High Community-Level Social Vulnerability is Associated with Worse Recurrence-Free Survival (RFS) After Resection of Extremity and Truncal Soft Tissue Sarcoma.

BACKGROUND: Although social vulnerability has been associated with worse postoperative and oncologic outcomes in other cancer types, these effects have not been characterized in patients with soft tissue sarcoma. This study evaluated the association of social vulnerability and oncologic outcomes. METHODS: The authors conducted a single-institution cohort study of adult patients with primary and locally recurrent extremity or truncal soft tissue sarcoma undergoing resection between January 2016 and December 2021. The social vulnerability index (SVI) was measured on a low (SVI 1-39%, least vulnerable) to high (60-100%, most vulnerable) SVI scale. The association of SVI with overall survival (OS) and recurrence-free survival (RFS) was evaluated by Kaplan-Meier analysis and Cox proportional hazard regression. RESULTS: The study identified 577 patients. The median SVI was 44 (interquartile range [IQR], 19-67), with 195 patients categorized as high SVI and 265 patients as low SVI. The median age, tumor size, histologic subtype, grade, comorbidities, stage, follow-up time, and perioperative chemotherapy and radiation utilization were similar between the high and low SVI cohorts. The patients with high SVI had worse OS (p = 0.07) and RFS (p = 0.016) than the patients with low SVI. High SVI was independently associated with shorter RFS in the multivariate analysis (hazard ratio, 1.64; 95% confidence interval, 1.06-2.54) but not with OS (HR, 1.47; 95% CI 0.84-2.56). CONCLUSION: High community-level social vulnerability appears to be independently associated with worse RFS for patients undergoing resection of extremity and truncal soft tissue sarcoma. The effect of patient and community-level social risk factors should be considered in the treatment of patients with extremity sarcoma.

Regional variation in the survival of patients with a soft-tissue sarcoma of the extremity and trunk wall under a centralized care system : what has been the impact of national policies in the UK?

AIMS: While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK. METHODS: The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management. RESULTS: There had been a significant difference in survival between patients referred from the North East, North West, East Midlands, West Midlands, South West, and Wales in the pre-NICE era (five-year disease-specific survival (DSS); South West, 74% vs North East, 47% (p = 0.045) or West Midlands, 54% (p = 0.049)), which was most evident for patients with a high-grade STS. However, this variation disappeared in the post-NICE era, in which the overall DSS for high-grade STS improved from 47% to 68% at five years (p < 0.001). Variation in the size of the tumour closely correlated with the variation in DSS, and the overall size of the tumour and incidence of metastasis at the time of diagnosis also decreased after the national policies were issued. CONCLUSION: The survival of patients with a STS improved and regional variation corrected after the introduction of national policies, as a result of a decreasing size of tumour and incidence of metastasis at the time of diagnosis, particularly in patients with a high-grade STS. This highlights the positive impact of national guidelines on regional variation in the presentation, management, and outcome in patients with a STS. Cite this article: Bone Joint J 2021;103-B(9):1541-1549.

Socio-economic factors do not affect overall survival in soft tissue sarcoma when patients treated at a single high-volume center.

BACKGROUND: Treatments for soft tissue sarcoma (STS) include extensive surgical resection, radiation and chemotherapy, and can necessitate specialized care and excellent social support. Studies have demonstrated that socioeconomic factors, such as income, marital status, urban/rural residence, and educational attainment as well as treatment at high-volume institution may be associated with overall survival (OS) in STS. METHODS: In order to explore the effect of socio-economic factors on OS in patients treated at a high-volume center, we performed a retrospective analysis of STS patients treated at a single institution. RESULTS: Overall, 435 patients were included. Thirty-seven percent had grade 3 tumors and 44% had disease larger than 5 cm. Patients were most commonly privately insured (38%), married (67%) and retired or unemployed (43%). Median distance from the treatment center was 42 miles and median area deprivation index (ADI) was 5 (10 representing most deprived communities). The majority of patients (52%) were treated with neoadjuvant therapy followed by resection. As expected, higher tumor grade (HR 3.1), tumor size > 5 cm (HR 1.3), and involved lymph nodes (HR 3.2) were significantly associated with OS on multivariate analysis. Demographic and socioeconomic factors, including sex, age at diagnosis, marital status, employment status, urban vs. rural location, income, education, distance to the treatment center, and ADI were not associated with OS. CONCLUSIONS: In contrast to prior studies, we did not identify a significant association between socioeconomic factors and OS of patients with STS when patients were treated at a single high-volume center. Treatment at a high volume institution may mitigate the importance of socio-economic factors in the OS of STS.

