Geospatial Disparities in the Treatment of Curable Breast Cancer Across the US.

IMPORTANCE: Patient factors help explain disparities in breast cancer treatments and outcomes. OBJECTIVE: To determine the extent to which geospatial variation in initial breast cancer care can be attributed to region vs patient factors with the aim of guiding quality improvement efforts. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective population-based cohort study from January 1, 2007, through December 31, 2016, using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database that included 31 571 patients diagnosed with stage I to III breast cancer from 2007 through 2013. Five metrics of care delivery were defined: stage I at diagnosis, chemotherapy receipt, radiation therapy receipt, endocrine therapy (ET) initiation (year 1), and ET continuation (years 3-5). Data analysis was performed from January to June 2021. EXPOSURES: Stage I diagnosis and treatment with chemotherapy, radiation therapy, or ET. MAIN OUTCOMES AND MEASURES: For each metric, total variance was attributed proportionally to 4 domains-random, patient factors (eg, age, race and ethnicity, socioeconomic status), region (health service area [HSA]), and unexplained-using hierarchical multivariable modeling. RESULTS: Of 31 571 total patients (median [IQR] age, 71 [68-75] years), 19 391 (61.4%) had stage I disease at diagnosis. Among eligible patients, 17 297 of 21 190 (81.6%) received radiation therapy, 7204 of 9903 (72.8%) received chemotherapy, 13 115 of 26 855 (48.8%) initiated ET, and 13 944 of 26 855 (52.1%) continued ET. Geospatial density (ie, heat) maps highlight regional performance patterns. For all 5 metrics, region/HSA explained more observed variation (24%-48%) than patient factors (1%-4%); the largest share of variation was unexplained (35%-54%). The metrics with the largest proportion of total variance attributed to region/HSA were ET initiation and continuation (28% and 39%, respectively). CONCLUSIONS AND RELEVANCE: In this cohort study, there was substantial unexplained geospatial variation in initial breast cancer care. The variance attributed to region/HSA was multifold larger than that explained by patient factors. The importance of patient factors such as race and ethnicity notwithstanding, future quality improvement efforts should focus on reducing unwarranted geospatial variation, especially including optimizing the delivery of ET in low-performing regions.

Location as Destiny: Identifying Geospatial Disparities in Radiation Treatment Interruption by Neighborhood, Race, and Insurance.

PURPOSE: Radiation therapy interruption (RTI) worsens cancer outcomes. Our purpose was to benchmark and map RTI across a region in the United States with known cancer outcome disparities. METHODS AND MATERIALS: All radiation therapy (RT) treatments at our academic center were cataloged. Major RTI was defined as ≥5 unplanned RT appointment cancellations. Univariate and multivariable logistic and linear regression analyses identified associated factors. Major RTI was mapped by patient residence. A 2-sided P value <.0001 was considered statistically significant. RESULTS: Between 2015 and 2017, a total of 3754 patients received RT, of whom 3744 were eligible for analysis: 962 patients (25.8%) had ≥2 RT interruptions and 337 patients (9%) had major RTI. Disparities in major RTI were seen across Medicaid versus commercial/Medicare insurance (22.5% vs 7.2%; P < .0001), low versus high predicted income (13.0% vs 5.9%; P < .0001), Black versus White race (12.0% vs 6.6%; P < .0001), and urban versus suburban treatment location (12.0% vs 6.3%; P < .0001). On multivariable analysis, increased odds of major RTI were seen for Medicaid patients (odds ratio [OR], 3.35; 95% confidence interval [CI], 2.25-5.00; P < .0001) versus those with commercial/Medicare insurance and for head and neck (OR, 3.74; 95% CI, 2.56-5.46; P < .0001), gynecologic (OR, 3.28; 95% CI, 2.09-5.15; P < .0001), and lung cancers (OR, 3.12; 95% CI, 1.96-4.97; P < .0001) compared with breast cancer. Major RTI was mapped to urban, majority Black, low-income neighborhoods and to rural, majority White, low-income regions. CONCLUSIONS: Radiation treatment interruption disproportionately affects financially and socially vulnerable patient populations and maps to high-poverty neighborhoods. Geospatial mapping affords an opportunity to correlate RT access on a neighborhood level to inform potential intervention strategies.

Cost Effectiveness of DCISionRT for Guiding Treatment of Ductal Carcinoma in Situ.

