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.

A virtual multi-disciplinary meeting is a cost-effective method of triaging referrals to a regional musculoskeletal oncology service.

BACKGROUND AND AIMS: In 2010, a virtual sarcoma referral model was implemented, which aims to provide a centralised multidisciplinary team (MDT) to provide rapid advice, avoiding unnecessary appointments and providing a streamlined service. The aim of this study is to examine the feasibility of this screening tool in reducing the service burden and expediting patient journey. METHODS AND RESULTS: All referrals made to a single tertiary referral sarcoma unit from January 2010 to December 2018 were extracted from a prospective database. Only 26.0% events discussed required review directly. 30.3% were discharged back to referrer. 16.5% required further investigations. 22.5% required a biopsy prior to review. There was a reduction in the rate of patients reviewed at the sarcoma clinic, and a higher discharge rate from the MDT in 2018 versus 2010 (p < 0.001). This gives a potential cost saving of 670,700 GBP over the 9 year period. CONCLUSION: An MDT meeting which triages referrals is cost-effective at reducing unnecessary referrals. This can limit unnecessary exposure of patients who may have an underlying diagnosis of cancer to a high-risk environment, and reduces burden on services as it copes with increasing demands during the COVID-19 pandemic.

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.

Career and Financial Situation of Patients Diagnosed with Soft Tissue Sarcomas.

BACKGROUND: After receiving a cancer diagnosis patients face many challenges. The association between career situation and financial problems caused by cancer has a substantial impact on quality of life (QoL) among cancer patients. Indeed, the QoL such as physical and mental health of cancer patients is lower when the risk of psychological disorders or distress increases, and chances for cancer cure are reduced. Progress in therapeutic intervention allows many cancer patients a social reintegration into their careers. About one third of cancer patients are younger than 65 years, and with the constant increase in work life periods, a cancer diagnosis also presents a financial burden for those affected. OBJECTIVES: The main objective of this study was to analyse the social QoL in the context of factors related to career and financial situation among patients diagnosed with soft tissue sarcomas (STS). METHODS: A descriptive non-experimental research design was used to conduct a cross-sectional survey over a period of 6 months, between May and November 2016, in collaboration with the Sarcoma Unit at the Mannheim University Medical Centre, Mannheim, Germany, the patient organisation "Das Lebenshaus e.V.," and the German Pension Insurance Hessen (Deutsche Ren-tenversicherung: DRV Hessen)/Pension Fund. We analysed data of 30 patients diagnosed with STS using self-outcome questionnaires in combination with retirement insurance data from the date of first diagnosis up to 3 years afterwards. Out of 280 questionnaires, we received 86 completed forms, of which 56 were excluded. The remaining questionnaires of 30 patients were analysed according to self-determined outcomes and included a calculation of the financial changes caused by the disease. Only patients covered by pension insurance were included in the study. RESULTS: Thirty patients (24 women) whose median age at first diagnosis was 48.7 years (range 31-61 years) were included in the analysis. The average unemployment rate was 8.8 months, and for 67% (20 patients) the employment situation changed after the period of unemployment. Eight patients requested a retirement pension (reduced income insurance), 4 patients reduced their weekly working hours, and 3 patients lost their jobs due to complications of the disease. The data analysis revealed that, among these patients, one benefited from an income increase of about 24%, another one received a regular old-age pension, and 4 patients reported reduced income for other reasons. In total, mean income has been reduced by 26%. Considering only the 8 patients who applied for a pension, partial or total unemployment benefits resulted in an average loss of income of up to 62%. CONCLUSIONS: Reduced ability to work may cause severe financial problems for those affected by the diagnosis of STS. We found an average income reduction of 26%, for those requesting pension payments of 62%. This eventually relates to a higher risk of reduced wealth and may lower the patients' social standing.

Sarcoma epidemiology and cancer-related hospitalisation in Western Australia from 1982 to 2016: a descriptive study using linked administrative data.