Assessment of Synergistic Contribution of Histone Deacetylases in Prognosis and Therapeutic Management of Sarcoma.

Sarcomas are a rare group of neoplasms with a mesenchymal origin that are mainly characterized by the abnormal growth of connective tissue cells. The standard treatment for local control of sarcomas includes surgery and radiation, while for adjuvant and palliative therapy, chemotherapy has been strongly recommended. Despite the availability of multimodal therapies, the survival rate for patients with sarcoma is still not satisfactory. In recent decades, there has been a considerable effort to overcome chemotherapy resistance in sarcoma cells. This has led to the investigation of more cellular compounds implicated in gene expression and transcription processes. Furthermore, it has been discovered that histone acetylation/deacetylation equilibrium is affected in carcinogenesis, leading to a modified chromatin structure and therefore changes in gene expression. In addition, histone deacetylase inhibition is found to play a key role in limiting the tumor burden in sarcomas, as histone deacetylase inhibitors act on well-described oncogenic signaling pathways. Histone deacetylase inhibitors disrupt the increased cell motility and invasiveness of sarcoma cells, undermining their metastatic potential. Moreover, their activity on evoking cell arrest has been extensively described, with histone deacetylase inhibitors regulating the reactivation of tumor suppressor genes and induction of apoptosis. Promoting autophagy and increasing cellular reactive oxygen species are also included in the antitumor activity of histone deacetylase inhibitors. It should be noted that many studies revealed the synergy between histone deacetylase inhibitors and other drugs, leading to the enhancement of an antitumor effect in sarcomas. Therefore, there is an urgent need for therapeutic interventions modulated according to the distinct clinical and molecular characteristics of each sarcoma subtype. It is concluded that a better understanding of histone deacetylase and histone deacetylase inhibitors could provide patients with sarcoma with more targeted and efficient therapies, which may contribute to significant improvement of their survival potential.

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.

Lung Surveillance Strategy for High-Grade Soft Tissue Sarcomas: Chest X-Ray or CT Scan?

BACKGROUND: Given the propensity for lung metastases, National Comprehensive Cancer Network guidelines recommend lung surveillance with either chest x-ray (CXR) or CT in high-grade soft tissue sarcoma. Considering survival, diagnostic sensitivity, and cost, the optimal modality is unknown. METHODS: The US Sarcoma Collaborative database (2000 to 2016) was reviewed for patients who underwent resection of a primary high-grade soft tissue sarcoma. Primary end point was overall survival (OS). Cost analysis was performed. RESULTS: Among 909 patients, 83% had truncal/extremity and 17% had retroperitoneal tumors. Recurrence occurred in 48%, of which 54% were lung metastases. Lung surveillance was performed with CT in 80% and CXR in 20%. Both groups were clinically similar, although CT patients had more retroperitoneal tumors and recurrences. Regardless of modality, 85% to 90% of lung metastases were detected within the first 2 years with a similar re-intervention rate. When considering age, tumor size, location, margin status, and receipt of radiation, lung metastasis was independently associated with worse OS (hazard ratio 4.26; p < 0.01) and imaging modality was not (hazard ratio 1.01; p = 0.97). Chest x-ray patients did not have an inferior 5-year OS rate compared with CT (71% vs 60%; p < 0.01). When analyzing patients in whom no lung metastases were detected, both cohorts had a similar 5-year OS rate (73% vs 74%; p = 0.42), suggesting CXR was not missing clinically relevant lung nodules. When adhering to a guideline-specified protocol for 2018 projected 4,406 cases, surveillance with CXR for 5 years results in savings of $5 million to $8 million/year to the US healthcare system. CONCLUSIONS: In this large multicenter study, lung surveillance with CXR did not result in worse overall survival compared with CT. With considerable savings, a CXR-based protocol can optimize resource use for lung surveillance in high-grade soft tissue sarcoma; prospective trials are needed.

