Factors for Overall Survival in Patients with Skull Base Chordoma: A Retrospective Analysis of 225 Patients

Background

Although a controversial and complex issue, the prognostic factors of skull base chordomas are worth exploring.

Methods

Prognostic factors associated with overall survival (OS) were retrospectively estimated in an individual cohort of skull base chordomas prospectively maintained for 10 years by a Kaplan-Meier method and univariate Cox proportional hazards model. Multivariate analysis by Cox regression analysis was performed to identify the independent prognostic factors. A nomogram was then formulated by R software based on the results.

Results

A total of 180 primary patients and 45 recurrent cases were included, with a mean follow-up period of 43.7 months (range, 4–127 months). The OS of the primary group at 5 years and 7 years was 84% and 78%, and the mean OS was 103.8 months, which was significantly longer than the recurrent group, in which the mean postrecurrent OS was 68.4 months. In the primary group, preoperative Karnofsky Performance Status (KPS) score (P = 0.004) and a decline of perioperative KPS score (P = 0.015) were identified as independent predictors of OS. A nomogram was contracted to predict 5-year, and 7-year OS, which was well calibrated and had good discriminative ability (adjusted Harrell C statistic, 0.74). In the recurrent group, visual deficit was verified as an independent risk factor associated with postrecurrent OS (P = 0.014).

Conclusions

Both pathologic and perioperative KPS score evaluations are significant in OS prediction of both primary and recurrent cases. The nomogram for primary lesions, consisting of preoperative functional status and its perioperative changes, appears useful for risk stratification of long-term survival.

Introduction

Chordoma is a rare bone cancer with an annual incidence of 0.1 in every 100,000 individuals; it is aggressive, locally invasive, and has a poor prognosis.1, 2 It was believed to arise from the remnants of notochord, with an almost equal distribution in the skull base (32%), mobile spine (32.8%), and sacrum (29.2%).¹ Skull base chordomas, which need more comprehensive consideration of preservation of neurologic function, are usually more complicated than lesions in other locations, in terms of treatment strategies, which usually consist of maximum but safe resection and postoperative external-beam radiation therapy.

Since a study by Eriksson et al.³ in 1981, some clinical studies have focused on the prognostic factors of skull base chordoma. Several attempts have been made to correlate clinical and histologic features, such as age, gender, and pathologic subtype, with prognosis.4, 5, 6, 7, 8, 9, 10, 11, 12 Some studies examined the correlations between their treatment choices, including extent of resection, timing and options of postoperative radiotherapy, and prognosis.4, 6, 8, 13, 14, 15, 16, 17

However, these studies did not reach any consensus on prognostic factors of overall survival (OS). For example, Forsyth et al.⁴ found that patients younger than 40 years survived longer than the older patients, and Samii et al.⁷ found that the outcome was better in patients older than 40 years. In a more recent systematic review by Jian et al.,⁹ there was no difference in OS between 2 groups when a cutoff point was set as 40 years old. A similar controversy also existed for gender. The long-term outcomes were better for male patients in some studies,⁷ whereas, on the contrary, men had a higher risk of progressive disease and death in other studies.¹⁰ A retrospective study by the authors identified an association of chondroid chordoma and prolonged survival,⁸ which could not be verified by subsequent studies.9, 12, 14 Even gross total resection, which was associated consistently with better outcomes in most series,4, 6, 8, 13 failed to show its prognostic value in a study by Choy et al.¹⁴

For the last decade, we have treated more than 250 patients with skull base chordoma, whose information was collected in a prospectively maintained database. For primary lesions, our treatment philosophy included maximally safe surgery, gross total resection whenever possible, and a consultation of oncologic radiotherapy, commonly Gamma Knife (Elekta, Stockholm, Sweden), 3 months postoperatively. Whether adjuvant radiation therapy is performed depends on the radiologist's specialized evaluation. For recurrent tumors, the treatment choices, including tumor re-resection, palliative surgery, such as ventriculoperitoneal shunt, radiation therapy, and a wait-and-see policy, were decided on in a comprehensive consideration of patients' physical status, their willingness, and the opinions of the consulting neurosurgeons and radiologists. In this study, the prognostic factors for OS in these patients were retrospectively evaluated by dividing them in to primary and recurrent groups. With relatively consistent treatment strategies and classification standards, the analysis results from this cohort may provide some helpful information for current controversies.