Disparities in incidence and survival for patients with Ewing sarcoma in Florida.

BACKGROUND: Ewing sarcoma (ES) is a malignant bone tumor most commonly affecting non-Hispanic White (NHW) adolescent males, though recognition among Hispanic individuals is rising. Prior population-based studies in the United States (US), utilizing Surveillance, Epidemiology, and End Results (SEER) have shown higher all-cause mortality among White Hispanics, Blacks, and those of low socioeconomic status (SES). Florida is not part of SEER but is home to unique Hispanic populations including Cubans, Puerto Ricans, South Americans that contrasts with the Mexican Hispanic majority in other US states. This study aimed to assess racial/ethnic disparities on incidence and survival outcomes among this diverse Florida patient population. METHODOLOGY: Our study examined all patients diagnosed with osseous ES (2005-2018) in Florida (n = 411) based on the state's population-based cancer registry dataset. Florida Age-adjusted Incidence Rates (AAIRs) were computed by sex and race-ethnicity and compared to the equivalent populations in SEER. Cause-specific survival disparities among Florida patients were examined using Kaplan-Meier analysis. Univariable and multivariable analyses using Cox regression were performed for race/ethnicity, with adjustment for age, sex, year of diagnosis, site of disease, staging, SES, and insurance type. RESULTS: There was a significantly higher incidence of osseous ES in Florida Hispanic males (AAIR 2.6/1,000,000); (95% CI: 2.0-3.2 per 1,000,000; n = 84) compared to the SEER Hispanic males (AAIR 1.2/1,000,000;1.1-1.4 per 1,000,000; n = 382). Older age, distant metastasis, lack of chemotherapy or surgical resection were statistically significant determinants of poor survival while SES, insurance status and race-ethnicity were not. However, among nonmetastatic ES, Florida Hispanics had an increased risk of death compared to Florida NHW (adjusted Hazard Ratio 2.32; 95%CI: 1.20-4.46; p = 0.012). CONCLUSIONS: Florida Hispanic males have a higher-than-expected incidence of osseous ES compared to the US. Hispanics of both sexes show remarkably worse survival for nonmetastatic disease compared to NHW. This disparity is likely multifactorial and requires further in-depth studies.

Expression of immune-related genes as prognostic biomarkers for the assessment of osteosarcoma clinical outcomes.

Cancer immunotherapy is a promising therapeutic approach, but the prognostic value of immune-related genes in osteosarcoma (OS) is unknown. Here, Target-OS RNA-seq data were analyzed to detect differentially expressed genes (DEGs) between OS subgroups, followed by functional enrichment analysis. Cox proportional risk regression was performed for each immune-related gene, and a risk score model to predict the prognosis of patients with OS was constructed. The risk scores were calculated using the risk signature to divide the training set into high-risk and low-risk groups, and validation was performed with GSE21257. We identified two immune-associated clusters, C1 and C2. C1 was closely related to immunity, and the immune score was significantly higher in C1 than in C2. Furthermore, we validated 6 immune cell hub genes related to the prognosis of OS: CD8A, KIR2DL1, CD79A, APBB1IP, GAL, and PLD3. Survival analysis revealed that the prognosis of the high-risk group was significantly worse than that of the low-risk group. We also explored whether the 6-gene prognostic risk model was effective for survival prediction. In conclusion, the constructed a risk score model based on immune-related genes and the survival of patients with OS could be a potential tool for targeted therapy.

Association of loss of spleen visualization on whole-body diffusion-weighted imaging with prognosis and tumor burden in patients with multiple myeloma.

This study investigated the clinical significance of loss of spleen visualization (LSV) on whole-body diffusion-weighted imaging (WB-DWI) in patients with multiple myeloma (MM). The WB-DWI of 96 patients with newly diagnosed MM (NDMM) and 15 patients with smoldering MM (sMM) were retrospectively reviewed. LSV was observed in 56 patients with NDMM (58.3%) and 1 patient with sMM (6.7%). Patients with NDMM with LSV had a higher median infiltration of bone marrow plasma cells (80.0% vs. 50.0%, p < 0.001) and median total diffusion volume (median; 540.2 vs. 137.0 mL, p = 0.003) than patients without LSV. Patients with LSV had a lower spleen-to-spinal cord ratio (0.36 vs. 0.96, p < 0.001) and worse 2-year overall survival (OS) (84.6% vs. 100%, p = 0.032). Patients who did not recover spleen visualization during treatment had a worse prognosis, even when they obtained very good partial response (median progression-free survival: 13.2 months). Spleen histopathological findings revealed higher cellularity and diffuse myeloma cell infiltration in a patient with LSV and splenic amyloidosis without extramedullary hematopoiesis in a patient without LSV. Therefore, LSV indicates worse prognosis for patients with MM, even when the patient responds to treatment. Further studies are warranted to clarify the immunological role of spleen in MM.

