery to receive 50Gy in 25 fractions of 2.0Gy over five weeks (1105 women) and 40Gy in 15 fractions of 2.6 Gy over three weeks (1110 women). It was found that the rate of tumour relapse at five years was 2.2% in the 40 y group and 3.3% in the 50Gy group.

In the respective START studies, photographic and patient self-assessments suggested lower rates of late adverse effects after 39Gy and 40Gy than with 50Gy.

The authors concluded: "After surgery for early breast cancer, a radiotherapy schedule delivering 40Gy in 15 fractions over three weeks seems to offer local regional tumour control and rates of late normal tissue effects at least as good as the accepted international standard of 50Gy in 25 fractions over five weeks."

However, in an editorial in The Lancet, Dr Harry Bartelink (Netherlands Cancer Institute, Amsterdam, The Netherlands), and Dr Rodrigo Arriagada (Institut Gustave Roussy, Villejuif, France) urged caution. "We realise," they said, "that hypofractionation is convenient for patients, because it reduces the number of visits to radiotherapy departments and waiting lists in several cancer centres. Nevertheless we have to wait for data on longer follow-up before final conclusions can be drawn from START."

They pointed out that several studies have shown that reducing the radiation dose per fraction while increasing the number of fractions and the total dose limits normal tissue damage- and, indeed, that in head and neck tumours, this hypofractionation had led to better tumour control and survival without an increase in toxicity.

"We therefore wonder why the outcomes of the START trials show the opposite effect?" they ask. "Will long-term follow-up show results consistent with those for head and neck cancer, or are the results of the START trials due to different biological features in breast cancer?"

They concluded that: "We should accept that this result could be a false negative that might chage with longer follow-up and more events."