Hepatocellular Carcinoma Incidence Threshold for Surveillance in Virologically Cured Hepatitis C Individuals.

BACKGROUND & AIMS: Guidelines recommend biannual surveillance for hepatocellular carcinoma (HCC) in hepatitis C individuals with cirrhosis if the HCC incidence rate is above 1.5 per 100 person-years (PY). However, the incidence threshold for surveillance in individuals who achieve a virologic cure is unknown. We estimated the HCC incidence rate above which routine HCC surveillance is cost-effective in this growing population of virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis. METHODS: We developed a Markov-based microsimulation model of the natural history of HCC in individuals with hepatitis C who achieved virologic cure with oral direct-acting antivirals. We used published data on the natural history of hepatitis C, competing risk post virologic cure, HCC tumor progression, real-world HCC surveillance adherence, contemporary HCC treatment options and associated costs, and utilities of different health states. We estimated the HCC incidence above which biannual HCC surveillance using ultrasound and alpha-fetoprotein would be cost-effective. RESULTS: In virologically cured hepatitis C individuals with cirrhosis or advanced fibrosis, HCC surveillance is cost-effective if HCC incidence exceeds 0.7 per 100 PY using $100,000 per quality-adjusted life year willingness-to-pay. At this HCC incidence, routine HCC surveillance would result in 2650 and 5700 additional life years per 100,000 cirrhosis and advanced fibrosis persons, respectively, compared with no surveillance. At $150,000 willingness-to-pay, surveillance is cost-effective if HCC incidence exceeds 0.4 per 100 PY. Sensitivity analysis showed that the threshold mostly remained below 1.5 per 100 PY. CONCLUSIONS: The contemporary HCC incidence threshold is much lower than the previous 1.5% incidence value used to guide HCC surveillance decisions. Updating clinical guidelines could improve the early diagnosis of HCC.

Duration and cost-effectiveness of hepatocellular carcinoma surveillance in hepatitis C patients after viral eradication.

BACKGROUND & AIMS: Successful treatment of chronic hepatitis C with oral direct-acting antivirals (DAAs) leads to virological cure, however, the subsequent risk of hepatocellular carcinoma (HCC) persists. Our objective was to evaluate the cost-effectiveness of biannual surveillance for HCC in patients cured of hepatitis C and the optimal age to stop surveillance. METHODS: We developed a microsimulation model of the natural history of HCC in individuals with hepatitis C and advanced fibrosis or cirrhosis who achieved virological cure with oral DAAs. We used published data on HCC incidence, tumor progression, real-world HCC surveillance adherence, and costs and utilities of different health states. We compared biannual HCC surveillance using ultrasound and alpha-fetoprotein for varying durations of surveillance (from 5 years to lifetime) vs. no surveillance. RESULTS: In virologically cured patients with cirrhosis, the incremental cost-effectiveness ratio (ICER) of biannual surveillance remained below $150,000 per additional quality-adjusted life year (QALY) (range: $79,500-$94,800) when surveillance was stopped at age 70, irrespective of the starting age (40-65). Compared with no surveillance, surveillance detected 130 additional HCCs in 'very early'/early stage and yielded 51 additional QALYs per 1,000 patients with cirrhosis. In virologically cured patients with advanced fibrosis, the ICER of biannual surveillance remained below $150,000/QALY (range: $124,600-$129,800) when surveillance was stopped at age 60, irrespective of the starting age (40-50). Compared with no surveillance, surveillance detected 24 additional HCCs in 'very early'/early stage and yielded 12 additional QALYs per 1,000 patients with advanced fibrosis. CONCLUSION: Biannual surveillance for HCC in patients cured of hepatitis C is cost-effective until the age of 70 for patients with cirrhosis, and until the age of 60 for patients with stable advanced fibrosis. LAY SUMMARY: Individuals who are cured of hepatitis C using oral antiviral drugs remain at risk of developing liver cancer. The value of lifelong screening for liver cancer in these individuals is not known. By simulating the life course of hepatitis C cured individuals, we found that ultrasound-based biannual screening for liver cancer is cost-effective up to age 70 in those with cirrhosis and up to age 60 in those with stable advanced fibrosis.

Optimal breast cancer risk reduction policies tailored to personal risk level.

