Remineralization Rate of Lytic Lesions of the Spine in Multiple Myeloma Patients Undergoing Radiation Therapy.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: In general, Multiple Myeloma (MM) patients are treated with systemic therapy including chemotherapy. Radiation therapy can have an important supportive role in the palliative management of MM-related osteolytic lesions. Our study aims to investigate the degree of radiation-induced remineralization in MM patients to gain a better understanding of its potential impact on bone mineral density and, consequently, fracture prevention. Our primary outcome measure was percent change in bone mineral density measured in Hounsfield Units (Δ% HU) between pre- and post-radiation measurements, compared to non-targeted vertebrae. METHODS: We included 119 patients with MM who underwent radiotherapy of the spine between January 2010 and June 2021 and who had a CT scan of the spine at baseline and between 3-24 months after radiation. A linear mixed effect model tested any differences in remineralization rate per month (ßdifference) between targeted and non-targeted vertebrae. RESULTS: Analyses of CT scans yielded 565 unique vertebrae (366 targeted and 199 non-targeted vertebrae). In both targeted and non-targeted vertebrae, there was an increase in bone density per month (ßoverall = .04; P = .002) with the largest effect being between 9-18 months post-radiation. Radiation did not cause a greater increase in bone density per month compared to non-targeted vertebrae (ßdifference = .67; P = .118). CONCLUSION: Our results demonstrate that following radiation, bone density increased over time for both targeted and non-targeted vertebrae. However, no conclusive evidence was found that targeted vertebrae have a higher remineralization rate than non-targeted vertebrae in patients with MM.

Patient-Reported Outcomes After Intramedullary Nailing of Oncologic Impending or Pathologic Fractures With Carbon Fiber or Titanium Implant.

INTRODUCTION: Despite the benefits of intramedullary nailing (IMN) of impending or pathologic fractures in oncologic patients, literature on patient-reported outcomes (PROs) is scarce in patients treated with carbon fiber (CF) nails. Our study compared postoperative PROs after IMN with CF or titanium implants. METHODS: We conducted a retrospective propensity score-matched cohort study of patients treated at our institution with CF or titanium nails for impending or pathologic fractures from metastatic bone disease. Patient-Reported Outcomes Measurement Information System (PROMIS) Global Health Short Form (SF) Physical, Mental, and Physical Function 10a scores were collected. Pain was assessed using visual analog scale (VAS). Absolute and differential scores were compared between groups. RESULTS: We included 207 patients, 51 treated with CF and 156 with titanium nails. One month postoperatively, patients had a one-point decrease in the pain VAS score while PROMIS scores did not improve. At 3 months, PROMIS SF Physical and SF 10a scores improved from preoperative values. Six months postoperatively, median PROMIS SF Physical, SF Mental, and SF 10a scores were higher than preoperative scores. Absolute and differential PROMIS and pain VAS scores were similar between groups at the 6-month and 1-year marks. CONCLUSION: Patient-reported outcomes were similar after intramedullary nailing with either CF or titanium implants.

Factors associated with skeletal-related events in patients with bone metastatic melanoma: A retrospective study of 481 patients.

OBJECTIVES: Metastatic bone disease is estimated to develop in up to 17% of patients with melanoma, compromising skeleton integrity resulting in skeletal-related events (SREs), which impair quality of life and reduce survival. The objective of the study was to investigate (1) the proportion of melanoma patients developing SREs following diagnosis of bone metastasis and (2) the predictors for SREs in this patient cohort. METHODS: Four hundred and eighty-one patients with bone metastatic melanoma from two tertiary centers in the United States from 2008 to 2018 were included. The primary outcome was 90-day and 1-year occurrence of a SRE, including pathological fractures of bones, cord compression, hypercalcemia, radiotherapy, and surgery. Fine-Gray regression analysis was performed for overall SREs and pathological fracture, with death as a competing risk. RESULTS: By 1-year, 52% (258/481) of patients experienced SREs, and 28% (137/481) had a pathological fracture. At 90-day, lytic lesions, bone pain, elevated calcium and absolute lymphocyte, and decreased albumin and hemoglobin were associated with higher SRE risk. The same factors, except for decreased hemoglobin, were shown to predict development of SREs at 1-year. CONCLUSION: The high incidence of SREs and pathological fractures warrants vigilance using the identified factors in this study and preventative measures during clinical oncological care.

The Influence of Patient Characteristics and Social Determinants of Health on Postoperative Complications Following Achilles Tendon Rupture.

