Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas.

BackgroundWhile 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.MethodsThe 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.ResultsOf 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.ConclusionsLow-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

A Resident-led Initiative Improves Screening and Treatment for Vitamin D Deficiency in Patients with Hip Fractures

BACKGROUND: Acute hip fractures carry a high risk of morbidity and are associated with low vitamin D levels. Improvements in screening and treating low vitamin D levels may lead to lower fall rates and a lower likelihood of additional fragility fractures. However, patients with low vitamin D levels often remain unassessed and untreated, even after they experience these fractures. QUESTIONS/PURPOSES: We wished to determine whether a resident-led initiative can improve (1) screening for and (2) treatment of vitamin D deficiency in patients with acute hip fractures. METHODS: Our department initiated a housestaff-led, quality improvement project focused on screening and treating vitamin D deficiency in patients with acute hip fractures. Screening encompassed checking serum 25-hydroxyvitamin D level during the acute hospitalization, and treating was defined as starting supplementation before discharge when the serum 25-hydroxyvitamin D level was less than 30 ng/mL. To evaluate the efficacy of this program, an administrative database identified 283 patients treated surgically for an acute hip fracture between July 2010 and June 2014. This period included 2 years before program initiation (Year 1, n = 65 patients; Year 2, n = 61 patients), the initial program year (Year 3, n = 66 patients), and the subsequent program year (Year 4, n = 91 patients). Followup was extended to 6 weeks after treatment with 9.2% (26/282) of patients lost to followup. Eight patients were excluded owing to documented intolerance of vitamin D supplementation. There were no differences regarding patient demographics, fracture type, or treatment rendered across these 4 years. The primary endpoints were the proportion of patients screened and treated for vitamin D deficiency. The secondary endpoint was the continuation of vitamin D supplementation at the patient’s 6 week followup, according to the patient’s medication list at that visit. This analysis included all patients, assuming those lost to followup had not continued supplementation. ANOVA and chi-square tests were used to evaluate the differences in demographic data and in screening and treating rates. RESULTS: Screening for vitamin D deficiency improved after initiation of the resident-led quality improvement program, with screening performed for 31% of patients in Year 1 (20/65; odds ratio [OR], 0.44; 95% CI, 0.26–0.75), 20% of patients in Year 2 (12/61; OR, 0.24; 95% CI, 0.13–0.46), 46% of patients in Year 3 (30/66; OR, 0.83; 95% CI, 0.51–1.35), and 88% of patients in Year 4 (80/91; OR, 7.27; 95% CI, 3.87–13.7) (p < 0.001). Vitamin D supplementation was initiated for 33% of patients in Year 1 (21/63; OR, 0.5; 95% CI, 0.30–0.84), 28% in Year 2 (17/61; OR, 0.39; 95% CI, 0.22–0.68), 50% in Year 3 (32/64; OR,1.00; 95% CI, 0.61–1.63), and 76% in Year 4 (65/86; OR, 3.10; 95% CI, 1.89–5.06) (p < 0.001). At early postoperative followup, we saw substantial improvement in the proportion of patients who continued receiving vitamin D supplementation: Year 1, 12% (8/64; OR, 0.14; 95% CI, 0.07–0.30); Year 2, 15% (9/61; OR, 0.17; 95% CI, 0.09–0.35); Year 3, 26% (16/64; OR, 0.33; 95% CI, 0.19–0.59); and Year 4, 46% (40/86; OR, 0.87; 95% CI, 0.57–1.33) (p < 0.001). CONCLUSIONS: Implementation of a resident-led quality improvement program resulted in higher rates of screening and treating vitamin D deficiency for patients with acute hip fractures. Housestaff-based initiatives may be an effective way to improve care processes that target improvements in bone health

How Often Does Spindle Failure Occur in Compressive Osseointegration Endoprostheses for Oncologic Reconstruction?

