J Neurol Surg B Skull Base 2016; 77 - FP-11-03
DOI: 10.1055/s-0036-1592492

Prospective Evaluation of Molecular Prognostication Markers in Clival Chordomas

George A. Zenonos 1, Juan C. Fernandez-Miranda 1, Eric W. Wang 2, Carl H. Snyderman 1, 2, Paul Gardner 1
  • 1Department of Neurological Surgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States
  • 2Department of Otolaryngology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, United States

Objective: To evaluate a molecular prognostication panel for clival chordomas.

Methods: The Ki-67 and fluorescent in situ hybridization for 1p36 and 9p21 (p16) were prospectively evaluated in 92 clival chordomas. Radiographic progression free survival after surgery (RPFSS), and radiation (RPFSR) were calculated using Kaplan-Meier curves, and the Cox Proportional Hazard Model was used to calculate hazard ratios (HR). Median follow-up was 45 months. Twenty-eight patients had multiple resections because of recurrences, and the evolution of their tumors' molecular profile was evaluated over time.

Results: We found that each percentile increase in tumor cells with homozygous 9p21 (p16) deletion (HR = 1.03; p = 0.001), 1p36 deletion (HR = 1.01; p = 0.012), 1p hyperploidy (HR = 1.02; p = 0.018), and Ki-67 staining (HR = 1.07; p = 0.001) to be predictive of a shorter RPFSS. Increasing percentages of cells with homozygous 9p21 (p16) deletions (HR = 1.03; p < 0.001), and Ki67 (HR = 1.05; p = 0.001) were also predictive of a shorter RPFSR.

Over recurrences, 9p21/1p36 deletions and 1p hyperploidy, were roughly equally divided between no change, increasing, and decreasing. The Ki-67 remained unchanged in 72% of recurring tumors, but increasing age correlated with increases in Ki-67 over recurrences (r = 0.479; p = 0.038). Prior irradiation inversely correlated with increases in Ki-67 over 5% (rϕ = −0.392; p = 0.029). Time between recurrences, gender, and chondroid chordomas did not correlate with changes.

Conclusion: We found multiple molecular markers to be promising predictors of clival chordoma outcomes. During the intermediate-term studied, radiation did not appear to have a detrimental effect on the tumor's biology based on our molecular profile, and it may be beneficial in terms of cellular proliferation (Ki-67).