The DCISionRT test estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) as well as the benefit of adjuvant radiation therapy (RT). We determined the cost-effectiveness of DCISionRT using a Markov model simulating 10-year outcomes for 60-year-old women with DCIS based on nonrandomized data. Three strategies were compared: no testing, no RT (strategy 1); test all, RT for elevated risk only (strategy 2); and no testing, RT for all (strategy 3). We used utilities and costs from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women irradiated per IBE prevented. In the base-case scenario, strategy 1 was the cost-effective strategy. Strategy 2 was cost-effective compared with strategy 3 when the cost of DCISionRT was less than $4588. The number irradiated per IBE prevented were 8.37 and 15.46 for strategies 2 and 3, respectively, relative to strategy 1.

Cost Effectiveness of the Oncotype DX Genomic Prostate Score for Guiding Treatment Decisions in Patients With Early Stage Prostate Cancer.

OBJECTIVE: To determine the cost-effectiveness of using the Oncotype DX Genomic Prostate Score (GPS), a 17-gene expression assay that can be used to inform decisions regarding active surveillance (AS) vs immediate treatment. METHODS: We developed a Markov model simulating 20-year outcomes for 65-year-old men with very low-, low-, or favorable intermediate-risk prostate cancer undergoing AS vs immediate treatment using GPS vs no testing. Utilities, costs, and probabilities were extracted from the literature and National Medicare Fee Schedules to determine incremental cost-effectiveness ratios (ICER) from a payer perspective. RESULTS: In the overall cohort, the ICER of GPS-guided therapy was $31,394 per quality-adjusted life-year (QALY). When stratified by risk group, the ICER was $25,343 per QALY in very low-risk, $28,911 per QALY in low-risk, and $39,695 per QALY in favorable intermediate-risk patients. On sensitivity analysis, findings were robust against a willingness-to-pay of $100,000 per QALY to variations in key model parameters, including the cost of annual management of AS, probability of exiting AS to treatment, cost of treatment, and probability of biochemical failure post-treatment. However, the cost-effectiveness was sensitive to small differences in the utility of AS and the utility of no evidence of disease post-treatment states. CONCLUSION: The use of the GPS was cost-effective in guiding treatment decisions regarding AS vs immediate treatment. The cost-effectiveness was sensitive to small differences in the utilities of the AS and no evidence of disease post-treatment states, highlighting the importance of assessing patient preferences.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus Proton Therapy for Oropharyngeal Squamous Cell Carcinoma.

PURPOSE: To compared the cost-effectiveness of intensity modulated proton beam therapy (PBT) and intensity modulated radiation therapy (IMRT) in the management of stage III-IVB oropharynx cancer (OPC). METHODS AND MATERIALS: A Markov model was constructed to compare IMRT with PBT for a 65-year-old patient with stage IVA OPSCC. We assumed PBT led to a 25% reduction in long-term xerostomia, short-term dysgeusia, and the need for gastrostomy tube. Fewer dental complications were also expected with PBT. Incremental cost-effectiveness ratios (ICERs) were calculated, and value of information analyses were performed. The societal willingness-to-pay was defined as $100K per quality-adjusted life year (QALY). RESULTS: The ICERs for PBT for favorable human papillomavirus (HPV)-positive OPC were $288,000/QALY and $390,000/QALY in the payer perspective (PP) and societal perspective, respectively. Under nearly every scenario, PBT was not cost-effective, with ICERs above $150,000/QALY in the PP. The ICERs for HPV-negative OPC were typically greater than $250K/QALY in both perspectives. For HPV-positive patients, the ICER was less than $100,000/QALY in the PP only in younger patients who experienced a 50% reduction in both xerostomia and gastrostomy use. On probabilistic sensitivity analyses, there were 0% and 0.4% probabilities that PBT was cost-effective for 65- and 55-year old patients, respectively. The value of information was zero or negligible for all ages and perspectives at willingness-to-pay of $100,000/QALY and only meaningful in the PP for younger patients at a willingness-to-pay of $150,000/QALY. CONCLUSIONS: Intensity modulated proton beam therapy was only cost-effective in the PP if assumed to achieve profound reductions in long-term morbidity for younger patients; it was never cost-effective in the societal perspective. Prospective data are needed (and may be valuable) to better characterize the comparative toxicities of these treatments but are unlikely to change this calculation, except potentially in the most favorable cohort of patients.

