Sex, racial/ethnic and socioeconomic disparities in patients with metastatic bone disease.

BACKGROUND: We have analyzed sex, race/ethnicity or socioeconomic disparities in the incidence of metastatic bone disease (MBD). METHODS: Patients with the diagnosis of MBD at presentation for five most common primary anatomical sites was extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset. Mean incidence of MBD for different sex, racial/ethnic and socioeconomic groups were compared. RESULTS: The five most common anatomical sites with MBD at presentation include "lung: (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal" (n = 7718) and "colon" (n = 3068). There was an increase in incidence of MBD among cancers originating from prostate (annual percentage change [APC] 4.94), renal (APC 2.55), and colon (APC 3.21) (p < 0.05 for all). Non-Hispanic Blacks had higher incidence of MBD for prostate and breast primary sites (p < 0.001). Non-Hispanic American Indian Alaskan Native had higher incidence of MBD for cancers originating from renal (p < 0.001) and colon (p = 0.049). A higher incidence of MBD was seen in lower socioeconomic status (SES) groups for the selected sites (p < 0.001). CONCLUSIONS: These findings suggest that there are multiple sex-related, racial/ethnic and SES disparities in the incidence of MBD from the 5 most common primary sites. Higher incidence seen among lower SES suggests delay in diagnosis and limited access to screening modalities.

Socioeconomic factors associated with limb salvage versus amputation for adult extremity bone sarcomas in patients with insurance coverage.

BACKGROUND: Limb salvage (LS) has become the preferred treatment for adult patients with bone sarcoma of the extremities. The decision to perform LS versus an amputation is often dictated by tumor characteristics, however there may be socioeconomic factors associated with LS. Previously this has been linked to insurance status, however currently there is a paucity of data examining socioeconomic factors in patients with medical insurance at the time of sarcoma diagnosis. Therefore, the purpose of the current study was to examine socioeconomic factors which could be associated with the decision to perform LS versus amputation for adult bone sarcoma patients. METHODS: Data from Optum Labs Data Warehouse, a national administrative claims database, was analyzed to identify patients with extremity bone sarcomas from 2006 to 2017. Bivariate regression was used to identify factors associated with LS versus amputation. RESULTS: Of 1,390 (743 males, 647 female) patients, 252 (18%) under amputation while 1,138 (82%) underwent LS. Lower extremity tumors (OR 4.72, p < 0.001), income <$75,000 (OR 1.85, p = 0.03), being treated a public hospital (OR 1.41, p = 0.04) and a hospital with <200 beds (OR 1.90, p = 0.006) were associated with amputation. Income ≥$125,000 (OR 0.62, 0.04) were associated with LS. CONCLUSION: In adult patients with medical insurance at the time of diagnosis, socioeconomic and hospital factors were associated with an amputation for bone sarcoma, with poorer patients, and those treated at smaller, and public hospitals more likely to undergo amputation.

Adjunct diagnostic strategies in improving diagnostic yields in image-guided biopsies of musculoskeletal neoplasms-A cost-effectiveness analysis.

BACKGROUND: Routine use of adjunct intraprocedural fresh frozen biopsy (FFP) or point-of-care (POC) cytology at the time of image-guided biopsy can improve diagnostic tissue yields for musculoskeletal neoplasms, but these are associated with increased costs. OBJECTIVE: This study aimed to ascertain the most cost-effective adjunctive test for image-guided biopsies of musculoskeletal neoplasms. METHODS: This expected value cost-effectiveness microsimulation compared the payoffs of cost (2020 United States dollars) and effectiveness (quality-adjusted life, in days) on each of the competing strategies. A literature review and institutional data were used to ascertain probabilities, diagnostic yields, utility values, and direct medical costs associated with each strategy. Payer and societal perspectives are presented. One- and two-way sensitivity analyses evaluated model uncertainties. RESULTS: The total cost and effectiveness for each of the strategies were $1248.98, $1414.09, $1980.53, and 80.31, 79.74, 79.69 days for the use of FFP, permanent pathology only, and POC cytology, respectively. The use of FFP dominated the competing strategies. Sensitivity analyses revealed FFP as the most cost-effective across all clinically plausible values. CONCLUSIONS: Adjunct FFP is most cost-effective in improving the diagnostic yield of image-guided biopsies for musculoskeletal neoplasms. These findings are robust to sensitivity analyses using clinically plausible probabilities.

IAP Chemotherapy Regimen Is a Viable and Cost-effective Option in Children and Adolescents With Osteosarcoma: A Comparative Analysis With MAP Regimen on Toxicity and Survival.