Effect assessment of methotrexate in combination with other chemotherapeutic agents for osteosarcoma in children: A protocol for systematic review and meta-analysis.

BACKGROUND: Osteosarcoma is a primary form of malignant bone tumor. It is commonly prevalent among children. Treating osteosarcoma with chemotherapy has had limited clinical outcomes due to side effects and the formation of drug resistance. Presently, a mixture of doxorubicin, cisplatin, ifosfamide, epirubicin methrotrexate, and other supplementary medications are used in osteosarcoma chemotherapy. Therefore, this study aims to investigate the clinical therapeutic effects of combining methotrexate with other chemotherapeutic agents to treat osteosarcoma in children. METHODS: The search of several electronic databases will lead to source related published studies. The electronic databases include both English (PubMed, EMBASE, Web of Science, and the Cochrane Library) and Chinese (China National Knowledge Infrastructure, WanFang, and China Biomedical Database) databases. All studies published from inception to November 19, 2020 are searched. Study selection, extraction of data, and evaluation of the bias risk in included studies are carried out by two authors independently. The software, RevMan 5.3, is used to analyze the data. RESULTS: This study provides evidence of substantial quality for the clinical therapeutic effects of methotrexate combined with other chemotherapeutic agents for treating osteosarcoma in children. CONCLUSION: The results of this study provide conclusive evidence with regards to the clinical application of methotrexate combined with other chemotherapeutic agents for treating osteosarcoma in children. ETHICS AND DISSEMINATION: Since this study will use published data, ethical approval is not required. SYSTEMATIC REVIEW REGISTRATION NUMBER: This protocol has been registered on INPLASY202110024.

Cost Effectiveness of External Beam Radiation Therapy versus Percutaneous Image-Guided Cryoablation for Palliation of Uncomplicated Bone Metastases.

PURPOSE: To evaluate the cost effectiveness of incorporating cryoablation in the treatment regimens for uncomplicated bone metastases using radiation therapy (RT) in single-fraction RT (SFRT) or multiple-fraction RT (MFRT) regimens. MATERIALS AND METHODS: A Markov model was constructed using 1-month cycles over a lifetime horizon to compare the cost effectiveness of multiple strategies, including RT followed by RT (RT-RT) for recurrent pain, RT followed by cryoablation (RT-ablation), and cryoablation followed by RT (ablation-RT). RT-RT consisted of 8 Gy in 1 fraction/8 Gy in 1 fraction (SFRT-SFRT) and 30 Gy in 10 fractions/20 Gy in 5 fractions (MFRT-MFRT). Probabilities and utilities were extracted from a search of the medical literature. Costs were calculated from a payer perspective using 2017 Medicare reimbursement in an outpatient setting. Incremental cost effectiveness ratios (ICERs) were calculated using strategies evaluated for willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). To account for model uncertainty, one-way and probabilistic sensitivity analyses were performed. RESULTS: In the base case analysis, SFRT-ablation was cost effective relative to SFRT-SFRT at $96,387/QALY. MFRT-ablation was cost effective relative to MFRT-MFRT at $85,576/QALY. Ablation-SFRT and ablation-MFRT were not cost effective with ICERs >$100,000/QALY. In one-way sensitivity analyses, results were highly sensitive to variation in multiple model parameters, including median survival (base: 9 months), with SFRT-SFRT favored at median survival ≤8.7 months. Probabilistic sensitivity analysis examining SFRT-based regimens showed that SFRT-ablation was preferred in 36.9% of simulations at WTP of $100,000/QALY. CONCLUSIONS: Cryoablation is a potentially cost-effective alternative to reirradiation with RT for recurrent of pain following RT; however, no strategy incorporating initial cryoablation was cost effective.