Cost-Effectiveness of Surveillance for Distant Recurrence in Extremity Soft Tissue Sarcoma.

BACKGROUND: Optimal distant recurrence (DR) surveillance strategies for extremity soft tissue sarcoma (STS) are unknown. We performed a cost-effectiveness analysis of different imaging modalities performed at guideline-specified intervals. METHODS: We developed a Markov model simulating lifetime outcomes for 54-year-old patients after definitive treatment for American Joint Committee on Cancer stage II-III extremity STS using four surveillance strategies: watchful waiting (WW), chest X-ray (CXR), chest computed tomography (CCT), and positron emission tomography-computed tomography (PET/CT). Probabilities, utilities, and costs were extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios (ICER). RESULTS: CCT was the most effective and most costly strategy with CXR the most cost-effective strategy at a societal willing-to-pay (WTP) of $100,000/quality-adjusted life year (QALY). The ICER was $12,113/QALY for CXR versus $104,366/QALY for CCT while PET/CT was never cost-effective. Sensitivity analyses demonstrated CCT becomes the preferred imaging modality as the lifetime risk of DR increases beyond 33% or as the WTP increases beyond $120,000/QALY. CONCLUSIONS: Optimal DR surveillance imaging for stage II-III extremity STS should be individualized based on patients' risks for DR. These results suggest CXR, or CCT performed at more protracted intervals, may be preferred for lower-risk patients (i.e., DR risk <33%), whereas CCT may be preferred for higher-risk patients (i.e., DR risk >33%). Further study of optimal strategies is needed. In the interim, these findings may help to refine guidelines to reduce resource overutilization during routine surveillance of lower-risk sarcoma patients.

Breast cancer prevention strategies in lobular carcinoma in situ: A decision analysis.

BACKGROUND: Women diagnosed with lobular carcinoma in situ (LCIS) have a 3-fold to 10-fold increased risk of developing invasive breast cancer. The objective of this study was to evaluate the life expectancy (LE) and differences in survival offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy among women with LCIS. METHODS: A Markov simulation model was constructed to determine average LE and quality-adjusted LE (QALE) gains for hypothetical cohorts of women diagnosed with LCIS at various ages under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, other-cause mortality and the effectiveness of preventive strategies were derived from published studies and from the National Cancer Institute's Surveillance, Epidemiology, and End Results database. RESULTS: Assuming a breast cancer incidence from 1.02% to 1.37% per year under active surveillance, a woman aged 50 years diagnosed with LCIS would have a total LE of 32.78 years and would gain 0.13 years (1.6 months) in LE by adding chemoprevention and 0.25 years (3.0 months) in LE by adding bilateral prophylactic mastectomy. After quality adjustment, chemoprevention resulted in the greatest QALE for women ages 40 to 60 years at LCIS diagnosis, whereas surveillance remained the preferred strategy for optimizing QALE among women diagnosed at age 65 years and older. CONCLUSIONS: In this model, among women with a diagnosis of LCIS, breast cancer prevention strategies only modestly affected overall survival, whereas chemoprevention was modeled as the preferred management strategy for optimizing invasive disease-free survival while prolonging QALE form women younger than 65 years. Cancer 2017;123:2609-17. © 2017 American Cancer Society.

Association of Regional Intensity of Ductal Carcinoma In Situ Treatment With Likelihood of Breast Preservation.

