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

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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."

SABCS: Radiotherapy Can Be Avoided in Some Breast Cancers

Dec 12, 2013 - Some older women with breast cancer who receive hormone treatment after surgical removal of the tumor can avoid radiotherapy, as radiotherapy has no significant effect on recurrence or survival, according to a study presented at the annual San Antonio Breast Cancer Symposium, held from Dec. 10 to 14 in San Antonio.

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