Morbidity, mortality and temporal trends in the surgical management of retroperitoneal sarcoma: An ACS-NSQIP follow up analysis.

BACKGROUND: Calls for multivisceral resection (MVR) of retroperitoneal sarcoma (RPS) are increasing, although the risks and benefits remain controversial. We sought to analyze current 30-day morbidity and mortality rates, and trends in utilization of MVR in a national database. METHODS: Overall morbidity, severe morbidity, mortality rates, and temporal trends were analyzed utilizing the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). RESULTS: From 2012 to 2015, a total of 564 patients underwent RPS resection with 233 patients (41%) undergoing MVR. The MVR group had a higher rate of preoperative weight loss and larger tumors overall. When comparing MVR to non-MVR, there was no significant difference in overall morbidity (22% vs 17%, P = .13), severe morbidity (11% vs 8%, P = .18), or mortality (<1% vs 2%, P = .25). On multivariate analysis, MVR was not associated with increased overall morbidity or severe morbidity. Mortality rates were too low for meaningful statistical analysis. Annual rates of MVR ranged from 37% to 46% with no significant change over time (P = .47). RESULTS: Short-term morbidity and mortality rates after MVR for RPS remain acceptable, but rates of MVR show little change over time in NSQIP hospitals. Concerns about increased morbidity and mortality should not be viewed as a contraindication to wider implementation of MVR for RPS.

Soft-Tissue Sarcomas: Assessment of MRI Features Correlating with Histologic Grade and Patient Outcome.

Background Managing soft-tissue sarcoma (STS) relies on histologic grade, which is the strongest prognostic factor and a routine assessment at biopsy. However, underestimation of histologic grade may occur because of tumor heterogeneity. Purpose To identify MRI features that are associated with high-grade STS (grade III) and to determine the relationship between MRI features and patient survival. Materials and Methods In this retrospective single-center study, patients (age ≥16 years) were included if they presented with STS diagnosed between 2008 and 2015, had a baseline contrast material-enhanced MRI study, had a pathologic grade assessed on the whole surgical specimen, and had no history of neoadjuvant treatment. Visceral sarcomas, well-differentiated liposarcomas, and angiosarcomas were excluded. Images were evaluated for size, heterogeneity, architecture, margins, and surrounding tissue at T2-weighted, T1-weighted precontrast, and T1-weighted postcontrast MRI. χ2 tests, Fisher tests, and multivariable binary logistic regression were performed to identify features associated with a final grade of III. The associations between combinations of these features and overall survival and metastasis-free survival were investigated with Kaplan-Meier curves and multivariable Cox models. Results A total of 130 patients were included (53 women [mean age ± standard deviation, 60.7 years ± 19.2]); 72 of the 130 (55.4%) STSs were grade III. At multivariable analysis, three MRI features were associated with grade III STS: peritumoral enhancement (odds ratio [OR], 3.4; P = .003), presence of an area compatible with necrosis (OR, 2.4; P = .03), and heterogeneous signal intensities greater than or equal to 50% at T2-weighted imaging (OR, 2.3; P = .04). The presence of at least two of these three features was an independent predictor of metastasis-free survival (hazard ratio, 4.5; P = .01) and overall survival (hazard ratio, 4.2; P = .04). Conclusion MRI features including necrosis, heterogeneity, and peritumoral enhancement of soft-tissue sarcomas were associated with grade III tumors, metastasis-free survival, and overall survival. © RSNA, 2019 Online supplemental material is available for this article.

