The Lynx Group

Hypofractionation Validated for Breast Radiotherapy: Less Potential for Toxicity Shown

March 2013, Highlights

Ten-year disease control in patients with nonmetastatic breast cancer did not differ significantly between patients treated with a reduced-dose hypofractionated radiation therapy compared with a standard protocol, according to a study presented at the meeting.

The 10-year locoregional recurrence rate was 4.3% in patients who received a 40-Gy radiation dose in 15 fractions and 5.5% in patients randomized to 50 Gy in 25 fractions.

Delivering a lower radiation dose in fewer fractions led to a significant reduction in the rate of adverse effects (AEs) to normal tissue, resulting in an absolute difference of 8.1% at 10 years, said John R. Yarnold, BSc, MBBS, MRCP, FRCR, Professor of Clinical Oncology, the Royal Marsden in London, and a senior investigator at the UK National Institute for Health Research.

“Patients can be safely and effectively treated to a lower total dose with fewer fractions than the historical standard of 50 Gy in 25 fractions,” said Dr Yarnold. “No detrimental effects of hypofractionation were identified in the subgroups studied.”

“These results support 40 Gy in 15 fractions as the United Kingdom standard for all patients with invasive breast cancer,” he maintained.

A companion trial that randomized patients to 3 radiation protocols showed an absolute difference of 4.1% in moderate or marked AEs at 10 years with a 39-Gy radiation dose administered in 13 fractions versus 50 Gy in 25 fractions. However, women receiving the lower dose had a 1% decrement in relapse-free survival compared with the standard-protocol group.

These findings came from the Standardisation of Breast Radiother­apy (START) clinical trial program, comprising a pilot study and 2 randomized trials involving patients with early (T1-T3) breast cancer. Started in 1999, the START A and B trials involved more than 4000 patients who were enrolled at 35 centers throughout the United Kingdom.

Both trials examined the relative safety and efficacy of hypofractionation versus the 50-Gy/25-fraction standard protocol for breast radiotherapy. Investigators hypothesized that a lower total dose of radiation delivered in fewer but larger fractions would reduce toxicity with no loss of disease control compared with the standard protocol. START B also evaluated the effects of administering the lower-dose protocol over a shorter time period.

After complete excision, patients in START A were randomized to 3 radiotherapy protocols: 50 Gy in 25 fractions over 5 weeks, 41.6 Gy in 13 fractions over 5 weeks, and 39 Gy in 13 fractions over 5 weeks. START B patients were randomized to radiation doses of 50 Gy in 25 fractions over 5 weeks or to 40 Gy in 13 fractions over 3 weeks.

The primary end point of both trials was locoregional recurrence; how­ever, investigators in START A also examined the relative sensitivity of normal and malignant tissue to radiation fraction size.

The START A results confirmed that the rates of recurrence at 5 years did not differ significantly by radiotherapy protocol, and also that breast cancer and normal breast tissue have similar sensitivity to radiation fraction.

Dr Yarnold reported data from a median follow-up of 9.3 years in START A and 9.9 years in START B. The 10-year relapse rates in START A were 7.4% with 50 Gy, 6.3% with 41.6 Gy, and 8.8% with 39 Gy. Although still not significantly different, the results showed a trend toward a higher recurrence rate with the 39-Gy protocol.

The 10-year START B data showed a 23% reduction in the relative risk of relapse with the 40-Gy protocol. In addition, the lower dose was associated with fewer AEs for normal tissue, including lower rates of the individual effects that were evaluated, such as breast shrinkage, induration, and edema.

“These results are consistent with the hypothesis that small fractions are as gentle on breast tissue as on healthy tissues,” explained Dr Yarnold.

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