Risk Evaluation of Denosumab And Zoledronic Acid For Medication-Related Osteonecrosis of The Jaw In Patients With Bone Metastases: A Propensity Score-Matched Analysis

Abstract Purpose: This study evaluated the risk of medication-related osteonecrosis of the jaw (MRONJ) in patients with cancer who received denosumab or zoledronic acid (ZA) for treating bone metastasis.Methods: The medical records of patients were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. The primary endpoint was a comparison of the risk of developing MRONJ between the denosumab and ZA groups. Propensity score matching was used to control for baseline differences between patient characteristics and compare outcomes for both groups.Results: Among the 799 patients enrolled, 58 (7.3%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the ZA group (9.6% [39/406] vs. 4.8% [19/393], p = 0.009). Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment (hazard ratio [HR], 2.89; 95% confidence interval [CI], 1.65–5.25; p < 0.001) and tooth extraction after starting ZA or denosumab (HR, 4.26; 95% CI, 2.38–7.44; p < 0.001) were significant risk factors for MRONJ. Propensity score-matched analysis confirmed that the risk of developing MRONJ was significantly higher in the denosumab group than in the ZA group (HR, 2.34; 95% CI, 1.17–5.01; p = 0.016). Conclusion: The results of this study suggest that denosumab poses a significant risk for developing MRONJ in patients treated for bone metastasis, and thus these patients require close monitoring.

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Associated characteristics and treatment outcomes of medication-related osteonecrosis of the jaw in patients receiving denosumab or zoledronic acid for bone metastases

Supportive Care in Cancer ◽

10.1007/s00520-021-06018-x ◽

2021 ◽

Author(s):

Hiroaki Ikesue ◽

Moe Mouri ◽

Hideaki Tomita ◽

Masaki Hirabatake ◽

Mai Ikemura ◽

...

Keyword(s):

Zoledronic Acid ◽

Bone Metastases ◽

Tooth Extraction ◽

Proportional Hazards ◽

Osteonecrosis Of The Jaw ◽

Cox Proportional Hazards ◽

Patients With Cancer ◽

Proportional Hazards Regression ◽

Before And After ◽

Denosumab Treatment

Abstract Purpose This study aimed to evaluate the association between clinical characteristics and development of medication-related osteonecrosis of the jaw (MRONJ) in patients who underwent dental examinations before the initiation of treatment with denosumab or zoledronic acid, which are bone-modifying agents (BMAs), for bone metastases. Additionally, the clinical outcomes of patients who developed MRONJ were evaluated along with the time to resolution of MRONJ. Methods The medical charts of patients with cancer who received denosumab or zoledronic acid for bone metastases between January 2012 and September 2016 were retrospectively reviewed. Patients were excluded if they did not undergo a dental examination at baseline. Results Among the 374 included patients, 34 (9.1%) developed MRONJ. The incidence of MRONJ was significantly higher in the denosumab group than in the zoledronic acid (27/215 [12.6%] vs 7/159 [4.4%], P = 0.006) group. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment, older age, and tooth extraction before and after starting BMA treatments were significantly associated with developing MRONJ. The time to resolution of MRONJ was significantly shorter for patients who received denosumab (median 26.8 months) than for those who received zoledronic acid (median not reached; P = 0.024). Conclusion The results of this study suggest that treatment with denosumab, age > 65 years, and tooth extraction before and after starting BMA treatments are significantly associated with developing MRONJ in patients undergoing treatment for bone metastases. However, MRONJ caused by denosumab resolves faster than that caused by zoledronic acid.

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Switching from zoledronic acid to denosumab increases the risk for developing medication-related osteonecrosis of the jaw in patients with bone metastases

Cancer Chemotherapy and Pharmacology ◽

10.1007/s00280-021-04262-w ◽

2021 ◽

Author(s):

Hiroaki Ikesue ◽

Kohei Doi ◽

Mayu Morimoto ◽

Masaki Hirabatake ◽

Nobuyuki Muroi ◽

...

