Impact of radiation dose on local control, fibrosis and survival after breast conserving treatment: 10 years results of the EORTC trial 22881-10882

Reviewer: John P. Plastaras, MD, PhD
The Abramson Cancer Center of the University of Pennsylvania
Last Modified: December 16, 2006

Presenter: H. Bartelink
Affiliation: The Netherlands Cancer Institute, Amsterdam, Netherlands


  • After lumpectomy and whole breast irradiation, the tumor bed is a major site of recurrence
  • Several trials, including this one, demonstrated that boosting the tumor bed with additional radiation, either by insterstitial brachytherapy or en face electrons, improves local control
  • This EORTC 22881 trial was published in NEJM in 2001. This study investigates the long term impact of a 16 Gy boost in early stage breast cancer


  • 5318 patients with microscopically complete excision of stage I/II breast cancer treated with whole breast radiation, 50 Gy
  • Randomized, phase III, two-arms:
    • 16 Gy boost (n = 2661)
    • No boost (n = 2657)
  • Powered to detect a 5% difference in 10 year overall survival with 90% power
  • 90.5% of boosts were delivered with external radiation, 8.5% were given with interstitial brachytherapy
  • Endpoints:
    • Llocal control survival, fibrosis


  • The data monitoring committee recommended publication based on local control difference at 5 years. Now reporting with 10.8 yr median follow-up.
  • Patients: The arms were well-balanced. The median age was 55 years.18% used tamoxifen. 12% were treated with chemotherapy. 78-79% were T1, 19-20% were T2. 78% were N0. 52% were ER positive.
  • Survival at 10 years was 82% but did not differ between the arms.
  • Local recurrence was less in the boost arm:
    • 10.2% in no boost, 6.2% in the boost arm, p<0.0001)
    • HR 0.59 (0.46-0.76)
  • Age was an important prognostic factor for local recurrence
  • The absolute risk reduction was greatest in younger women:
    • The hazard rate for young and old women was the same (0.59) but absolute rates were affected by age
    • >/= 40 yr: 23.9% to 13.5% (P=0.0014, Gray test)
    • 41-50 yr: 12.5% to 8.7% (P=0.0099)
    • 51-60 yr: 7.8% to 4.9% (P=0.016)
    • >60 yr: 7.3% to 3.8% (P=0.0008)
  • The cumulative incidence of severe fibrosis was greater in the boost group at 10 years:
    • 4.4% vs. 1.6%, p<0.0001
    • A tumor bed boost was associated with higher rates of moderate fibrosis
    • There was no effect of age on incidence of fibrosis

Author's Conclusions

  • A 16 Gy boost after whole breast radiation following lumpectomy significantly decreased local recurrence.
  • The relative reduction is the same for all age groups, but the absolute benefit was greatest in younger women (10% at 40 yr, but only 3% in patients over 50)
  • The boost was associated with a higher incidence of severe fibrosis

Clinical/Scientific Implications

  • A tumor bed boost is effective in reducing local recurrence, but the price is a higher, but still infrequent incidence of fibrosis
  • Despite being powered to detect a 5% difference in survival in this very large trial, there was no difference in overall survival.
  • Like all adjuvant therapies, the decision to use adjuvant radiation with or without a boost should be individualized to the patient's risk of recurrence, expected survival, and tolerance of excess recurrences from "under treatment."