IMPORTANCE: Large regional variation exists in the use of radiotherapy after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS). Although patients who do not receive initial radiotherapy for DCIS are candidates for subsequent BCS if they experience a second breast event, many undergo mastectomy instead. OBJECTIVE: To examine whether regional practice patterns of radiotherapy for DCIS affect the use of mastectomy in these patients. DESIGN, SETTING, AND PARTICIPANTS: A retrospective analysis of population-based databases (Surveillance, Epidemiology, and End Results [SEER] and SEER-Medicare). Data were obtained for 2679 women in SEER with a diagnosis of DCIS between 1990 and 2011 and for 757 women in SEER-Medicare with a DCIS diagnosis between 1991 and 2009 who had not undergone radiotherapy for DCIS and experienced a subsequent breast cancer or DCIS diagnosis. EXPOSURES: Treatment intensity for primary DCIS (high, medium, low), as defined by separating health service areas (HSAs) into 3 clusters based on radiotherapy use. MAIN OUTCOMES AND MEASURES: Mastectomy vs BCS at a second breast event defined as DCIS recurrence or new invasive cancer. RESULTS: The median (SD) ages of the participants was 64 (13) years for the 2679 SEER population and 79 (6) years for the SEER-Medicare cohort. Residence in an HSA characterized by greater radiotherapy use for DCIS increased the likelihood of receiving mastectomy vs BCS at a subsequent breast event, even among women who had not previously received radiotherapy for DCIS. Adjusted odds ratios for receiving mastectomy were 1.43 (95% CI, 1.10-1.85) and 1.90 (95% CI, 1.27-2.84) in SEER and SEER-Medicare databases, respectively, among women residing in an HSA with the greatest radiotherapy use vs the least, corresponding to an adjusted increase from 40.8% to 49.6%, and from 38.6% to 54.5%. CONCLUSIONS AND RELEVANCE: Areas with more radiotherapy use for DCIS had increased use of mastectomy at the time of a second breast event even among patients eligible for breast conservation. This association suggests that physician-related factors are affecting the likelihood of breast preservation.

Cost Effectiveness of the Oncotype DX DCIS Score for Guiding Treatment of Patients With Ductal Carcinoma In Situ.

Purpose The Oncotype DX DCIS Score short form (DCIS Score) estimates the risk of an ipsilateral breast event (IBE) in patients with ductal carcinoma in situ (DCIS) treated with breast-conserving surgery without adjuvant radiation therapy (RT). We determined the cost effectiveness of strategies using this test. Materials and Methods We developed a Markov model simulating 10-year outcomes for 60-year-old women eligible for the Eastern Cooperative Oncology Group E5194 study (cohort 1: low/intermediate-grade DCIS, ≤ 2.5 cm; cohort 2: high-grade DCIS, ≤ 1 cm) with each of five strategies: (1) no testing, no RT; (2) no testing, RT only for cohort 2; (3) no RT for low-grade DCIS, test for intermediate- and high-grade DCIS, RT for intermediate- or high-risk scores; (4) test all, RT for intermediate- or high-risk scores; and (5) no testing, RT for all. We used utilities and costs extracted from the literature and Medicare claims to determine incremental cost-effectiveness ratios and examined the number of women needed to irradiate per IBE prevented. Results No strategy using the DCIS Score was cost effective. The most cost-effective strategy (RT for none or RT for all) was sensitive to small differences between the utilities of receiving or not receiving RT and remaining without recurrence. The numbers needed to irradiate per IBE prevented were 10.5, 9.1, 7.5, and 13.1 for strategies 2 to 5, respectively, relative to strategy 1. Conclusion Strategies using the DCIS Score lowered the proportion of women undergoing RT per IBE prevented. However, no strategy incorporating the DCIS Score was cost effective. The cost effectiveness of RT was exquisitely utility sensitive, highlighting the importance of engaging patient preferences in this decision. Physicians should discuss trade-offs associated with omitting or adding adjuvant RT with each patient to maximize quality-of-life outcomes.

The Role of Intraoperative Pathologic Assessment in the Surgical Management of Ductal Carcinoma In Situ.

BACKGROUND: Re-excision surgeries for the treatment of ductal carcinoma in situ (DCIS) put a strain on patients and healthcare resources; however, intraoperative pathologic assessment of DCIS may lead to a reduction in these additional surgeries. This study examined the relationship between intraoperative pathologic assessment and subsequent operations in patients with a diagnosis of DCIS. METHODS: Surveillance, Epidemiology, and End Results-Medicare patients diagnosed with DCIS from 1999 to 2007 who initially underwent partial mastectomy, without axillary surgery, were included in this study. Use of intraoperative frozen section or touch preparation during the initial surgery was assessed. Multivariable logistic regression was used to describe the relationship between the use of intraoperative pathologic assessment and any subsequent mastectomy or partial mastectomy within 90 days of the initial partial mastectomy. RESULTS: Of 8259 DCIS patients, 3509 (43 %) required a second surgery, and intraoperative pathologic assessment was performed for 2186 (26 %). Intraoperative pathologic assessment had no statistically significant effect on whether or not a subsequent breast surgery occurred (adjusted odds ratio 1.07, 95 % confidence interval 0.95-1.21; p = 0.293). Patient residence in a rural area, tumor size ≥2 cm, and poorly differentiated tumor grade were associated with a greater likelihood of subsequent surgery, while age 80 years and older was associated with a lower likelihood of subsequent surgery. CONCLUSIONS: The use of intraoperative frozen section or touch preparation during partial mastectomy from 1999 to 2007 was not associated with a reduction in subsequent breast operations in women with DCIS. These results highlight the need to identify cost-effective tools and strategies to reduce the need for additional surgery in patients with DCIS.