BACKGROUND: Cisplatin and doxorubicin are integral components of chemotherapy regimens in the treatment of osteosarcoma. Choice of third agent high-dose methotrexate (HDMTX) or an alkylating agent such as ifosfamide is debatable. The present study compared the impact of MAP (HDMTX-doxorubicin-cisplatin) and IAP (ifosfamide-doxorubicin-cisplatin) chemotherapy regimens on toxicity and survival in children and adolescents with osteosarcoma. MATERIALS AND METHODS: This was a retrospective study including patients 18 years and younger with osteosarcoma during the study period. Clinical, demographic, chemotherapy regimen, and surgical details and treatment-related toxicity were retrieved from hospital medical records. Prognostic factors affecting overall survival (OS) and event-free survival (EFS) were analyzed. RESULTS: Among 102 patients included in the study, 59 (57.8%) and 43 (42.2%) patients were treated with MAP and IAP regimens, respectively. Two groups were comparable in terms of pretreatment characteristics and surgical treatment. Overall, 95.9% patients underwent limb salvage surgery. There was a statistically increased incidence in supportive care admissions and delay in starting the next cycle of chemotherapy in the MAP group. Among the MAP cohort, the 5-year OS and EFS were 62% and 55% compared with 47% and 44%, respectively, in the IAP cohort (P=0.143 and 0.316, respectively). On univariate and multivariate analyses, statistically significant factors affecting EFS of the whole group included tumor size, stage, site of metastasis, histologic necrosis, and type of surgery. CONCLUSIONS: OS and EFS with both regimens were similar. However, the MAP regimen was associated with a statistically significant increase in incidence of supportive care admissions, delay in next cycle of chemotherapy, and predicted higher cost of treatment.

Has the Affordable Care Act Been Associated with Increased Insurance Coverage and Early-stage Diagnoses of Bone and Soft-tissue Sarcomas in Adults?

BACKGROUND: Treatment of bone and soft-tissue sarcomas can be costly, and therefore, it is not surprising that insurance status of patients is a prognostic factor in determining overall survival. Furthermore, uninsured individuals with suspected bone and/or soft-tissue masses routinely encounter difficulty in obtaining access to basic healthcare (such as office visits, radiology scans), and therefore are more likely to be diagnosed with later stages at presentation. The Patient Protection and Affordable Care Act (ACA) mandate of 2010 aimed to increase access to care for uninsured individuals by launching initiatives, such as expanding Medicaid eligibility, subsidizing private insurance, and developing statewide mandates requiring individuals to have a prescribed minimum level of health insurance. Although prior reports have demonstrated that the ACA increased both coverage and the proportion of early-stage diagnoses among patients with common cancers (including breast, colon, prostate, and lung), it is unknown whether similar improvements have occurred for patients with bone and soft-tissue sarcomas. Understanding changes in insurance coverages and stage at diagnosis of patients with bone and soft-tissue sarcomas would be paramount in establishing policies that will ensure orthopaedic cancer care is made equitable and accessible to all. QUESTIONS/PURPOSES: (1) Has the introduction of the ACA been associated with changes in insurance coverage for adult patients with newly diagnosed bone and soft-tissue sarcomas? (2) Did the introduction of health reforms under the ACA lead to an increased proportion of sarcoma diagnoses occurring at earlier disease stages? METHODS: The 2007 to 2015 Surveillance, Epidemiology and End Results database was queried using International Classification of Diseases for Oncology codes for primary malignant bone tumors of the upper and lower extremity (C40.0 to C40.3), unspecified or other overlapping bone, articular cartilage, and joint and/or ribs, sternum, or clavicle (C40.8 to C40.9, C41.3, and C41.8 to C41.9), vertebral column (C41.2), pelvis (C41.4, C41.8, and C41.9), and soft-tissue sarcomas of the upper or lower extremity and/or pelvis (C49.1, C49.2, and C49.5). A total of 15,287 patients with newly diagnosed cancers were included, of which 3647 (24%) were malignant bone tumors and 11,640 (76%) were soft-tissue sarcomas. The study sample was divided into three cohorts according to specified time periods: pre-ACA from 2007 to 2010 (6537 patients), pre-Medicaid expansion from 2011 to 2013 (5076 patients), and post-Medicaid expansion from 2014 to 2015 (3674 patients). The Pearson chi square tests were used to assess for changes in the proportion of Medicaid and uninsured patients across the specified time periods: pre-ACA, pre-expansion and post-expansion. A differences-in-differences analysis was also performed to assess changes in insurance coverage for Medicaid and uninsured patients among states that chose to expand Medicaid coverage in 2014 under the ACA's provision versus those who opted out of Medicaid expansion. Since the database switched to using the American Joint Commission on Cancer (AJCC) 7th edition staging system in 2010, linear regression using data only from 2010 to 2015 was performed that assessed changes in cancer stage at diagnosis from 2010 to 2015 alone. After stratifying by cancer type (bone or soft-tissue sarcoma), Pearson chi square tests were used to assess for changes in the proportion of patients who were diagnosed with early, late, and unknown stage at presentation before Medicaid expansion (2011-2013) and after Medicaid expansion (2014-2015) among states that chose to expand versus those who did not. RESULTS: After stratifying by time cohorts: pre-ACA (2007 to 2010), pre-expansion (2011 to 2013) and post-expansion (2014 to 2015), we observed that the most dramatic changes occurred after Medicaid eligibility was expanded (2014 onwards), with Medicaid proportions increasing from 12% (pre-expansion, 2011 to 2013) to 14% (post-expansion, 2014 to 2015) (p < 0.001) and uninsured proportions decreasing from 5% (pre-expansion, 2011 to 2013) to 3% (post-expansion, 2014 to 2015) (p < 0.001). A differences-in-differences analysis that assessed the effect of Medicaid expansion showed that expanded states had an increase in the proportion of Medicaid patients compared with non-expanded states, (3.6% [95% confidence interval 0.4 to 6.8]; p = 0.03) from 2014 onwards. For the entire study sample, the proportion of early-stage diagnoses (I/II) increased from 56% (939 of 1667) in 2010 to 62% (1137 of 1840) in 2015 (p = 0.003). Similarly, the proportion of unknown stage diagnoses decreased from 11% (188 of 1667) in 2010 to 7% (128 of 1840) in 2015 (p = 0.002). There was no change in proportion of late-stage diagnoses (III/IV) from 32% (540 of 1667) in 2010 to 31% (575 of 1840) in 2015 (p = 0.13). CONCLUSION: Access to cancer care for patients with primary bone or soft-tissue sarcomas improved after the ACA was introduced, as evidenced by a decrease in the proportion of uninsured patients and corresponding increase in Medicaid coverage. Improvements in coverage were most significant among states that adopted the Medicaid expansion of 2014. Furthermore, we observed an increasing proportion of early-stage diagnoses after the ACA was implemented. The findings support the preservation of the ACA to ensure cancer care is equitable and accessible to all vulnerable patient populations. LEVEL OF EVIDENCE: Level III, therapeutic study.

