Cost-Effectiveness of Adjuvant Treatment for Ductal Carcinoma In Situ.

PURPOSE: Ductal carcinoma in situ (DCIS) accounts for 20% of breast cancer cases in the United States and is potentially overtreated, leading to high expenditures and low-value care. We conducted a cost-effectiveness analysis evaluating all adjuvant treatment strategies for DCIS. METHODS: A Markov model was created with six competing treatment strategies: observation, tamoxifen (TAM) alone, aromatase inhibitor (AI) alone, radiation treatment (RT) alone, RT + TAM, and RT + AI. Baseline recurrence rates were modeled using the NSABP B17 and RTOG 9804 trials for standard-risk and good-risk DCIS, respectively. Relative risk reductions and adverse event rates for each treatment strategy were derived from meta-analyses of large randomized trials. We used a willingness-to-pay threshold of $100,000 in US dollars/quality-adjusted life-year and a lifetime horizon for two cohorts of women, age 40 and 60 years. Comprehensive sensitivity analyses evaluated the robustness of base-case results. RESULTS: RT alone was cost-effective for patients with standard-risk DCIS, and observation was cost-effective for patients with good-risk DCIS, across both age groups. Strategies including TAM or AI resulted in fewer quality-adjusted life-years than observation, because of the prolonged decrement in quality of life outweighing the modest benefit in ipsilateral risk reduction. In sensitivity analysis, RT alone was cost-effective for age 40, good-risk patients when ipsilateral risk reduction matched that of the RTOG 9804 trial, there was minimal increased risk of contralateral breast secondary malignancy, or there was strong patient willingness to pursue RT. CONCLUSION: Our findings suggest that cost-effective and clinically optimal treatment strategies are RT alone for standard-risk DCIS and observation for good-risk DCIS, with personalization on the basis of patient age and preference for RT. Hormonal therapy is likely suboptimal for most patients with DCIS.

5-Year Update of a Multi-Institution, Prospective Phase 2 Hypofractionated Postmastectomy Radiation Therapy Trial.

PURPOSE: Hypofractionation in the setting of postmastectomy radiation (PMRT) is not currently the standard of care in most countries. Here we present a 5-year update of our multi-institutional, phase 2 prospective trial evaluating a novel 15-day hypofractionated PMRT regimen. METHODS AND MATERIALS: Patients were enrolled to receive 3.33 Gy daily to the chest wall (or reconstructed breast) and regional lymphatics in 11 fractions with an optional 4-fraction mastectomy scar boost. The primary endpoint was freedom from grade 3 or higher late non-reconstruction-related radiation toxicities. Toxicities were scored using Common Terminology Criteria for Adverse Events v4.0. Secondary endpoints included local and locoregional recurrence rates, cosmesis, and reconstruction complications. RESULTS: After enrolling 69 patients with stage II-IIIa breast cancer, 67 women were eligible for analysis. At a median follow up of 54 months, there were no acute or late grade 3 and 4 nonreconstruction reported toxicities. The grade 2 or greater late toxicity rate was only 12% and comprised grade 2 pain, fatigue, and lymphedema that persisted beyond 6 months after completion of radiation therapy. Only 3 women (4.6%) experienced a chest wall or nodal recurrence as a first site of relapse. Freedom from local failure, including local failure after distant relapse, was 92% at 5 years, and the 5-year overall survival was 90%. CONCLUSIONS: This is the first prospective trial conducted in the United States to demonstrate the safe and effective use of hypofractionated PMRT. We have demonstrated a low complication rate while achieving excellent local control. Toxicity was better than anticipated based on previously published series of PMRT toxicities. Although our fractionation was novel, the radiobiological equivalent dose is similar to other hypofractionation schedules. This trial was the basis for the creation of Alliance A221505 (RT CHARM), which is currently accruing patients in a phase 3 randomized design.