START Spreading the News About Hypofractionated RT to Breast

Neil Osterweil

December 06, 2012

SAN ANTONIO, Texas — Radiation to the breast at a dose of 40 Gy delivered over 3 weeks is as effective as a dose of 50 Gy delivered over 5 weeks, according to a new study.

In addition to being more convenient for patients, the hypofractionated regimen of 40 Gy delivered in 15 fractions was associated with fewer adverse events over 10 years than the regimen of 50 Gy delivered in 25 fractions, which is the standard in the United States and elsewhere in the world, said John Yarnold, MD, professor of clinical oncology at the Institute of Cancer Research in London, United Kingdom.

He presented data from the START (Standardization of Breast Radiotherapy) A and B trials here at the 35th Annual San Antonio Breast Cancer Symposium.

The shorter regimen was not inferior in efficacy, he emphasized.

"We can say that breast cancer and the dose-limiting normal tissues respond similarly to fraction size, that there is no continuing the practice of 2 Gy fractions over 5 to 6 and a half weeks, and that the 15-fraction regimen over just 3 weeks is gentler on normal tissue and noninferior in terms of locoregional control of the cancer at 10 years, Dr. Yarnold said at a press briefing. "This schedule has been the standard of care in the United Kingdom since 2009 for all patients with invasive breast cancer," he explained.

A German clinician suggested that the trial results would not immediately change practice there. "Our standard is still 50 Gy, with 1.8 Gy per session over 5 to 6 weeks," said Sibylle Loibl, MD, associate professor at the University of Frankfurt in Germany, when she was asked about START by Medscape Medical News.

Dr. Loibl, who was not involved in the study, noted that 50 Gy in 25 to 30 fractions is standard treatment for patients undergoing breast-conserving procedures and for those who have undergone mastectomy but have residual locally invasive disease.

German oncologists will hold their annual guidelines meeting in January, but "I doubt very much that these data will make a difference," she said.

Two Trials, 1 Result

START A enrolled 2236 patients from 35 centers in the United Kingdom with T1 to 3, N0 to 1 breast cancer with no distant metastases. They were randomly assigned to receive 50 Gy in 25 fractions of 2 Gy delivered over 5 weeks, 39 Gy in 13 fractions of 3 Gy delivered over 5 weeks, or 41.6 Gy in 13 fractions of 3.2 Gy delivered over 5 weeks.

In START B, 2215 women were randomly assigned to 50 Gy in 25 fractions of 2 Gy delivered over 5 weeks or 40 Gy in 15 fractions of 2.67 Gy delivered over 3 weeks.

In START A, over a median follow-up of 9.3 years, the adverse-event profile of the 41.6 Gy regimen was similar to that of the 50 Gy regimen (hazard ratio [HR], 0.94, 95% confidence interval [CI, 0.79 - 1.11). The rates of locoregional tumor relapse for the 2 regimens were also comparable (HR, 0.91; CI, 0.59 - 1.38).

However, the 39 Gy dose was associated with fewer adverse events than the 50 Gy dose (HR, 0.80; 95% CI, 0.67 - 0.96); there were more relapses numerically, but not significantly (HR, 1.18; 95% CI, 0.79 - 1.76).

In START B, over a median follow-up of 9.9 years, the 40 Gy regimen was associated with significantly fewer adverse events than the 50 Gy regimen (HR, 0.77; 95% CI, 0.66 - 0.89). The efficacy of the 2 regimens was comparable, with a nonsignificant trend toward modest superiority for the 40 Gy regimen (HR, 0.77; 95% CI, 0.51 - 1.16), Dr. Yarnold said.

The study was supported by Cancer Research UK, the Medical Research Council, and the National Cancer Research Institute. Dr. Yarnold and Dr. Loibl have disclosed no relevant financial relationships.

35th Annual San Antonio Breast Cancer Symposium (SABCS): Abstract S4-1. Presented December 6, 2012.