BACKGROUND: Sarcomas are a heterogeneous group of malignancies arising from mesenchymal cells. Epidemiological studies on sarcoma from Australia are lacking, as previous studies have focused on a sarcoma type (e.g. soft tissue) or anatomical sites. METHODS: Linked cancer registry, hospital morbidity and death registration data were available for Western Australia (WA) from 1982 to 2016. All new sarcoma cases among WA residents were included to estimate incidence, prevalence, relative survival and cancer-related hospitalisation, using the Information Network on Rare Cancers (RARECARENet) definitions. To provide a reference point, comparisons were made with female breast, colorectal, prostate and lung cancers. RESULTS: For 2012-16, the combined sarcoma crude annual incidence was 7.3 per 100,000, with the majority of these soft tissue sarcoma (STS, incidence of 5.9 per 100,000). The age-standardised incidence and prevalence of STS increased over time, while bone sarcoma remained more stable. Five-year relative survival for the period 2012-16 for STS was 65% for STS (higher than lung cancer, but lower than prostate, female breast and colorectal cancers), while five-year relative survival was 71% for bone sarcoma. Cancer-related hospitalisations cost an estimated $(Australian) 29.1 million over the study period. CONCLUSIONS: STS incidence has increased over time in WA, with an increasing proportion of people diagnosed aged ≥65 years. The analysis of health service use showed sarcoma had a lower mean episode of cancer-related hospitalisation compared to the reference cancers in 2016, but the mean cost per prevalent person was higher for sarcoma than for female breast, colorectal and prostate cancers.

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.

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.

Economic evaluation of the GENESIS-SEFH report of olaratumab with doxorubicin in soft tissue sarcoma in advanced stages.

OBJECTIVE: The economic evaluation of the drug olaratumab is carried out in the treatment of soft tissue sarcoma. METHOD: The data were analyzed following the recommendations contained in  the MADRE program of the GENESIS-SEFH report model. RESULTS: Progression free survival and overall survival results published in the  pivotal clinical trial; Tap, WD. et al. (2016) were improvement of 2.5 months in  median progression free survival (primary endpoint) HR = 0.672; IC95%  (0.442-1.021) and gain of 11.8 months in median OS (secondary endpoint) HR  = 0.463; IC95% (0.301-0.710). A cost-effectiveness analyses was performed  considering 2 scenarios; scenario 1: with use of whole vials and scenario 2: use  of whole vials and associating non-pharmacological costs (day hospital visits,  mucositis, neutropenia and dexrazoxane use). In both cases we considered the  cost of drugs and the efficacy data of the pivotal clinical trial. In Scenario 1, we  would have an Incremental-Cost-Effectiveness-Ratio of €28,443.81/month of  progression-free survival and €72,560.74 per year of life gained and in scenario  2 we would have an incremental-cost-effectivenessratio of €30,879.79/  progression-free survival and €78,774.99/ year of life gained. The budgetary  impact of this drug would range from €61,759.592 to €92,639.388 estimated to  be 800 to 1,200 patients likely to receive treatment in Spain. CONCLUSIONS: Olaratumab is a drug that provides a significant benefit in overall  survival but not in progression free survival. To be used in soft tissue sarcoma  and to be cost-effective, the acquisition cost of the 500 mg vial should be  between €101.91 and €506.54 and that of the 190 mg vial between €39.31 and  €195.37.

Objetivo: Desarrollar la evaluación económica del fármaco olaratumab en el  tratamiento del sarcoma de partes blandas.Método: Los datos se analizaron siguiendo las recomendaciones contenidas en  el programa MADRE del modelo de informe GENESIS-SEFH.Resultados: Los resultados de supervivencia libre de progresión y supervivencia global publicados en el ensayo clínico pivotal: Tapm WD. et al.  (2016) fueron: la ganancia en supervivencia libre de progresión (variable  principal) en términos absolutos fue de 2,5 meses, HR = 0,672; IC95% (0,442- 1,021). La ganancia absoluta en supervivencia global (variable secundaria) fue  de 11,8 meses, HR = 0,463; IC95% (0,301-0,710). Se realizó un análisis coste- efectividad considerando dos escenarios; escenario uno: sin aprovechamiento de viales; y escenario dos: sin aprovechamiento de viales y asociando costes no  farmacológicos. En ambos casos se consideraron los costes de adquisición de los medicamentos y los datos de eficacia del ensayo clínico pivotal. En el primero  determinamos una ratio coste-efectividad-incremental de 28.443,81 euros/mes  libre de progresión ganado y 72.560,74 euros/año de vida ganado. En el  segundo obtenemos una ratio coste-efectividad incremental de 30.879,79 euros libre de progresión ganado y 78.774,99 euros/año de vida ganado. El  impacto económico estatal, por tanto, se situaría entre 61.759.592 millones de  euros y 92.639.388 de euros, considerando una población diana de 800-1.200  pacientes a nivel nacional.Conclusiones: Olaratumab es un fármaco que aporta un beneficio significativo  en la supervivencia global, no así en la supervivencia libre de progresión. Para  poder utilizarse en el sarcoma de partes blancas y que resultase costeefectivo, el coste de adquisición del vial de 500 mg debería situarse entre 101,91 y 506,54  euros y el del vial de 190 mg entre 39,31 y 195,37 euros.