Keyword(s):

Risk Factors ◽

Zoledronic Acid ◽

Bone Metastases ◽

Proportional Hazards ◽

Significant Risk ◽

Osteonecrosis Of The Jaw ◽

Cox Proportional Hazards ◽

Antiangiogenic Agents ◽

Secondary Endpoints ◽

Denosumab Treatment

Abstract Purpose Switch from zoledronic acid (ZA) to denosumab may increase the risk of medication-related osteonecrosis of the jaw (MRONJ) owing to the additive effect of denosumab on the jawbone and residual ZA activities. We evaluated the risk of developing MRONJ in patients who received ZA, denosumab, or ZA-to-denosumab for the treatment of bone metastases. Methods The medical charts of patients with cancer who received denosumab or ZA for bone metastases were retrospectively reviewed. Patients who did not undergo a dental examination at baseline were excluded. Primary endpoint was the evaluation of the risk of developing MRONJ in the ZA-to-denosumab group. Secondary endpoints were probability of MRONJ and the relationship between risk factors and the time to the development of MRONJ. Results Among the 795 patients included in this study, 65 (8.2%) developed MRONJ. The incidence of MRONJ was significantly higher in the ZA-to-denosumab group than in the ZA group [7/43 (16.3%) vs. 19/350 (5.4%), p = 0.007]. Multivariate Cox proportional hazards regression analysis revealed that denosumab treatment [hazard ratio (HR), 2.41; 95% confidence interval (CI), 1.37–4.39; p = 0.002], ZA-to-denosumab treatment (HR, 4.36; 95% CI, 1.63–10.54, p = 0.005), tooth extraction after starting ZA or denosumab (HR, 4.86; 95% CI, 2.75–8.36; p < 0.001), and concomitant use of antiangiogenic agents (HR, 1.78; 95% CI, 1.06–2.96; p = 0.030) were significant risk factors for MRONJ. Conclusion Our results suggest that switching from ZA to denosumab significantly increases the risk for developing MRONJ in patients with bone metastases.

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Response patterns of routinely measured inflammatory and coagulatory parameters in sepsis

PeerJ ◽

10.7717/peerj.7147 ◽

2019 ◽

Vol 7 ◽

pp. e7147

Author(s):

Mirjam Bachler ◽

Tobias Hell ◽

Lukas Schausberger ◽

Christine Schlömmer ◽

Volker Schäfer ◽

...

Keyword(s):

Risk Stratification ◽

Proportional Hazards ◽

Peak Level ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Close Monitoring ◽

Response Patterns ◽

C Reactive Protein ◽

Disease Etiology ◽

Reactive Protein

BackgroundSepsis is characterized by a pro-inflammatory and pro-coagulatory shift which can induce life-threatening complications. Close monitoring and risk stratification of sepsis patients is crucial for proper treatment and consequently patient outcome. Therefore, this study focuses on the response patterns of inflammatory and coagulatory parameters used in clinical routines to estimate the course of sepsis.MethodsA total of 1,110 patients diagnosed with sepsis were retrospectively analyzed to identify response patterns for risk stratification of routine parameters measured at the peak level of C-reactive protein. Cluster analysis was used and the differences in the patient characteristics and 28-day survival were assessed. Cox proportional hazards regression model for survival stratified by the clusters was performed.ResultsThe analyses revealed the parameters to have five distinct response patterns. These clusters reflect the etiology as well as the course of sepsis associated with different mortalities. Here, impairment of the liver plays a crucial role in the ability to appropriately respond to sepsis. Of the routinely measured parameters, C-reactive protein and antithrombin seem to be unspecific for stratification of septic patients. Adjusted for the individual clusters, survival was associated with an increase in fibrinogen (p = 0.0042), platelets (p = 0.0003) and PT (p = 0.001) as well as a decrease in leukocytes (p = 0.034).ConclusionsThis study reveals that patients have distinct response patterns of inflammatory and coagulatory parameters depending on disease etiology. These patterns are associated with different mortalities although the patients have similar levels of C-reactive protein. Independently of the type of response, good coagulatory capacity seems to be crucial for patient survival.

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Role of cytoreductive nephrectomy (CN) in metastatic renal cell carcinoma (mRCC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4582 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4582-4582

Author(s):

Pooja Ghatalia ◽

Elizabeth A. Handorf ◽

Mengying Deng ◽

Matthew R. Zibelman ◽

Philip Abbosh ◽

...

