Extra RT Boost in Breast Cancer Has Benefits, But Not on Survival

Kate Johnson

April 14, 2014

VIENNA, Austria — A 20-year follow-up of patients with early-stage breast cancer shows that boosting them with an extra radiotherapy dose to the tumor bed after breast-conserving surgery significantly decreases the rate of local disease recurrence and the need for salvage mastectomy but has no effect on overall survival.

Results of the so-called EORTC 22881-10882 trial show that "no extra complications or second malignancies are caused by the higher radiation dose. On the other hand, we can reduce the need for mastectomies by 35%," lead investigator Harry Bartelink, MD, from The Netherlands Cancer Institute in Amsterdam, told Medscape Medical News.

However, compared with patients who did not receive the radiotherapy boost, those who did had almost triple the rate of severe fibrosis at 10, 15, and 20 years after treatment, the study showed.

Dr. Bartelink presented the results here at European Society for Radiotherapy and Oncology (ESTRO) 33 annual conference here.

"A major surprise for me was the fact that 20 years later, 60% of the patients are still alive. It is impressive to see that from such a large trial with more than 5000 patients we still have the follow-up and know in detail what happens to these patients, including recurrences and second malignancies," he said in an interview.

The trial enrolled patients with early stage I and II breast cancer following complete excision with breast-conserving surgery and whole-breast irradiation (50 Gy).

The patients (median age, 55 years) were randomly assigned to receive a radiotherapy boost of 16 Gy (n = 2643) or no boost (n = 2637).

Previous results from the study at a median of 10.8 years of follow-up (J Clin Oncol. 2007;25:3259-3265) showed a local recurrence rate in favor of the boost group (6.2% vs 10.2%; hazard ratio [HR], 0.59; P < .0001), with the largest absolute risk reduction in younger patients (40 years or younger), but no difference between treatment arms in terms of overall survival.

The latest results show the same trend: The new data presented at the meeting come from a median follow-up of 17.2 years, with 237 patients in the radiation boost group and 354 patients in the no boost group.

Recurrence rates remain in favor of boost radiotherapy at 5, 10, and 20 years after treatment (HR, 0.65; P < .001), with cumulative incidence of local failure of 6.4%, 8.8%, and 12.0%, respectively, in boosted patients compared with 10.2%, 13.1%, and 16.4% in the nonboost group.

Similar to the earlier findings, younger patients (up to 40 years) had the most benefit from the boost in terms of local recurrence (HR, 0.56; P .003), but the beneficial effects were also seen in the other age groups (41 to 50 years: HR, 0.66 [P = .007]; 51 to 60 years: HR, 0.69 [P = .020]; and 60 years or older: HR, 0.66 [P = .019], respectively).

However, at 20 years the boost and nonboost groups did not differ for rate of overall survival (61.1% in the nonboost group vs 59.7% in the boost group; HR, 1.05; P = .323). This was seen regardless of age, Dr. Bartelnik said. "Even in the youngest age group there is absolutely no difference in overall survival, despite boost having a significant impact on local control in this group."

About half of all patients with recurrences had them in the primary tumor bed (45.5% in the nonboost group and 41.8% in the boost group) or the scar (8.2% and 7.6%), with the other recurrences elsewhere in the breast, noted Dr. Bartelink. If the recurrence location was diffuse rather than in the tumor bed, survival was significantly worse (HR, 2.7; P = .0002), and if time to failure was short (less than 1.5 years), survival was also significantly worse (P < .001).

In addition, multivariate analysis showed poorer survival after local failure if patients were menopausal (HR, 1.36; P = .0972), had larger tumors (HR, 1.8; P = .0017), or had been treated previously with tamoxifen (HR, 2.2; P = .0002).

Patients with progesterone receptor–positive disease had better survival (HR, 0.54; P = .0126).

Most patients who had salvage treatment for their first local failure had mastectomy (73.4%); 8.4% underwent tumorectomy, 5.5% none, and 12.7% "other." Overall, however, the need for salvage mastectomy was 35% lower in the boost group than in the nonboost group. At 10, 15, and 20 years, the rates of salvage mastectomy were 6.4%, 9.0%, and 11.8%, respectively, in the nonboost group compared with 10.3%, 13.5%, and 16.9% in the boost group (HR, 0.65; P < .001).

The nonboost and boost groups did not differ for distant metastasis (21.4% vs 22.5%), second primary contralateral or homolateral breast cancer (7.8% vs 8.7% and 1.1% vs 0.8%, respectively) or second primary nonbreast cancer (8.4% vs 9.1%), including second primary lung cancer (11.6% vs 14.2%), said Dr. Bartelink.

And causes of death were similar in nonboost and boost patients for breast cancer (16.8% vs 17.1%), second cancer (3.3% vs 3.5%), and cardiovascular disease (2.4% vs 2.6%).

"In this large study with more than 5000 patients which was aimed to show that local control has an impact on survival, there is absolutely no difference at all in survival," he concluded.

However, the rate of severe fibrosis was significantly higher in patients who received a boost (HR, 2.78; P < .0001). At 10, 15, and 20 years the rates were 4.3%, 4.8%, and 5.2%, respectively, in the boost group compared with 1.6%, 1.7%, and 1.8% in the nonboost group. "Fortunately the increase in fibrosis was less in young patients, while in this group the absolute  increase in local control was the largest," he told Medscape Medical News.

Approached by Medscape Medical News to comment on the findings, Céline Bourgier, MD, PhD, said "now, we are waiting for results of the "Young Boost Trial," to see the benefit of an additional 10 Gy boost specifically in young patients as well as the risk of severe fibrosis development."

Dr. Bourgier, from the Institut Gustave Roussy, Villejuif, France, wrote a commentary after the publication of the trial's 10-year results in which she pointed out that adverse events, such as severe fibrosis, are likely to have more impact on young patients.

"One of the challenges of modern radiation oncology is to develop treatments able to mitigate or reverse undesirable side-effects," she wrote. "Improved treatment modalities will require a careful evaluation of quality of life, especially for younger patients with a potential longer follow-up time."

Dr. Bartelink and Dr. Bourgier have disclosed no relevant financial relationships.

European Society for Radiotherapy and Oncology (ESTRO) 33. Abstract OC-0488. Presented April 7, 2014.

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