BACKGROUND: The influence of social determinants of health (SDH) on postoperative complications has been investigated in several studies, although correlation with Achilles tendon rupture (ATR) repair remains uninvestigated. SDH encompasses several factors, including insurance status and area-based measurements, including the Area Deprivation Index (ADI) and Social Vulnerability Index (SVI), which ranks neighborhoods by social disadvantage. This study investigated the correlation between patient demographics, SDH, and complications following ATR repair. METHODS: A retrospective cohort study was conducted on 521 patients who presented with acute ATR and met the inclusion criteria, including age ≥18 years, a minimum of 30-day follow-up, and repair within 28 days of rupture. We reviewed patient demographics, time to surgery (TTS), and postoperative complications, including venous thromboembolism (VTE), rerupture, surgical site infection (SSI), wound dehiscence, and sural nerve injury. SDH variables included race, smoking status, insurance status, level of education, ADI, and SVI. Univariate regression tested the correlation between complications and SDH indicators. Significant variables (P < .05) were included in a multivariate regression. RESULTS: Sixty-eight complications occurred in 59 patients (11.3%). Multivariate regression showed that a higher ADI, that is, socially deprived individuals, was associated with lower rates of VTE (OR = 0.41, P = .04). Higher body mass index (BMI) was associated with rerupture (OR = 8.73, P < .01). Male patients had lower rates of wound dehiscence (OR = 0.31, P = .03) and VTE (OR = 0.32, P = .02) compared with women. Longer TTS correlated with sural nerve injuries (OR = 2.23, P < .01) and shorter TTS with reruptures (OR = 0.02, P = .02). CONCLUSION: Some measures of SDH were associated with postoperative complications. Gender also may have an effect, with male sex associated with lower rates of wound dehiscence and VTE. BMI was associated with higher rates of reruptures and overall general complications. LEVEL OF EVIDENCE: Level IV, case series.

Wound vacuum-assisted closure temporization after tumor resection of soft tissue sarcomas-A cost analysis in a propensity-score matched population.

BACKGROUND: Vacuum-assisted closure (VAC) temporization is a technique associated with high local control rates used in myxofibrosarcoma. We sought to compare the costs and postoperative outcomes of VAC temporization and single-stage (SS) excision/reconstruction. METHODS: We conducted a retrospective analysis of patients with myxofibrosarcoma surgically treated at our institution between 2000 and 2022. Variables of interest included total, direct, and indirect costs for initial episode of care, 90 days and 1 year after initial admission, and postoperative outcomes. Costs were compared between the VAC temporization and SS groups. RESULTS: After matching, 13 patients in the SS group and 23 in the VAC group were analyzed. We found no difference in median and mean total inpatient costs, between the VAC temporization and SS group. While total 90-day and 1-year costs were higher in the VAC group compared to the SS group, mean costs were similar. There were no differences in postoperative complications between groups. A subanalysis of the entire cohort (n = 139) revealed lower local recurrence and overall death rates in the VAC temporization group. CONCLUSION: VAC temporization had similar inpatient costs and postoperative outcomes to SS excision/reconstruction. While median 90-day and 1-year costs were higher in the VAC group, mean costs did not differ.

Prediction of 5-year survival in soft tissue leiomyosarcoma using a machine learning model algorithm.

BACKGROUND AND OBJECTIVES: Leiomyosarcoma (LMS) is associated with one of the poorest overall survivals among soft tissue sarcomas. We sought to develop and externally validate a model for 5-year survival prediction in patients with appendicular or truncal LMS using machine learning algorithms. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was used for development and internal validation of the models; external validation was assessed using our institutional database. Five machine learning algorithms were developed and then tested on our institutional database. Area under the receiver operating characteristic curve (AUC) and Brier score were used to assess model performance. RESULTS: A total of 2209 patients from the SEER database and 81 patients from our tertiary institution were included. All models had excellent calibration with AUC 0.84-0.85 and Brier score 0.15-0.16. After assessing the performance indicators according to the TRIPOD model, we found that the Elastic-Net Penalized Logistic Regression outperformed other models. The AUCs of the institutional data were 0.83 (imputed) and 0.85 (complete-case analysis) with a Brier score of 0.16. CONCLUSION: Our study successfully developed five machine learning algorithms to assess 5-year survival in patients with LMS. The Elastic-Net Penalized Logistic Regression retained performance upon external validation with an AUC of 0.85 and Brier score of 0.15.

Limited health literacy results in lower health-related quality of life in spine patients.

