Journal of clinical oncology : official journal of the American Society of Clinical Oncology 2015-03-01
RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation.
Abstract
Purpose
The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.
Patients and methods
This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method.
Results
Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.
Conclusion
In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.
Related Questions
How would you approach reirradiation in a patient with a history of whole-breast RT many years ago, now with a small intermediate-grade DCIS s/p lumpectomy with an elevated DCISionRT?
I would favor PBI with 40 in 15 or 45 in 30 (BID) with VMAT/IMRT.
How does the potential for a patient to accept or forego adjuvant tamoxifen factor into your recommendations on adjuvant RT for DCIS?
In the RTOG 9804 trial, the only factors predicting for local control in the breast were the use of radiation and of tamoxifen. So for women who have hormone positive tumors, I strongly advocate for some treatment in addition to the lumpectomy.I find the results of the UK, Australia, and New Zealand...
How do you approach the decision to boost patients diagnosed with DCIS?
Based on prospective and also retrospective data Chua, AACR Volume 81, Issue 4 Supplement, pp. GS2-04. We would recommend for high grade, < 50 years and close margin and in the era of genomic testing to patients with high genomic score.
What resection margins are required for DCIS with a component of invasive disease?
The SSO-ASTRO-ASCO guidelines of 2016 on margin status for patients with tumors that are pure DCIS or predominantly DCIS requiring a minimum of 2 mm for those receiving RT were based on a meta-analysis of (mostly older) published studies, not individual patient data. Three much more recent studies f...
Do you offer ultra-hypofractionated 5-fraction RT regimens for DCIS s/p lumpectomy?
The premise of this question attempts to "split" DCIS from early-stage invasive disease. When we live in an eternal present-tense, we naturally repeat the mistakes of the past. Again, as for modest hypofractionation, we are not going to see a "separate" clinical trial for pure DCIS in this space. In...
How are you using predictive tests such as DCISionRT (PreludeDx) or OncotypeDX DCIS in the management of DCIS?
Advantages: It's a relatively cheap, simple assay to better individualize risk of DCIS. Not only prognostic like Oncotype DCIS but also predictive of the absolute benefit of radiation. Supposed to be a better risk assessment tool than traditional clinical pathologic factors. Can identify those who ...
Would you offer radiation to an elderly patient with DCIS who would otherwise not meet criteria for RTOG 9804?
I counsel elderly patients with DCIS about the risks and benefits of receiving radiation therapy. I offer radiation in patients with excellent performance status who are uncomfortable with the 1-2%/year recurrence risk with omission of radiation (extrapolating from RTOG 9804 as well as ECOG (Solin e...
Do you recommend omitting radiation therapy in young women with favorable DCIS?
If someone can get a screening mammogram, diagnostic mammogram, image-guided biopsy, segmental mastectomy, entertain a conversation about 5 years of ET, they can most certainly handle 5-15 days of PBI where the grade 0 toxicity rate is exceedingly high. Whole breast RT with the Whelan regimen is als...
What is the best management of early stage breast cancer in patients with a minimal life expectancy (<10yrs)?
I believe in individualized, whole patient care. Life expectancy is incredibly difficult to estimate, but if we are somehow certain a patient will live less than 10 years, then quality (rather than quantity) of life likely becomes the primary concern of a patient with early stage breast cancer. We d...
In which patients do you omit a boost following whole breast irradiation?
In a woman over 60 with a T1 or T2, low to intermediate grade tumor resected with clean margins (preferably greater than or equal to 2 mm), I think it is very reasonable to omit a boost. I tend to take these on a case by case basis. If I can deliver a boost with a small field (for example 8 cm or le...
Which patients with DCIS can be observed following lumpectomy?
Based on ECOG and RTOG data, patients with small volume (less than 1 cm), grade 1 and 2 DCIS with no necrosis, and a good margin of excision (3mm or more) or those with definitive excision showing no disease have a smaller benefit with RT. After discussing the pros and cons and respecting the patien...