Adjuvant Radiation Therapy in Ductal Carcinoma In Situ Treated with Breast Conservation Therapy

The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 phase III randomized clinical trial and three other prospective randomized clinical trials and their follow-up studies:
- Have demonstrated and continue to show the benefit of radiation therapy (RT) following breast-conserving surgery for patients with DCIS:
  - With a significant 50% reduction in IBTR
In a report by Wapnir et al. on long-term outcomes of the NSABP B-17 and B-24 trials:
- Patients who only received lumpectomy:
  - Had a local recurrence rate of 19.4% compared with 8.9% in the lumpectomy plus RT group at 15 years of follow-up:
    - Demonstrating a 52% reduction in the risk of IBTR
Similarly, European Organisation for Research and Treatment of Cancer (EORTC) 10853:
- Showed a risk reduction of 48% with the addition of radiotherapy to locally excised DCIS
The Radiation Therapy Oncology Group (RTOG) 9804 trial:
Evaluated the impact of RT after breast-conserving therapy (BCT) in patients with mammographically detected low-risk DCIS:
- As defined by size less than 2.5 cm, unicentricity, low- and intermediate-grade, and margins > 3 mm
The primary endpoint of ipsilateral local failure was:
- 0.9% in the RT arm versus 6.7% in the observation arm
The E5194 trial:
- Included a similar patient population of 665 patients placed into two cohorts:
  - Low- and intermediate-grade DCIS with a tumor size less than 2.5 cm or
  - High-grade DCIS with a tumor size < 1 cm
- All patients were treated with BCT yielding > 3 mm margins without RT with a median follow-up of 12.3 years
- These results demonstrated tumor size and cohort to be significant predictors of developing an ipsilateral breast event:
  - 14.4% for the low-risk cohort versus 24.6% for the high-risk cohort
  - This risk continued to increase without plateau through the follow-up period:
    - Necessitating further follow-up to determine long-term outcomes
Differences in the IBTR rates between these studies may be due to the effect of tamoxifen use:
- Which was not controlled in either trial and which is known to reduce the risk of IBTR in combination with RT after BCT as shown by the NSABP B-24 trial
Together, the results of both RTOG 9804 and E5194 support the individualized treatment of DCIS:
- Based on identification of patients at low risk for IBTR determined by pathologic and clinical features that may omit RT
A 12-year follow-up study of RTOG 9804:
- Demonstrated that the 12-year cumulative incidence of local recurrence (LR) was:
  - 2.8% with RT and 11.4% with observation alone:
    - The 12-year cumulative incidence of invasive LR was:
  - 1.5% with RT and 5.8% with observation alone
References
Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103(6):478-488.
EORTC Breast Cancer Cooperative Group; and EORTC Radiotherapy Group; Bijker N, Meijnen P, Peterse JL, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853—a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24(21):3381-3387.
McCormick B, Winter K, Hudis C, Kuerer HM, Rakovitch E, Smith BL, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33(7):709-715.
Solin LJ, Gray R, Hughes L, Wood WC, Lowen MA, Badve SS, et al. Surgical excision without radiation for ductal carcinoma in situ of the breast: 12-year results from the ECOG-ACRIN E5194 Study. J Clin Oncol. 2015;33(33):3938-3944.
McCormick B. Randomized trial evaluating radiation following surgical excision for “good risk” DCIS: 12-year report from NRG/RTOG 9804. Int J Radiat Oncol Biol Phys.2018;102(5):1603.