Healthcare resource utilization and costs in patients with multiple myeloma with and without skeletal-related events.

AIM: To compare healthcare resource use and costs between newly diagnosed multiple myeloma (NDMM) patients with and without skeletal-related events (SREs). METHODS: Adults newly diagnosed with MM (1 January 2006 and 30 June 2017) with at least 12 months continuous health coverage prior to diagnosis were identified using the IBM MarketScan administrative claims. To control for baseline differences, NDMM patients with SREs were propensity score matched to NDMM patients without SREs. Outcomes included annual HRU and costs during follow-up along with number and type of SREs (SRE cohort only). Patients with SREs were stratified by number of SREs, and annual SRE-related costs were reported. Student's t test and Chi-squared test were used to compare outcomes. RESULTS: Before matching, the 6648 patients in the SRE cohort had more comorbidities, were more likely to have MM treatment, and had higher pre-index healthcare costs than the 7458 patients in the non-SRE cohort. After matching, cohorts of 3432 patients were well balanced on baseline characteristics. Patients with SREs (vs. without SREs) had significantly higher inpatient, outpatient, and pharmacy HRU. Patients with SREs had significantly higher mean annual all-cause healthcare costs ($213,361 vs. $94,896, p < 0.001) with hospitalization being the leading driver of increased costs (38.7% of total). Among 6648 patients with SREs, the mean annual SRE-related healthcare costs were $39,603, $45,463, and $50,111 for patients with one, two, and three or more events, respectively. CONCLUSIONS: NDMM patients with SREs have more than twice the all-cause healthcare costs than matched patients without SREs. Costs increase with the number of SRE events.

Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas.

BACKGROUND: While racial/ethnic survival disparities have been described in pediatric oncology, the impact of income has not been extensively explored. We analyzed how public insurance influences 5-year overall survival (OS) in young patients with sarcomas. METHODS: The University of California San Francisco Cancer Registry was used to identify patients aged 0-39 diagnosed with bone or soft tissue sarcomas between 2000 and 2015. Low-income patients were defined as those with no insurance or Medicaid, a means-tested form of public insurance. Survival curves were computed using the Kaplan-Meier method and compared using log-rank tests and Cox models. Causal mediation was used to assess whether the association between public insurance and mortality is mediated by metastatic disease. RESULTS: Of 1106 patients, 39% patients were classified as low-income. Low-income patients were more likely to be racial/ethnic minorities and to present with metastatic disease (OR 1.96, 95% CI 1.35-2.86). Low-income patients had significantly worse OS (61% vs 71%). Age at diagnosis and extent of disease at diagnosis were also independent predictors of OS. When stratified by extent of disease, low-income patients consistently had significantly worse OS (localized: 78% vs 84%, regional: 64% vs 73%, metastatic: 23% vs 30%, respectively). Mediation analysis indicated that metastatic disease at diagnosis mediated 15% of the effect of public insurance on OS. CONCLUSIONS: Low-income patients with bone and soft tissue sarcomas had decreased OS regardless of disease stage at presentation. The mechanism by which insurance status impacts survival requires additional investigation, but may be through reduced access to care.