BackgroundCompressive osseointegration is a promising modality for limb salvage in distal femoral oncologic tumors. However, few studies have explored short-term survival rates in a large patient cohort of distal femur compressive endoprostheses or highlighted the risk factors for spindle failures.Questions/purposesWe asked: (1) What is the frequency of compressive osseointegration spindle failure in distal femoral reconstructions? (2) What are the characteristics of rotational failure cases with distal femur compressive osseointegration endoprostheses? (3) What are the risk factors for mechanical and rotational failure of distal femur compressive osseointegration implantation? (4) What are other modalities of failure or causes of revision surgery, which affect patients undergoing distal femur compressive osseointegration implantation for oncologic reconstruction?MethodsBetween 1996 and 2013, 127 distal femoral reconstructions with the Compress(®) prosthesis were performed in 121 patients. During that time, 116 Compress(®) prostheses were implanted for aggressive primary tumors of the distal femur and/or failure of previous oncologic reconstruction. This approach represented approximately 91% of the distal femoral reconstructions performed during that time. Of the patients with prostheses implanted, four patients (four of 116, 3%) had died, and 37 (37 of 116, 32%) were lost to followup before 24 months. The median followup was 84 months (range, 24-198 months), and 71 patients (66% of all patients) were seen within the last 3 years. A retrospective chart review was performed to determine failure modality as defined by radiographs, clinical history, and intraoperative findings. Risk factors including age, sex, BMI, resection length, and perioperative chemotherapy were analyzed to determine effect on spindle and rotational failure rates. Survival analysis was determined using the Kaplan-Meier estimator. Differences in survival between groups were analyzed using the log rank test. Risk factors were determined using Cox proportional hazard modeling.ResultsSpindle survival at 5 and 10 years was 91% (95% CI, 82%-95%). Survival rates from rotational failure at 5 and 10 years were 92% (95% CI, 83%-96%); the majority of failures occurred within the first 2 years postoperatively and were the result of a twisting mechanism of injury. With the numbers available, none of the potential risk factors examined were associated with mechanical failure. The 5-year and 10-year all-cause revision-free survival rates were 57% (95% CI, 44%-67%) and 50% (95% CI, 36%-61%), respectively.ConclusionsDistal femur compressive osseointegration is a viable method for endoprosthetic reconstruction. Rotational failure is rare with the majority occurring early. No variables were found to correlate with increased risk of mechanical failure. More research is needed to evaluate methods of preventing mechanical and rotational failures in addition to other common causes of revision such as infection in these massive endoprosthetic reconstructions.Level of evidenceLevel IV, therapeutic study

How Often Does Spindle Failure Occur in Compressive Osseointegration Endoprostheses for Oncologic Reconstruction?

BACKGROUND: Compressive osseointegration is a promising modality for limb salvage in distal femoral oncologic tumors. However, few studies have explored short-term survival rates in a large patient cohort of distal femur compressive endoprostheses or highlighted the risk factors for spindle failures. QUESTIONS/PURPOSES: We asked: (1) What is the frequency of compressive osseointegration spindle failure in distal femoral reconstructions? (2) What are the characteristics of rotational failure cases with distal femur compressive osseointegration endoprostheses? (3) What are the risk factors for mechanical and rotational failure of distal femur compressive osseointegration implantation? (4) What are other modalities of failure or causes of revision surgery, which affect patients undergoing distal femur compressive osseointegration implantation for oncologic reconstruction? METHODS: Between 1996 and 2013, 127 distal femoral reconstructions with the Compress(®) prosthesis were performed in 121 patients. During that time, 116 Compress(®) prostheses were implanted for aggressive primary tumors of the distal femur and/or failure of previous oncologic reconstruction. This approach represented approximately 91% of the distal femoral reconstructions performed during that time. Of the patients with prostheses implanted, four patients (four of 116, 3%) had died, and 37 (37 of 116, 32%) were lost to followup before 24 months. The median followup was 84 months (range, 24–198 months), and 71 patients (66% of all patients) were seen within the last 3 years. A retrospective chart review was performed to determine failure modality as defined by radiographs, clinical history, and intraoperative findings. Risk factors including age, sex, BMI, resection length, and perioperative chemotherapy were analyzed to determine effect on spindle and rotational failure rates. Survival analysis was determined using the Kaplan-Meier estimator. Differences in survival between groups were analyzed using the log rank test. Risk factors were determined using Cox proportional hazard modeling. RESULTS: Spindle survival at 5 and 10 years was 91% (95% CI, 82%–95%). Survival rates from rotational failure at 5 and 10 years were 92% (95% CI, 83%–96%); the majority of failures occurred within the first 2 years postoperatively and were the result of a twisting mechanism of injury. With the numbers available, none of the potential risk factors examined were associated with mechanical failure. The 5-year and 10-year all-cause revision-free survival rates were 57% (95% CI, 44%–67%) and 50% (95% CI, 36%–61%), respectively. CONCLUSIONS: Distal femur compressive osseointegration is a viable method for endoprosthetic reconstruction. Rotational failure is rare with the majority occurring early. No variables were found to correlate with increased risk of mechanical failure. More research is needed to evaluate methods of preventing mechanical and rotational failures in addition to other common causes of revision such as infection in these massive endoprosthetic reconstructions. LEVEL OF EVIDENCE: Level IV, therapeutic study

Use of three-dimensional printing and intraoperative navigation in the surgical resection of metastatic acetabular osteosarcoma

A 21-year-old man underwent a joint-preserving posterior acetabular resection of metastatic osteosarcoma using a three-dimensional (3D) printed model and intraoperative navigation. The combined application of these advanced technologies can allow for surgical planning of osteotomies involving complex anatomy and help guide resections intraoperatively. They can maximise the achievement of negative oncological margins, preservation of native hip stability and critical neurovascular structures, and optimal postoperative function in an effort to resect all clinically evident disease. For this particular patient, with secondary bony metastases, they allowed for a safe and well-tolerated procedure that ultimately afforded him palliative benefit, improved quality of life and, conceivably, prolonged survival in the setting of a devastating prognosis. Although he, sadly, has since passed away, he survived for over 2 years after initial metastasis with preserved hip stability and the ability to graduate college, stay active and maintain a quality of life that addressed his goals of care

A Case of Hypercalcemia from PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy.

