Cost-effectiveness of the McGill interactive pediatric oncogenetic guidelines in identifying Li-Fraumeni syndrome in female patients with osteosarcoma.

BACKGROUND: Li-Fraumeni syndrome (LFS) is a penetrant cancer predisposition syndrome (CPS) associated with the development of many tumor types in young people including osteosarcoma and breast cancer (BC). The McGill Interactive Pediatric OncoGenetic Guidelines (MIPOGG) decision-support tool provides a standardized approach to identify patients at risk of CPSs. METHODS: We conducted a cost-utility analysis, from the healthcare payer perspective, to compare MIPOGG-guided, physician-guided, and universal genetic testing strategies to detect LFS in female patients diagnosed at an age of less than 18 years with osteosarcoma. We developed a decision tree and discrete-event simulation model to simulate the clinical and cost outcomes of the three genetic referral strategies on a cohort of female children diagnosed with osteosarcoma, especially focused on BC as subsequent cancer. Outcomes included BC incidence, quality-adjusted life-years (QALYs), healthcare costs, and incremental cost-utility ratios (ICURs). We conducted probabilistic and scenario analyses to assess the uncertainty surrounding model parameters. RESULTS: Compared to the physician-guided testing, the MIPOGG-guided strategy was marginally more expensive by $105 (-$516; $743), but slightly more effective by 0.003 (-0.04; 0.045) QALYs. Compared to MIPOGG, the universal testing strategy was $1333 ($732; $1953) more costly and associated with 0.011 (-0.043; 0.064) additional QALYs. The ICUR for the MIPOGG strategy was $33,947/QALY when compared to the physician strategy; the ICUR for universal testing strategy was $118,631/QALY when compared to the MIPOGG strategy. DISCUSSION: This study provides evidence for clinical and policy decision-making on the cost-effectiveness of genetic referral strategies to identify LFS in the setting of osteosarcoma. MIPOGG-guided strategy was most likely to be cost-effective at a willingness-to-pay threshold value of $50,000/QALY.

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.

Cost-utility of osteoarticular allograft versus endoprosthetic reconstruction for primary bone sarcoma of the knee: A markov analysis.

BACKGROUND: The most cost-effective reconstruction after resection of bone sarcoma is unknown. The goal of this study was to compare the cost effectiveness of osteoarticular allograft to endoprosthetic reconstruction of the proximal tibia or distal femur. METHODS: A Markov model was used. Revision and complication rates were taken from existing studies. Costs were based on Medicare reimbursement rates and implant prices. Health-state utilities were derived from the Health Utilities Index 3 survey with additional assumptions. Incremental cost-effectiveness ratios (ICER) were used with less than $100 000 per quality-adjusted life year (QALY) considered cost-effective. Sensitivity analyses were performed for comparison over a range of costs, utilities, complication rates, and revisions rates. RESULTS: Osteoarticular allografts, and a 30% price-discounted endoprosthesis were cost-effective with ICERs of $92.59 and $6 114.77. One-way sensitivity analysis revealed discounted endoprostheses were favored if allografts cost over $21 900 or endoprostheses cost less than $51 900. Allograft reconstruction was favored over discounted endoprosthetic reconstruction if the allograft complication rate was less than 1.3%. Allografts were more cost-effective than full-price endoprostheses. CONCLUSIONS: Osteoarticular allografts and price-discounted endoprosthetic reconstructions are cost-effective. Sensitivity analysis, using plausible complication and revision rates, favored the use of discounted endoprostheses over allografts. Allografts are more cost-effective than full-price endoprostheses.

Making a case for the socioeconomic determinacy of survival in osteosarcoma.

BACKGROUND: The literature on osteosarcoma survival generally focuses on tumor and treatment variables, although it is unclear whether and how ethnic and socioeconomic factors might influence survival. QUESTIONS/PURPOSES: We therefore investigated the relative contribution of socioeconomic influences together with more traditional tumor-specific factors on osteosarcoma survival. METHODS: We performed survival analyses on two national databases in two countries. Using multivariable analyses, we compared these with corresponding institution-specific survival to determine if socioeconomic factors might impact osteosarcoma survival. RESULTS: East Asian descent, state-specific treatment, female sex, treatment in the 1990s, low-grade disease, intracompartmental disease, small size, wide resections as opposed to forequarter or hindquarter amputations, and single primaries were good prognostic factors. Survival was better in the more affluent states. Males were affected at an older age than females. Blacks tended to have larger tumors, although their overall survival was similar to whites. East Asians were more likely to be treated in the 1990s with wide resections for smaller tumors and were located around states associated with good treatment. East Asians in Singapore and the United States had the same survival. Survival in East Asians in Singapore was similar to that of other races. The provision of health care for osteosarcoma varies greatly across the United States but is uniform in the socialized medical system in Singapore. Hence, the observed differences in the United States were likely the result of socioeconomic factors. CONCLUSIONS: Our analysis suggests ethnic and economic bias may influence survival in osteosarcoma and should receive greater attention in the collective literature on survival analyses. LEVEL OF EVIDENCE: Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

What are estimated reimbursements for lower extremity prostheses capable of surgical and nonsurgical lengthening?

