Initiation of Somatostatin analogues for neuroendocrine tumor patients: a cost-effectiveness analysis.

BACKGROUND & AIMS: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are heterogeneous neoplasms. Although some have a relatively benign and indolent natural history, others can be aggressive and ultimately fatal. Somatostatin analogues (SSAs) improve both quality of life and survival for these patients once they develop metastatic disease. However, these drugs are costly and their cost-effectiveness is not known. METHODS: A decision-analytic model was developed and analyzed to compare two treatment strategies for patients with Stage IV GEP-NETs. The first strategy had all patients start SSA immediately while the second strategy waited, reserving SSA initiation until the patient showed signs of progression. Sensitivity analysis was performed to explore model parameter uncertainty. RESULTS: Our model of patients age 60 with metastatic GEP-NETs suggests empiric initiation of SSA led to an increase 0.62 unadjusted life-years and incremental increase in quality-adjusted life years (QALYs) of 0.44. The incremental costs were $388,966 per QALY and not cost-effective at a willingness-to-pay threshold of $100,000. Death was attributed to GEP-NETs for 94.1% of patients in the SSA arm vs. 94.9% of patients in the DELAY SSA arm. Sensitivity analysis found that the model was most sensitive to costs of SSAs. Using probabilistic sensitivity analysis, the SSA strategy was only cost-effective 1.4% of the time at a WTP threshold of $100,000 per QALY. CONCLUSIONS: Our modeling study finds it is not cost-effective to initiate SSAs at time of presentation for patients with metastatic GEP-NETs. Further clinical studies are needed to identify the optimal timing to initiate these drugs.

Projected Effects of Radiation-Induced Cancers on Life Expectancy in Patients Undergoing CT Surveillance for Limited-Stage Hodgkin Lymphoma: A Markov Model.

OBJECTIVE: Patients with limited-stage Hodgkin lymphoma (HL) undergo frequent posttreatment surveillance CT examinations, raising concerns about the cumulative magnitude of radiation exposure. The purpose of this study was to project radiation-induced cancer risks relative to competing risks of HL and account for the differential timing of each. MATERIALS AND METHODS: We adapted a previously developed Markov model to project lifetime mortality risks and life expectancy losses due to HL versus radiation-induced cancers in HL patients undergoing surveillance CT. In the base case, we modeled 35-year-old men and women undergoing seven CT examinations of the chest, abdomen, and pelvis over 5 years. Radiation-induced cancer risks and deaths for 17 organ systems were modeled using an organ-specific approach, accounting for specific anatomy exposed at CT. Cohorts of 20-, 50-, and 65-year-old men and women were evaluated in secondary analyses. Markov chain Monte Carlo methods were used to estimate the uncertainty of radiation risk projections. RESULTS: For 35-year-old adults, we projected 3324/100,000 (men) and 3345/100,000 (women) deaths from recurrent lymphoma and 245/100,000 (men, 95% uncertainty interval [UI]: 121-369) and 317/100,000 (women, 95% UI: 202-432) radiation-induced cancer deaths. Discrepancies in life expectancy losses between HL (428 days in men, 482 days in women) and radiation-induced cancers (11.6 days in men, [95% UI: 5.7-17.5], 15.6 days in women [95% UI: 9.8-21.4]) were proportionately greater because of the delayed timing of radiation-induced cancers relative to recurrent HL. Deaths and life expectancy losses from radiation-induced cancers were highest in the youngest cohorts. CONCLUSION: Given the low rate of radiation-induced cancer deaths associated with CT surveillance, modest CT benefits would justify its use in patients with limited-stage HL.

Annual financial impact of well-differentiated thyroid cancer care in the United States.

BACKGROUND: Well-differentiated thyroid cancer (WDTC) is a prevalent disease, which is increasing in incidence faster than any other cancer. Substantial direct medical care costs are related to the diagnosis and treatment of newly diagnosed patients as well as the ongoing surveillance of patients who have a long life expectancy. Prior analyses of the aggregate health care costs attributable to WDTC in the United States have not been reported. METHODS: A stacked cohort cost analysis was performed on the US population from 1985 to 2013 to estimate the number of WDTC survivors in 2013. Incidence rates, and cancer-specific and overall survival were based on Surveillance, Epidemiology, and End Results (SEER) data. Current and projected direct medical care costs attributable to the care of patients with WDTC were then estimated. Health care-related costs and event probabilities were based on Medicare reimbursement schedules and the literature. RESULTS: Estimated overall societal cost of WDTC care in 2013 for all US patients diagnosed after 1985 is $1.6 billion. Diagnosis, surgery, and adjuvant therapy for newly diagnosed patients (41%) constitutes the greatest proportion of costs, followed by surveillance of survivors (37%), and nonoperative death costs attributable to thyroid cancer care (22%). Projected 2030 costs (in 2013 US dollars) based on current incidence trends exceed $3.5 billion. CONCLUSIONS: Health care costs of WDTC are substantial. Unlike other cancers, the majority of the cost is incurred in the initial and continuing phases of care. With the projected increasing incidence, population, and survival trends, costs will continue to escalate.

