Kate O'Rourke

September 29, 2016

BOSTON — A retrospective study involving 4000 patients with ductal carcinoma in situ (DCIS) has demonstrated that a radiation boost after breast-conserving surgery plus whole-breast radiation therapy (WBRT) provides a clinically relevant reduction in local recurrence of 3.6% at 15 years.

In the absence of a phase 3 trial, it is the strongest evidence to date for providing a boost to patients with this common breast abnormality that often develops into cancer.

"This series represents the largest cohort to address the benefit of a boost in DCIS, with data from 10 institutions in the United States, Canada, and France," said Meena Moran, MD, lead study author and director of the radiation oncology breast program at Smilow Cancer Hospital at Yale, New Haven, Connecticut.

"Our findings suggest that the DCIS boost results in a small, statistically significant benefit in decreasing local relapse across all age groups, in a similar magnitude of what is seen with invasive cancer," Dr Moran told reporters at a press conference at the American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting.

So should all women with DCIS receive the boost?

There is no absolutely clear answer here, but some patients probably should, suggested Rachel Blitzblau, MD, PhD, assistant professor of radiation oncology at Duke Cancer Institute in Durham, North Carolina, who was not involved in the study.

"I think [the study] supports what we have been doing in practice, which is extrapolating from the invasive breast cancer data that boost adds a benefit, particularly for some higher-risk patients," she told Medscape Medical News.

A common clinical practice in the treatment of breast cancers is delivery of a radiation boost directed to the tumor bed. This provides an additional four to eight fractions to allow dose escalation to this region at highest risk for local recurrence. This practice provides a 4% reduction in the risk for ipsilateral breast tumor recurrence (IBTR) by 20 years, at a cost of increased fibrosis in the region of the boost.

The data for DCIS, however, are not very robust. "When we boost in DCIS, which we routinely do, we do it extrapolating the data from invasive cancers," said Dr Moran.

To date, no phase 3 trial has compared boost to no boost in patients with DCIS. Because the prognosis for patients with DCIS is excellent, with very few recurrences after WBRT, to demonstrate similar results specific to DCIS would require a large number of patients with very long follow-up.

For this reason, the new study pooled data from ten academic institutions in the United States, Canada, and France. The investigators created a database of patients with newly diagnosed DCIS who were treated with breast-conserving surgery and WBRT with and without a boost. They then conducted an analysis of the effects of the boost specifically for DCIS. An a priori power calculation determined that roughly 3000 patients would be required to demonstrate a significant difference of 3% between the boost or no boost. The data were uniformly recoded at the host institution and underwent primary and secondary reviews prior to analysis.

The final cohort of patients included 4131 DCIS patients. The median follow-up of patients was 9 years, the median boost dose was 14 Gy, the median age was 56.1 years, and 4% of patients had positive margins.

"If you look at [the data] for 5, 10, and 15 years for the entire cohort, it's as you would expect. The recurrence rates are less than 1% per year," said Dr Moran.

IBTR-free survival was more common in patients who received boost compared with those who did not at 5 years (97.1% vs 96.3%), 10 years (94.1% vs 92.5%), and 15 years (91.6% vs 88.0%) (P = .0389 for all).

In a multivariate analysis that took into account other factors, including grade, comedo, tamoxifen use, margins, and age, the benefit of boost still remained statistically significant (hazard ratio, 0.69; 95% confidence interval [CI], 0.53 - 0.91; P < .010). "Boost is an independent predictor of decreasing local relapse," said Dr Moran.

In patients with negative margins, the boost yielded a statistically significant decrease in the rate of local relapse. This was true irrespective of how negative margins were defined ― as ink on tumor (National Surgical Adjuvant Breast and Bowel Project definition), or by margins <2 mm (ASTRO, ASCO definition).

The boost was beneficial in all age groups studied (<50 years vs >50 years, <60 vs 60, and <70 vs >70), but younger patients benefited more. "The magnitude of benefit was greater in younger patients, which is very similar to what we see in invasive cancers," said Dr Moran. She pointed out that a decrease of 4% at 20 years or 3% at 15 years does not seem like a lot, but it is clinically important for patients.

"What we have learned from the invasive cancer data is that this small incremental decrease results in about a 40% less mastectomy rate for salvage mastectomies for recurrences," said Dr Moran. "Although DCIS is a very complex treatment management course, in any patient who has the anticipated longevity of 10 or 15 years and who is planning to get whole-breast radiation therapy, I think it is very reasonable to offer them a radiation boost."

Duke's Dr Blitzblau applauded the work. "This is an area where retrospective data can be really helpful, and it is so powerful when you can get a retrospective study that has so many people," she said.

She agreed that risk stratification of patients with DCIS is very important, as the DCIS population is very heterogeneous. "For some clinicians, the study will support what they have already been doing in practice, and for some people, it may help them start to change their practice to consider boost for patients they didn't previously boost," said Dr Blitzblau.

There are two ongoing phase 3 randomized trials examining the question of whether a boost reduces recurrence in patients with DCIS. TROG 07.01, an international effort involving multiple collaborative clinical trials groups, includes 1600 patients. It involves a double randomization that examines boost vs no boost and hypofractionation. The second trial, the BONBIS trial from France, is still accruing patients. The goal is to enroll 2000 patients.

Dr Moran said it was unclear whether the trials would be statistically powered to detect a small difference, but she looks forward to the results.

Dr Moran and Dr Blitzblau have disclosed no relevant financial relationships.

2016 American Society for Radiation Oncology (ASTRO) 2016 Annual Meeting. Abstract 324. Presented September 28, 2016.

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