Socioeconomic and insurance-related disparities in disease-specific survival among patients with metastatic bone disease.

BACKGROUND: Approximately 5% of cancer patients in the United States presented with metastatic bone disease (MBD) at diagnosis. Current study explores the disparities in survival for patients with MBD. METHODS: Patients with the diagnosis of MBD at presentation for the five most common primary anatomical sites were extracted from Surveillance, Epidemiology, and End Results Census tract-level dataset (2010-2016). Kaplan-Meier and Cox Proportional Hazard models were used to evaluate survival, and prognostic factors for each cohort. Prognostic significance of socioeconomic status (SES) and insurance status were ascertained. RESULTS: The five most common anatomical-sites with MBD at presentation included "lung" (n = 59 739), "prostate" (n = 19 732), "breast" (n = 16 244), "renal and urothelium" (n = 7718) and "colon" (n= 3068). Lower SES was an independent risk factor for worse disease-specific survival (DSS) for patients with MBD originating from lung, prostate, breast and colon. Lack of insurance was an independent risk factor for worse DSS for MBD patients with primary tumors in lung and breast. CONCLUSIONS: MBD patients from the five most common primary sites demonstrated SES and insurance-related disparities in disease-specific survival. This is the first and largest study to explore SES and insurance-related disparities among patients specifically afflicted with MBD. Our findings highlight vulnerability of patients with MBD across multiple primary sites to financial toxicity.

Non-Private Health Insurance Predicts Advanced Stage at Presentation and Amputation in Lower Extremity High Grade Bone Sarcoma: A National Cancer Database Study : Amputation Predicts Survival: An Effect Most Pronounced in Pediatric and AYA Age Group.

INTRODUCTION: Advances in diagnostic and treatment modalities for high grade bone sarcomas (HGBS) of lower extremity (LE) have enabled limb salvage resections as a feasible first-line surgical option. However, amputations are still performed. Impact of amputation on survival and predictive factors for amputation and the stage at presentation for HGBS of LE remain unknown. METHODS: National Cancer Database was used to extract 5781 cases of high-grade bone sarcoma of the LE from 2004 to 2017. Kaplan-Meier and Cox regression were used to determine the impact of amputation on survival. Chi square test and logistic regression were used to assess the correlation of predictive factors with amputation and stage at presentation. RESULTS: Amputation [hazard ratio (HR) 1.516; 95% confidence interval (CI) 1.259-1.826; p < 0.001] and advanced stage (HR 0.248; 95% CI 0.176-0.351; p < 0.001) were independent predictors of poor overall survival. The impact of amputation on survival was most pronounced for pediatric and adolescents and young adults (AYA) age groups (18% decrease in 10-year survival). Amputation was more likely to be performed among those with nonprivate insurance (HR 1.736; 95% CI 1.191-2.531; p = 0.004), a finding that was mirrored for advanced stage at presentation (HR 0.611; 95% CI 0.414-0.902; p = 0.013). DISCUSSION: Amputation is an independent predictor of poor outcomes among patients with HGBS of LE. The impact of amputation on survival is the highest for the pediatric and AYA age group. Nonprivate insurance is associated with increased likelihood of amputation and an advanced stage at presentation among patients with high-grade bone sarcoma of the LE. This is the largest study highlighting insurance-related disparities in this cohort.

Impact of local treatment modality on overall- and disease-specific survival for nonmetastatic pelvic and sacral Ewing sarcoma.