Clinical Outcomes and Costs Following Unplanned Excisions of Soft Tissue Sarcomas in the Elderly.

BACKGROUND: Surgical guidelines for soft tissue sarcoma (STS) emphasize pretreatment evaluation and reports of the perils of unplanned excision exist. Given the paucity of population-based data on this topic, our objective was to analyze clinical outcomes and costs of planned versus unplanned STS excisions in the Medicare population. METHODS: We analyzed 3913 surgical patients with STS ≥66 y old from 1992 to 2011 using the Surveillance, Epidemiology, and End Results-Medicare datafiles. Planned excisions were classified based on preoperative MRI and/or biopsy, whereas unplanned excisions were classified by excision as the first procedure. Inverse probability of treatment weighting with propensity scores was used to adjust for clinicopathologic differences. Re-excisions, complications, and Medicare payments were compared with multivariate models. Overall survival and disease-specific survival were analyzed using Cox proportional hazards and competing risk models. RESULTS: Before the first excision, 24.3% had an MRI and biopsy, 27.3% had an MRI, 11.4% had a biopsy, and 36.9% were unplanned. Re-excision rates were highest for unplanned excisions: 46.3% compared to 18.1%, 36.4%, and 29.7% for other groups (P < 0.0001). There was no difference in disease-specific survival or overall survival between groups (P > 0.05). Planned excisions were associated with increased Medicare costs (P < 0.05), with the first resection contributing to the majority of costs. Subgroup analyses by histologic grade and tumor size revealed similar results. CONCLUSIONS: Survival was comparable with greater health care costs in elderly patients undergoing planned STS excision. Although unplanned excisions remain a quality of care issue with high re-excision rates, these data have important implications for the surgical management of STS in the elderly.

MRI assessment of surrounding tissues in soft-tissue sarcoma during neoadjuvant chemotherapy can help predicting response and prognosis.

OBJECTIVES: To determine if changes in surrounding tissues of soft-tissue sarcomas (STS) evaluated by MRI during neoadjuvant chemotherapy (NAC) are associated with the histological response and satellite tumorous cells beyond the pseudocapsule on surgical specimen, disease-free survival (DFS) and overall survival (OS). METHODS: Fifty-seven adult patients with locally advanced high-grade STS of extremities and trunk wall were included in this single-centre retrospective study. All were uniformly treated by 5-6 cycles of anthracycline-based NAC, curative surgery and adjuvant radiotherapy and had available MRI with a gadolinium-chelates administration at baseline and after 2 cycles. Thirty-seven patients also had a pre-operative MRI. Two senior radiologists evaluated MRI growth pattern, oedema, contrast-enhanced oedema, aponeurotic enhancement, and their qualitative changes during NAC. An expert pathologist reviewed all surgical specimens. A good histological response was defined as <10% viable cells. Associations with pathological findings were estimated with Fisher and Chi-square tests and multivariate analysis with binary logistic regression. Survival analyses included log-rank tests. RESULTS: Forty-two patients had poor responses and 25 had satellite tumorous cells on surgical specimen. Changes in surrounding oedema and in contrast-enhanced oedema were associated with responses (p = 0.008 and 0.011, respectively). Diffuse infiltrative growth pattern (IGP) on baseline MRI, changes in margin definition and in contrast-enhanced oedema at early evaluation were associated with satellite tumorous cells (p = 0.039, 0.011 and 0.009, respectively). Diffuse IGP on baseline MRI and stable or increased oedema during treatment were predictors of DFS (p = 0.009 and 0.040, respectively). CONCLUSION: Surrounding tissues of STS during NAC should be carefully evaluated as they may steer treatment efficacy and patient 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.

Validation of Different Nutritional Assessment Tools in Predicting Prognosis of Patients with Soft Tissue Spindle-Cell Sarcomas.