The cost-saving effect of centralized histological reviews with soft tissue and visceral sarcomas, GIST, and desmoid tumors: The experiences of the pathologists of the French Sarcoma Group.

OBJECTIVE: This study examined the types of discordance occurring in the diagnosis of soft tissue and visceral sarcomas, gastrointestinal stromal tumors (GIST), and desmoid tumors, as well as the economic impact of diagnostic discrepancies. METHODS: We carried out a retrospective, multicenter analysis using prospectively implemented databases performed on a cohort of patients within the French RRePS network in 2010. Diagnoses were deemed to be discordant based on the 2013 World Health Organization (WHO) classification. Predictive factors of discordant diagnoses were explored. A decision tree was used to assess the expected costs of two strategies of disease management: one based on revised diagnoses after centralized histological review (option 1), the other on diagnoses without centralized review (option 2). Both were defined based on the patient and the disease characteristics, according to national or international guidelines. The time horizon was 12 months and the perspective of the French National Health Insurance (NHI) was retained. Costs were expressed in Euros for 2013. Sensitivity analyses were performed using low and high scenarios that included ± 20% estimates for cost. RESULTS: A total of 2,425 patients were included. Three hundred forty-one patients (14%) had received discordant diagnoses. These discordances were determined to mainly be benign tumors diagnosed as sarcomas (n = 124), or non-sarcoma malignant tumors diagnosed as sarcomas (n = 77). The probability of discordance was higher for a final diagnosis of desmoid tumors when compared to liposarcomas (odds ratio = 5.1; 95%CI [2.6-10.4]). The expected costs per patient for the base-case analysis (low- and high-case scenarios) amounted to €8,791 (€7,033 and €10,549, respectively) for option 1 and €8,904 (€7,057 and €10,750, respectively) for option 2. CONCLUSIONS: Our findings highlight misdiagnoses of sarcomas, which were found to most often be confused with benign tumors. Centralized histological reviews are likely to provide cost-savings for the French NHI.

Olaratumab in Combination with Doxorubicin for the Treatment of Advanced Soft Tissue Sarcoma: An Evidence Review Group Perspective of a National Institute for Health and Care Excellence Single Technology Appraisal.

The manufacturer of olaratumab (Lartruvo®), Eli Lilly & Company Limited, submitted evidence for the clinical and cost effectiveness of this drug, in combination with doxorubicin, for untreated advanced soft tissue sarcoma (STS) not amenable to surgery or radiotherapy, as part of the National Institute for Health and Care Excellence (NICE) Single Technology Appraisal process. The Peninsula Technology Assessment Group, commissioned to act as the Evidence Review Group (ERG), critically reviewed the company's submission. Clinical effectiveness evidence for the company's analysis was derived from an open-label, randomised controlled trial, JGDG. The analysis was based on a partitioned survival model with a time horizon of 25 years, and the perspective was of the UK National Health Service (NHS) and Personal Social Services. Costs and benefits were discounted at 3.5% per year. Given the available evidence, olaratumab is likely to meet NICE's end-of-life criteria. To improve the cost effectiveness of olaratumab, the company offered a discount through a Commercial Access Agreement (CAA) with the NHS England. When the discount was applied, the mean base-case and probabilistic incremental cost-effectiveness ratios (ICERs) for olaratumab plus doxorubicin versus the standard-of-care doxorubicin were £46,076 and £47,127 per quality-adjusted life-year (QALY) gained, respectively; the probability of this treatment being cost effective at the willingness-to-pay threshold of £50,000 per QALY gained, applicable to end-of-life treatments, was 0.54. The respective ICERs from the ERG's analysis were approximately £60,000/QALY gained, and the probability of the treatment being cost effective was 0.21. In August 2017, the NICE Appraisal Committee recommended olaratumab in combination with doxorubicin for this indication for use via the UK Cancer Drugs Fund under the agreed CAA until further evidence being collected in the ongoing phase III trial-ANNOUNCE-becomes available in December 2020.

Olaratumab: A Novel Platelet-Derived Growth Factor Receptor α-Inhibitor for Advanced Soft Tissue Sarcoma.