Contemporary outcomes of metastatic breast cancer among 22,000 women from the multicentre ESME cohort 2008-2016.

AIM: Real-world data inform the outcome comparisons and help the development of new therapeutic strategies. To this end, we aimed to describe the full characteristics and outcomes in the Epidemiological Strategy and Medical Economics (ESME) cohort, a large national contemporary observational database of patients with metastatic breast cancer (MBC). METHODS: Women aged ≥18 years with newly diagnosed MBC and who initiated MBC treatment between January 2008 and December 2016 in one of the 18 French Comprehensive Cancer Centers (N = 22,109) were included. We assessed the full patients' characteristics, first-line treatments, overall survival (OS) and first-line progression-free survival, as well as updated prognostic factors in the whole cohort and among the 3 major subtypes: hormone receptor positive and HER2-negative (HR+/HER2-, n = 13,656), HER2-positive (HER2+, n = 4017) and triple-negative (n = 2963) tumours. RESULTS: The median OS of the whole cohort was 39.5 months (95% confidence interval [CI], 38.7-40.3). Five-year OS was 33.8%. OS differed significantly between the 3 subtypes (p < 0.0001) with a median OS of 43.3 (95% CI, 42.5-44.5) in HR+/HER2-; 50.1 (95% CI, 47.6-53.1) in HER2+; and 14.8 months (95% CI, 14.1-15.5) in triple-negative subgroups, respectively. Beyond performance status, the following variables had a constant significant negative prognostic impact on OS in the whole cohort and among subtypes: older age at diagnosis of metastases (except for the triple-negative subtype), metastasis-free interval between 6 and 24 months, presence of visceral metastases and number of metastatic sites ≥ 3. CONCLUSIONS: The ESME program represents a unique large-scale real-life cohort on MBC. This study highlights important situations of high medical need within MBC patients. DATABASE REGISTRATION: clinicaltrials.gov Identifier NCT032753.

Cost-effectiveness of denosumab for the prevention of skeletal-related events in patients with solid tumors and bone metastases in the United States.

Aims: Bone complications (also known as skeletal-related events [SREs]) pose significant health and financial burdens on patients with bone metastases. Denosumab demonstrated superiority over zoledronic acid in delaying the time to first SRE. This study examined the lifetime cost-effectiveness of denosumab vs zoledronic acid from both US payer and societal perspectives.Methods: This analysis used a lifetime Markov model and included patients with breast cancer, prostate cancer, and other solid tumors and bone metastases. The societal perspective included direct medical, direct non-medical, and indirect costs associated with denosumab and zoledronic acid; the payer perspective included direct medical costs only. Bone complication rates for each tumor type were estimated from three pivotal phase 3 studies and modified to reflect real-world incidence.Results: From a societal perspective, compared with zoledronic acid, denosumab use resulted in an incremental cost of $9,043, an incremental benefit of 0.128 quality-adjusted life-years (QALYs), a lifetime cost per QALY of $70,730, and a net monetary benefit (NMB) of $10,135 in favor of denosumab. Direct drug costs for denosumab ($28,352) were higher than zoledronic acid/untreated ($578), but were offset by reduced costs associated with bone complications. From a payer perspective, denosumab use was associated with an incremental cost of $13,396, and an incremental benefit of 0.128 QALYs, for a cost of $104,778 per QALY and an NMB of $5,782 in favor of denosumab.Limitations: Some model inputs had limited information and, given that the results may be sensitive to changes in these inputs, our findings should be interpreted within the context of the data inputs and modeling assumptions used in the analysis.Conclusions: Denosumab is a cost-effective option to prevent bone complications in patients with solid tumors when considering both payer and broader societal perspectives.

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.

Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms.

BACKGROUND: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs). OBJECTIVES: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement. METHODS: A retrospective study of all patients with NENs, except Grade 3 lung NENs (April 2002 to March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 23.0/STATA v12. RESULTS: Of 1,212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-entero-pancreatic primary (49%, n = 42) followed by lung (25%, n = 21), unknown primary (20%, n = 17), and "others" (6%, n = 5). Two-thirds (n = 57) had G1-2 neuroendocrine tumours, and 41% (n = 35) had functional tumours. Overall, 28% (n = 24) presented with synchronous BMs at first NEN diagnosis, and 55% (n = 47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n = 38), median time to development of BMs was 14.0 months. BMs were "widespread" in 61% (n = 52). Although only 22% (n = 19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n = 37). Radiotherapy and bisphosphonates were used in 34% (n = 29) and 22% (n = 19) respectively. Surgery was rarely performed (2%, n = 2). Median OS from identification of BMs was 31.0, and 18.9 months from development of BMs-related symptoms. CONCLUSIONS: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients' quality of life and survival outcomes.

