Prospective validation of a molecular prognostication panel for clival chordoma

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OBJECTIVE

There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor’s response to radiation therapy.

METHODS

A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR).

RESULTS

Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%–15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%–3%, 4%–24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR.

CONCLUSIONS

Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.

ABBREVIATIONS FISH = fluorescence in situ hybridization; PFS = progression-free survival; PFSR = PFS after radiotherapy; PFSS = PFS after surgery.

Downloadable materials

  • Supplementary Table 1 (PDF 402 KB)

Article Information

Correspondence Paul A. Gardner: UPMC Presbyterian Hospital, Pittsburgh, PA. gardpa@upmc.edu.

INCLUDE WHEN CITING Published online June 15, 2018; DOI: 10.3171/2018.3.JNS172321.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.

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    Kaplan-Meier curves showing overall PFSS for each of the molecular index strata. Log-rank p values showing the statistical significance of the differences among the survival curves of each panel. Cox proportional hazard ratios of each stratum compared to the first are shown next to each panel. The mean PFSS in months and the 95% CI for each stratum are also provided. PFSS refers to the interval between surgery and either the time of recurrence or the last time the patient was censored, whichever came first. n/a = not applicable. Figure is available in color online only.

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    Kaplan-Meier curves showing PFSR for each of the molecular index strata. Log-rank p values show the statistical significance of the differences among each survival curve. Cox proportional hazard ratios of each stratum compared to the first are shown next to each panel. The mean PFSR in months and the 95% CI for each stratum are also provided. PFSR refers to the time interval between radiation and either the time of recurrence or the last time the patient was censored, whichever came first. Figure is available in color online only.

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    A proposed management algorithm for clival chordoma based on the tumor’s molecular panel. A: After resection of a clival chordoma, FISH for 1p36 deletions and homozygous 9p21 deletions can be used to guide management with regard to observation, radiotherapy, reoperation, or early consideration of experimental therapies. B: Kaplan-Meier curves showing overall PFSS (left) and PFSR (right) for each of the 3 groups. Figure is available in color online only.

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