OBJECTIVE: To review and summarize data on olaratumab, which was approved by the US Food and Drug Administration (FDA) in October 2016, in combination with doxorubicin, for the treatment of advanced soft tissue sarcoma. DATA SOURCES: A literature search using PubMed was conducted using the search terms olaratumab, IMC-3G3, and advanced soft tissue sarcoma from January 2005 to June 2017. STUDY SELECTION AND DATA EXTRACTION: The literature search was confined to human studies published in English. Trials of olaratumab for advanced soft tissue sarcomas were prioritized. DATA SYNTHESIS: Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody. Its accelerated FDA approval was based on a phase II randomized trial of olaratumab plus doxorubicin (n = 66) versus doxorubicin monotherapy (n = 67) in patients with advanced soft tissue sarcoma. Olaratumab 15 mg/kg was administered intravenously (IV) on days 1 and 8 in combination with doxorubicin 75 mg/m2 IV on day 1 every 21 days for a total of 8 cycles compared to doxorubicin 75 mg/m2 IV monotherapy. The response rate was 18.2% with combination therapy versus 11.9% with monotherapy and median progression-free survival of 6.6 and 4.1 months, respectively. Additionally, overall survival was increased by 11.8 months in the olaratumab arm (26.5 months vs 14.7 months). Clinically relevant adverse effects in the olaratumab + doxorubicin arm included neutropenia (58%), mucositis (53%), nausea (73%), vomiting (45%), and diarrhea (34%). CONCLUSION: Olaratumab, in combination with doxorubicin, represents a novel treatment strategy for advanced soft tissue sarcoma and provides a significant survival advantage for this rare disease state with limited treatment options.

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.

Cost-Effectiveness Analysis of Intensity Modulated Radiation Therapy Versus 3-Dimensional Conformal Radiation Therapy for Preoperative Treatment of Extremity Soft Tissue Sarcomas.

PURPOSE: Create a cost-effectiveness model comparing preoperative intensity modulated radiation therapy (IMRT) versus 3-dimensional conformal radiation therapy (3DCRT) for extremity soft tissue sarcomas. METHODS AND MATERIALS: Input parameters included 5-year local recurrence rates, rates of acute wound adverse events, and chronic toxicities (edema, fracture, joint stiffness, and fibrosis). Health-state utilities were used to calculate quality-adjusted life years (QALYs). Overall treatment costs per QALY or incremental cost-effectiveness ratio (ICER) were calculated. Roll-back analysis was performed using average costs and utilities to determine the baseline preferred radiation technique. One-way, 2-way, and probabilistic sensitivity analyses (PSA) were performed for input parameters with the largest impact on the ICER. RESULTS: Overall treatment costs were $17,515.58 for 3DCRT compared with $22,920.51 for IMRT. The effectiveness was higher for IMRT (3.68 QALYs) than for 3DCRT (3.35 QALYs). The baseline ICER for IMRT was $16,842.75/QALY, making it the preferable treatment. The ICER was most sensitive to the probability of local recurrence, upfront radiation costs, local recurrence costs, certain utilities (no toxicity/no recurrence, grade 1 toxicity/no local recurrence, grade 4 toxicity/no local recurrence), and life expectancy. Dominance patterns emerged when the cost of 3DCRT exceeded $15,532.05 (IMRT dominates) or the life expectancy was under 1.68 years (3DCRT dominates). Furthermore, preference patterns changed based on the rate of local recurrence (threshold: 13%). The PSA results demonstrated that IMRT was the preferred cost-effective technique for 64% of trials compared with 36% for 3DCRT. CONCLUSIONS: Based on our model, IMRT is the preferred technique by lowering rates of local recurrence, severe toxicities, and improving QALYs. From a third-party payer perspective, IMRT should be a supported approach for extremity soft tissue sarcomas.

Delayed diagnosis in primary care-The main cause of sarcoma litigation in the United Kingdom.

BACKGROUND: Poor awareness and knowledge of lumps and bumps can impact on patient outcomes and survival. Late referrals or false reassurance may lead to litigation proceedings. The aim of this study was to identify the litigation cost in sarcoma care and identify areas for improvement. METHOD: Orthopaedic litigation between 1995-2010 in England and Wales was obtained from the National Health Service Litigation Authority. Litigation specifically relating to sarcoma in the extremities was identified. Causation, compensation fee, cost of legal defense, and compensation were analyzed. RESULTS: There were 52 litigation claims. Negligence was proven in 71% (n = 37) of cases. The total cost was £4.4 million (mean of £84,000/case). The mean compensation award was £92,000 (range £650-£978,000) and the mean defense cost was £22,000 (range £0-£102,000). Delayed diagnosis accounted for 89% of cases (n = 48). Negligence following diagnosis was infrequent; inappropriate treatment (n = 2), failure to recognize complications of surgery (n = 2), intra-operative problems (n = 1), failure to refer to a specialist unit after a "whoops procedure" (n = 1). CONCLUSIONS: Once the patient is within the specialist sarcoma unit, there is a very low rate of litigation. Efforts to reduce litigation in sarcoma treatment should focus on early diagnosis and raising awareness of sarcomas. J. Surg. Oncol. 2016;113:361-363. © 2016 Wiley Periodicals, Inc.