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.

Female sex is associated with a lower risk of bone metastases and favourable prognosis in non-sex-specific cancers.

BACKGROUND: The objectives were to investigate the disparity in the prevalence of bone metastases (BM) between the sexes and to assess the effect of female sex on the development and prognosis of BM. METHODS: Cases of invasive non-sex-specific cancers diagnosed between 2010 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) program were used. The prevalence of BM was calculated by combining the prevalence of BM among different cancers. Multivariable logistic regression and proportion hazard regression were conducted to investigate the effect of female sex, and the results were pooled by meta-analysis. RESULTS: The pooled prevalence of BM among male and female patients was 2.3% (95% CI: 1.6-3.2%) and 1.8% (95% CI: 1.2-2.6%), respectively. The pooled prevalence of BM dramatically decreased for patients aged 11-40 years old, plateaued for patients aged 41-90 years old and increased for patients aged > 90 years old in both male and female patients. Meta-analysis suggested that female sex had a protective effect on the development of BM (pooled OR = 0.80; 95% CI: 0.75-0.84; p < .001) and a favourable prognosis for respiratory system cancers (pooled HR = 0.81; 95% CI: 0.71-0.92; p < .001). However, no significant associations existed for other cancers. Male non-sex-specific cancer patients and those with male-leaning genetic variations or hormonal status have a greater likelihood of developing BM than female patients. CONCLUSIONS: Female sex was associated with fewer BM in various non-sex-specific cancers, and the effect was constant with changes in age. Female sex showed a protective effect exclusively on the prognosis of respiratory system cancers.

Does the SORG Algorithm Predict 5-year Survival in Patients with Chondrosarcoma? An External Validation.