Prospective assessment of deep inspiration breath-hold using 3-dimensional surface tracking for irradiation of left-sided breast cancer.

PURPOSE: Deep inspiration breath hold (DIBH) is used to decrease cardiac irradiation during radiation therapy (RT) for breast cancer. The patients most likely to benefit and the impact on treatment time remain largely unknown. We sought to identify predictors for the use of DIBH and to quantify differences in dosimetry and treatment time using a prospective registry. METHODS AND MATERIALS: A total of 150 patients with left breast cancer were enrolled. All patients were simulated with both free breathing (FB) and DIBH. RT was delivered by either modality. Alternate scans were planned with use of deformable registration to include identical RT volumes. DIBH patients were monitored by a real-time surface tracking system, AlignRT (Vision RT, Ltd, London, United Kingdom). Baseline characteristics and treatment times were compared by Fisher exact test and Wilcoxon rank sum test. Dosimetric endpoints were analyzed by Wilcoxon signed rank test, and linear regression identified predictors for change in mean heart dose (∆MHD). RESULTS: We treated 38 patients with FB and 110 with DIBH. FB patients were older, more likely to have heart and lung disease, and less likely to receive chemotherapy or immediate reconstruction (all P < .05). Treatment times were not significantly different, but DIBH patients had greater variability in times (P = .0002). Of 146 evaluable patients, DIBH resulted in >20 cGy improvement in MHD in 107 patients but a >20 cGy increase in MHD in 14. Both MHD and lung V20 were significantly lower in DIBH than in paired FB plans. On multivariate analysis, younger age (4.18 cGy per year; P < .0001), higher body mass index (6.06 cGy/kg/m(2); P = .0018), and greater change in lung volumes (130 cGy/L; P = .003) were associated with greater ∆MHD. CONCLUSIONS: DIBH improves cardiac dosimetry without significantly impacting treatment time in most patients. Greater inspiratory lung volumes augment this benefit. Because the improvement with DIBH was not uniform, patients should be scanned with both FB and DIBH.

Medical Malpractice Claims in Radiation Oncology: A Population-Based Study 1985-2012.

PURPOSE: The purpose of this study was to determine trends in radiation oncology malpractice claims and expenses during the last 28 years and to compare radiation oncology malpractice claims to those of other specialties. METHODS AND MATERIALS: We performed a retrospective analysis of closed malpractice claims filed from 1985 to 2012, collected by a nationwide medical liability insurance trade association. We analyzed characteristics and trends among closed claims, indemnity payments (payments to plaintiff), and litigation expenses. We also compared radiation oncology malpractice claims to those of 21 other medical specialties. Time series dollar amounts were adjusted for inflation (2012 was the index year). RESULTS: There were 1517 closed claims involving radiation oncology, of which 342 (22.5%) were paid. Average and median indemnity payments were $276,792 and $122,500, respectively, ranking fifth and eighth, respectively, among the 22 specialty groups. Linear regression modeling of time trends showed decreasing total numbers of claims (ß = -1.96 annually, P=.003), increasing average litigation expenses paid (ß = +$1472 annually, P ≤ .001), and no significant changes in average indemnity payments (ß = -$681, P=.89). CONCLUSIONS: Medical professional liability claims filed against radiation oncologists are not common and have declined in recent years. However, indemnity payments in radiation oncology are large relative to those of many other specialties. In recent years, the average indemnity payment has been stable, whereas litigation expenses have increased.

Cost-effectiveness analysis of SBRT versus IMRT for low-risk prostate cancer.

