Synchronous Radiotherapy With Chemotherapy Improves Local Control in Early Breast Cancer Patients

Stockholm, Sweden—Radiotherapy can be given between or during chemotherapy cycles, rather than sequentially (ie, after or before chemotherapy), for women with early breast cancer, according to a large study from the United Kingdom presented at the 2011 European Multidisciplinary Cancer Congress.

In fact, patients who received “synchronous” radiotherapy and chemotherapy had a reduced risk of local recurrence, though no improvement in survival, reported Indrajit Fernando, MD, of University Hospitals Birmingham NHS Foundation Trust.

“With this approach, patients are also able to avoid the delay of radiotherapy, to potentially shorten the treatment time, which is very important to them,” Fernando said.

The randomized phase III SECRAB trial enrolled 2296 women who underwent breast-conserving surgery or mastectomy. All received chemoradiation after surgery, either sequential (n = 1146) or synchronous (n = 1150). With the synchronous approach, radiotherapy was given in the time interval between chemotherapy cycles, either sandwiched between cycles (when 3 weeks of radiotherapy was prescribed) or given concomitantly (when >3 weeks of radiotherapy was prescribed). The women were followed for a median time of 8.8 years.

The chemotherapy regimens were CMF (cyclophosphamide/methotrexate/fluorouracil) or anthracycline─CMF. CMF was chosen because it is considered the most acceptable regimen for combining with radiotherapy, Fernando explained.

A number of radiotherapy schedules were considered suitable; more than 60% of patients received 40 Gy in 15 fractions over 3 weeks. The 5-year local recurrence rate was significantly improved with the synchronous approach: 2.8% versus 5.1% with sequential chemoradiation, which was a 35% reduction in risk (P = .03), Fernando reported.

He noted the importance of this seemingly small but statistically significant difference. “According to the Early Breast Cancer Trialists’ Collaborative Group, one breast cancer death can be avoided for every four local recurrences prevented. Therefore, even a 2.3% reduction in local recurrence rates will have an impact worldwide when we consider that this is a very common cancer.”

There was no difference, however, in locoregional recurrence rates, which were 6.8% with the synchronous approach and 8.2% with the sequential approach, a nonsignificant 17% reduction in risk. Closer examination of this outcome showed that most of these recurrences were observed in tissue outside the radiation field. The in-field locoregional recurrence rate was 2.9% with the synchronous approach and 5.3% with the sequential approach, for a significant 35% reduction in risk (P = .028), he reported.

There was a “modest” increase in acute skin toxicity in patients in the synchronous arm, 24% versus 15% (P < .001), he noted, and borderline significant difference in moderate to severe telangiectasia, 2.5% versus 1.3% (P = .05). There were no differences in other late effects of radiotherapy. There were no differences in global quality of life.

Fernando suggested that with more modern radiotherapy techniques, the incidence of acute toxicity would be much lower.

Lori J. Pierce, MD, of the University of Michigan Comprehensive Cancer Center, Ann Arbor, commented that at the present time the results of the SECRAB trial show no improvement in disease-free survival or overall survival with the synchronous approach, but the absolute benefit in local control might spark conversation between clinicians and their patients.

“Are the results practice-changing? Perhaps,” Pierce commented. “With longer follow-up, if survival gains are observed, absolutely. If subgroups are identified who derive a greater absolute local benefit, it’s very likely.”