Is There an Association Between Insurance Status and Survival and Treatment of Primary Bone and Extremity Soft-tissue Sarcomas? A SEER Database Study.

BACKGROUND: Several recently published population-based studies have highlighted the association between insurance status and survival in patients with various cancers such as breast, head and neck, testicular, and lymphoma [22, 24, 38, 41]. Generally, these studies demonstrate that uninsured patients or those with Medicaid insurance had poorer survival than did those who had non-Medicaid insurance. However, this discrepancy has not been studied in patients with primary bone and extremity soft-tissue sarcomas, a unique oncological population that typically presents late in the disease course and often requires referral and complex treatment at tertiary care centers-issues that health insurance coverage disparities could aggravate. QUESTIONS/PURPOSES: (1) What is the relationship between insurance status and cause-specific mortality? (2) What is the relationship between insurance status and the prevalence of distant metastases? (3) What is the relationship between insurance status and the proportion of limb salvage surgery versus amputation? METHODS: The Surveillance, Epidemiology, and End Results database (SEER) was used to identify a total of 12,008 patients: 4257 patients with primary bone sarcomas and 7751 patients with extremity soft-tissue sarcomas, who were diagnosed and treated between 2007 and 2014. Patients were categorized into one of three insurance groups: insured with non-Medicaid insurance, insured with Medicaid, and uninsured. Patients without information available regarding insurance status were excluded (2.7% [113 patients] with primary bone sarcomas and 3.1% [243 patients] with extremity soft-tissue sarcomas.) The association between insurance status and survival was assessed using a Cox proportional hazards regression analysis adjusted for patient age, sex, race, ethnicity, extent of disease (lymph node and metastatic involvement), tumor grade, tumor size, histology, and primary tumor site. RESULTS: Patients with primary bone sarcomas with Medicaid insurance had reduced disease-specific survival than did patients with non-Medicaid insurance (hazard ratio 1.3 [95% confidence interval 1.1 to 1.6]; p = 0.003). Patients with extremity soft-tissue sarcomas with Medicaid insurance also had reduced disease-specific survival compared with those with non-Medicaid insurance (HR 1.2 [95% CI 1.0 to 1.5]; p = 0.019). Patients with primary bone sarcomas (relative risk 1.8 [95% CI 1.3 to 2.4]; p < 0.001) and extremity soft-tissue sarcomas (RR 2.4 [95% CI 1.9 to 3.1]; p < 0.001) who had Medicaid insurance were more likely to have distant metastases at the time of diagnosis than those with non-Medicaid insurance. Patients with primary bone sarcomas (RR 1.8 [95% CI 1.4 to 2.1]; p < 0.001), and extremity soft-tissue sarcomas (RR 2.4 [95% CI 1.9 to 3.0]; p < 0.001) that had Medicaid insurance were more likely to undergo amputation than patients with non-Medicaid insurance. Patients with primary bone and extremity soft-tissue sarcomas who were uninsured were not more likely to have distant metastases at the time of diagnosis and did not have a higher proportion of amputation surgery as compared with patients with non-Medicaid insurance. However, uninsured patients with extremity soft-tissue sarcomas still displayed reduction in disease-specific survival (HR 1.6 [95% CI 1.2 to 2.1]; p = 0.001). CONCLUSIONS: Disparities manifested by differences in insurance status were correlated with an increased risk of metastasis at the time of diagnosis, reduced likelihood of treatment with limb salvage procedures, and reduced disease-specific survival in patients with primary bone or extremity soft-tissue sarcomas. Although several potentially confounding variables were controlled for, unmeasured confounding played a role in these results. Future studies should seek to identify what factors drive the finding that substandard insurance status is associated with poorer survival after a cancer diagnosis. Candidate variables might include medical comorbidities, treatment delays, time to first presentation to medical care and time to diagnosis, type of treatment received, distance travelled to treatments and transportation barriers, out-of-pocket payment burden, as well as educational and literacy status. These variables are almost certainly associated with socioeconomic deprivation in a vulnerable patient population, and once identified, treatment can become targeted to address these systemic inequities. LEVEL OF EVIDENCE: Level III, therapeutic study.

Persistent Use of Extended Fractionation Palliative Radiotherapy for Medicare Beneficiaries With Metastatic Breast Cancer, 2011 to 2014.

