The Effect of Treatment Advances on the Mortality Results of Breast Cancer Screening Trials: A Microsimulation Model.

BACKGROUND: Mammography trials, which are the primary sources of evidence for screening benefit, were conducted decades ago. Whether advances in systemic therapies have rendered previously observed benefits of screening less significant is unknown. OBJECTIVE: To compare the outcomes of breast cancer screening trials had they been conducted using contemporary systemic treatments with outcomes of trials conducted with previously used treatments. DESIGN: Computer simulation model of 3 virtual screening trials with similar reductions in advanced-stage cancer cases but reflecting treatment patterns in 1975 (prechemotherapy era), 1999, or 2015 (treatment according to receptor status). DATA SOURCES: Meta-analyses of screening and treatment trials; study of dissemination of primary systemic treatments; SEER (Surveillance, Epidemiology, and End Results) registry. TARGET POPULATION: U.S. women aged 50 to 74 years. TIME HORIZON: 10 and 25 years. PERSPECTIVE: Population. INTERVENTION: Mammography, chemotherapy, tamoxifen, aromatase inhibitors, and trastuzumab. OUTCOME MEASURES: Breast cancer mortality rate ratio (MRR) and absolute risk reduction (ARR) obtained by the difference in cumulative breast cancer mortality between control and screening groups. RESULTS OF BASE-CASE ANALYSIS: At 10 years, screening in a 1975 trial yielded an MRR of 90% and an ARR of 5 deaths per 10,000 women. A 2015 screening trial yielded a 10-year MRR of 90% and an ARR of 3 deaths per 10,000 women. RESULTS OF SENSITIVITY ANALYSIS: Greater reductions in advanced-stage disease yielded a greater screening effect, but MRRs remained similar across trials. However, ARRs were consistently lower under contemporary treatments. When contemporary treatments were available only for early-stage cases, the MRR was 88%. LIMITATION: Disease models simplify reality and cannot capture all breast cancer subtypes. CONCLUSION: Advances in systemic therapies for breast cancer have not substantively reduced the relative benefits of screening but have likely reduced the absolute benefits because of their positive effect on breast cancer survival. PRIMARY FUNDING SOURCE: University of Washington and National Cancer Institute.

Single-fraction radiation therapy in patients with metastatic Merkel cell carcinoma.

Merkel cell carcinoma (MCC) is an aggressive, polyomavirus-associated cancer with limited therapeutic options for metastatic disease. Cytotoxic chemotherapy is associated with high response rates, but responses are seldom durable and toxicity is considerable. Here, we report our experience with palliative single-fraction radiotherapy (SFRT) in patients with metastatic MCC. We conducted retrospective analyses of safety and efficacy outcomes in patients that received SFRT (8 Gy) to MCC metastases between 2010 and 2013. Twenty-six patients were treated with SFRT to 93 MCC tumors located in diverse sites that included skin, lymph nodes, and visceral organs. Objective responses were observed in 94% of the measurable irradiated tumors (86/92). Complete responses were observed in 45% of tumors (including bulky tumors up to 16 cm). "In field" lesion control was durable with no progression in 77% (69/89) of treated tumors during median follow-up of 277 days among 16 living patients. Clinically significant toxicity was seen in only two patients who had transient side effects. An exploratory analysis suggested a higher rate of in-field progression in patients with an immunosuppressive comorbidity or prior recent chemotherapy versus those without (30% and 9%, respectively; P = 0.03). Use of SFRT in palliating MCC patients was associated with an excellent in field control rate and durable responses at treated sites, and with minimal toxicity. SFRT may represent a convenient and appealing alternative to systemic chemotherapy for palliation, for which most patients with oligometastatic MCC are eligible. SFRT may also synergize with emerging systemic immune stimulants by lowering tumor burden and enhancing presentation of viral/tumor antigens.