Cost of treatment in patients with metastatic soft tissue sarcoma who respond favourably to chemotherpy. The SArcoma treatment and Burden of Illness in North America and Europe (SABINE) study.

Treatment of metastatic soft tissue sarcoma (mSTS) commonly includes multiple lines of chemotherapy, until a decline in performance status precludes further treatment. The primary objective of this study was to describe the lifetime healthcare resource utilisation and cost among mSTS patients with favourable response to chemotherapy. SABINE was a multi-centre (n = 25), multi-country (n = 9) retrospective chart review study of mSTS patients with favourable response to chemotherapy following 4 cycles. Healthcare resource utilisation was collected from first line until death or end of follow-up. Costs were analysed by health states (defined by treatment line, chemotherapy use and disease progression) and estimated by multiplying the mean weekly cost per health state by the expected number of weeks spent in each health state. Expected per-patient lifetime medical cost was €65 616 (95% CI: €51 454-€85 003); comprised of IV chemotherapy (31.7%), inpatient care (24.8%), concomitant medication (11.0%), oral chemotherapy (8.9%), outpatient visits (8.8%), radiotherapy (6.3%), hospice (4.0%), imaging (3.7%) and laboratory (0.7%). Weekly costs were 280-330% higher during chemotherapy treatment periods than off-chemotherapy, especially after disease progression. Per-patient costs were highest in the USA and lowest in the Netherlands and UK. The economic burden of mSTS is considerable and the amount of resources devoted to its treatment varies across countries.

Comparative effectiveness research for sarcoma.

Modern multidisciplinary management of sarcoma represents several opportunities for comparative effectiveness research. Focusing on the outcomes of survival, quality of life and cost-effectiveness of care, the current state of the art is summarized. Specialized/regional care for sarcoma and the utility of tumor boards or multispecialty discussion is discussed. Issues related to treatment efficacy and sequencing in relation to chemotherapy, radiation, and surgery as well as margin reporting and surveillance are also discussed. Finally, future avenues of comparative effectiveness research for sarcoma are highlighted throughout the chapter.

Cost-effectiveness analysis of pazopanib in second-line treatment of advanced soft tissue sarcoma in Spain

Purpose. To assess the efficiency of pazopanib compared with trabectedin in the treatment of adult patients with selective subtypes of advanced soft-tissue sarcoma (STS) after chemotherapy failure. Methods. The progression of STS was modeled using a partitioned survival analysis model. Survival curves for pazopanib and trabectedin were modeled using data from PALETTE phase III clinical trial and based on unadjusted indirect comparison. Effectiveness was measured in quality-adjusted life years (QALY). The Spanish National Health System perspective was considered over a 10-year time horizon, including direct health care costs (Euros, 2014). A discount rate of 3 % was applied to both costs and outcomes. The robustness of the results was evaluated using univariate and probabilistic sensitivity analyses (PSA). Results. Pazopanib was associated with better health outcomes than trabectedin (0.705 versus 0.686 QALY). Pazopanib also showed lower direct health care costs (€21,861 versus €45,338), mainly due to lower cost of pharmacological treatment (€13,762 versus €33,392), administration (€57 versus €2,955) and AE management (€658 versus €1,695) costs. PSA confirmed that pazopanib was a dominant option in 71 % of the simulations performed. Conclusions. In this analysis, and from a health economics perspective, pazopanib was the option of choice versus trabectedin in the treatment of adult patients with advanced soft-tissue sarcoma after chemotherapy failure (AU)

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Cost-effectiveness analysis of pazopanib in second-line treatment of advanced soft tissue sarcoma in Spain.

