1. Skull Base Chordoma and Chondrosarcoma: Changes in National Radiotherapy Patterns and Survival Outcomes Henry S. Park, MD, MPH; Kenneth B. Roberts, MD; James B. Yu, MD Department of Therapeutic Radiology, Yale University School of Medicine Table 1: Demographic and clinical information of patients receiving RT vs. those not receiving RT. CharacteristicRT (n, %) (n=170) No RT (n=%) (n=196) P-value Age (median ± SD, years)49 ± 1743 ± 160.011 Sex 0.946 Male 87 (46)101 (54) Female 83 (47)95 (53) Race 0.434 White 144 (47)160 (53) Non-White 26 (42)36 (58) Hispanic Origin 0.548 Hispanic 28 (43)37 (57) Non-Hispanic 142 (47)159 (53) Year 0.699 1988-2000* 60 (45)73 (55) 2001-2004 52 (46)60 (54) 2005-2008 58 (48)63 (52) Histology 0.195 Chordoma NOS* 87 (50) Chondroid / Dedifferentiated 10 (50) Chondrosarcoma 73 (42)99 (58) Surgery 0.672 Gross total resection* 39 (45)47 (55) Subtotal resection 53 (49)55 (51) Surgery NOS 8 (47)9 (53) None / Biopsy only 70 (45)85 (55) * Reference category RT = radiation therapy; NOS = not otherwise specified Note: RT data missing for 10 patients BACKGROUND METHODS RESULTS Study design: Retrospective cohort analysis using prospectively collected data from the National Cancer Institute’s Surveillance Epidemiology, and End Results (SEER) database, which captures ~28% of all U.S. cancer diagnoses. Subjects: 376 adult patients with histologically-diagnosed chordoma not otherwise specified (NOS) [ICD-O-3 code 9370], chondroid or dedifferentiated chordoma [9371, 9372] or chondrosarcoma [9220, 9221, 9230, 9240, 9242, 9243] located in the bones of the skull or face (C410) diagnosed from 1988-2008. Statistical Analysis: Chi-square tests, Wilcoxon rank sum test, logistic regression analysis, Kaplan-Meier analysis, and Cox proportional hazards model analysis. Skull base chordoma and chondrosarcoma are rare tumors that arise from embryonic remnants along the neuroaxis. Indolent course typical, but local recurrences common despite maximal surgical resection and high-dose radiotherapy (RT), especially in skull base. Single-institution retrospective evidence indicates that proton beam radiotherapy (PBRT) may improve long-term outcomes, but meta- analyses do not conclusively demonstrate progression-free survival or overall survival benefit for PBRT. We sought to assess the evolving role of RT and its effect on survival of skull base chordoma and chondrosarcoma. Among 57% of patients who underwent surgical resection, 42% received gross total resection (GTR). RT was utilized in 46% of patients overall and in 45% of patients following GTR. Utilization of surgical resection or RT was not significantly different by sex, race, diagnosis year, or histology on univariate or multivariate analysis. After adjustment, patients ≥ 65 years were less likely to receive GTR (OR 0.39, p=0.018) and more likely to receive RT (OR 1.75, p=0.048). After adjustment, diagnosis after 2001 (HR 0.42, p=0.002) and chondrosarcoma histology (HR 0.47, p=0.003), but not surgical extent or RT utilization, were associated with improved survival. Table 2: Multivariate logistic regression analysis identifying predictors of gross total resection and radiation therapy utilization. Gross Total Resection Odds Ratio 95% CI Lower 95% CI UpperP Age≥ 650.390.180.85 0.018 SexFemale1.260.772.05 0.353 RaceNon-White0.920.471.80 0.804 Hispanic OriginNon-Hispanic0.810.431.51 0.504 Diagnosis Year≥ 20010.650.391.07 0.093 HistologyNot Chordoma NOS 1.330.812.18 0.260 Radiation Therapy Odds Ratio 95% CI Lower 95% CI Upper P Age≥ 651.751.013.05 0.048 SexFemale1.040.691.59 0.843 RaceNon-White0.790.451.39 0.410 Hispanic OriginNon-Hispanic1.240.712.16 0.457 Diagnosis Year≥ 20011.190.771.85 0.431 HistologyNot Chordoma NOS 0.750.491.14 0.181 SurgeryNo GTR 0.970.591.59 0.900 95% CI = 95% confidence interval; NOS = not otherwise specified. Overall Survival Hazards Ratio 95% CI Lower 95% CI UpperP Age1.041.031.06 <0.001 SexFemale0.860.531.38 0.523 RaceNon-White1.370.712.65 0.353 Hispanic OriginNon-Hispanic0.850.451.61 0.615 Diagnosis Year≥ 20010.420.240.74 0.002 HistologyNot Chordoma NOS 0.470.280.78 0.003 SurgeryNo GTR 1.090.631.91 0.752 RTNo RT 0.900.561.54 0.664 95% CI = 95% confidence interval; NOS = not otherwise specified. Table 3: Cox proportional hazards model identifying predictors of overall survival. Figure 1: Kaplan-Meier survival curves by (A) year of diagnosis and (B) histology. A Log-rank p < 0.001 B CONCLUSIONS On a national scale, overall survival from skull base chordoma and chondrosarcoma has improved significantly over time, though rates of surgical resection and RT have not increased over time. Older patients less likely to receive GTR and more likely to receive RT. Lack of association between GTR/RT utilization and improved survival may be confounded by unmeasured variables. Future research is needed to evaluate potential determinants of this improved survival, including PBRT utilization, imaging technology, surgical technique, and supportive care. For reprints, please contact: Henry Park, henryspark@gmail.com