Predicting outcomes in patients with soft tissue sarcoma (STS) is challenging. To improve these predictions, we retrospectively analyzed common nutritional assessment systems, including Glasgow prognostic score (GPS), Geriatric Nutritional Risk Index (GNRI), neutrophil⁻lymphocyte ratio (NLR), platelet⁻lymphocyte ratio (PLR), and controlling nutritional (CONUT) score against outcomes in 103 patients with STS, of whom 15 (14.6%) died within 1 year of diagnosis. GPS, GNRI, NLR, PLR, and CONUT scores significantly differed between patients who died within one year and patients who lived longer. Binomial logistic regression analysis showed that male sex, older age at diagnosis, higher GPS, higher stage, and unresectable STS were risk factors for death within a year of diagnosis. Overall survival was evaluated by Cox proportional hazards models, which correlated higher NLR, higher PLR, larger maximum diameter of tumor, higher stage, and unresectable STS with poor prognosis. We next examined prognostic factors in the 93 patients with resectable STS, and found male sex, higher GPS, and higher stage were correlated with poor prognosis in these patients. Our findings suggest that GPS, NLR, and PLR are simple predictors of outcome in patients with STS. Nutritional therapies might improve their GPS and prognosis.

The impact of racial/ethnic disparities on survival for children and young adults with chest wall sarcoma: A population-based study.

BACKGROUND: To determine whether there are racial/ethnic disparities in disease presentation, treatment and survival outcomes among children and young adults with chest wall sarcomas. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was analyzed for patients 21 years old and younger with chest wall sarcoma. We performed multivariate logistic regression to investigate the association of race/ethnicity with advanced stage of disease at presentation and likelihood of undergoing surgical resection. Overall survival (OS) was evaluated using Cox regression modeling to calculate hazard ratios with 95% confidence intervals. RESULTS: A total of 669 patients were identified: 393 non-Hispanic whites (NHW) (59%), 151 Hispanics (23%), 64 non-Hispanic blacks (NHB) (11%), and 64 other race/ethnicity (9%). The 5- and 10-year OS rates for the entire cohort were 69% and 64%, respectively. NHB had significantly worse 5-year and 10-year OS compared to NHW based on the log rank test (61% versus 70%, 52% versus 66%, respectively; p = 0.037).). Most patients (80%) underwent surgical resection. However, NHB were less likely than NHW to undergo surgical resection by multivariate analysis (OR 0.43, 95% CI 0.22-0.82). CONCLUSIONS: NHB children and young adults with chest wall sarcoma have decreased overall survival. In addition, NHB are less likely to undergo surgical resection which may contribute to survival disparities. It is paramount that health care providers work to close the treatment gap between racial/ethnic groups to improve survival in children and young adults with chest wall sarcoma. LEVEL OF EVIDENCE: Level III Treatment Study.

Association Between Treatment at High-Volume Facilities and Improved Overall Survival in Soft Tissue Sarcomas.

PURPOSE: Soft tissue sarcomas (STS) are rare malignancies that require complex multidisciplinary management. Therefore, facilities with high sarcoma case volume may demonstrate superior outcomes. We hypothesized that STS treatment at high-volume (HV) facilities would be associated with improved overall survival (OS). METHODS AND MATERIALS: Patients aged ≥18 years with nonmetastatic STS treated with surgery and radiation therapy at a single facility from 2004 through 2013 were identified from the National Cancer Database. Facilities were dichotomized into HV and low-volume (LV) cohorts based on total case volume over the study period. OS was assessed using multivariable Cox regression with propensity score-matching. Patterns of care were assessed using multivariable logistic regression analysis. RESULTS: Of 9025 total patients, 1578 (17%) and 7447 (83%) were treated at HV and LV facilities, respectively. On multivariable analysis, high educational attainment, larger tumor size, higher grade, and negative surgical margins were statistically significantly associated with treatment at HV facilities; conversely, black race and non-metropolitan residence were negative predictors of treatment at HV facilities. On propensity score-matched multivariable analysis, treatment at HV facilities versus LV facilities was associated with improved OS (hazard ratio, 0.87, 95% confidence interval, 0.80-0.95; P = .001). Older age, lack of insurance, greater comorbidity, larger tumor size, higher tumor grade, and positive surgical margins were associated with statistically significantly worse OS. CONCLUSIONS: In this observational cohort study using the National Cancer Database, receipt of surgery and radiation therapy at HV facilities was associated with improved OS in patients with STS. Potential sociodemographic disparities limit access to care at HV facilities for certain populations. Our findings highlight the importance of receipt of care at HV facilities for patients with STS and warrant further study into improving access to care at HV facilities.