PURPOSE: The ideal local treatment modality for pelvic and sacral Ewing sarcoma (EWS) is controversial. METHODS: We present the data from the American College of Surgeon's National Cancer Database (NCDB) and the National Cancer Institute's Surveillance, Epidemiology and End Result (SEER) database to investigate the impact of local treatment modalities on survival for nonmetastatic pelvic and sacral Ewing sarcoma. Local treatment includes "surgery," "radiation," and a combination of "surgery and radiation." RESULTS: A total of 235 cases from SEER and 285 cases from NCDB were analyzed. Patients with "localized" stage (intraosseous) in the SEER database did not show any statistically significant difference in the disease-specific survival (DSS) for any of the local treatment modalities. Similar findings were observed for overall survival among patients with American Joint Committee on Cancer (AJCC) stage II and III in the NCDB database. However, patients with nonmetastatic disease, particularly regional disease (extraosseous), showed improved DSS with surgery only, in the SEER. CONCLUSION: We found similar levels of efficacy for different treatment modalities for patients with intraosseous and AJCC II and III pelvic and sacral EWS. "Radiotherapy" is the most common local treatment modality employed in the United States. A prospective, randomized controlled trial with a direct head-to-head comparison is needed for a definitive conclusion.

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

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

Wild-type C-Raf gene dosage and dimerization drive prostate cancer metastasis.

Mutated Ras and Raf kinases are well-known to promote cancer metastasis via flux through the Ras/Raf/MEK/ERK (mitogen-activated protein kinase [MAPK]) pathway. A role for non-mutated Raf in metastasis is also emerging, but the key mechanisms remain unclear. Elevated expression of any of the three wild-type Raf family members (C, A, or B) can drive metastasis. We utilized an in vivo model to show that wild-type C-Raf overexpression can promote metastasis of immortalized prostate cells in a gene dosage-dependent manner. Analysis of the transcriptomic and phosphoproteomic landscape indicated that C-Raf-driven metastasis is accompanied by upregulated MAPK signaling. Use of C-Raf mutants demonstrated that the dimerization domain, but not its kinase activity, is essential for metastasis. Endogenous Raf monomer knockouts revealed that C-Raf's ability to form dimers with endogenous Raf molecules is important for promoting metastasis. These data identify wild-type C-Raf heterodimer signaling as a potential target for treating metastatic disease.

Case report: Treatment of metastatic dedifferentiated chondrosarcoma with pembrolizumab yields sustained complete response.

Dedifferentiated chondrosarcomas (DDCS) are aggressive tumors with poor outcomes. Treatment of localized DDCS is primarily surgical, though most patients present with unresectable or metastatic disease. Systemic treatment options for advanced DDCS are limited, and the benefits of chemotherapy in this patient population remain controversial. Among other systemic therapy options, there is emerging clinical evidence to support the use of immunotherapy in patients with advanced DDCS. However, studies regarding the efficacy of immunotherapy in advanced DDCS are limited. Here, we present the case of a patient with metastatic, programmed death-ligand 1 (PD-L1)-positive DDCS treated with pembrolizumab who showed a sustained complete response for 24 months after initiation of therapy. To our knowledge, this case represents one of few documented cases of metastatic chondrosarcoma with sustained response to immunotherapy. The impressive response seen with PD-L1 inhibition in our patient indicates that immunotherapy is a successful treatment option in a subset of DDCS patients, and further investigation is needed to identify potential responders to immunotherapy.

Head and Neck Cutaneous Soft-Tissue Sarcoma Demonstrate Sex and Racial/Ethnic Disparities in Incidence and Socioeconomic Disparities in Survival.

BACKGROUND: Cutaneous soft-tissue sarcoma (CSTS) of the head and neck are rare and are known to have aggressive clinical course. The current study utilizes a population-based registry in the U.S. to characterize these malignancies and explore disparities. METHODS: National Cancer Institute's (NCI) Surveillance, Epidemiology and End Result (SEER) database from 2000 to 2018 was queried to report incidence and survival data in 4253 cases in the U.S. RESULTS: Males were 5.37 times more likely and Non-Hispanic-White people (NHW) were 4.62 times more likely than females and Non-Hispanic-Black people (NHB) to develop CSTS of the head and neck. The overall incidence was 0.27 per 100,000 persons in 2018, with a significant increase since 2000. Advanced age and stage, histologic group other than 'fibromatous sarcoma' and lower SES groups were independent factors for worse overall survival. CONCLUSIONS: CSTS of the head and neck demonstrate sex and racial/ethnic disparities in incidence and socioeconomic disparities in overall survival. LEVEL OF EVIDENCE: II.