Shorter Radiotherapy Courses May Achieve Similar Reductions In Breast Cancer Relapse As Standard Regimens
Radiotherapy after surgery for breast cancer has been shown to reduce local recurrence, with previous research showing that avoiding four local recurrences saves one woman from dying of breast cancer. Radiotherapy is traditionally given in 25 daily doses (called fractions) of 2.0 Gray (Gy), achieving a total dose of 50 Gy over five weeks. However, hospitals in the UK and Canada have been delivering a lower total dose in fewer, larger fractions - termed hypofractionation - for some time.
Studies looking back at women with early breast cancer given hypofractionated radiotherapy showed that it appeared to be as effective as standard radiotherapy in reducing the risk of relapse, without increasing adverse events. But this type of retrospective study is not as accurate as a forward-looking (prospective) study in determining the effects of a new treatment approach. So UK researchers carried out two studies randomly allocating women to different radiotherapy regimens and following them up for five to six years to assess the rate of recurrence of breast cancer and the adverse effects associated with the different approaches.
In the first study, the UK Standardisation of Breast Radiotherapy (START) Trial A, researchers randomly allocated 2236 women who had had surgery for early breast cancer to receive the standard radiotherapy schedule (50 Gy in 25 fractions of 2.0 Gy over five weeks), or a lower total dose of 41.6 Gy (13 fractions of 3.2 Gy over five weeks) or 39 Gy (13 fractions of 3.0 Gy over five weeks).
After an average follow-up of just over five years, the results showed that the rate of local-regional tumour relapse (cancer recurrence near the site of the original tumour) was similar in women given 41.6 Gy (3.5%) as in those given 50 Gy (3.6%). However, it was slightly higher in women given the lowest total radiotherapy dose of 39 Gy (5.2%).
In the second study, START Trial B, a further 2215 women who had undergone surgery for early breast cancer were randomly allocated to the standard radiotherapy schedule (50 Gy in 25 fractions of 2.0 Gy over five weeks) or a hypofractionated schedule (40 Gy in 15 fractions of 2.67 Gy over three weeks).
Results showed similar rates of local-regional tumour relapse after five years, affecting 3.3% of women given standard radiotherapy and 2.2% of those given the hypofractionated (40 Gy) regimen. The range of results indicated that the absolute difference in the rate of relapse could be up to 1.7% better after 40 Gy radiotherapy and, at most, 1% worse than after 50 Gy. Further results showed a significant reduction in the rate of cancer in different parts of the body to the original tumour (distant metastasis) and overall risk of death at five years with the hypofractionated schedule, which also caused lower rates of late side-effects.
Professor John Yarnold, the chief investigator for the two studies, said: "The results suggest that a high total dose given in 25 small treatments is no better than simpler schedules, using fewer exposures to a total dose." He added: "Shorter therapies giving fewer, larger treatments are obviously convenient for patients. These results support the current use of shorter schedules in the UK and in other countries."
However, other breast cancer specialists have argued that increasing the radiation dose per fraction would be expected to increase normal tissue damage and reduce the therapeutic benefit. They pointed out that the results from the START trials seemed to be opposite to those seen in studies in head and neck cancer, showing that reducing the radiation dose per fraction at the same time as increasing the number of fractions (hyperfractionation) and the total dose leads to better tumour control and survival without increased toxicity.
Much longer follow-up is needed, they argued, to see if the apparently similar reduction in rate of relapse with hypofractionated radiotherapy to standard radiotherapy is maintained over time. They were concerned that the result seen so far could be a false negative that might change with longer follow-up and more cases of relapse.
Writing in an editorial on the START trials, the specialists, Harry Bartelink, from the Netherlands Cancer Institute, Amsterdam, Netherlands, and Rodrigo Arriagada, from the Institut Gustave Roussy, Villejuif, France, and the Karolinska Insitutet Stockholm, Sweden, said: "We realise the 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 the START trials." They suggested that the START investigators should study tissue taken from patients in their trial to see if it might be possible to identify what type of fractionation might be best for each individual patient in the future.
The UK Standardisation of Breast Radiotherapy (START) Trial A of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.
The START Trialists' Group.
Lancet Oncology 2008; 9: 331-41
The UK Standardisation of Breast Radiotherapy (START) Trial B of radiotherapy hypofractionation for treatment of early breast cancer: a randomised trial.
The START Trialists' Group.
Lancet 2008; 371: 1098-107
Hypofractionation in radiotherapy for breast cancer.
Lancet Oncology, published online March 19, 2008 DOI:10.1016/S0140-6736(08)60349-9
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Cursuri de scurtã Radioterapia poate obþine similare reduceri în cancerul de sân recidiva standard regimuri - Shorter Radiotherapy Courses May Achieve Similar Reductions In Breast Cancer Relapse As Standard Regimens - articole medicale engleza - startsanatate