Semiparametric accelerated failure time cure rate mixture models with competing risks.

Modern medical treatments have substantially improved survival rates for many chronic diseases and have generated considerable interest in developing cure fraction models for survival data with a non-ignorable cured proportion. Statistical analysis of such data may be further complicated by competing risks that involve multiple types of endpoints. Regression analysis of competing risks is typically undertaken via a proportional hazards model adapted on cause-specific hazard or subdistribution hazard. In this article, we propose an alternative approach that treats competing events as distinct outcomes in a mixture. We consider semiparametric accelerated failure time models for the cause-conditional survival function that are combined through a multinomial logistic model within the cure-mixture modeling framework. The cure-mixture approach to competing risks provides a means to determine the overall effect of a treatment and insights into how this treatment modifies the components of the mixture in the presence of a cure fraction. The regression and nonparametric parameters are estimated by a nonparametric kernel-based maximum likelihood estimation method. Variance estimation is achieved through resampling methods for the kernel-smoothed likelihood function. Simulation studies show that the procedures work well in practical settings. Application to a sarcoma study demonstrates the use of the proposed method for competing risk data with a cure fraction.

Racial and ethnic disparities in treatment and survival of pediatric sarcoma.

BACKGROUND: Childhood sarcomas are rare and require complex interdisciplinary care including surgery, chemotherapy, and radiation. The goal of this study was to determine if racial or ethnic disparities exist for pediatric sarcoma patients in the United States. METHODS: The United States' National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify patients aged 0-21 diagnosed with primary sarcomas from 1973 to 2012. Patients were considered by race and ethnicity. Survival curves were computed using the Kaplan-Meier method and the log-rank test. RESULTS: A total of 11,502 patients were included in this study. When stratified by race, non-Hispanic black and Hispanic patients were significantly more likely to present with advanced stage disease than white patients. White patients were more likely to receive radiation therapy than black and Hispanic patients (P = 0.01). There was no significant difference between patients who underwent surgery (P = 0.21). Overall survival was better for white patients than black or Hispanic ones. Despite the overall 5-year survival improvement during the study period (56.2%-70.3%), survival disparities between race and ethnicity have grown. CONCLUSIONS: Racial and ethnic disparities do exist with respect to stage, treatment, and survival of these rare tumors. Black and Hispanic patients are presenting at more advanced stage and have overall worse survival. This survival disparity has widened over the past 4 decades.

The modified frailty index to predict morbidity and mortality for retroperitoneal sarcoma resections.

BACKGROUND: The modified frailty index (mFI) is an important method to risk-stratify surgical patients and has been validated for general surgery and selected surgical subspecialties. However, there are currently no data assessing the efficacy of the mFI to predict acute morbidity and mortality in patients undergoing surgery for retroperitoneal sarcoma. METHODS: Using the American College of Surgeons' National Surgical Quality Improvement Program from 2007 to 2012, we performed a retrospective analysis of patients with a diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The mFI was calculated according to standard published methods. Univariate and multivariate statistical analyses including χ2 and logistic regression were used to identify predictors of 30-d overall morbidity, 30-d severe morbidity (Clavien III/IV), and 30-d mortality. RESULTS: We identified 846 patients with the diagnosis of primary malignant retroperitoneal neoplasm who underwent surgical resection. The distribution mFI scores was 0 (48.5%) or 1 (36.3%), with only 4.5% of patients presenting with a score ≥3. Rates of 30-d overall morbidity, serious morbidity, and mortality were 22.6%, 12.9%, and 1.2%, respectively. Only selected mFI scores were associated with serious morbidity and overall morbidity on multivariate analysis (P < 0.05), and mFI did not predict 30-d mortality (P > 0.05). CONCLUSIONS: Our data demonstrate that the majority of patients undergoing retroperitoneal sarcoma resections have few, if any, comorbidities. The mFI was a limited predictor of overall and serious complications and was not a significant predictor of mortality. Better discriminators of preoperative risk stratification may be needed for this patient population.

