Distinct relapse pattern across molecular ependymoma types

Abstract

Background: Ependymoma (EPN) is not a uniform disease but represents different disease types with biological and clinical heterogeneity. However, the pattern of when and where different types of EPN relapse is not yet comprehensively described.

Methods: We assembled 269 relapsed intracranial EPN from pediatric (n = 233) and adult (n = 36) patients from European and Northern American cohorts and correlated DNA methylation patterns and copy-number alterations with clinical information.

Results: The cohort comprised the following molecular EPN types: PF-EPN-A (n = 177), ST-EPN-ZFTA (n = 45), PF-EPN-B (n = 31), PF-EPN-SE (n = 12), and ST-EPN-YAP (n = 4). First relapses of PF-EPN-B (PF: posterior-fossa) and PF-EPN-SE (SE: subependymoma) occurred later than of PF-EPN-A, ST-EPN-YAP (ST: supratentorial), or ST-EPN-ZFTA (median time to relapse: 4.3 and 6.0 years vs. 1.9/1.0/2.4 years; P < .01). Metastatic or combined recurrences in PF-EPN-B and -A more often involved the spinal cord than in ST-EPN-ZFTA (72.7% and 40.0 vs. 12.5%; P < .01). No distant relapses were observed in ST-EPN-YAP (n = 4) or PF-EPN-SE (n = 12). Post-relapse survival (PRS) was poor for PF-EPN-A and ST-EPN-ZFTA (5-year PRS: 44.5% ± 4.4%/47.8% ± 9.1%), whereas PF-EPN-B and PF-EPN-SE displayed a 5-year PRS of 89.5% ± 7.1%/90.0% ± 9.5% (P = .03). However, 10-year PRS for PF-EPN-B dropped to 45.8% ± 17.3%. Neither between the radiation field and relapse pattern nor between the radiation field and spinal involvement at relapse an impact was identified. Notably, all patients with relapsed ST-EPN-YAP did not receive upfront radiotherapy but were successfully salvaged using irradiation at relapse.

Conclusions: Relapse patterns of specific EPN types are different. Future clinical trials, treatment adaptions, duration of surveillance, and diagnostics should be planned to incorporate entity-specific relapse information.

Keywords: ependymoma; metastatic; recurrence; relapse.

Figure 1.

CONSORT diagram.

Figure 2.

Overview of ependymoma-type-specific pattern of the first relapse. (A) Distribution of molecular EPN-types across the relapse cohort (n = 269). PF-EPN-A: n = 177, 66%; PF-EPN-B: n = 31, 11%; ST-EPN-ZFTA: n = 45, 16%; ST-EPN-YAP: n = 4, 2%; PF-EPN-SE: n = 12, 5%. (B) Box-plot showing the EPN-type interval in years from initial diagnosis (first tumor surgery) to the first relapse. Dots representing relapses outside the 5%-confidence interval. (C) Diagram showing the EPN-type-specific proportion of localized and distant/combined localized and distant first relapses. (D) Image displaying the preferred EPN-type-specific localization of metastases at first relapse, if distant (n = 78). (E) Kaplan–Meier Plot showing the EPN-type specific overall survival after first relapse.