Keyword(s):

Propensity Score ◽

Systemic Therapy ◽

Proportional Hazards ◽

Statistical Significance ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Time Varying ◽

Health Database ◽

Time Varying Covariates

4582 Background: The role of CN in mRCC was challenged by the results of the CARMENA trial in the targeted therapy (TT) era. We sought to evaluate the role of both upfront and deferred CN in pts receiving modern IO-based and TT regimens. Methods: Pts with synchronous mRCC who received systemic therapy (tx) for mRCC after 2011 were included from the de-identified nationwide Flatiron Health database. We evaluated 3 groups: systemic tx alone, systemic-> CN, and CN-> systemic tx. Overall survival (OS) was calculated from the time of initiation of first therapy – systemic or CN. Patient characteristics were compared using chi-squared tests or t-test. Weighted Kaplan-Meier curves, log-rank tests, and Cox proportional hazards regressions with time-varying covariates were used to assess the effect of tx on survival. Adjustment was conducted via inverse probability of treatment weighing based on the generalized propensity score, estimated via Bayesian Additive Regression Trees. Covariates in the model were age, gender, race, insurance at mRCC diagnosis, and IMDC risk group. Results: Of 1719 pts with mRCC, 972 (56.5%) received systemic tx alone, 605 (35.1%) received CN-> systemic tx, and 142 (8.2%) received systemic->CN. 310 pts received IO or IO/IO, 123 pts received IO+TT and 1152 pts received only TT. The median follow-up was 37.1 months. In adjusted analyses using propensity score weighting and time-varying covariates, CN-> systemic was significantly associated with improved OS compared with systemic tx alone (Table). When stratifying groups by type of systemic treatment (IO and TT), there was improvement of OS in the CN groups compared to systemic tx alone, although we lacked power to reach statistical significance. Among CN-treated patients, the order of systemic tx relative to CN did not change OS (hazard ratio [HR] = 1.00, 95% CI 0.76-1.32, p=0.96). Conclusions: Using a national, EHR-based cohort, which includes a large number of IO treated pts, our findings support an oncologic role for CN in select mRCC pts. The timing of CN, for pts who were able to receive both systemic therapy and CN, may not affect overall outcome. The associated improvement in survival of CN is seen in pts receiving IO and TKI based systemic tx.[Table: see text]

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Prevalence and Risk Factors for Fecal Incontinence in Home Hospice

American Journal of Hospice and Palliative Medicine® ◽

10.1177/1049909118784891 ◽

2018 ◽

Vol 36 (1) ◽

pp. 33-37 ◽

Cited By ~ 3

Author(s):

Bilal Chughtai ◽

Dominique Thomas ◽

David Russell ◽

Veerawat Phongtankuel ◽

Kathryn Bowles ◽

...

Keyword(s):

Risk Factors ◽

Fecal Incontinence ◽

Proportional Hazards ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Health Care Proxy ◽

Patients With Cancer ◽

Increased Risk ◽

Onset Period ◽

Time To Detection

Introduction: We sought to determine the prevalence and risk factors associated with fecal incontinence (FI) in the home hospice setting. Methods: We conducted a retrospective cohort study of patients served by a hospice agency. Data on patient characteristics were extracted from hospice medical records. The primary outcome, FI, was assessed routinely during clinical visits to the patient’s home. Descriptive statistics were used to summarize patient characteristics. A Cox proportional hazards regression model was estimated for FI to examine associations with sociodemographic and clinical characteristics of patients. Results: A total of 15 432 patients were eligible. Patients were female (59.0%) and 75 years or older (23.5% were 75-84; 39.9% were 85+). Most patients with FI indicated incontinence at the time of hospice admission (64.5%; n = 4314), with the average onset period being approximately 18 days from admission (mean = 17.9, standard deviation = 50.6). Increasing age represented a risk factor for FI (hazard ratio [HR] = 1.01 [confidence interval, CI = 1.01-1.01]). The absence of a health-care proxy was associated with an increased risk of FI (HR = 1.11 [CI = 1.04-1.19]). Greater risk of FI was observed among patients with dementia (HR = 1.34 [1.24-1.46]) and stroke (HR = 1.42 [1.26-1.60]) compared to patients with cancer. Patients referred to hospice from settings other than the hospital also had a greater risk of FI compared to those referred from the hospital (HR = 1.17 [1.11-1.23]). Conclusion: Fecal incontinence is a highly prevalent condition among home hospice patients and most patients indicated FI upon admission (median time to detection = 18 days). Further studies are needed to identify modifiable risk factors for FI detection and its symptom management in this patient population.