BACKGROUND: Growing prostheses accommodate skeletally immature patients with bone tumors undergoing limb-preserving surgery. Early devices required surgical procedures for lengthening; recent devices lengthen without surgery. Expenses for newer expandable devices that lengthen without surgery are more than for their predecessors but overall reimbursement amounts are not known. QUESTIONS/PURPOSES: We sought to determine reimbursement amounts associated with lengthening of growing prostheses requiring surgical and nonsurgical lengthening. METHODS: We retrospectively reviewed 17 patients with growing prostheses requiring surgical expansion and eight patients with prostheses capable of nonsurgical expansion. Insurance documents were reviewed to determine the reimbursement for implantation, lengthening, and complications. Growth data were obtained from the literature. RESULTS: Mean reimbursement amounts of surgical and nonsurgical lengthenings were $9950 and $272, respectively. Estimated reimbursements associated with implantation of a growing prosthesis varied depending on age, sex, and location. The largest difference was found for 4-year-old boys with distal femoral replacement where reimbursement for expansion to maturity for surgical and nonsurgical lengthening prostheses would be $379,000 and $208,000, respectively. For children requiring more than one surgical expansion, net reimbursements were lower when a noninvasive lengthening device was used. Annual per-prosthesis maintenance reimbursements to address complications for surgical and nonsurgical lengthening prostheses were $3386 and $1856, respectively. CONCLUSIONS: This study showed that reimbursements for lengthening of growing endoprostheses capable of nonsurgical expansion may be less expensive in younger patients, particularly male patients undergoing distal femur replacement, than endoprostheses requiring surgical lengthening. Longer outcomes studies are required to see if reimbursements for complications differ between devices. LEVEL OF EVIDENCE: Level III, economic and decision analysis. See the Guidelines for Authors for a complete description of levels of evidence.

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.

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.

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.

Socioeconomic measures influence survival in osteosarcoma: an analysis of the National Cancer Data Base.

BACKGROUND: While previous studies have identified low socioeconomic status as a risk factor for metastatic disease in patients with high-grade osteosarcoma, the influence of socioeconomic status on overall survival remains unclear. The present study aims to investigate the relationship between survival and socioeconomic status in patients with high-grade conventional osteosarcoma. METHODS: The National Cancer Data Base (NCDB) was queried from 1998-2012 to identify all patients <40years of age with a diagnosis of high-grade conventional osteosarcoma. A total of 3,503 patients were identified that met inclusion and exclusion criteria. Univariate relationships were investigated using Kaplan-Meier survival analysis and associated log-rank tests in order to determine patient, socioeconomic, tumor, and treatment variables associated with overall survival. Multivariate analysis was performed to determine independent predictors of survival. RESULTS: In order of decreasing magnitude, metastatic disease (Hazard Ratio [HR] 3.28, 95% Confidence Interval [CI] 2.82-3.82), primary site in the pelvis or spine (HR 2.15, 95% CI 1.79-2.59), positive surgical margins (HR 1.82, 95% CI 1.46-2.27), tumor size >8cm (HR 1.47, 95% CI 1.24-1.74), age ≥18 years (HR 1.30, 95% CI 1.14-1.48), lowest quartile of composite socioeconomic status (HR 1.23, 95% CI 1.02-1.51), and Medicaid insurance (HR 1.18, 95% CI 1.02-1.38) were predictors of decreased survival at 5 years. CONCLUSION: Treating providers should be aware that some of their patients may have challenges unrelated to their diagnosis that make timely presentation, adherence to treatment, and continued close surveillance difficult. This investigation suggests that socioeconomic variables influence overall survival for osteosarcoma in the United States, although not as dramatically as established tumor- and treatment-related risk factors.

Cost effective treatment of osteogenic sarcoma of the extremities.