Depending on personal and hereditary factors, each woman has a different risk of developing breast cancer, one of the leading causes of death for women. For women with a high-risk of breast cancer, their risk can be reduced by two main therapeutic approaches: 1) preventive treatments such as hormonal therapies (i.e., tamoxifen, raloxifene, exemestane); or 2) a risk reduction surgery (i.e., mastectomy). Existing national clinical guidelines either fail to incorporate or have limited use of the personal risk of developing breast cancer in their proposed risk reduction strategies. As a result, they do not provide enough resolution on the benefit-risk trade-off of an intervention policy as personal risk changes. In addressing this problem, we develop a discrete-time, finite-horizon Markov decision process (MDP) model with the objective of maximizing the patient's total expected quality-adjusted life years. We find several useful insights some of which contradict the existing national breast cancer risk reduction recommendations. For example, we find that mastectomy is the optimal choice for the border-line high-risk women who are between ages 22 and 38. Additionally, in contrast to the National Comprehensive Cancer Network recommendations, we find that exemestane is a plausible, in fact, the best, option for high-risk postmenopausal women.

Benefits and Harms of Mammography Screening for Women With Down Syndrome: a Collaborative Modeling Study.

BACKGROUND: Women with Down syndrome have a lower breast cancer risk and significantly lower life expectancies than women without Down syndrome. Therefore, it is not clear whether mammography screening strategies used for women without Down syndrome would benefit women with Down syndrome in the same way. OBJECTIVE: To determine the benefits and harms of various mammography screening strategies for women with Down syndrome using collaborative simulation modeling. DESIGN: Two established Cancer Intervention and Surveillance Modeling Network (CISNET) simulation models estimated the benefits and harms of various screening strategies for women with Down syndrome over a lifetime horizon. PARTICIPANTS: We modeled a hypothetical cohort of US women with Down syndrome who were born in 1970. INTERVENTIONS: Annual, biennial, triennial, and one-time digital mammography screenings during the ages 40-74. MAIN MEASURES: The models estimated numbers of mammograms, false-positives, benign biopsies, breast cancer deaths prevented, and life-years gained per 1000 screened women when compared with no screening. KEY RESULTS: In average-risk women 50-74, biennial screening incurred 122 mammograms, 10 false-positive mammograms, and 1.4 benign biopsies per one life-year gained compared with no screening. In women with Down syndrome, the same screening strategy incurred 2752 mammograms, 242 false-positive mammograms, and 34 benign biopsies per one life-year gained compared with no screening. The harm/benefit ratio varied for other screening strategies, and was most favorable for one-time screening at age 50, which incurred 1629 mammograms, 144 false-positive mammograms, and 20 benign biopsies per one life-year gained compared with no screening. CONCLUSIONS: The harm/benefit ratios for various mammography screening strategies in women with Down syndrome are not as favorable as those for average-risk women. The benefit of screening mammography for women with Down syndrome is less pronounced due to lower breast cancer risk and shorter life expectancy.

Breast cancer risk for women with diabetes and the impact of metformin: A meta-analysis.

BACKGROUND: Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM). METHODS: Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021. RESULTS: A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users. CONCLUSIONS: Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users. IMPACT: These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.

Cost-effectiveness of adjuvant paclitaxel and trastuzumab for early-stage node-negative, HER2-positive breast cancer.

OBJECTIVES: Adjuvant paclitaxel and trastuzumab has been shown to be an effective regimen with low risk of cancer recurrence and treatment-related toxicities in early-stage node-negative, HER2-positive breast cancer. We investigated the cost-effectiveness of this regimen. METHODS: A Markov-based microsimulation model with six health states is used to simulate four adjuvant therapy options for women with early-stage node-negative, HER2-positive breast cancer at different age groups. The four treatment arms are 1) adjuvant paclitaxel and trastuzumab (TH), 2) doxorubicin, cyclophosphamide, paclitaxel and trastuzumab (ACTH), 3) docetaxel, carboplatin and trastuzumab (TCH), and 4) no adjuvant trastuzumab (NT). Data from randomized trials were used to estimate treatment efficacy. Societal perspective was used in this cost-effectiveness analysis. Costs were measured in 2016 US dollars (US$) and quality-adjusted life-years (QALYs) was used for health outcomes. Sensitivity analyses were performed to evaluate the impact of uncertainty in parameter estimation. RESULTS: We found that 40-year-old women undergoing TH treatment would have an average of 16.17 QALYs for the cost of $178,650 when lifetime horizon is used. Compared to NT, TH has incremental cost-effectiveness ratios ranged from $10,584 (ages 40-49) to $84,981 (age 80+) per additional QALYs. The sensitivity analysis showed that TH is cheaper and leads to higher QALYs compared to both ACTH and TCH for all age groups and time horizons. CONCLUSIONS: TH is cost-effective for all age groups in the base case scenario and in the sensitivity analysis. In order to reduce the parameter uncertainty, clinical trials with longer follow-up times are needed.