INTRODUCTION: With no evidence to support extended radiation courses for the palliation of bone metastases, multiple guidelines were issued discouraging its use. We assessed contemporary use and cost of prolonged palliative radiotherapy in Medicare beneficiaries with bone metastases from breast cancer. METHODS: We conducted a retrospective, longitudinal study of palliative radiotherapy use among fee-for-service Medicare beneficiaries with bone metastasis from breast cancer who underwent palliative radiotherapy during 2011 to 2014. Patients were categorized according to the number of days (fractions) on which they received palliative radiotherapy: 1, 2 to 10, 11 to 19, or 20 to 30. We examined the association of clinical, demographic, and provider characteristics with the use of extended (≥11 fractions) or very extended (≥20 fractions) fractionation with logistic regression models. We also compared the cost of different fractionation schemes from the payer perspective. RESULTS: Of the 7547 patients in the sample (mean age, 71 y), 3084 (40.8%) received extended fractionation. The proportion of patients receiving 11 to 19 (34.7% in 2011 and 28.1% in 2014, trend P<0.001) and 20 to 30 treatments (10.3% in 2011 to 9.0% in 2014, trend P=0.07) decreased modestly over time. Patients with comorbidities were less likely to undergo extended fractionation (34.4% for ≥3 comorbidities vs. 44.9% for 0 comorbidities; adjusted odds ratio 0.67 [95% confidence interval, 0.58-0.76]). Patients treated at free-standing practices were more likely to undergo extended fractionation (47.9%) compared with those treated at hospital-based practices (37.3%, P<0.001; adjusted odds ratio, 1.49 [95% confidence interval, 1.35-1.65]). The mean cost of treatment varied from $633 (SD $240) for single-fraction treatment, to $3566 (SD $1349) for 11 to 19 fractions, to $6597 (SD $2893) for 20 to 30 fractions. CONCLUSION: The use of prolonged courses of palliative radiotherapy among Medicare beneficiaries with breast cancer remained high in 2011 to 2014. The association between free-standing facility status and use of extended fractionation suggests that provider financial incentives may impact choice of treatment.

Evaluation of Treatment Patterns and Costs in Patients with Prostate Cancer and Bone Metastases.

BACKGROUND: There are a lack of guideline recommendations for patients with metastatic castration-resistant prostate cancer (mCRPC) undergoing treatment progression and sequencing. Understanding treatment patterns and associated utilization and costs may help inform stakeholders and guide decision making. OBJECTIVE: To describe treatment patterns and health care costs in prostate cancer (PC) patients with bone metastases treated with agents approved by the FDA for mCRPC. METHODS: 2 large integrated claims databases (MarketScan and PharMetrics) were used to identify males aged ≥ 18 years who were diagnosed and treated for PC (ICD-9-CM code 185.xx or 233.4) with bone metastases (ICD-9-CM code 198.5) from June 2013 to September 2014. Patients were required to be continuously enrolled for ≥ 6 months before and after initiation of treatment with abiraterone, cabazitaxel, docetaxel, enzalutamide, mitoxantrone, radium-223, sipuleucel-T, or other chemotherapy. Study endpoints included lines of therapy, health care resource utilization per patient per month (PPPM), PPPM costs, and mortality rate. Descriptive analysis was completed for the study sample, and survival function was calculated via Kaplan-Meier estimates. RESULTS: There were 953 patients meeting all inclusion criteria in the MarketScan database and 565 patients in the PharMetrics database. The median follow-up time was 18 months (interquartile range [IQR] = 14-23) for MarketScan and 14 months (IQR = 11-18) for PharMetrics. Mean age (SD) was 71 (± 10.7) and 66 (± 9.3) years, respectively. Before mCRPC treatment initiation, patients received palliative radiation therapy and bone antiresorptive therapy. For MarketScan and PharMetrics, respectively, 14.0% and 18.2% of patients received radiation therapy, 36.1% and 40.0% received denosumab; 16.5% and 16.8% received zoledronic acid; and 0.2% and 0.8% received pamidronate. Across both databases, abiraterone was the most commonly received bone metastasis treatment agent across all lines of therapy, except fourth line. Radium-223, cabazitaxel, and mitoxantrone were the least utilized therapies. The median cost PPPM during the post-index period was $10,916 (IQR=$5,334-$13,457) in MarketScan and $10,292 (IQR = $7,245-$14,699) in PharMetrics. The cost PPPM during the 6-month pre-index period was $2,643 (IQR = $850-$4,357) in MarketScan and $2,742 (IQR = $1,484-$4,730) in PharMetrics. CONCLUSIONS: Patients were treated mainly with abiraterone across most lines of care, with radium-223, cabazitaxel, and mitoxantrone as the least utilized therapies. Median costs PPPM increased by approximately $8,900 after initiation of FDA-approved agents for mCRPC, with the largest increase in cost stemming from oral medications. DISCLOSURES: Funding for this study was provided by Bayer HealthCare Pharmaceuticals. All authors were employees at Bayer HealthCare Pharmaceuticals at the time this study was conducted. This study was presented as a poster at the 2017 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.

[Cost of radiotherapy for bone metastases in France: A monocentric retrospective study]. / Coût de la radiothérapie des métastases osseuses en France : étude rétrospective monocentrique.