BACKGROUND: We developed a machine learning algorithm to predict the survival of patients with chondrosarcoma. The algorithm demonstrated excellent discrimination and calibration on internal validation in a derivation cohort based on data from the Surveillance, Epidemiology, and End Results (SEER) registry. However, the algorithm has not been validated in an independent external dataset. QUESTIONS/PURPOSES: Does the Skeletal Oncology Research Group (SORG) algorithm accurately predict 5-year survival in an independent patient population surgically treated for chondrosarcoma? METHODS: The SORG algorithm was developed using the SEER registry, which contains demographic data, tumor characteristics, treatment, and outcome values; and includes approximately 30% of the cancer patients in the United States. The SEER registry was ideal for creating the derivation cohort, and consequently the SORG algorithm, because of the high number of eligible patients and the availability of most (explanatory) variables of interest. Between 1992 to 2013, 326 patients were treated surgically for extracranial chondrosarcoma of the bone at two tertiary care referral centers. Of those, 179 were accounted for at a minimum of 5 years after diagnosis in a clinical note at one of the two institutions, unless they died earlier, and were included in the validation cohort. In all, 147 (45%) did not meet the minimum 5 years of followup at the institution and were not included in the validation of the SORG algorithm. The outcome (survival at 5 years) was checked for all 326 patients in the Social Security death index and were included in the supplemental validation cohort, to also ascertain validity for patients with less than 5 years of institutional followup. Variables used in the SORG algorithm to predict 5-year survival including sex, age, histologic subtype, tumor grade, tumor size, tumor extension, and tumor location were collected manually from medical records. The tumor characteristics were collected from the postoperative musculoskeletal pathology report. Predicted probabilities of 5-year survival were calculated for each patient in the validation cohort using the SORG algorithm, followed by an assessment of performance using the same metrics as used for internal validation, namely: discrimination, calibration, and overall performance. Discrimination was calculated using the concordance statistic (or the area under the Receiver Operating Characteristic (ROC) curve) to determine how well the algorithm discriminates between the outcome, which ranges from 0.5 (no better than a coin-toss) to 1.0 (perfect discrimination). Calibration was assessed using the calibration slope and intercept from a calibration plot to measure the agreement between predicted and observed outcomes. A perfect calibration plot should show a 45° upwards line. Overall performance was determined using the Brier score, ranging from 0 (excellent prediction) to 1 (worst prediction). The Brier score was compared with the null-model Brier score, which showed the performance of a model that ignored all the covariates. A Brier score lower than the null model Brier score indicated greater performance of the algorithm. For the external validation an F1-score was added to measure the overall accuracy of the algorithm, which ranges between 0 (total failure of an algorithm) and 1 (perfect algorithm).The 5-year survival was lower in the validation cohort than it was in the derivation cohort from SEER (61.5% [110 of 179] versus 76% [1131 of 1544] ; p < 0.001). This difference was driven by higher proportion of dedifferentiated chondrosarcoma in the institutional population than in the derivation cohort (27% [49 of 179] versus 9% [131 of 1544]; p < 0.001). Patients in the validation cohort also had larger tumor sizes, higher grades, and nonextremity tumor locations than did those in the derivation cohort. These differences between the study groups emphasize that the external validation is performed not only in a different patient cohort, but also in terms of disease characteristics. Five-year survival was not different for both patient groups between subpopulations of patients with conventional chondrosarcomas and those with dedifferentiated chondrosarcomas. RESULTS: The concordance statistic for the validation cohort was 0.87 (95% CI, 0.80-0.91). Evaluation of the algorithm's calibration in the institutional population resulted in a calibration slope of 0.97 (95% CI, 0.68-1.3) and calibration intercept of -0.58 (95% CI, -0.20 to -0.97). Finally, on overall performance, the algorithm had a Brier score of 0.152 compared with a null-model Brier score of 0.237 for a high level of overall performance. The F1-score was 0.836. For the supplementary validation in the total of 326 patients, the SORG algorithm had a validation of 0.89 (95% CI, 0.85-0.93). The calibration slope was 1.13 (95% CI, 0.87-1.39) and the calibration intercept was -0.26 (95% CI, -0.57 to 0.06). The Brier score was 0.11, with a null-model Brier score of 0.19. The F1-score was 0.901. CONCLUSIONS: On external validation, the SORG algorithm retained good discriminative ability and overall performance but overestimated 5-year survival in patients surgically treated for chondrosarcoma. This internet-based tool can help guide patient counseling and shared decision making. LEVEL OF EVIDENCE: Level III, prognostic study.

Overall Survival Trends and Clinical Characteristics of Plasmacytoma in the United States: A National Cancer Database Analysis.

BACKGROUND: Given the rarity of plasmacytoma, large-scale database analysis can provide useful information regarding the clinical presentation and patient-related factors impacting overall survival (OS). MATERIALS AND METHODS: The National Cancer Data Base was queried for patients with plasmacytoma between 2004 and 2013, excluding patients with systemic disease. Plasmacytomas were classified as originating in bone (P-bone), in extramedullary tissue (P-EM), or unspecified. Survival was estimated using the Kaplan-Meier and log-rank test method. We used Cox regression to determine specific outcomes adjusting for demographic, socioeconomic, geographic, facility type, year of diagnosis, and comorbid factors. RESULTS: In total, 6225 patients were identified, of which 61.5% were men. The median age at diagnosis was 64 years (range, 18-90 years), and the median follow-up was 58 months. The primary site of disease was P-bone in 4056 (65.1%) patients and P-EM in 1468 (23.6%), and the remaining 701 patients were P-unspecified. The unadjusted median survival for solitary P-bone was 89 months (95% confidence interval, 82.9-95.0 months), and for solitary P-EM was 117.3 months (95% confidence interval, 108.8 months to not reached). Factors associated with improved OS include younger age, private insurance, higher income, solitary lesion, and lower comorbidity score. Patients with P-bone disease treated at academic facilities had improved OS. Only 65% of patients with solitary plasmacytoma lesions received radiation treatment. Age greater than 75 years and increased distance to treatment facility was associated with a decreased likelihood of receiving radiation. CONCLUSIONS: This is the largest study examining outcomes of patients with plasmacytoma using a large database analysis, revealing unique aspects of P-EM versus P-bone and underutilization of radiation treatment.

