Background Current clinical guidelines recommend earlier, more intensive breast cancer screening with both MRI and mammography for women with BRCA mutations. Unspecified details of screening schedules are a challenge for implementing guidelines. Methods A Markov Monte Carlo computer model simulated screening in asymptomatic female BRCA1 and BRCA2 mutation carriers. Three dual-modality strategies were compared with digital mammography (DM) alone: 1) DM and MRI alternating at 6-month intervals beginning at age 25 [Alt25], 2) annual MRI beginning at age 25 with alternating DM added at age 30 [MRI25/Alt30], and 3) DM and MRI alternating at 6-month intervals beginning at age 30 [Alt30]. Primary outcomes were quality-adjusted life years (QALYs), lifetime costs (in 2010 USD), and incremental cost-effectiveness ($/QALY gained). Additional outcomes included potential harms of screening, and lifetime costs stratified into component categories (screening and diagnosis, treatment, mortality, and patient time costs). Results All three dual-modality screening strategies increased QALYs and costs. Alt30 screening had the lowest incremental costs per additional QALY gained: (BRCA1: $74,200/QALY; BRCA2: $215,700/QALY). False-positive test results increased substantially with dual-modality screening, occurring more frequently in BRCA2 carriers. Downstream savings in both breast cancer treatment and mortality costs were outweighed by increases in up-front screening and diagnosis costs. Results were most influenced by estimates of breast cancer risk and MRI cost. Conclusions Alternating MRI and DM screening at 6-month intervals beginning at age 30 is a clinically effective approach to applying current guidelines, and is more cost-effective in BRCA1 compared with BRCA2 gene mutation carriers.
Background While breast cancer screening with mammography and MRI is recommended for BRCA mutation carriers, there is no current consensus on the optimal screening regimen. Methods We used a computer simulation model to compare six annual screening strategies [film mammography (FM), digital mammography (DM), FM and magnetic resonance imaging (MRI) or DM and MRI contemporaneously, and alternating FM/MRI or DM/MRI at six-month intervals] beginning at ages 25, 30, 35, and 40, and two strategies of annual MRI with delayed alternating DM/FM to clinical surveillance alone. Strategies were evaluated without and with mammography-induced breast cancer risk, using two models of excess relative risk. Input parameters were obtained from the medical literature, publicly available databases, and calibration. Results Without radiation risk effects, alternating DM/MRI starting at age 25 provided the highest life expectancy (BRCA1: 72.52 years, BRCA2: 77.63 years). When radiation risk was included, a small proportion of diagnosed cancers were attributable to radiation exposure (BRCA1: <2%, BRCA2: <4%). With radiation risk, alternating DM/MRI at age 25 or annual MRI at age 25/delayed alternating DM at age 30 were most effective, depending on the radiation risk model used. Alternating DM/MRI starting at age 25 also had the highest number of false-positive screens/person (BRCA1: 4.5, BRCA2: 8.1). Conclusions Annual MRI at 25/delayed alternating DM at age 30 is likely the most effective screening strategy in BRCA mutation carriers. Screening benefits, associated risks and personal acceptance of false-positive results, should be considered in choosing the optimal screening strategy for individual women.
Background Pulmonary nodules (PN) are often incidentally detected during coronary CT angiography (CCTA) which is increasingly used to evaluate patients with chest pain symptoms. However, the efficiency of following up on incidentally detected PN is unknown. Methods and Results We determined demographic and clinical characteristics of stable symptomatic patients referred for CCTA in whom incidentally detected PN warranted follow-up. A validated lung cancer simulation model was populated with data from these patients and clinical and economic consequences of follow-up per Fleischner guidelines versus no follow-up were simulated. Of the 3,665 patients referred to CCTA, 591 (16%) had PN requiring follow-up. Mean age of patients with PN was 59±10 years, 66% were male, 67% had ever smoked, and 21% had obstructive CAD. The projected overall lung cancer incidence was 5.8% in these patients, but the majority died from CAD (38%) and other causes (57%). Follow-up of PN was associated with a 4.6% relative reduction in cumulative lung cancer mortality (absolute mortality:FU: 4.33% vs. non-FU: 4.54%), more downstream testing (FU: 2.34 CTs/patient vs. non-FU: 1.01 CTs/patient), and an average increase of quality-adjusted life of seven days. Costs per quality adjusted life year (QALY) gained were $154,700 to follow-up the entire cohort and $129,800/QALY when only smokers were included. Conclusions Follow-up of PN incidentally detected in patients undergoing CCTA for chest pain evaluation is associated with a small reduction in lung cancer mortality. However, significant downstream testing contributes to limited efficiency as demonstrated by a high cost per QALY, especially in non-smokers.
Purpose:To demonstrate a limitation of lifetime radiation-induced cancer risk metrics in the setting of testicular cancer surveillance-in particular, their failure to capture the delayed timing of radiation-induced cancers over the course of a patient's lifetime. Materials and Methods:Institutional review board approval was obtained for the use of computed tomographic (CT) dosimetry data in this study. Informed consent was waived. This study was HIPAA compliant. A Markov model was developed to project outcomes in patients with testicular cancer who were undergoing CT surveillance in the decade after orchiectomy. To quantify effects of early versus delayed risks, life expectancy losses and lifetime mortality risks due to testicular cancer were compared with life expectancy losses and lifetime mortality risks due to radiation-induced cancers from CT. Projections of life expectancy loss, unlike lifetime risk estimates, account for the timing of risks over the course of a lifetime, which enabled evaluation of the described limitation of lifetime risk estimates. Markov chain Monte Carlo methods were used to estimate the uncertainty of the results. Results:As an example of evidence yielded, 33-year-old men with stage I seminoma who were undergoing CT surveillance were projected to incur a slightly higher lifetime mortality risk from testicular cancer (598 per 100 000; 95% uncertainty interval [UI]: 302, 894) than from radiation-induced cancers (505 per 100 000; 95% UI: 280, 730). However, life expectancy loss attributable to testicular cancer (83 days; 95% UI: 42, 124) was more than three times greater than life expectancy loss attributable to radiationinduced cancers (24 days; 95% UI: 13, 35). Trends were consistent across modeled scenarios. Conclusion:Lifetime radiation risk estimates, when used for decision making, may overemphasize radiation-induced cancer risks relative to short-term health risks.q RSNA, 2012 Supplemental material: http://radiology.rsna.org/lookup /suppl
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