BACKGROUND CONTEXT: Spinal conditions impact health-related quality of life (HRQoL). Patient education and counseling improve HRQoL, yet the effects may be limited for patients with inadequate health literacy (HL). Despite the established relationship between HRQoL and HL in other fields, research in the orthopedic spine population is lacking. PURPOSE: To investigate if limited HL results in lower HRQoL and to evaluate factors are associated with HRQoL in patients seen at an outpatient orthopedic spine center. STUDY DESIGN/SETTING: Prospective single-center cross-sectional study. PATIENT SAMPLE: Patients 18 years of age or older seen at a tertiary urban academic hospital- based multi-surgeon outpatient spine center. OUTCOME MEASURES: EQ-5D-5L health-related quality of life (HRQoL) questionnaire, and the Newest Vital Sign (NVS) HL assessment tool. METHODS: Between October 2022 and February 2023, consecutive English-speaking patients over the age of 18 and new to the outpatient spine clinic were approached for participation in this cross-sectional survey study. Patients completed a sociodemographic survey, EQ-5D-5L HRQoL questionnaire, and Newest Vital Sign (NVS) HL assessment tool. The EQ-5D-5L yields two continuous outcomes: an index score ranging from below 0 to 1 and a visual analog scale (EQ-VAS) score ranging from 0 to 100. The NVS scores were divided into limited (0-3) and adequate (4-6) HL. Multivariate linear regression with purposeful selection of variables was performed to identify independent factors associated with HRQoL. RESULTS: Out of 397 eligible patients, 348 (88%) agreed to participate and were included in statistical analysis. Limited HL was independently associated with lower EQ-5D-5L index scores (B=1.07 [95% CI 1.00-1.15], p=.049. Other factors associated with lower EQ-5D-5L index scores were being obese (BMI≥30), having housing concerns, and being an active smoker. Factors associated with lower EQ-VAS scores were being underweight (BMI<18.5), obese, having housing concerns, and higher updated Charlson comorbidity index (uCCI) scores. Being married was associated with higher EQ-VAS scores. CONCLUSIONS: Limited HL is associated with lower EQ-5D-5L index scores in spine patients, indicating lower HRQoL. To effectively apply HL-related interventions in this population, a better understanding of the complex interactions between patient characteristics, social determinants of health, and HRQoL outcomes is required. Further research should focus on interventions to improve HRQoL in patients with limited HL and how to accurately identify these patients. LEVEL OF EVIDENCE: Level II prognostic.

Does the SORG Machine-learning Algorithm for Extremity Metastases Generalize to a Contemporary Cohort of Patients? Temporal Validation From 2016 to 2020.

BACKGROUND: The ability to predict survival accurately in patients with osseous metastatic disease of the extremities is vital for patient counseling and guiding surgical intervention. We, the Skeletal Oncology Research Group (SORG), previously developed a machine-learning algorithm (MLA) based on data from 1999 to 2016 to predict 90-day and 1-year survival of surgically treated patients with extremity bone metastasis. As treatment regimens for oncology patients continue to evolve, this SORG MLA-driven probability calculator requires temporal reassessment of its accuracy. QUESTION/PURPOSE: Does the SORG-MLA accurately predict 90-day and 1-year survival in patients who receive surgical treatment for a metastatic long-bone lesion in a more recent cohort of patients treated between 2016 and 2020? METHODS: Between 2017 and 2021, we identified 674 patients 18 years and older through the ICD codes for secondary malignant neoplasm of bone and bone marrow and CPT codes for completed pathologic fractures or prophylactic treatment of an impending fracture. We excluded 40% (268 of 674) of patients, including 18% (118) who did not receive surgery; 11% (72) who had metastases in places other than the long bones of the extremities; 3% (23) who received treatment other than intramedullary nailing, endoprosthetic reconstruction, or dynamic hip screw; 3% (23) who underwent revision surgery, 3% (17) in whom there was no tumor, and 2% (15) who were lost to follow-up within 1 year. Temporal validation was performed using data on 406 patients treated surgically for bony metastatic disease of the extremities from 2016 to 2020 at the same two institutions where the MLA was developed. Variables used to predict survival in the SORG algorithm included perioperative laboratory values, tumor characteristics, and general demographics. To assess the models' discrimination, we computed the c-statistic, commonly referred to as the area under the receiver operating characteristic (AUC) curve for binary classification. This value ranged from 0.5 (representing chance-level performance) to 1.0 (indicating excellent discrimination) Generally, an AUC of 0.75 is considered high enough for use in clinical practice. To evaluate the agreement between predicted and observed outcomes, a calibration plot was used, and the calibration slope and intercept were calculated. Perfect calibration would result in a slope of 1 and intercept of 0. For overall performance, the Brier score and null-model Brier score were determined. The Brier score can range from 0 (representing perfect prediction) to 1 (indicating the poorest prediction). Proper interpretation of the Brier score necessitates a comparison with the null-model Brier score, which represents the score for an algorithm that predicts a probability equal to the population prevalence of the outcome for each patient. Finally, a decision curve analysis was conducted to compare the potential net benefit of the algorithm with other decision-support methods, such as treating all or none of the patients. Overall, 90-day and 1-year mortality were lower in the temporal validation cohort than in the development cohort (90 day: 23% versus 28%; p < 0.001, and 1 year: 51% versus 59%; p<0.001). RESULTS: Overall survival of the patients in the validation cohort improved from 28% mortality at the 90-day timepoint in the cohort on which the model was trained to 23%, and 59% mortality at the 1-year timepoint to 51%. The AUC was 0.78 (95% CI 0.72 to 0.82) for 90-day survival and 0.75 (95% CI 0.70 to 0.79) for 1-year survival, indicating the model could distinguish the two outcomes reasonably. For the 90-day model, the calibration slope was 0.71 (95% CI 0.53 to 0.89), and the intercept was -0.66 (95% CI -0.94 to -0.39), suggesting the predicted risks were overly extreme, and that in general, the risk of the observed outcome was overestimated. For the 1-year model, the calibration slope was 0.73 (95% CI 0.56 to 0.91) and the intercept was -0.67 (95% CI -0.90 to -0.43). With respect to overall performance, the model's Brier scores for the 90-day and 1-year models were 0.16 and 0.22. These scores were higher than the Brier scores of internal validation of the development study (0.13 and 0.14) models, indicating the models' performance has declined over time. CONCLUSION: The SORG MLA to predict survival after surgical treatment of extremity metastatic disease showed decreased performance on temporal validation. Moreover, in patients undergoing innovative immunotherapy, the possibility of mortality risk was overestimated in varying severity. Clinicians should be aware of this overestimation and discount the prediction of the SORG MLA according to their own experience with this patient population. Generally, these results show that temporal reassessment of these MLA-driven probability calculators is of paramount importance because the predictive performance may decline over time as treatment regimens evolve. The SORG-MLA is available as a freely accessible internet application at https://sorg-apps.shinyapps.io/extremitymetssurvival/ .Level of Evidence Level III, prognostic study.

