Kathryn P. Lowry

Annual Screening Strategies in BRCA1 and BRCA2 Gene Mutation Carriers: A Comparative Effectiveness Analysis

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.

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

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.

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.

Personalizing annual lung cancer screening for patients with chronic obstructive pulmonary disease: A decision analysis

Lung cancer screening with annual chest computed tomography (CT) is recommended for current and former smokers with a ≥30‐pack‐year smoking history. Patients with chronic obstructive pulmonary disease (COPD) are at increased risk of developing lung cancer and may benefit from screening at lower pack‐year thresholds.

Breast Cancer Characteristics Associated with 2D Digital Mammography versus Digital Breast Tomosynthesis for Screening-detected and Interval Cancers

Purpose To determine whether the rates and tumor characteristics of screening-detected and interval cancers differ for two-dimensional digital mammography (DM) versus digital breast tomosynthesis (DBT) mammography. Materials and Methods Consecutive screening mammograms from January 2009 to February 2011 (DM group, before DBT integration) and from January 2013 to February 2015 (DBT group, after complete DBT integration) were reviewed. Cancers were considered screening detected if diagnosed within 365 days of a positive screening examination and interval if diagnosed within 365 days of a negative screening examination. Z tests were used to compare cancers on DM versus DBT examinations. Results A total of 948 breast cancers were diagnosed after 78 385 DM and 76 896 DBT examinations. Although the overall rate of screening-detected cancers was similar with DM and DBT (5.0 vs 5.0 per 1000 examinations, P = .98), a higher proportion of screening-detected cancers were invasive rather than in situ with DBT (74.2% [287 of 387] vs 66.0% [260 of 394], P = .01). There were no significant differences in tumor characteristics, including size at pathologic examination, grade, hormone receptor status, and nodal status, between the screening-detected invasive cancers on DM versus DBT (P = .09-.99). The rate of interval cancers was similar with DM and DBT (1.1 vs 1.1 per 1000 examinations, P = .84). Compared with symptomatic interval cancers, magnetic resonance imaging-detected interval cancers were more likely to be minimal cancers. Conclusion The overall rates of screening-detected and interval cancers are similar with DM and DBT, but a higher proportion of screening-detected cancers are invasive rather than in situ with DBT.

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.

Imaging and Screening of Ovarian Cancer

Ovarian cancer has a high mortality, attributed to its typically advanced stage at detection. Despite much effort to identify an effective approach for ovarian cancer screening, to date no screening test has proven to reduce ovarian cancer mortality. The natural history of ovarian cancer is reviewed as well as data from the largest trials of ovarian cancer screening. Currently, no North American society recommends routine ovarian cancer screening; some societies recommend consideration of screening with pelvic ultrasound and CA-125 in women at high risk, although its use in this setting is not supported by data demonstrating a mortality benefit.

ACR Appropriateness Criteria® Ovarian Cancer Screening

There has been much interest in the identification of a successful ovarian cancer screening test, in particular, one that can detect ovarian cancer at an early stage and improve survival. We reviewed the currently available data from randomized and observational trials that examine the role of imaging for ovarian cancer screening in average-risk and high-risk women. We found insufficient evidence to recommend ovarian cancer screening, when considering the imaging modality (pelvic ultrasound) and population (average-risk postmenopausal women) for which there is the greatest available published evidence; randomized controlled trials have not demonstrated a mortality benefit in this setting. Screening high-risk women using pelvic ultrasound may be appropriate in some clinical situations; however, related data are limited because large, randomized trials have not been performed in this setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.

Case 27-2016: A 71-Year-Old Woman with Müllerian Carcinoma, Fever, Fatigue, and Myalgias

A 71-year-old woman with mullerian carcinoma was admitted to the hospital because of fever, fatigue, and myalgias 3.5 weeks after extensive cytoreductive surgery. Anorexia, abdominal pain, and bloating had developed 1 day earlier. Diagnostic studies were performed.

Case 27-2016

A 71-year-old woman with mullerian carcinoma was admitted to the hospital because of fever, fatigue, and myalgias 3.5 weeks after extensive cytoreductive surgery. Anorexia, abdominal pain, and bloating had developed 1 day earlier. Diagnostic studies were performed.