Percutaneous breast biopsy: effect on short-term quality of life.

PURPOSE: To examine the effects of percutaneous breast biopsy on short-term quality of life. MATERIALS AND METHODS: The institutional review board approved this HIPAA-compliant prospective study. From December 1, 2007, through February 28, 2010, women undergoing percutaneous breast biopsy in an academic medical center were recruited to participate in a mixed-mode survey 2-4 days after biopsy. Patients described their biopsy experience by using the Testing Morbidities Index (TMI), a validated instrument for assessing short-term quality of life related to diagnostic testing. The scale ranged from 0 (worst possible experience) to 100 (no adverse effects). Seven attributes were assessed: pain or discomfort before and during testing, fear or anxiety before and during testing, embarrassment during testing, and physical and mental function after testing. Demographic and clinical information were also collected. Univariate and multivariate linear regression analyses were performed to identify significant predictors of TMI score. RESULTS: In 188 women (mean age, 51.4 years; range, 22-80 years), the mean TMI score (±standard deviation) was 82 ± 12. Univariate analysis revealed age and race as significant predictors of the TMI score (P < .05). In the multivariate model, only patient age remained a significant independent predictor (P = .001). TMI scores decreased by approximately three points for every decade decrease in patient age, which suggests that younger women were more adversely affected by the biopsy experience. CONCLUSION: Younger patient age is a significant predictor of decreased short-term quality of life related to percutaneous breast biopsy procedures. Tailored prebiopsy counseling may better prepare women for percutaneous biopsy procedures and improve their experience.

MRI-guided focused ultrasound surgery for uterine fibroid treatment: a cost-effectiveness analysis.

OBJECTIVE. The purpose of this article is to evaluate the cost effectiveness of a treatment strategy for symptomatic uterine fibroids that uses MRI-guided focused ultrasound as a first-line therapy relative to uterine artery embolization (UAE) or hysterectomy. MATERIALS AND METHODS. We developed a decision-analytic model to compare the cost effectiveness of three first-line treatment strategies: MRI-guided focused ultrasound, UAE, and hysterectomy. Treatment-specific short- and long-term utilities, lifetime costs, and quality-adjusted life years (QALYs) were incorporated, allowing us to conduct an incremental cost-effectiveness analysis, using a societal willingness-to-pay (WTP) threshold of $50,000/QALY to designate a strategy as cost effective. Sensitivity analyses were subsequently performed on all key parameters. RESULTS. In the base-case analysis, UAE as a first-line treatment of symptomatic fibroids was the most effective and expensive strategy (22.75 QALYs; $22,968), followed by MRI-guided focused ultrasound (22.73 QALYs; $20,252) and hysterectomy (22.54 QALYs; $11,253). MRI-guided focused ultrasound was cost effective relative to hysterectomy, with an associated incremental cost-effectiveness ratio (ICER) of $47,891/QALY. The ICER of UAE relative to MRI-guided focused ultrasound was $234,565/QALY, exceeding the WTP threshold of $50,000/QALY, therefore rendering MRI-guided focused ultrasound also cost effective relative to UAE. In sensitivity analyses, results were robust to changes in most parameters but were sensitive to changes in probabilities of recurrence, symptom relief, and quality-of-life measures. CONCLUSION. First-line treatment of eligible women with MRI-guided focused ultra-sound is a cost-effective noninvasive strategy. For those not eligible for MRI-guided focused ultra-sound, UAE remains a cost-effective option. These recommendations integrate both the short- and long-term decrements in quality of life associated with the specific treatment modalities.

Cost-effectiveness of alternating magnetic resonance imaging and digital mammography screening in BRCA1 and BRCA2 gene mutation carriers.