Preoperative embolization in surgical treatment of spinal metastases originating from non-hypervascular primary tumors: a propensity score matched study using 495 patients.

BACKGROUND CONTEXT: Preoperative embolization (PE) reduces intraoperative blood loss during surgery for spinal metastases of hypervascular primary tumors such as thyroid and renal cell tumors. However, most spinal metastases originate from primary breast, prostate, and lung tumors and it remains unclear whether these and other spinal metastases benefit from PE. PURPOSE: To assess the (1) efficacy of PE on the amount of intraoperative blood loss and safety in patients with spinal metastases originating from non-hypervascular primary tumors, and (2) secondary outcomes including perioperative allogeneic blood transfusion, anesthesia time, hospitalization, postoperative complication within 30 days, reoperation, 90-day mortality, and 1-year mortality. STUDY DESIGN: Retrospective propensity-score matched, case-control study at 2 academic tertiary medical centers. PATIENT SAMPLE: Patients 18 years of age or older undergoing surgery for spinal metastases originating from primary non-thyroid, non-renal cell, and non-hepatocellular tumors between January 1, 2002 and December 31, 2016 were included. OUTCOME MEASURES: The primary outcomes were estimated amount of intraoperative blood loss and complications attributable to PE, such as neurologic injury, wound infection, thrombosis, or dissection. The secondary outcomes included perioperative allogeneic blood transfusion, anesthesia time, hospitalization, postoperative complication within 30 days, reoperation, 90-day mortality, and 1-year mortality. METHODS: In total, 495 patients were identified, of which 54 (11%) underwent PE. After propensity score matching on 21 variables, including primary tumor, number of spinal levels, and surgical treatment, 53 non-PE patients were matched to 53 PE patients. Matching was adequate measured by comparing the matched variables, testing the standardized mean differences (<0.25), and inspecting Kernel density plots. The degree of embolization was noted to be complete, until stasis, or successful in 43 (80%) patients. RESULTS: Intraoperative blood loss did not differ between both groups with a median blood loss in liters of 0.6 (IQR, 0.4-1.2) for non-PE patients and 0.9 (IQR, 0.6-1.2) for PE patients (p=.32). No complications occurred during embolization or the time between embolization and surgery. No differences were found in terms of the secondary outcomes. CONCLUSIONS: Our data suggest that, although no complications occurred and the embolization procedure can be considered safe, patients with non-hypervascular spinal metastases might not benefit from PE. A larger, prospective study could confirm or refute these study findings and aid in elucidating a subset of spinal metastases that might benefit from PE.