Early response assessment of re-ossification after palliative conventional radiotherapy for vertebral bone metastases.

BACKGROUND: To evaluate the therapeutic outcomes in patients with bone metastases receiving radiotherapy (RT), it is important to use objective radiological response criteria. The aim of this study was to investigate the changes in pain and re-ossification after RT for painful vertebral bone metastases without paralysis by malignant spinal cord compression. METHODS: The participants included 55 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. Bone modifying agents (BMAs) were administered in all patients. Follow-up assessments were done just before the start of RT and at 1, 2, 3, 4, and 6 months after RT. Radiological responses of irradiated vertebrae by RT were assessed by computed tomography (CT) using MD Anderson response classification criteria (MDA criteria) and the pain response was assessed by Numeric Rating Scale (NRS). Response was classified as complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD). RESULTS: The rates of CR were 2%, 7%, 20%, 30%, and 56% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were 15%, 49%, 77%, 91%, and 91% at 1, 2, 3, 4, and 6 months, respectively. The rates of CR or PR were significantly higher in patients with breast cancer than in patients with lung cancer (p = 0.043). At one month, there was an association between the NRS and radiological response assessed by MDA criteria. There was a significant trend that, with a better response, there were more patients without pain (p = 0.021). CONCLUSIONS: Under BMAs administration, successful RT for vertebral bone metastases decreased pain and caused re-ossification. The MD Anderson criteria could be useful for assessment of radiological responses of irradiated vertebrae.

Timing of Local Therapy Affects Survival in Ewing Sarcoma.

PURPOSE: We aimed to investigate the relationship between survival and time to local therapy after initiation of up-front chemotherapy in the treatment of patients with localized Ewing sarcoma. METHODS AND MATERIALS: The National Cancer Database was queried for patients with localized Ewing sarcoma treated with primary chemotherapy and subsequent local therapy. Kaplan-Meier survival curves were generated for patients initiating local therapy 6 to 15 weeks and ≥16 weeks after chemotherapy initiation. Multivariable binomial logistic regression was used to identify factors associated with prolonged time to local therapy. A multivariable Cox proportional hazards model was used to identify factors associated with overall survival (OS). RESULTS: The final cohort included 1318 patients. A higher proportion of patients initiating local therapy 6 to 15 weeks after chemotherapy initiation versus ≥16 weeks after chemotherapy initiation were ≤21 years old (79.5% vs 72.0%; P = .004). Age >21 years (P < .001; hazard ratio, 1.65; 95% confidence interval, 1.28-2.12), tumor size >8 cm (P = .016), and time to local therapy ≥16 weeks (P = .005; hazard ratio, 1.41; 95% confidence interval, 1.11-1.80) were associated with reduced OS; after review of margin status, negative margins were associated with improved OS compared with gross disease (P = .029). Patients initiating local therapy at 6 to 15 weeks versus ≥16 weeks had a 5-year OS of 78.7% versus 70.4% and a 10-year OS of 70.3% versus 57.1%, respectively (P < .001). The difference in OS according to time to local therapy was particularly more important in patients receiving radiation therapy alone. Age >21 years and treatment by radiation therapy alone were associated with delayed time (>16 weeks) to local therapy, whereas private insurance and income >$48,000 were less likely to be associated with delayed local therapy. CONCLUSIONS: Delayed time to local therapy ≥16 weeks after chemotherapy initiation was independently associated with worse survival in patients with localized Ewing sarcoma.

Survival Impact of Locoregional Treatment of the Primary Tumor in De Novo Metastatic Breast Cancers in a Large Multicentric Cohort Study: A Propensity Score-Matched Analysis.

