Socioeconomic disparities in musculoskeletal oncology.

Musculoskeletal oncology is a clinical specialty dealing with a diverse population of patients with metastatic bone disease, hematological malignancies with musculoskeletal manifestations, primary bone malignancies and soft tissue sarcomas. There are wide-spread disparities including socioeconomic (SES) and insurance-related disparities reported in the literature. In this review, we'll summarize the disparities surrounding the musculoskeletal oncology.

Primary mobile vertebral column sarcomas: Prognostic factors vary by histologic subtypes.

BACKGROUND: Primary sarcomas originating from the mobile spine portends a particularly sinister outcome. Rarity of the disease process has resulted in inconsistent data due to small sample size and heterogeneity in patient selection and analytics. METHODS: Surveillance, Epidemiology and End Result (SEER) database from 1975 to 2017 was queried to report incidence and survival data in 712 patients in the United States. Kaplan-Meier and Cox Regression were used to determine the prognostic factors affecting survival. RESULTS: Incidence of spinal sarcoma was 0.019 per 100,000 persons in 2017 and has not significantly changed since 2000 (p > 0.05). Disease-specific 5-year survival for the entire cohort was 57%. Osteosarcoma has the worst 5-year survival (39%) and chondrosarcoma has the best 5-year survival (69%). Independent predictors of survival for the entire cohort included age, grade, and stage. Stage was an independent predictor of survival for every histologic subtype. Additional predictors of survival for spinal osteosarcoma, Ewing sarcoma, and chondrosarcoma included age, size, and grade, respectively. CONCLUSIONS: The current study is an analysis of a population-based registry reporting incidence survival data for patients with sarcoma of mobile vertebral column. Survival and prognostic factors vary by histologic subtypes. There is lack of improvement in survival over the last three decades.

Upregulation of Cystathionine-ß-Synthase in Colonic Epithelia Reprograms Metabolism and Promotes Carcinogenesis.

The trans-sulfuration enzyme cystathionine-ß-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells. Differentially expressed metabolites (65 increased and 20 decreased) clustered into the glycolytic pathway, nucleotide sugars, intermediates of the pentose phosphate pathway, and lipogenesis, including primarily phospholipids, sphingolipids, and bile acids. CBS upregulation induced broad changes in the NCM356 cell transcriptome with over 350 differentially expressed genes. These genes overlapped significantly with gene sets related to glycolysis, hypoxia, and a colon cancer cell phenotype, including genes regulated by NF-κB, KRAS, p53, and Wnt signaling, genes downregulated after E-cadherin knockdown, and genes related to increased extracellular matrix, cell adhesion, and epithelial-to-mesenchymal transition. The CBS-induced switch to an anabolic metabolism was associated with increased NCM356 cell bioenergetics, proliferation, invasion through Matrigel, resistance to anoikis, and CBS-dependent tumorigenesis in immunocompromised mice. Genetic ablation of CBS in CBS heterozygous mice (CBS+/- ) reduced the number of mutagen-induced aberrant colonic crypt foci. Taken together, these results establish that activation of the CBS/H2S axis promotes colon carcinogenesis. Cancer Res; 77(21); 5741-54. ©2017 AACR.

Effects of sclerostin antibody on healing of a non-critical size femoral bone defect.

Sclerostin is a glycoprotein secreted by osteocytes and inhibits osteoblastogenesis via inhibition of Wnt signaling. We hypothesized that sclerostin antibody (Scl-AbIII) would accelerate the healing of a murine femoral non-critical size bone defect model. A unilateral and unicortical 0.8 mm-sized drill hole was made in the proximal femoral shaft of adult female nude mice. One group of mice received subcutaneous injections of Scl-AbIII and a second group received vehicle only. Reporter MC3T3 osteoprogenitor cells were injected via the tail vein 3 days after surgery to monitor systemic trafficking of exogenous osteoprogenitors. Bioluminescence imaging (BLI), microcomputed tomography (microCT), micropositron emission tomography (microPET) and histological analysis were used to compare the bone healing responses to Scl-AbIII treatment. Bone mineral density (BMD) significantly increased at the defect site after week 1, and was significantly higher in the treatment compared with the control group at all time points. This finding was also confirmed on histological analysis by increased deposition of new woven bone. MicroPET scanning showed a trend for greater activity in the control group at day 21 compared with the Scl-AbIII group, indicating early bone maturation following treatment with Scl-AbIII. Whereas the BLI signals derived from the injected osteoprogenitor cells showed no differences between vehicle and Scl-AbIII treated groups, systemic migration of MC3T3 cells to the bone defect was clearly identified in both groups using immunohistochemistry. Systemic administration of Scl-AbIII resulted in earlier healing and maturation of a non-critical size bone defect. These findings underscore the potential use of Scl-AbIII for treatment of complicated fractures, non-unions, and other clinical scenarios.

Primary lymphoma of bone in adult patients.

BACKGROUND: The low incidence of primary lymphoma of bone (PLB) has led to discrepancies in classification as well as difficulty in prognostication. The authors of this report used the Surveillance, Epidemiology, and End Results (SEER) database to analyze a large, population-based cohort of adult patients with this disease. The database provides a standardized classification and documentation of outcomes and enables a meaningful evaluation of prognostic factors. METHODS: The SEER database was used to identify all patients who were diagnosed with PLB from 1973 through 2005. Survival was analyzed with the Kaplan-Meier method, and the influence of clinical parameters on survival was analyzed with the log-rank test. A Cox proportional hazards model was used for multivariate analysis. RESULTS: Fifteen hundred adult patients with PLB were analyzed. The 5-year and 10-year survival rates for adult patients were 58% and 45%, respectively. Multivariate analysis revealed that younger age and localized disease were independent predictors of survival. It is noteworthy that the incidence of disease, as determined by the annual percentage change, increased during the study period (P < .05). CONCLUSIONS: This analysis of a large cohort of adults with PLB indicated that the only identifiable prognostic indicators were localized disease and younger age. The authors concluded that future treatment for patients with PLB need to be based on strict staging criteria and adherence to successful published protocols using collaborative clinical trials.

Ewing sarcoma demonstrates racial disparities in incidence-related and sex-related differences in outcome: an analysis of 1631 cases from the SEER database, 1973-2005.

BACKGROUND: Previous reports of Ewing sarcoma cohorts suggested that there is a difference in incidence according to racial origin. However, to the authors' knowledge, this finding has never been tested in a population-based database, and the impact of race on clinical outcome and the significance of known risk factors stratified to racial groups have not been reported. METHODS: Patients who had Ewing sarcoma diagnosed between 1973 and 2005 were identified in the Surveillance, Epidemiology, and End Results database. Patient demographic and clinical characteristics; incidence; year of diagnosis; tumor location, tumor size, and disease stage at diagnosis; treatment(s); cause of death; and survival were extracted. Kaplan-Meier, log-rank, and Cox regressions were used to analyze the significance of prognostic factors. RESULTS: Race-specific incidence indicated that Caucasians have the highest incidence (0.155), followed by Asians/Pacific Islanders (0.082), and African Americans (0.017). The difference in incidence between Caucasians and African Americans was 9-fold and significant (P<.001). The incidence of Ewing sarcoma increased over the past 3 decades among Caucasians (P<.05). Survival was not impacted by race. Local disease stage, primary tumor location in the appendicular skeleton, and tumor size