Histologic Appearance After Preoperative Radiation Therapy for Soft Tissue Sarcoma: Assessment of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group Response Score.

PURPOSE: To critically assess the prognostic value of the European Organization for Research and Treatment of Cancer-Soft Tissue and Bone Sarcoma Group (EORTC-STBSG) response score and define histologic appearance after preoperative radiation therapy (RT) for soft tissue sarcoma (STS). METHODS AND MATERIALS: For a cohort of 100 patients with STS of the extremity/trunk treated at our institution with preoperative RT followed by resection, 2 expert sarcoma pathologists evaluated the resected specimens for percent residual viable cells, necrosis, hyalinization/fibrosis, and infarction. The EORTC response score and other predictors of recurrence-free survival (RFS) and overall survival (OS) were assessed by Kaplan-Meier and proportional hazard models. RESULTS: Median tumor size was 7.5 cm; 92% were intermediate or high grade. Most common histologies were unclassified sarcoma (34%) and myxofibrosarcoma (25%). Median follow-up was 60 months. The 5-year local recurrence rate was 5%, 5-year RFS was 68%, and 5-year OS was 75%. Distribution of cases according to EORTC response score tiers was as follows: no residual viable tumor for 9 cases (9% pathologic complete response); <1% viable tumor for 0, ≥1% to <10% for 9, ≥10% to <50% for 44, and ≥50% for 38. There was no association between EORTC-STBSG response score and RFS or OS. Conversely, hyalinization/fibrosis was a significant independent favorable predictor for RFS (hazard ratio 0.49, P=.007) and OS (hazard ratio 0.36, P=.02). CONCLUSION: Histologic evaluation after preoperative RT for STS showed a 9% pathologic complete response rate. The EORTC-STBSG response score and percent viable cells were not prognostic. Hyalinization/fibrosis was associated with favorable outcome, and if validated, may become a valid endpoint for neoadjuvant trials.

Cost-Effectiveness Analysis of Preoperative Versus Postoperative Radiation Therapy in Extremity Soft Tissue Sarcoma.

PURPOSE: Surgery combined with radiation therapy (RT) is the cornerstone of multidisciplinary management of extremity soft tissue sarcoma (STS). Although RT can be given in either the preoperative or the postoperative setting with similar local recurrence and survival outcomes, the side effect profiles, costs, and long-term functional outcomes are different. The aim of this study was to use decision analysis to determine optimal sequencing of RT with surgery in patients with extremity STS. METHODS AND MATERIALS: A cost-effectiveness analysis was conducted using a state transition Markov model, with quality-adjusted life years (QALYs) as the primary outcome. A time horizon of 5 years, a cycle length of 3 months, and a willingness-to-pay threshold of $50,000/QALY was used. One-way deterministic sensitivity analyses were performed to determine the thresholds at which each strategy would be preferred. The robustness of the model was assessed by probabilistic sensitivity analysis. RESULTS: Preoperative RT is a more cost-effective strategy ($26,633/3.00 QALYs) than postoperative RT ($28,028/2.86 QALYs) in our base case scenario. Preoperative RT is the superior strategy with either 3-dimensional conformal RT or intensity-modulated RT. One-way sensitivity analyses identified the relative risk of chronic adverse events as having the greatest influence on the preferred timing of RT. The likelihood of preoperative RT being the preferred strategy was 82% on probabilistic sensitivity analysis. CONCLUSIONS: Preoperative RT is more cost effective than postoperative RT in the management of resectable extremity STS, primarily because of the higher incidence of chronic adverse events with RT in the postoperative setting.