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Abstract 13950: Predicted Heart Mass and BMI: Evaluating Undersized Heart Transplantation in Obese vs. Non-Obese Patients

Circulation ◽

10.1161/circ.142.suppl_3.13950 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Samuel T Kim ◽

Mark R Helmers ◽

Peter Altshuler ◽

Amit Iyengar ◽

Jason Han ◽

...

Keyword(s):

Propensity Score ◽

Heart Transplantation ◽

Propensity Score Matching ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Hazard Ratio ◽

Obese Patients ◽

Heart Transplants ◽

Term Survival ◽

Heart Mass

Introduction: Although guidelines for heart transplant currently recommend against donors weighing ≥ 30% less than the recipient, recent studies have shown that the detriment of under-sizing may not be as severe in obese recipients. Furthermore, predicted heart mass (PHM) has been shown to be more reliable for size matching compared to metrics such as weight and body surface area. In this study, we use PHM to characterize the effects of undersized heart transplantation (UHT) in obese vs. non-obese recipients. Methods: Retrospective analysis of the UNOS database was performed for heart transplants from Jan. 1995 to Sep. 2020. Recipients were stratified by obese (BMI ≥ 30) and non-obese (30 > BMI ≥ 18.5). Undersized donors were defined as PHM ≥ 20% less than recipient PHM. Obese and non-obese populations separately underwent propensity score matching, and Kaplan-Meier estimates were used to graph survival. Multivariable Cox proportional-hazards analyses were used to adjust for confounders and estimate the hazard ratio for death attributable to under-sizing. Results: Overall, 50,722 heart transplants were included in the analysis. Propensity-score matching resulted in 2,214, and 1,011 well-matched pairs, respectively, for non-obese and obese populations. UHT in non-obese recipients resulted in similar 30-day mortality (5.7% vs. 6.3%, p = 0.38), but worse 15-year survival (38% vs. 35%, P = 0.04). In contrast, obese recipients with UHT saw similar 30-day mortality (6.4% vs. 5.5%, p = 0.45) and slightly increased 15-year survival (31% vs. 35%, P = 0.04). Multivariate Cox analysis showed that UHT resulted in an adjusted hazard ratio of 1.08 (95% CI 1.01 - 1.16) in non-obese recipients, and 0.87 (95% CI 0.78 - 0.98) in obese recipients. Conclusions: Non-obese patients with UHT saw worse long-term survival, while obese patients with UHT saw slightly increased survival. These findings may warrant reevaluation of the current size criteria for obese patients awaiting a heart.

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Lobectomy Versus Segmentectomy in Patients with Stage T (>2 cm and ≤3 cm) N0M0 Non-small Cell Lung Cancer: A Propensity Score Matching Study

10.21203/rs.3.rs-97312/v1 ◽

2020 ◽

Author(s):

Linlin Wang ◽

Lihui Ge ◽

Guofeng Zhang ◽

Yi Ren ◽

Yongyu Liu

Keyword(s):

Lung Cancer ◽

Propensity Score ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Small Cell ◽