OBJECTIVES: Intensity-modulated radiation therapy (IMRT) has been established as the standard external-beam modality in treating low-risk prostate cancer. Stereotactic body radiotherapy (SBRT) is a novel approach involving high-dose radiotherapy in 5 fractions. This analysis compared their cost-effectiveness. METHODS: A Markov model was constructed to delineate the health states after treatment with IMRT and SBRT. Disease, treatment, and toxicity data were extracted from the literature. Costs included both robotic (R-SBRT) and nonrobotic (NR-SBRT) reimbursement. Deterministic and probabilistic sensitivity analyses (PSA) were performed over a wide range of potential parameters. RESULTS: The quality-adjusted life expectancy after IMRT was slightly higher than after SBRT, because we assumed worse toxicity after SBRT. However, the incremental cost-effectiveness ratios (ICER) for IMRT over R-SBRT and NR-SBRT were $285,000 and $591,100/quality-adjusted life year (QALY), respectively. On sensitivity analysis, SBRT was almost always the cost-effective therapy, in which the ICER for IMRT was generally over $100,000/QALY. Reimbursement for R-SBRT versus NR-SBRT significantly influenced its ICER. Treatment efficacy, rectal toxicity and impotence, and the potential for unforeseen SBRT late effects were the most critical parameters in the model; when including these uncertain parameters in a PSA, SBRT was still most likely to be cost-effective at a willingness to pay of $100,000/QALY. CONCLUSIONS: SBRT clearly contained more value than IMRT for external-beam treatment. Given the increasing prevalence of the disease and its superb convenience, intensive research should be performed on this novel modality, including the marginal benefit and cost of robotic treatment.

Decision analysis and cost-effectiveness analysis for comparative effectiveness research--a primer.

Although the analysis of real-world data is the foundation of comparative effectiveness analysis, not all clinical questions are easily approached with patient-derived information. Decision analysis is a set of modeling and analytic tools that simulate treatment and disease processes, including the incorporation of patient preferences, thus generating optimal treatment strategies for varying patient, disease, and treatment conditions. Although decision analysis is informed by evidence-derived outcomes, its ability to test treatment strategies under different conditions that are realistic but not necessarily reported in the literature makes it a useful and complementary technique to more standard data analysis. Similarly, cost-effectiveness analysis is a discipline in which the relative costs and benefits of treatment alternatives are rigorously compared. With the well-recognized increase in highly technical, costly radiation therapy technologies, the cost-effectiveness of these different treatments would come under progressively more scrutiny. In this review, we discuss the theoretical and practical aspects of decision analysis and cost-effectiveness analysis, providing examples that highlight their methodology and utility.

Use of stereotactic radiosurgery for brain metastases from non-small cell lung cancer in the United States.

PURPOSE: The indications for treatment of brain metastases from non-small cell lung cancer (NSCLC) with stereotactic radiosurgery (SRS) remain controversial. We studied patterns, predictors, and cost of SRS use in elderly patients with NSCLC. METHODS AND MATERIALS: Using the Surveillance, Epidemiology, and End Results-Medicare (SEER-Medicare) database, we identified patients with NSCLC who were diagnosed with brain metastases between 2000 and 2007. Our cohort included patients treated with radiation therapy and not surgical resection as initial treatment for brain metastases. RESULTS: We identified 7684 patients treated with radiation therapy within 2 months after brain metastases diagnosis, of whom 469 (6.1%) cases had billing codes for SRS. Annual SRS use increased from 3.0% in 2000 to 8.2% in 2005 and varied from 3.4% to 12.5% by specific SEER registry site. After controlling for clinical and sociodemographic characteristics, we found SRS use was significantly associated with increasing year of diagnosis, specific SEER registry, higher socioeconomic status, admission to a teaching hospital, no history of participation in low-income state buy-in programs (a proxy for Medicaid eligibility), no extracranial metastases, and longer intervals from NSCLC diagnosis. The average cost per patient associated with radiation therapy was 2.19 times greater for those who received SRS than for those who did not. CONCLUSIONS: The use of SRS in patients with metastatic NSCLC increased almost 3-fold from 2000 to 2005. In addition, we found significant variations in SRS use across SEER registries and socioeconomic quartiles. National practice patterns in this study suggested both a lack of consensus and an overall limited use of the approach among elderly patients before 2008.

Radiation therapy for ductal carcinoma in situ: a decision analysis.