PURPOSE: To assess the efficiency of pazopanib compared with trabectedin in the treatment of adult patients with selective subtypes of advanced soft-tissue sarcoma (STS) after chemotherapy failure. METHODS: The progression of STS was modeled using a partitioned survival analysis model. Survival curves for pazopanib and trabectedin were modeled using data from PALETTE phase III clinical trial and based on unadjusted indirect comparison. Effectiveness was measured in quality-adjusted life years (QALY). The Spanish National Health System perspective was considered over a 10-year time horizon, including direct health care costs (, 2014). A discount rate of 3% was applied to both costs and outcomes. The robustness of the results was evaluated using univariate and probabilistic sensitivity analyses (PSA). RESULTS: Pazopanib was associated with better health outcomes than trabectedin (0.705 versus 0.686 QALY). Pazopanib also showed lower direct health care costs (21,861 versus 45,338), mainly due to lower cost of pharmacological treatment (13,762 versus 33,392), administration (57 versus 2,955) and AE management (658 versus 1,695) costs. PSA confirmed that pazopanib was a dominant option in 71% of the simulations performed. CONCLUSIONS: In this analysis, and from a health economics perspective, pazopanib was the option of choice versus trabectedin in the treatment of adult patients with advanced soft-tissue sarcoma after chemotherapy failure.

Barriers to effective treatment of pediatric solid tumors in middle-income countries: can we make sense of the spectrum of nonbiologic factors that influence outcomes?

BACKGROUND: The delivery of effective treatment for pediatric solid tumors poses a particular challenge to centers in middle-income countries (MICs) that already are vigorously addressing pediatric cancer. The objective of this study was to improve the current understanding of barriers to effective treatment of pediatric solid tumors in MICs. METHODS: An ecologic model centered on pediatric sarcoma and expanded to country as the environment was used as a benchmark for studying the delivery of solid tumor care in MICs. Data on resources were gathered from 7 centers that were members of the Central American Association of Pediatric Hematologists and Oncologists (AHOPCA) using an infrastructure assessment tool. Pediatric sarcoma outcomes data were available, were retrieved from hospital-based cancer registries for 6 of the 7 centers, and were analyzed by country. Patients who were diagnosed from January 1, 2000 to December 31, 2009 with osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, and other soft tissue sarcomas were included in the analysis. To explore correlations between resources and outcomes, a pilot performance index was created. RESULTS: The analyses identified specific deficits in human resources, communication, quality, and infrastructure. The treatment abandonment rate, the proportion of metastatic disease at diagnosis, the relapse rate, and the 4-year abandonment-sensitive overall survival (AOS) rate varied considerably by country, ranging from 1% to 38%, from 15% to 54%, from 24% to 52%, and from 21% to 51%, respectively. The treatment abandonment rate correlated inversely with health economic expenditure per capita (r = -0.86; P = .03) and life expectancy at birth (r = -0.93; P = .007). The 4-year AOS rate correlated inversely with the mortality rate among children aged <5 years (r = -0.80; P = 0.05) and correlated directly with the pilot performance index (r = 0.98; P = 0.005). CONCLUSIONS: Initiatives to improve the effectiveness of treatment for pediatric solid tumors in MICs are warranted, particularly for pediatric sarcomas. Building capacity and infrastructure, improving supportive care and communication, and fostering comprehensive, multidisciplinary teams are identified as keystones in Central America. A measure that meaningfully describes performance in delivering pediatric cancer care is feasible and needed to advance comparative, prospective analysis of pediatric cancer care and to define resource clusters internationally.

Incomplete excisions of extremity soft tissue sarcomas are unaffected by insurance status or distance from a sarcoma center.

BACKGROUND: Soft tissue sarcomas (STS) continue to be excised inappropriately without proper preoperative planning. The reasons for this remain elusive. The role of insurance status and patient distance from sarcoma center in influencing such inappropriate excisions were examined in this study. METHODS: This retrospective review of a single institution prospective database evaluated 400 patients treated for STS of the extremities between January 2000 and December 2008. Two hundred fifty three patients had a primary excision while 147 patients underwent re-excision. Wilcoxon rank sum test and either χ(2) or Fisher's exact were used to compare variables. Multivariable regression analyses were used to take into account potential confounders and identify variables that affected excision status. RESULTS: Tumor size, site, depth, stage, margins, and histology were significantly different between the primary excision and re-excision groups; P < 0.05. Insurance status and patient distance from the treatment center were not statistically different between the two groups. Large and deep tumors and certain histology types predicted appropriate referral. CONCLUSIONS: Inappropriate excision of STS is not influenced by patient distance from a sarcoma center or by a patient's insurance status. In this study, tumor size, depth, and certain histology types predicted the appropriate referral of a STS to a sarcoma center.