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Radiotherapy Dose Squandered in Balancing Between-treatment Tumor Growth

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For the first time, researchers have approximated the daily dose of radiotherapy that could be expended in compensating for cancer cell growth that happens overnight and during weekends in patients with early breast cancer.

In research presented to the 2013 European Cancer Congress (ECC2013), Professor John Yarnold said that, “until now, there has been contradictory evidence as to whether gaps between radiotherapy treatments, for instance overnight or at weekends, makes any difference to the overall effectiveness of radiotherapy on breast cancer, and, if it does make a difference, why that could be.”

"Traditionally, breast cancer has not been regarded as a fast growing cancer, unlike some other cancer types, but our research now suggests that a significant part of the daily radiotherapy curative dose is 'used up' in compensating for tumor growth overnight and over weekends. We have estimated that the amount of radiotherapy dose that is used up in this way corresponds to approximately 0.60 Gray (Gy) [2] per day," added Yarnold who is also a Professor of Clinical Oncology at The Institute of Cancer Research, London, and Honorary Consultant at the Royal Marsden NHS Foundation Trust (London, UK).

"This is the first numerical estimate to suggest that the duration of a course of radiotherapy has an effect on local cancer cure for patients with early breast cancer. The results of our analysis are hypothesis-generating; they offer an explanation as to why prolonged radiotherapy schedules may allow cancer cells to fight back, anRadiotherapy dose wasted in compensating for between-treatment tumor growthd suggest that breast cancer cell growth rates after surgery are higher than historically assumed. If confirmed, it means that current trends to deliver shorter radiotherapy schedules are likely to bear fruit in the future. However, I should emphasise that current schedules delivered over five weeks or more remain highly effective, and patients should follow recommendations from their specialists."

Radiotherapy is typically administered as a succession of treatments over a number of weeks in order to eradicate any remaining cancer cells in the breast, chest wall or underarm area after surgery, and to lessen the risk of the cancer recurrence in the same breast, while, simultaneously reducing any collateral damage to healthy tissues.

Yarnold and Ms Jo Haviland, who is a senior statistician at The Institute of Cancer Research (ICR) Clinical Trials and Statistics Unit (CTSU) predicated their research on the Standardization of Breast Radiotherapy (START) trials (START Pilot, START A and START B), which have been assessing the outcomes of administering shorter radiotherapy sessions following surgery for early breast cancer patients in the UK since 1986.

The researchers collected and utilized data from 5,861 UK patients who were registered between 1986 and 2002 into the three START randomized clinical trials that compared different sessions for administering radiotherapy. The START Pilot and START A trials compared the international standard of giving a total of 50 Gy in 25 daily doses of 2.0 Gy over a five week period versus two other sessions of somewhat higher daily doses of 3.0-.3 Gy over the same time period.

The START B trial compared the international standard (50 Gy in 25 daily doses of 2.0 Gy over five weeks) with a shorter schedule administering a total of 40 Gy in 15 daily doses of 2.67 Gy over three weeks. After a follow-up period of ten years, the three-week schedule was shown to be as effective as the five-week schedule at preventing the cancer from recurring in the same breast and has since been incorporated and used as the standard in the UK. In terms of safety, the three-week schedule was more advantageous on normal tissues, with fewer late side-effects.

Utilizing the data gathered from these trials, the researchers then estimated the effect of overall radiotherapy treatment time on the risk of the cancer recurring, comparing the three-week schedule with the five-week schedules. They employed a statistical tool that took the total dose into consideration, the size of the daily dose, the length of time over which the radiotherapy was given, and factors known to be connected to the risk of the cancer recurring in the same breast. They discovered that around 0.60 Gy of the daily radiotherapy dose was being squandered during the five-week treatment schedules to compensate for cancer cells growing.

"This suggests that a shorter one-week radiotherapy schedule, replacing the five to seven-week schedules that were more usual in the past, may be more effective against breast cancer recurrence and reduce the chances of side-effects on the surrounding normal tissues. In addition, shorter treatment schedules would be more convenient for patients, with benefits including fewer trips to the hospital, and also highly cost-effective for health services," said Yarnold.

More work on the study in the near future will determine whether reducing the overall treatment time further is as safe and as effective as the current three-week schedule which has been standard practice in the UK since 2009, following publication of the five-year results from the START A and START B trials.

"The UK FAST Forward phase III trial is an example of this research, comparing the current UK standard three-week schedule with two radiotherapy dose levels of a one-week schedule in women with early breast cancer. This trial is well on the way to recruiting 4000 women," Yarnold determined.

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