INTRODUCTION: Improvement in overall survival (OS) by locoregional treatment (LRT) of the primary tumor in de novo metastatic breast cancer (MBC) patients remains controversial. OBJECTIVE: The aim of our study was to evaluate the impact of LRT on OS in a large retrospective cohort of de novo MBC patients, with regard to immunohistochemical characteristics and pattern of metastatic dissemination. METHODS: We conducted a multicentric retrospective study of patients diagnosed with de novo MBC selected from the French Epidemiological Strategy and Medical Economics MBC database (NCT03275311) between 2008 and 2014. Overall, 4276 women were included in the study. LRT comprised either radiotherapy, surgery, or both. RESULTS: LRT was used in 40% of patients. Compared with no LRT, patients who received LRT were younger (p < 0.0001) and were more likely to have only one metastatic site (p < 0.0001) or bone-only metastases (p < 0.0001). LRT was associated with a significantly better OS based on landmark multivariate analysis at 1-year (hazard ratio 0.65, 95% confidence interval 0.55-0.76, p < 0.001). Similar results were observed in all sensitivity analyses, including propensity score matching. In subgroup analysis, LRT was associated with better OS in patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (61.6 vs. 45.9 months, p < 0.001) and HER2-positive tumors (77.2 vs. 52.6 months, p = 0.008), but not in triple-negative tumors (19 vs. 18.6 months, p = 0.54), and was also associated with a reduction in the risk of death in visceral metastatic patients (p < 0.001). CONCLUSIONS: LRT was associated with a significantly better OS in de novo MBC patients, including patients with visceral involvement at diagnosis; however, LRT did not impact OS in triple-negative MBC.

Choosing Wisely at the End of Life: Use of Shorter Courses of Palliative Radiation Therapy for Bone Metastasis.

PURPOSE: American Society for Radiation Choosing Wisely guidelines recommend ≤10 fractions of radiation therapy (RT) for bone metastasis, with consideration for 1 fraction in patients with a poor prognosis. The purpose of this analysis was to evaluate characteristic differences in guideline concordance to fractionation regimens in a modern cohort of older patients with a diagnosis of bone metastasis. METHODS AND MATERIALS: Medicare beneficiaries aged ≥65 years treated with RT for bone metastasis from 2012 to 2015 were identified. Guideline-concordant RT fractionation was defined in the entire cohort as ≤10 fractions. Utilization of 1 fraction versus ≥2 fractions was analyzed in deceased patients. Patient demographic, disease, and facility characteristics associated with shorter fractionation were analyzed. RESULTS: In 569 patients treated with RT, the median age at diagnosis was 73 years. The most common cancer types were lung (37%), genitourinary (26%), breast (15%), and gastrointestinal (10%). Among all patients, 34%, 30%, and 36% received 1 fraction, 2 to 10 fractions, and ≥11 fractions, respectively. In comparison with receipt of 1 to 10 fractions, receipt of ≥11 fractions was associated with a $1467 increase in per-patient cost to Medicare during the calendar quarter of RT. Almost two-thirds of patients who died within 30 days of RT completion were treated with >1 fraction. CONCLUSIONS: Although guideline concordance was high overall, a large number of patients received longer courses of RT at the end of life. Strong consideration should be made for utilization of shorter courses, particularly in patients with a limited prognosis.

Disparities in Adolescent and Young Adult Sarcoma Survival: Analyses of the Texas Cancer Registry and the National SEER Data.

PURPOSE: Examine disparities in survival for adolescents and young adults (AYAs) diagnosed with bone and soft tissue sarcomas in Texas compared with national estimates. METHODS: AYAs with sarcomas diagnosed between 1995 and 2012 at ages 15-39 years were identified from the Texas Cancer Registry (TCR) and Surveillance, Epidemiology, and End Results (SEER) program. Patient demographic, treatment, and clinical characteristics were compared between TCR and SEER using chi-squared tests. Five-year survival was computed using the Kaplan-Meier method. Cox proportional hazards (CPH) models evaluated the factors associated with the risk of mortality between and within the two datasets. RESULTS: Sarcoma patients in TCR were more likely to be Hispanic, uninsured, diagnosed at late stage, and have lower rates of surgery as the first line of treatment than those in SEER. In Texas, 5-year survival was 68.7% versus 72.2% in SEER (p < 0.001). However, after including surgery in our fully adjusted CPH model, survival differences between the two datasets were no longer observed. In these models, males, and those living in nonmetropolitan areas were more likely to die than their counterparts in both datasets. In TCR, those who lived in the U.S. and Mexico border had higher mortality. In SEER, Hispanics and non-Hispanic blacks had higher mortality. CONCLUSION: The adjusted AYA sarcoma survival in Texas was similar to that of SEER, but patients in Texas were more likely to be uninsured and have lower surgery rates. Those living in the U.S. and Mexico border in Texas faced lower survival. These results are important for delineating effective care for this high-risk patient group.

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.