PURPOSE: The cost of radiotherapy is a concern for health systems. The conventional non fractionated or multifractionated schemes have shown the same efficacy in terms of pain relief but a non fractionated treatment seems less expensive. However, in general practice, multifractionated treatments are still the majority, which represents an additional cost for society. Moreover, the use of stereotactic body radiotherapy becomes more democratic and offers new curative perspectives, but at what price? MATERIAL AND METHODS: A monocentric retrospective study was conducted in a French radiotherapy department to evaluate and compare the cost of irradiation of uncomplicated bone metastases according to the selected radiotherapy regimen : 30Gy in 10 fractions, 20Gy in five fractions, 8Gy in one fraction or stereotactic body radiotherapy. RESULTS: Between January 2014 and December 2015, 91 patients receiving 116 treatments were included in the study, including 44 men (48%) and 47 women (52%) were 63 years old (25-88 years). Thirty-four treatments (29%) were performed by 30Gy in 10 fractions (30Gy group), 24 treatments (21%) by 20Gy in 5 fractions (20Gy group), 25 treatments (22%) by 8Gy in one fraction (8Gy group) and 33 treatments (28%) by stereotactic body radiotherapy (SBRT group). The cost of stereotactic body radiotherapy was significantly higher than that of three-dimensional treatments (P<0.001). If the cost of transport was added to this cost, stereotactic body radiotherapy remained the most expensive (P<0.001). The cost of the irradiation delivering 30Gy treatment was significantly higher than the cost of treatment with 20Gy (P=0.006) or 8Gy (P<0.001), even after adding the transport cost (P<0.001), with no significant difference between 20Gy and 8Gy (P=0.11). For the overall cost of treatment including the total cost of treatments, associated transport and reirradiation, stereotactic body radiotherapy was the most expensive treatment (P<0.001) and this cost was significantly higher in the 30Gy group than in the 20Gy group (P=0.012) or 8Gy group (P=0.001), with no significant difference between 20Gy and 8Gy (P=0.38). There was no significant difference in the cost of follow-up between 30Gy, 20Gy, 8Gy and stereotactic body radiotherapy at one month (P=0.09) but at three months (P=0.01) and six months (P=0.0001), this cost was significantly higher after a three-dimensional treatment. There was no significant difference in overall cost including initial radiotherapy, transport and overall follow-up over 6 months between groups (P=0.04). CONCLUSION: Stereotactic body radiotherapy is an efficient and curative irradiation technique but more expensive. It is preferred for some patients with a longer life expectancy in a non-palliative treatment setting. The treatment delivering 8Gy treatment appears to be the most cost-effective while leading to an equivalent efficiency to multifractionated treatments and preserving the quality of life of patients.

Denosumab versus bisphosphonates for the treatment of bone metastases from solid tumors: a systematic review.

BACKGROUND: Bone metastases are highly prevalent in breast, prostate, lung and colon cancers. Their symptoms negatively affect quality of life and functionality and optimal management can mitigate these problems. There are two different targeted agents to treat them: bisphosphonates (pamidronate and zoledronic acid) and the monoclonal antibody denosumab. Estimates of cost-effectiveness are still mixed. OBJECTIVE: To conduct a systematic review of economic studies that compares these two options. METHOD: Literature search comprised eight databases and keywords for bone metastases, bisphosphonates, denosumab, and economic studies were used. Data were extracted regarding their methodologic characteristics and cost-effectiveness analyses. All studies were evaluated regarding to its methodological quality. RESULTS: A total of 263 unique studies were retrieved and six met inclusion criteria. All studies were based on clinical trials and other existing literature data, and they had high methodological quality. Most found unfavorable cost-effectiveness for denosumab compared with zoledronic acid, with adjusted ICERS that ranged from $4638-87,354 per SRE avoided and from US$57,274-4.81 M. per QALY gained, which varied widely according to type of tumor, time horizon, among others. Results were sensitive to drug costs, time to first skeletal-related event (SRE), time horizon, and utility. CONCLUSIONS: Denosumab had unfavorable cost-effectiveness compared with zoledronic acid in most of the included studies. New economic studies based on real-world data and longer time horizons comparing these therapeutic options are needed.

Economic Evaluation of Treating Skeletal-Related Events among Prostate Cancer Patients.