BACKGROUND: Current clinical guidelines recommend earlier, more intensive breast cancer screening with both magnetic resonance imaging (MRI) and mammography for women with breast cancer susceptibility gene (BRCA) mutations. Unspecified details of screening schedules are a challenge for implementing guidelines. METHODS: A Markov Monte Carlo computer model was used to simulate screening in asymptomatic women who were 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 years (Alt25), 2) annual MRI beginning at age 25 years with alternating DM added at age 30 years (MRI25/Alt30), and 3) DM and MRI alternating at 6-month intervals beginning at age 30 years (Alt30). Primary outcomes were quality-adjusted life years (QALYs), lifetime costs (in 2010 US dollars), and incremental cost-effectiveness (dollars per 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 3 dual-modality screening strategies increased QALYs and costs. Alt30 screening had the lowest incremental costs per additional QALY gained (BRCA1, $74,200 per QALY; BRCA2, $215,700 per QALY). False-positive test results increased substantially with dual-modality screening and occurred 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. The results were influenced most by estimates of breast cancer risk and MRI costs. CONCLUSIONS: Alternating MRI and DM screening at 6-month intervals beginning at age 30 years was identified as a clinically effective approach to applying current guidelines, and was more cost-effective in BRCA1 gene mutation carriers compared with BRCA2 gene mutation carriers.

Annual screening strategies in BRCA1 and BRCA2 gene mutation carriers: a comparative effectiveness analysis.

BACKGROUND: Although breast cancer screening with mammography and magnetic resonance imaging (MRI) is recommended for breast cancer-susceptibility gene (BRCA) mutation carriers, there is no current consensus on the optimal screening regimen. METHODS: The authors used a computer simulation model to compare 6 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 6-month intervals) beginning at ages 25 years, 30 years, 35 years, and 40 years, and 2 strategies of annual MRI with delayed alternating DM/FM versus clinical surveillance alone. Strategies were evaluated without and with mammography-induced breast cancer risk using 2 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 years provided the highest life expectancy (BRCA1, 72.52 years, BRCA2, 77.63 years). When radiation risk was included, a small proportion of diagnosed cancers was attributable to radiation exposure (BRCA1, <2%; BRCA2, <4%). With radiation risk, alternating DM/MRI at age 25 years or annual MRI at age 25 years/delayed alternating DM at age 30 years was the most effective, depending on the radiation risk model used. Alternating DM/MRI starting at age 25 years also produced the highest number of false-positive screens per woman (BRCA1, 4.5 BRCA2, 8.1). CONCLUSIONS: Annual MRI at age 25 years/delayed alternating DM at age 30 years is probably 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.

Using radiation risk models in cancer screening simulations: important assumptions and effects on outcome projections.

PURPOSE: To evaluate the effect of incorporating radiation risk into microsimulation (first-order Monte Carlo) models for breast and lung cancer screening to illustrate effects of including radiation risk on patient outcome projections. MATERIALS AND METHODS: All data used in this study were derived from publicly available or deidentified human subject data. Institutional review board approval was not required. The challenges of incorporating radiation risk into simulation models are illustrated with two cancer screening models (Breast Cancer Model and Lung Cancer Policy Model) adapted to include radiation exposure effects from mammography and chest computed tomography (CT), respectively. The primary outcome projected by the breast model was life expectancy (LE) for BRCA1 mutation carriers. Digital mammographic screening beginning at ages 25, 30, 35, and 40 years was evaluated in the context of screenings with false-positive results and radiation exposure effects. The primary outcome of the lung model was lung cancer-specific mortality reduction due to annual screening, comparing two diagnostic CT protocols for lung nodule evaluation. The Metropolis-Hastings algorithm was used to estimate the mean values of the results with 95% uncertainty intervals (UIs). RESULTS: Without radiation exposure effects, the breast model indicated that annual digital mammography starting at age 25 years maximized LE (72.03 years; 95% UI: 72.01 years, 72.05 years) and had the highest number of screenings with false-positive results (2.0 per woman). When radiation effects were included, annual digital mammography beginning at age 30 years maximized LE (71.90 years; 95% UI: 71.87 years, 71.94 years) with a lower number of screenings with false-positive results (1.4 per woman). For annual chest CT screening of 50-year-old females with no follow-up for nodules smaller than 4 mm in diameter, the lung model predicted lung cancer-specific mortality reduction of 21.50% (95% UI: 20.90%, 22.10%) without radiation risk and 17.75% (95% UI: 16.97%, 18.41%) with radiation risk. CONCLUSION: Because including radiation exposure risk can influence long-term projections from simulation models, it is important to include these risks when conducting modeling-based assessments of diagnostic imaging.