BACKGROUND: The benefit of adding radiation therapy after excision of ductal carcinoma in situ (DCIS) is widely debated. Randomized clinical trials are underpowered to delineate long-term outcomes after radiation. METHODS: The authors of this report constructed a Markov decision model to simulate the clinical course of DCIS in a woman aged 60 years who received treatment with either of 2 breast-conserving strategies: excision alone or excision plus radiation therapy. Sensitivity analyses were used to study the influence of risk of local recurrence, likelihood of invasive disease at recurrence, surgical choice at recurrence, and patient age at diagnosis on treatment outcomes. RESULTS: The addition of radiation therapy was associated with slight improvements in invasive disease-free and overall survival. However, radiation therapy decreased the chance of having both breasts intact over a patient's lifetime. Radiation therapy improved survival by 2.1 months for women who were diagnosed with DCIS at age 60 years but decreased the chance of having both breasts by 8.6% relative to excision alone. The differences in outcomes between the treatment strategies became smaller with increasing age at diagnosis. Sensitivity analyses revealed a greater benefit for radiation with an increased likelihood of invasive recurrence. The decrement in breast preservation with radiation therapy was mitigated by an increased likelihood of mastectomy at the time of recurrence or new breast cancer diagnosis. CONCLUSIONS: The current analysis quantified the benefits of radiation after excision of DCIS but also revealed that radiation therapy may increase the likelihood of eventual mastectomy. Therefore, the authors concluded that patient age and preferences should be considered when making the decision to add or forgo radiation for DCIS.

Cost-effectiveness analysis of stereotactic body radiotherapy and radiofrequency ablation for medically inoperable, early-stage non-small cell lung cancer.

PURPOSE: The standard management of medically inoperable Stage I non-small-cell lung cancer (NSCLC) conventionally has been fractionated three-dimensional conformal radiation therapy (3D-CRT). The relatively poor local control rate and inconvenience associated with this therapy have prompted the development of stereotactic body radiotherapy (SBRT), a technique that delivers very high doses of irradiation typically over 3 to 5 sessions. Radiofrequency ablation (RFA) has also been investigated as a less costly, single-day therapy that thermally ablates small, peripheral tumors. The cost-effectiveness of these three techniques has never been compared. METHODS AND MATERIALS: We developed a Markov model to describe health states of 65-year-old men with medically inoperable NSCLC after treatment with 3D-CRT, SBRT, and RFA. Given their frail state, patients were assumed to receive supportive care after recurrence. Utility values, recurrence risks, and costs were adapted from the literature. Sensitivity analyses were performed to model uncertainty in these parameters. RESULTS: The incremental cost-effectiveness ratio for SBRT over 3D-CRT was $6,000/quality-adjusted life-year, and the incremental cost-effectiveness ratio for SBRT over RFA was $14,100/quality-adjusted life-year. One-way sensitivity analysis showed that the results were robust across a range of tumor sizes, patient utility values, and costs. This result was confirmed with probabilistic sensitivity analyses that varied local control rates and utilities. CONCLUSION: In comparison to 3D-CRT and RFA, SBRT was the most cost-effective treatment for medically inoperable NSCLC over a wide range of treatment and disease assumptions. On the basis of efficacy and cost, SBRT should be the primary treatment approach for this disease.

Cost effectiveness and screening interval of lipid screening in Hodgkin's lymphoma survivors.

PURPOSE: Survivors of Hodgkin's lymphoma (HL) who received mediastinal irradiation have an increased risk of coronary heart disease. We evaluated the cost effectiveness of lipid screening in survivors of HL and compared different screening intervals. METHODS: We developed a decision-analytic model to evaluate lipid screening in a hypothetical cohort of 30-year-old survivors of HL who survived 5 years after mediastinal irradiation. We compared the following strategies: no screening, and screening at 1-, 3-, 5-, or 7-year intervals. Screen-positive patients were treated with statins. Markov models were used to calculate life expectancy, quality-adjusted life expectancy, and lifetime costs. Baseline probabilities, transition probabilities, and utilities were derived from published studies and US population data. Costs were estimated from Medicare fee schedules and the medical literature. Sensitivity analyses were performed. RESULTS: Using an incremental cost-effectiveness ratio (ICER) threshold of $100,000 per quality-adjusted life-year (QALY) saved, lipid screening at every interval was cost effective relative to a strategy of no screening. When comparing screening intervals, a 3-year interval was cost effective relative to a 5-year interval, but annual screening, relative to screening every 3 years, had an ICER of more than $100,000/QALY saved. Factors with the most influence on the results included risk of cardiac events/death after HL, efficacy of statins in reducing cardiac events/death, and costs of statins. CONCLUSION: Lipid screening in survivors of HL, with statin therapy for screen-positive patients, improves survival and is cost effective. A screening interval of 3 years seems reasonable in the long-term follow-up of survivors of HL.

