Impact of the boost dose of 10 Gy versus 26 Gy in patients with early stage breast cancer after a microscopically incomplete lumpectomy: 10-year results of the randomised EORTC boost trial.

PURPOSE: To assess the impact of the boost dose in patients with involved surgical margins. PATIENTS AND METHODS: In the EORTC "boost versus no boost" trial, 251 patients with a microscopically incomplete tumour excision were randomised to receive either a low boost dose of 10 Gy (126 patients) or a high boost dose of 26 Gy (125 patients). Overall survival and the cumulative incidence of local recurrence as first event were compared by Logrank and Gray test, respectively (2-sided alpha=0.05), with a median follow-up of 11.3 years. The planned sample size was 660 patients, but only 251 were recruited. RESULTS: The median age at randomisation was 54 years. Thirty-seven patient initially relapsed locally. At 10 years, the cumulative incidence of local recurrence was 17.5% (95% CI: 10.4-24.6%) versus 10.8% (95% CI: 5.2-16.4%) for the low and high boost dose groups, respectively (HR=0.83, 95% CI: 0.43-1.57, Gray p>0.1). Overall, 64 patients have died (25.5%), 47 of them of breast cancer, without a difference in duration of survival between the two groups (HR=0.97, 95% CI=0.59-1.5, p>0.1). Severe fibrosis was palpated in the breast in 1% versus 5% and in the boost area in 3% versus 13% in the low and high boost dose groups, respectively. CONCLUSIONS: There was no statistically significant difference in local control or survival between the high boost dose of 26 Gy and the low boost dose of 10 Gy in patients with microscopically incomplete excision of early breast cancer. Fibrosis, however, was noted significantly more frequently in cases treated with the high boost dose.

Predictors of the risk of fibrosis at 10 years after breast conserving therapy for early breast cancer: a study based on the EORTC Trial 22881-10882 'boost versus no boost'.

The EORTC 22881-10882 trial in 5178 conservatively treated early breast cancer patients showed that a 16 Gy boost dose significantly improved local control, but increased the risk of breast fibrosis. To investigate predictors for the long-term risk of fibrosis, Cox regression models of the time to moderate or severe fibrosis were developed on a random set of 1797 patients with and 1827 patients without a boost, and validated in the remaining set. The median follow-up was 10.7 years. The risk of fibrosis significantly increased (P<0.01) with increasing maximum whole breast irradiation (WBI) dose and with concomitant chemotherapy, but was independent of age. In the boost arm, the risk further increased (P<0.01) if patients had post-operative breast oedema or haematoma, but it decreased (P<0.01) if WBI was given with >6 MV photons. The c-index was around 0.62. Nomograms with these factors are proposed to forecast the long-term risk of moderate or severe fibrosis.

Impact of a higher radiation dose on local control and survival in breast-conserving therapy of early breast cancer: 10-year results of the randomized boost versus no boost EORTC 22881-10882 trial.

PURPOSE: To investigate the long-term impact of a boost radiation dose of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breast-conserving therapy. PATIENTS AND METHODS: A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years. RESULTS: The median age was 55 years. Local recurrence was reported as the first treatment failure in 278 patients with no boost versus 165 patients with boost; at 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the no boost and the boost group, respectively (P < .0001). The hazard ratio of local recurrence was 0.59 (0.46 to 0.76) in favor of the boost, with no statistically significant interaction per age group. The absolute risk reduction at 10 years per age group was the largest in patients

Effect of age and radiation dose on local control after breast conserving treatment: EORTC trial 22881-10882.

PURPOSE: To determine whether the effect of an additional "boost" radiation after breast conservative therapy (BCT) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age. PATIENTS AND METHODS: We used data from EORTC 22881-10882 trial, with median follow-up of 77.4 months. Patients receiving BCT and 50Gy whole breast irradiation were randomized to no boost and 16Gy boost (N=5318). RESULTS: In univariate analysis, a boost reduced local failure by a factor of 2 (P<0.0001). Multivariate analysis showed local control increased with age (P=0.0003). There was no evidence that the relative effect of a boost on local control depends on age (P=0.97) However in younger patients the 5-year local failure was higher, therefore the absolute reduction was greater. If the threshold-age for boost treatment were set at 40 years, 8.4% of the study population would receive a boost, resulting in a 5-year local failure of 6.1% in the study population. Changing the threshold-age to 60 years, 67% of the study population would receive a boost and the 5-year local failure would be reduced to 4.4%. CONCLUSIONS: In younger patients a boost dose resulted in a greater absolute reduction of local failure. The relative risk reduction was however similar for all ages. Applying a treatment policy with a threshold-age of 60 would result in 0.6% increase in local failure in the total study population, while sparing the boost to 1/3 of the patients.

The influence of the boost technique on local control in breast conserving treatment in the EORTC 'boost versus no boost' randomised trial.

BACKGROUND AND PURPOSE: The EORTC Trial 22881/10882 investigating the role of a boost dose in breast conserving therapy demonstrated a significantly better local control rate with the higher radiotherapy dose, especially in women younger than 50 years of age. This paper investigates the potential impact of the different boost techniques on local control and on fibrosis after breast conserving therapy. PATIENTS AND METHODS: From 1989 to 1996, 2661 patients were randomised to receive a boost dose of 16Gy to the primary tumour bed after microscopically complete tumorectomy and 50Gy whole breast irradiation. The choice of the boost technique was left to the treating investigator. Treatment data were prospectively recorded as well as the clinical outcome in terms of local control and fibrosis. Sixty-three percent of the patients received a boost dose with fast electrons, 28% with photon beams and 9% with interstitial brachytherapy. RESULTS: At 5 years, local recurrences were seen in 74 of the 1635 patients who received an electron boost (4.8%, CI 3.6-5.9%), in 28 of the 753 patients who received a photon boost (4.0%, CI 3.4-5.5%) and in 6 of the 225 patients after an interstitial boost (2.5%, CI 0.3-4.6%). The grade of fibrosis in the whole breast as well as at the primary tumour bed, as scored by the treating radiation oncologist, was similar in the three groups. CONCLUSIONS: Although the three groups are of a rather unequal size, the results of the interstitial boost seem similar in terms of fibrosis and at least as good in terms of local control, despite a lower treatment volume and a longer overall treatment time.