In an ongoing trial at our institute 10 patients of high grade osteogenic sarcoma of the extremities have been treated with preoperative chemotherapy including ifosfamide 2 mg/M2/day i.v. for 5 days, doxorubicin 20 mg/M2/day i.v. for 3 days and cisplatinum 120 mg/M2 i.v. on day 1 at 3-4 weeks interval for 2 courses followed by surgery. One patient refused surgery and further treatment. Pathological study of the 9 surgical specimens showed grade IV necrosis in 5, grade III necrosis in 2 and grade I & II necrosis in 2. Overall response rate (Grade III & IV) was 87.5%. The patients showing Grade III/IV response received a further 3 cycles of the same chemotherapy postoperatively. The patient who refused surgery is still alive at 30 months. Our followup ranges from 4-34 months. All patients developed myelosuppression and one patient died after 4th course of chemotherapy due to septicemia. We expect grade IV response to preoperative chemotherapy will be translated into longer disease free survival. Protocols followed in western countries are not practicable in Asian countries. Hence this new combination has been developed without compromising response rate.

[Diagnostic x-ray computed tomography pf craniocerebral tumors. Apropos of 108 cases collected at the Soweto Center of Dakar]. / Diagnostic tomodensitométrique des tumeurs crânio-encéphaliques. A propos de 108 cas colligés au Centre Soweto de Dakar.

The authors report a retrospective study over two years in order to assess computed tomography (CT) in the diagnosis of intracranial tumors. Results were analysed on the epidemiological, clinical and CT point of view. CT is a sensitive and non invasive exploration which should be performed first when intracranial tumor is suspected. However its cost remain high for most of the patient.

Cost analysis of three different surgical procedures for treatment of a pelvic tumour.

INTRODUCTION: Malignant pelvic tumours are rare, but adequate treatment is difficult because of anatomical and functional reasons. Different surgical procedures are recommended. Besides aspects influencing the quality of life due to the different surgical techniques, costs of these surgical procedures and the perioperative time interval, depending on the chosen surgical procedure, must also be considered. METHODS: Costs of three kinds of surgical treatment - internal hemipelvectomy vs external hemipelvectomy and application of an orthotic device vs ilio-femoral pseudoarthrosis - were compared, including costs of the immediate period of rehabilitation. Costs of the preoperative diagnostic procedure were excluded because they were assumed to be equal. For all calculations, treatment of a periacetabular pelvic tumour type II-b was assumed, according to the Enneking classification, with the need for a pelvic resection with wide margins including removal of the hipjoint. This analysis was performed based on the average costs per hour of physicians, nurses and physiotherapists, including a basic daily rate for additional costs, such as housekeeping and administrative costs of the hospital. In all cases, the costs of the operative procedure and the perioperative period up to 3 months were calculated, including the costs for the endoprosthetic device after internal hemipelvectomy and those for the orthotic devices after necessary external hemipelvectomy. RESULTS: For a postoperative period of 3 months, the cost for treatment with resection of the tumour and performing an ilio-femoral pseudoarthrosis is nearly DM 56,741.54; treatment with an internal hemipelvectomy including the endoprosthetic pelvic replacement costs DM 81,439.34; and treatment with external hemipelvectomy and application of an orthotic device with a pelvic cage costs DM 69,138.46. In this analysis, social costs due to the different rates of disability for years or costs of a new prosthetic device after years and aspects related to resulting quality of life were excluded. In contrast, costs of three different actual cases can differ significantly from the estimated costs. The most important influencing items are surgical implants, blood units and similar products, and surgical treatment of postoperative complications. CONCLUSIONS: Regarding all these aspects, limb salvage seems to be advantageous over amputation. Whether an ileo-femoral pseudoarthrosis or endoprosthetic pelvic replacement should be performed is a decision that should be made by the physicians. based on the underlying diagnosis and the correlated expected survival. Furthermore, additional factors probably reducing the rate of postoperative complications, such as infections or necrosis following radiotherapy and being summarised under the term "quality of life", should also be regarded.

Childhood cancer. Medical costs.

The financial burden of cancer treatment is a major source of stress for families of children with cancer. A previous study demonstrated that out of pocket nonmedical costs incurred because of the illness were consuming 26% of the weekly budget. A one-month sampling of medical charges were collected for 64 families of children undergoing outpatient treatment of cancer. Families of ten patients who had died also participated; total cancer center medical charges throughout the illness were collected. Monthly charges for living patients varied greatly with diagnosis, ranging from $100 to $1800. Total cancer center charges throughout the illness for the decreased patients ranged from $8000 to $53,000 (mean, +34,558). More than 50% of the charges were incurred in the diagnostic and terminal stages of illness. One sign of the hardship endured by the families was the outstanding debts to the cancer center long after the patient's death. Medical costs constituted an average of 5.8% of the families' weekly budgets. Overall, medical costs to the family were found to be much less than the nonmedical costs incurred during treatment.