The treatment of parathyroid hormone-related protein (PTHrP)-mediated hypercalcemia of malignancy includes treating the malignancy, intravenous fluids, and anti-resorptive therapies such as zoledronic acid or denosumab. PTHrP-mediated hypercalcemia has been reported in benign conditions such as systemic lupus erythematous (SLE) and sarcoidosis and appears to be responsive to glucocorticoids. We report a case of PTHrP-induced hypercalcemia due to a malignancy-low grade fibromyxoid sarcoma-that responded to glucocorticoid treatment. This is the first report of glucocorticoids controlling PTHrP-mediated hypercalcemia of malignancy. Immunohistochemistry of the surgical pathology localized PTHrP staining to the vascular endothelial cells within the tumor. Further studies are needed to elucidate the mechanism of glucocorticoid action in the treatment of PTHrP-mediated hypercalcemia of malignancy

Insurance impacts survival for children, adolescents, and young adults with bone and soft tissue sarcomas.

BackgroundWhile 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.MethodsThe 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.ResultsOf 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.ConclusionsLow-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

Intraoperative Radiotherapy in the Management of Locally Recurrent Extremity Soft Tissue Sarcoma

Purpose. To investigate the efficacy and morbidity of limb-sparing surgery with intraoperative radiotherapy (IORT) for patients with locally recurrent extremity soft tissue sarcoma (ESTS). Methods and Materials. Twenty-six consecutively treated patients were identified in a single institution retrospective analysis of patients with locally recurrent ESTS treated with IORT following salvage limb-sparing resection from May 2000 to July 2011. Fifteen (58%) patients received external beam radiotherapy (EBRT) prior to recurrence (median dose 63 Gy), while 11 (42%) patients received EBRT following IORT (median dose 52 Gy). The Kaplan-Meier product limit method was used to estimate disease control and survival and subsets were compared using a log rank statistic, Cox’s regression model was used to determine independent predictors of disease outcome, and toxicity was reported according to CTCAE v4.0 guidelines. Results. With a median duration of follow-up from surgery and IORT of 34.9 months (range: 4 to 139 mos.), 10 patients developed a local recurrence with 4 subsequently undergoing amputation. The 5-year estimate for local control (LC) was 58% (95% CI: 36–75%), for amputation-free was 81% (95% CI: 57–93%), for metastasis-free control (MFC) was 56% (95% CI: 31–75%), for disease-free survival (DFS) was 35% (95% CI: 17–54%), and for overall survival (OS) was 50% (95% CI: 24–71%). Prior EBRT did not appear to influence disease control (LC, p=0.74; MFC, p=0.66) or survival (DFS, p=0.16; OS, p=0.58). Grade 3 or higher acute and late toxicities were reported for 6 (23%) and 8 (31%) patients, respectively. The frequency of both acute and late grade 3 or higher toxicities occurred equally between patients who received EBRT prior to or after IORT. Conclusions. IORT in combination with oncologic resection of recurrent ESTS yields good rates of local control and limb-salvage with acceptable morbidity. Within the limitations of small subsets, these data suggest that prior EBRT does not significantly influence disease control or toxicity

Tumor morphology and location associate with immune cell composition in pleomorphic sarcoma.

BackgroundSoft-tissue sarcomas (STS) are a rare group of mesenchymal malignancies that account for approximately 1% of adult human cancer. Undifferentiated pleomorphic sarcoma (UPS) is one of the most common subtypes of adult STS. Clinical stratification of UPS patients has not evolved for decades and continues to rely on tumor-centric metrics including tumor size and depth. Our understanding of how the tumor microenvironment correlates to these clinicopathologic parameters remains limited.MethodsHere, we performed single-cell flow cytometric immune-based profiling of 15 freshly resected UPS tumors and integrated this analysis with clinical, histopathologic, and outcomes data using both a prospective and retrospective cohort of UPS patients.ResultsWe uncovered a correlation between physiologic and anatomic properties of UPS tumors and the composition of immune cells in the tumor microenvironment. Specifically, we identified an inverse correlation between tumor-infiltrating CD8 + T cells and UPS tumor size; and a positive correlation between tumor-infiltrating CD8 + T cells and overall survival. Moreover, we demonstrate an association between anatomical location (deep or superficial) and frequency of CD4 + PD1hi infiltrating T cells in UPS tumors.ConclusionsOur study provides an immune-based analysis of the tumor microenvironment in UPS patients and describes the different composition of tumor infiltrating lymphocytes based on size and tumor depth