Hypofractionated Breast Radiotherapy Appears Effective

Allison Gandey

June 21, 2007

June 21, 2007 (Chicago) — The largest study to date to explore hypofractionation in breast radiotherapy has found that fewer, larger doses are as effective as conventional schedules in reducing the risk for recurrence. The results were presented here at the American Society of Clinical Oncology 43rd Annual Meeting. "We're seeing more evidence that giving fewer, larger fractions to a lower total dose is as safe and effective as giving 50-Gy fractions over 5 weeks," lead investigator John Dewar, MD, from the University of Dundee, in Scotland, told Medscape.


During a press briefing outlining the findings, moderator Julie Gralow, MD, from the University of Washington, in Seattle, told reporters that the results are promising and the dosing schedule makes sense. "At my center in Seattle, we have patients who come from Alaska for treatment and have to stay in the city. Those patients are the first that I would consider converting to a 3-week cycle," she said.

One United Kingdom–based physician attending the meeting congratulated the investigators after the presentation on "a superb trial and a good result." But despite new evidence, many clinicians have been reluctant to change radiotherapy schedules. Lawrence Solin, MD, from the University of Pennsylvania, in Philadelphia, told those attending the meeting that there are a number of reasons accelerated breast radiation has not become more popular — particularly in the United States. "High-quality long-term results are all with standard fractionation," he said, and there are few published randomized trials of hypofractionation.

"Clinicians are most familiar with standard schedules, and there has also been concern about the risk of late complications with large daily fractions," Dr. Solin explained during a discussion period following the presentation. "For most patients, time is not a major problem, and access to radiation is also not generally an issue." He pointed out that radiation complications could occur years or even decades after treatment, and so caution is advised in selecting treatment options. But, Dr. Solin noted, reported well-designed randomized trials such as this of whole-breast accelerated radiation provide an alternative to standard fractionation for selected patients.

Reluctance to Embrace Accelerated Radiation

During an interview with Medscape, Dr. Dewar agreed that there has been reluctance in the medical community to adopt hypofractionated radiotherapy. "Historical data have shown that if you give larger fractions without reducing the dose, you have higher morbidity, and that has understandably made people cautious," he said. "We used a lower dose and showed equivalent morbidity."

"There have been other studies, such as the Ontario study," Dr. Dewar added, "but that was smaller than ours, and I think clinicians understandably don't want to risk disadvantaging their patients and have been waiting for larger studies. This is another substantial block of evidence that I think will reassure physicians that this is now a potentially safe and effective way to go."

The Standardization of Breast Radiotherapy (START) trial is a multicenter United Kingdom–based phase 3 randomized controlled study of radiotherapy after surgery. The aim of the trial was to test the benefits of fraction sizes less than 2.0 Gy in terms of locoregional tumor control, late normal tissue responses, quality of life, and cost-effectiveness in patients with earlybreast cancer.

Divided into 2 studies, the START trial A looked at 2236 women who had completely excised invasive breast cancer. They were randomly assigned to receive either 50 Gy of radiation delivered in 25 fractions over 5 weeks or 41.6 Gy or 39 Gy delivered in 13 fractions on alternate days over 5 weeks. Patients were followed for a median of 5.1 years.

In trial B, 2215 women received either 50 Gy in 25 fractions over 5 weeks or 40 Gy delivered in 15 fractions over 3 weeks. Patients were followed for a median of 6 years.

Trial A: Locoregional Tumor Relapse
Gy
Hazard Ratios (95% CI)
Absolute Difference at 5 years, % (95% CI)
41.6 vs 50
1.05 (0.63 – 1.75)
+0.2 (-1.3 to 2.6)
39 vs 50
1.26 (0.77 – 2.08)
+ 0.9 (-0.8 to 3.7)

Trial B: Locoregional Tumor Relapse
Gy
Hazard Ratios (95% CI)
Absolute Difference at 5 years, % (95% CI)
40 vs 50
0.79 (0.48 – 1.29)
-0.6 (-1.7 to 0.9)

Severe Adverse Events
Outcome
TrialA, n (%)
Trial B, n (%)
Severe acute reactions
3 (0.1)
16 (0.7)
Brachial plexopathy
1

Symptomatic rib fracture
29 (1.3)
34 (1.5)
Symptomatic lung fibrosis
18 (0.8)
31 (1.4)
Ischemic heart disease
45 (2.0)
46 (2.1)

During his presentation, Dr. Dewar said these results support the hypothesis that breast cancer is as sensitive to fraction size as critical late-reacting normal tissues. And it is likely that patients can be safely and effectively treated to a lower total dose with fewer fractions.

The method is already being used in a number of UK centers, and Dr. Dewar reported that guideline development groups are working to establish new standards. While he acknowledged that additional trials are needed to test the limits of hypofractionation, he predicted that this represents the way of radiation therapy moving forward.

American Society of Clinical Oncology 43rd Annual Meeting: Late-breaking abstract 518. Presented June 4, 2007.

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