OBJECTIVES: To evaluate the economic burden of treating skeletal-related events (SREs) in prostate cancer (PC) patients with bone metastasis from an insurer perspective. METHODS: We conducted a retrospective cohort analysis using claims data. PC patients with bone metastasis were identified in the MarketScan Databases between January 1, 2004, and March 1, 2014. The propensity score matching approach was used to match patients with SREs to those without SREs. A pseudo-SRE date was assigned to the control group. We compared 6-month and 12-month total costs of patients between two groups after the SRE or pseudo-SRE date. All costs were adjusted to 2014 US$. RESULTS: We identified 4083 PC men with bone metastasis, from which 787 patients with SREs were matched (1:1) to those without SREs. On average, the total 6-month cost of treating patients with SREs was $43,746 compared with $25,956 in the matched control cohort (P < 0.05). The largest proportion of differences in costs between the two groups was incurred in the first month after the SRE index date or the pseudo-SRE date ($14,979 vs. $4,849; P < 0.05) and was mostly attributable to outpatient visits (43.4%; P < 0.05) and inpatient hospitalization (33.1%; P < 0.05). The total cost per patient over the 12-month period was $22,171 higher among patients with SREs than among patients without SREs (P < 0.05). CONCLUSIONS: Our findings suggest that SREs impose considerable burden on health resource utilization for payers. Costs attributable to SREs were substantial. Most costs were incurred in the first month after the occurrence of SREs. Although costs decreased thereafter, they remained significantly higher for patients with SREs in subsequent months compared with patients without SREs.

A Palliative Radiation Oncology Consult Service Reduces Total Costs During Hospitalization.

CONTEXT: Palliative radiation therapy (PRT) is a highly effective treatment in alleviating symptoms from bone metastases; however, currently used standard fractionation schedules can lead to costly care, especially when patients are treated in an inpatient setting. The Palliative Radiation Oncology Consult (PROC) service was developed in 2013 to improve appropriateness, timeliness, and care value from PRT. OBJECTIVES: Our primary objective was to compare total costs among two cohorts of inpatients with bone metastases treated with PRT before, or after, PROC establishment. Secondarily, we evaluated drivers of cost savings including hospital length of stay, utilization of specialty-care palliative services, and PRT schedules. METHODS: Patients were included in our observational cohort study if they received PRT for bone metastases at a single tertiary care hospital from 2010 to 2016. We compared total costs and length of stay using propensity score-adjusted analyses. Palliative care utilization and PRT schedules were compared by χ2 and Mann-Whitney U tests. RESULTS: We identified 181 inpatients, 76 treated before and 105 treated after PROC. Median total hospitalization cost was $76,792 (range $6380-$346,296) for patients treated before PROC and $50,582 (range $7585-$620,943) for patients treated after PROC. This amounted to an average savings of $20,719 in total hospitalization costs (95% CI [$3687, $37,750]). In addition, PROC was associated with shorter PRT schedules, increased palliative care utilization, and an 8.5 days reduction in hospital stay (95% CI [3.2,14]). CONCLUSION: The PROC service, a radiation oncology model integrating palliative care practice, was associated with cost-savings, shorter treatment courses and hospitalizations, and increased palliative care.

Increased resource use in men with metastatic prostate cancer does not result in improved survival or quality of care at the end of life.

BACKGROUND: Cancer care and end-of-life (EOL) care contribute substantially to health care expenditures. Outside of clinical trials, to our knowledge there exists no standardized protocol to monitor disease progression in men with metastatic prostate cancer (mPCa). The objective of the current study was to evaluate the factors and outcomes associated with increased imaging and serum prostate-specific antigen use in men with mPCa. METHODS: Using Surveillance, Epidemiology, and End Results-Medicare data from 2004 to 2012, the authors identified men diagnosed with mPCa with at least 6 months of follow-up. Extreme users were classified as those who had either received prostate-specific antigen testing greater than once per month, or who underwent cross-sectional imaging or bone scan more frequently than every 2 months over a 6-month period. Associations between extreme use and survival outcomes, costs, and quality of care at EOL, as measured by timing of hospice referral, frequency of emergency department visits, length of stay, and intensive care unit or hospital admissions, were examined. RESULTS: Overall, a total of 3026 men with mPCa were identified, 791 of whom (26%) were defined as extreme users. Extreme users were more commonly young, white/non-Hispanic, married, higher earning, and more educated (P<.001, respectively). Extreme use was not associated with improved quality of care at EOL. Yearly health care costs after diagnosis were 36.4% higher among extreme users (95% confidence interval, 27.4%-45.3%; P<.001). CONCLUSIONS: Increased monitoring among men with mPCa significantly increases health care costs, without a definitive improvement in survival nor quality of care at EOL noted. Monitoring for disease progression outside of clinical trials should be reserved for those in whom findings will change management. Cancer 2018;124:2212-9. © 2018 American Cancer Society.

Socio-economic patterning in early mortality of patients aged 0-49 years diagnosed with primary bone cancer in Great Britain, 1985-2008.