Seer Database ◽

Regression Analyses ◽

Small Cell Lung

Abstract Background: Whether lung segmentectomy is a safe and effective surgical treatment in patients with early non-small cell lung cancer (NSCLC) remains controversial. We have therefore reviewed the clinicopathologic characteristics and survival outcomes of patients receiving a lobectomy vs. segmentectomy to treat early T (>2 cm and ≤3 cm) N0M0 NSCLC.Methods: We obtained data from the Surveillance, Epidemiology, and End Results (SEER) database for patients who underwent lobectomy or segmentectomy between 2004 and 2015. To reduce bias and imbalance between the treatment groups, propensity score matching (PSM) analysis was performed. We used Kaplan-Meier curves to estimate overall survival (OS) and lung cancer-speciﬁc survival (LCSS), performed univariate and multivariate Cox proportional hazards regression analyses to identify independent prognostic factors for OS and CSS, and applied the Cox proportional hazards model to create forest plots. Results: A total of 5783 patients from the SEER database were included. Of these, 5531 patients underwent lobectomy, and 252 patients underwent segmentectomy. Before matching, both univariate and multivariate Cox regression analyses showed that patients who underwent lobectomy had better OS (hazard ratio [HR]: 1.561; 95% confidence interval [CI] 1.292-1.885; P <0.001) and LCSS (HR: 1.551; 95% CI 1.198-2.009; P=0.001) than patients who underwent segmentectomy. However, survival differences between the groups were not significant; OS (P=0.160) and LCSS (P=0.097) after matching. Regression analyses revealed that age, sex, lymph node dissection, and grade were independent predictors of OS and LCSS (P <0.05).Conclusions: For patients with stage T (>2 cm and ≤3 cm) N0M0 non-small cell lung cancer, segmentectomy can achieve the same OS and LCSS compared with lobectomy. A large number of patients require further long-term follow-up analyses.

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Effectiveness and safety of apixaban versus warfarin in non-valvular atrial fibrillation patients in “real-world” clinical practice

Thrombosis and Haemostasis ◽

10.1160/th17-01-0068 ◽

2017 ◽

Vol 117 (06) ◽

pp. 1072-1082 ◽

Cited By ~ 69

Author(s):

Xiaoyan Li ◽

Steve Deitelzweig ◽

Allison Keshishian ◽

Melissa Hamilton ◽

Ruslan Horblyuk ◽

...

Keyword(s):

Atrial Fibrillation ◽

Major Bleeding ◽

Real World ◽

Proportional Hazards ◽

Significant Risk ◽

Haemorrhagic Stroke ◽

Cox Proportional Hazards ◽

Kaplan Meier ◽

Cox Proportional Hazards Models ◽

Warfarin Treatment

SummaryThe ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59–0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54–0.65) than warfarin initiators. Different types of stroke/SE and major bleeding – including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding – were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest “real-world” study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard-and low-dose apixaban dose regimens.Note: The review process for this manuscript was fully handled by Christian Weber, Editor in Chief.Supplementary Material to this article is available online at www.thrombosis-online.com.

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Efficacy outcomes of nivolumab + cabozantinib versus pembrolizumab + axitinib in patients with advanced renal cell carcinoma (aRCC): Matching-adjusted indirect comparison (MAIC).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.4578 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 4578-4578

Author(s):

Bradley Alexander McGregor ◽

Daniel M. Geynisman ◽

Mauricio Burotto ◽

Camillo Porta ◽

Cristina Suarez Rodriguez ◽

...

Keyword(s):