Cost-effectiveness of breast MR imaging and screen-film mammography for screening BRCA1 gene mutation carriers.

PURPOSE: To evaluate the clinical effectiveness and cost-effectiveness of screening strategies in which MR imaging and screen-film mammography were used, alone and in combination, in women with BRCA1 mutations. MATERIALS AND METHODS: Because this study did not involve primary data collection from individual patients, institutional review board approval was not needed. By using a simulation model, we compared three annual screening strategies for a cohort of 25-year-old BRCA1 mutation carriers, as follows: (a) screen-film mammography, (b) MR imaging, and (c) combined MR imaging and screen-film mammography (combined screening). The model was used to estimate quality-adjusted life-years (QALYs) and lifetime costs. Incremental cost-effectiveness ratios were calculated. Input parameters were obtained from the medical literature, existing databases, and calibration. Costs (2007 U.S. dollars) and quality-of-life adjustments were derived from Medicare reimbursement rates and the medical literature. Sensitivity analysis was performed to evaluate the effect of uncertainty in parameter estimates on model results. RESULTS: In the base-case analysis, annual combined screening was most effective (44.62 QALYs), and had the highest cost ($110973), followed by annual MR imaging alone (44.50 QALYs, $108641), and annual mammography alone (44.46 QALYs, $100336). Adding annual MR imaging to annual mammographic screening cost $69125 for each additional QALY gained. Sensitivity analysis indicated that, when the screening MR imaging cost increased to $960 (base case, $577), or breast cancer risk by age 70 years decreased below 58% (base case, 65%), or the sensitivity of combined screening decreased below 76% (base case, 94%), the cost of adding MR imaging to mammography exceeded $100000 per QALY. CONCLUSION: Annual combined screening provides the greatest life expectancy and is likely cost-effective when the value placed on gaining an additional QALY is in the range of $50000-$100000. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.09091086/-/DC1.

Emphysema and soluble CD14 are associated with pulmonary nodules in HIV-infected patients: implications for lung cancer screening.

OBJECTIVE: Lung cancer screening may benefit HIV-infected (HIV) smokers because of an elevated risk of lung cancer, but may have unique harms because of HIV-specific risk factors for false-positive screens. This study seeks to understand whether inflammatory biomarkers and markers of chronic lung disease are associated with noncalcified nodules at least 4 mm (NCN) in HIV compared with uninfected patients. DESIGN: This is a cohort study of Examinations of HIV-Associated Lung Emphysema (EXHALE), including 158 HIV and 133 HIV-uninfected participants. METHODS: Participants underwent a laboratory assessment [including measurement of D-dimer, interleukin 6, and soluble CD14 (sCD14)], chest computed tomography (CT), and pulmonary function testing. We created multivariable logistic regression models to determine predictors of NCN in the participants stratified by HIV status, with attention to semiqualitative scoring of radiographic emphysema, markers of pulmonary function, and inflammatory biomarkers. RESULTS: Of the 291 participants, 69 had NCN on chest CT. As previously reported, there was no difference in prevalence of these nodules by HIV status. Emphysema and elevated sCD14 demonstrated an association with NCN in HIV participants independent of smoking status, CD4 cell count, HIV viral load, and pulmonary function. CONCLUSION: Emphysema and sCD14, a marker of immune activation, was associated with a higher prevalence of NCN on chest CT in HIV participants. Patients with chronic immune activation and emphysema may be at higher risk for both false-positive findings and incident lung cancer, thus screening in this group requires further study to understand the balance of benefits and harms.

Modeling of polynucleotide translocation through protein pores and nanotubes.

In an effort to understand recent experiments, we have performed Brownian dynamics simulations of polymer translocation through nanometer-scale protein pores under the influence of an external applied electric field. Multiple peaks in the translocation time distribution are observed in agreement with experiments. Under the same conditions, but replacing the protein pore with a rigid cylindrical tube of comparable size, only a single peak is observed in the translocation time distribution. These results directly show that the geometry of the protein pores is mainly responsible for multiple peaks observed in experiments. In the case of alpha-hemolysin channel, we find the vestibule, by confining many conformations of the translocating polymer, to be responsible for the second peak with longer translocation time.