BACKGROUND: Studies have shown marked improvements in survival between 1981 and 2000 for Ewing sarcoma patients but not for osteosarcoma. This study aimed to explore socio-economic patterning in early mortality rates for both tumours. PROCEDURE: The study analysed all 2432 osteosarcoma and 1619 Ewing sarcoma cases, aged 0-49 years, diagnosed in Great Britain 1985-2008 and followed to 31/12/2009. Logistic regression models were used to calculate risk of dying within three months, six months, one year, three years and five years after diagnosis. Associations with Townsend deprivation score and its components were examined at small-area level. Urban/rural status was studied at larger regional level. RESULTS: For osteosarcoma, after age adjustment, mortality at three months, six months and one year was associated with higher area unemployment, OR = 1.05 (95% CI 1.00, 1.10), OR = 1.04 (95% CI 1.01, 1.08) and OR = 1.04 (95% CI 1.02, 1.06) respectively per 1% increase in unemployment. Mortality at six months was associated with greater household non-car ownership, OR = 1.02 (95% CI 1.00, 1.03). For Ewing sarcoma, there were no significant associations between mortality and overall Townsend score, nor its components for any time period. For both tumours increasing mortality was associated with less urban and more remote rural areas. CONCLUSIONS: This study found that for osteosarcoma, early mortality was associated with residence at diagnosis in areas of higher unemployment, suggesting risk of early death may be socio-economically determined. For both tumours, distance from urban centres may lead to greater risk of early death.

Cost-Effectiveness of Treatments for the Management of Bone Metastases: A Systematic Literature Review.

BACKGROUND: Metastatic cancers occur when cancer cells break away from the primary tumour. One of the most common sites of metastasis is the bone, with several therapeutic options currently available for managing bone metastases. In a resource-constrained environment, policy makers and practitioners need to know which options are cost effective. OBJECTIVE: The aim of this systematic review was to review and appraise published economic evaluations on treatments for the management of bone metastases. METHODS: We searched eight bibliographic databases (MEDLINE, MEDLINE in Process, EMBASE, CSDR, DARE, HTA, EED and CPCI) for relevant economic evaluations published from each database's inception date until March 2017. Study selection, quality assessment and data extraction were carried out according to published guidelines. RESULTS: Twenty-four relevant economic analyses were identified. Seventeen of these studies focused on bone metastases resulting from a particular type of cancer, i.e. prostate (n = 8), breast (n = 7), lung (n = 1) or renal (n = 1), while seven report results for various primary tumours. Across types of cancer, evidence suggests that bisphosphonates result in lower morbidity and improved quality of life, for an additional cost, which is typically below conventional cost-effectiveness thresholds. While denosumab leads to health gains compared with zoledronic acid, it also results in substantial additional costs and is unlikely to represent value for money. The limited literature on the radiopharmaceutical strontium-89 (Sr89) and external beam radiotherapy (EBR) suggest that these treatments are cost effective compared with no treatment. CONCLUSIONS: The reviewed evidence suggests that bisphosphonate treatments are cost-effective options for bone metastases, while denosumab is unlikely to represent value for money. Evidence on EBR and Sr89 is limited and less conclusive.

Function and quality of life among primary osteosarcoma survivors in Iran: amputation versus limb salvage.

PURPOSE: This study aimed to evaluate the psychometric properties of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) in Iranian osteosarcoma patients and apply this to compare the functional level, quality of life, symptoms and financial burden of the patients who underwent amputation and limb-salvage operations. METHODS: This study was conducted at the main referral orthopedic centers in the southwest of Iran from 2006 to 2016. After complete review of medical records, 48 patients were invited to attend the outpatient clinic and participate in the study via initial telephone interview. All data were entered in the Statistical Package for the Social Sciences version 15.0, and p values <0.05 were considered statistically significant. RESULTS: In total, 48 patients with extremities osteosarcoma completed the study. Of these, 31 had been treated with limb-salvage operation and 17 had undergone amputation. In functioning subscale, all the mean score of items, except social function, were higher in the limb salvage group than the amputee group. The mean scores (SD) of global health and quality of life were 64.5(13.2) and 61.2± 12.4 in the limb salvage and amputee groups, respectively. In the financial impact subscale, the mean score (SD) in the limb salvage group was 68.8± (29.7) compared to 74.5(25.0) in the amputee group. CONCLUSION: Results support the responsiveness of the EORTC QLQ-C30 for Iranian osteosarcoma patients. Applying this questionnaire revealed similar functional outcome, quality of life, symptoms and financial burden between amputation and limb-salvage groups.

Cost of illness of metastatic prostate cancer: a perspective of costs for new treatment options in The Netherlands.

AIM: To assess the resource use and associated costs of treating patients with metastatic prostate cancer with a focus on skeletal-related events (SREs). METHODS: We performed a bottom-up cost of illness study in The Netherlands. RESULTS: A total of 136 patients were studied. The mean total costs were €17,931 per patient. SREs that required hospitalization (n = 53) were, at median costs of €2039-9346, depending on care. These SREs had median costs of €200-1912. CONCLUSION: Our data provide a basis to investigate the cost-effectiveness of novel treatment options for metastatic prostate cancer. The impact of SREs on total costs could justify policy aimed at actively preventing SREs, possibly resulting in better quality of life and cost-reduction.