Partial-breast irradiation versus whole-breast irradiation for early-stage breast cancer: a cost-effectiveness analysis.

PURPOSE: Accelerated partial-breast irradiation (PBI) is a new treatment paradigm for patients with early-stage breast cancer. Although PBI may lead to greater local recurrence rates, it may be cost-effective because of better tolerability and lower cost. We aim to determine the incremental cost-effectiveness of PBI compared with whole-breast radiation therapy (WBRT) for estrogen receptor-positive postmenopausal women treated for early-stage breast cancer. METHODS AND MATERIALS: We developed a Markov model to describe health states in the 15 years after radiotherapy for early-stage breast cancer. External beam (EB) and MammoSite (MS) PBI were considered and assumed to be equally effective, but carried different costs. Patients received tamoxifen, but not chemotherapy. Utilities, recurrence risks, and costs were adapted from the literature; the baseline utility for no disease after radiotherapy was set at 0.92. Probabilistic sensitivity analyses were performed to model uncertainty in the PBI hazard ratio, recurrence pattern, and patient utilities. Costs (in 2004 US dollars) and quality-adjusted life-years were discounted at 3%/y. RESULTS: The incremental cost-effectiveness ratio for WBRT compared with EB-PBI was $630,000/quality-adjusted life-year; WBRT strongly dominated MS-PBI. One-way sensitivity analysis found that results were sensitive to PBI hazard ratio, recurrence pattern, baseline recurrence risk, and no evidence of disease PBI utility values. Probabilistic sensitivity showed that EB-PBI was the most cost-effective technique over a wide range of assumptions and societal willingness-to-pay values. CONCLUSIONS: EB-PBI was the most cost-effective strategy for postmenopausal women with early-stage breast cancer. Unless the quality of life after MS-PBI proves to be superior, it is unlikely to be cost-effective.

Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: a modeling analysis.

BACKGROUND: Adjuvant endocrine treatment with aromatase inhibitors improves disease-free survival compared with tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer. This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). METHODS: We created a Markov model to determine whether tamoxifen or aromatase inhibitor monotherapy maximized 5-year disease-free survival for patients with the wild-type CYP2D6 genotype (wt/wt). Annual risks of recurrence with aromatase inhibitors and tamoxifen in breast cancer patients who were not selected by CYP2D6 genotype were derived from the Breast International Group 1-98 trial. Genotype frequencies and the hazard ratio for cancer recurrence on tamoxifen among patients with the *4/*4 genotype relative to the wt/wt or wt/*4 genotypes (HR(*4/*4) = 1.86) were based on data from an analysis of the North Central Cancer Treatment Group trial of adjuvant tamoxifen. We explored the impact of CYP2D6(*4) heterozygosity on disease-free survival for wt/wt patients by studying a range of effect (ie, recurrence on tamoxifen) estimates, from no effect of the single mutation (Eff(wt/*4) = 0, recurrence rate in wt/*4 patients same as that in wt/wt patients) to complete effect (Eff(wt/*4) = 1 recurrence rate in wt/*4 patients same as that in *4/*4 patients). RESULTS: With HR(*4/*4) = 1.86 and Eff(wt/*4) = 0.5, the 5-year disease-free survival of tamoxifen-treated patients with no mutations (wt/wt) was 83.9%, that is, essentially the same as that (84.0%) for genotypically unselected patients who were treated with aromatase inhibitors. With greater HR(*4/*4) estimates, disease-free survival with tamoxifen exceed that with aromatase inhibitors in wt/wt patients, even at lower assumed Eff(wt/*4) ratios. CONCLUSIONS: Modeling suggests that among patients who are wild type for CYP2D6, 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors. Endocrine therapy tailored to CYP2D6 genotype could be considered for women who are newly diagnosed with breast cancer, particularly those who have with concerns about either the relative toxicity or the increased cost of aromatase inhibitors.