Proportional Hazards ◽

Objective Response ◽

Indirect Comparison ◽

Progression Free Survival ◽

Wald Test ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Published Data ◽

Cox Proportional Hazards Models

4578 Background: Nivolumab in combination with cabozantinib (N+C) has demonstrated significantly improved progression-free survival (PFS), objective response rate (ORR), and overall survival (OS), compared with sunitinib as a first-line (1L) treatment for aRCC in the phase 3 CheckMate (CM) 9ER trial. As there are no head-to-head trials comparing N+C with pembrolizumab in combination with axitinib (P+A), this study compared the efficacy of N+C with P+A as 1L treatment in aRCC. Methods: An MAIC was conducted using individual patient data on N+C (N = 323) from the CM 9ER trial (median follow-up: 23.5 months) and published data on P+A (N = 432) from the KEYNOTE (KN)-426 trialof P+A (median follow-up: 30.6 months). Individual patients within the CM 9ER trial population were reweighted to match the key patient characteristics published in KN-426 trial, including age, gender, previous nephrectomy, International Metastatic RCC Database Consortium risk score, and sites of metastasis. After weighting, hazards ratios (HR) of PFS, duration of response (DoR), and OS comparing N+C vs. P+A were estimated using weighted Cox proportional hazards models, and ORR was compared using a weighted Wald test. All comparisons were conducted using the corresponding sunitinib arms as an anchor. Results: After weighting, patient characteristics in the CM 9ER trial were comparable to those in the KN-426 trial. In the weighted population, N+C had a median PFS of 19.3 months (95% CI: 15.2, 22.4) compared to a median PFS of 15.7 months (95% CI: 13.7, 20.6) for P+A. Using sunitinib as an anchor arm, N+C was associated with a 30% reduction in risk of progression or death compared to P+A, (HR: 0.70, 95% CI: 0.53, 0.93; P = 0.015; table). In addition, N+C was associated with numerically, although not statistically, higher improvement in ORR vs sunitinib (difference: 8.4%, 95% CI: -1.7%, 18.4%; P = 0.105) and improved DoR (HR: 0.79; 95% CI: 0.47, 1.31; P = 0.359). Similar OS outcomes were observed for N+C and P+A (HR: 0.99; 95% CI: 0.67, 1.44; P = 0.940). Conclusions: After adjusting for cross-trial differences, N+C had a more favorable efficacy profile compared to P+A, including statistically significant PFS benefits, numerically improved ORR and DoR, and similar OS.[Table: see text]

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RADT-33. LONG-TERM OUTCOMES, TREATMENT UTILIZATION, AND PROGNOSTIC FACTORS FOR PEDIATRIC CHORDOMA: AN NCDB ANALYSIS

Neuro-Oncology ◽

10.1093/neuonc/noab196.190 ◽

2021 ◽

Vol 23 (Supplement_6) ◽

pp. vi48-vi48

Author(s):

James Cantrell ◽

Pawan Acharya ◽

Sara Vesely ◽

Michael Confer ◽

Ozer Algan ◽

...

Keyword(s):

Prognostic Factors ◽

Radiation Dose ◽

Proportional Hazards ◽

Propensity Score Analysis ◽

Descriptive Analysis ◽

Patient Characteristics ◽

Cox Proportional Hazards ◽

Rank Test ◽

Total Resection ◽

Kaplan Meier

Abstract BACKGROUND Chordomas are rare tumors arising from the embryonal notochord presenting at the base of skull, spine, or sacrum. Pediatric chordomas (PC) comprise less than 5% of all chordomas and are more likely to be atypical or dedifferentiated. Evidence for management is limited to single institution series with 5-year overall survival (OS) between 60-100%. METHODS Using the NCDB Participant User File, a retrospective observational cohort study was performed. The cohort was defined using the bone-soft-tissue, brain, and central nervous system databases selecting for cases with chordoma ICD-03 codes and age ≤ 25 years. Kaplan Meier method, log-rank test, and Cox proportional hazards regression were performed. RESULTS 297 patients from 2004-2017 met inclusion criteria for descriptive analysis with 269 cases included for survival analysis. Mean age was 16.9 years, with 10% less than age 5. The cohort was 55% female, 8% Black, and 79% White. Primary sites included bones of the skull (70%), spine (22%), and pelvis (6%). Regarding treatment, 7% had no resection, 49% sub-total resection (STR), 33% gross-total resection (GTR), and 11% unspecified resection. 51% received radiation therapy with 46% of those receiving proton therapy. 7% received chemotherapy. The 1, 3, 5, and 10-year OS was 95%, 86%, 77%, and 72%. Selected prognostic factors from univariable OS model for OS analysis included: age > 5 (HR 0.30 (95% CI 0.16-0.57) p = 0.0002), surgical resection [GTR (HR 0.28 (95% CI 0.12-0.63) p = 0.0023) and STR (HR 0.27 (95% CI 0.12-0.59) p = 0.0011)], and radiation dose ≥ 7200cGy (HR 0.40 (95% CI 0.16-0.99) p = 0.047). CONCLUSION In the largest cohort reported for PC, 3 and 10-year OS was 86% and 72%. Age, surgery, and radiation dose are important prognostic factors. Propensity score analysis to gauge effect of treatment, tumor, and patient characteristics on OS is forthcoming.

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