Treatment Outcomes and Prognostic Factors of Patients With Primary Spinal Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumors

Abstract

Purpose: Primary spinal Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumors (pPNETs) are extremely rare, and the current understanding of these tumors is poor. The authors aimed to illustrate the clinical characteristics of primary spinal ES/pPNETs and to discuss prognostic factors by survival analysis. Methods: A total of 40 patients who were pathologically diagnosed with primary spinal ES/pPNETs between 2000 and 2018 were enrolled in this study. Progression-free survival (PFS) and overall survival (OS) were estimated by the Kaplan-Meier method to identify potential prognostic factors. Factors of p ≤ 0.1 in the Log-rank tests were subjected to multivariate analysis by Cox regression analysis. Results: The mean follow-up period was 23.8 (range, 2-93) months, and 24 (60.0%) patients had local recurrence and 11 (27.5%) patients had distant metastasis. The 1-, 2-, and 5-year PFS rates were 57.7, 30.4, and 9.5%, respectively. The 1-, 2-, and 5-year OS rates were 74.8, 50.7, and 12.2%, respectively. The univariate analysis suggested that resection mode, postoperative Frankel score, adjuvant chemotherapy and adjuvant radiotherapy were potential prognostic factors for OS and PFS. However, after these factors were subjected to multivariate analyses, only adjuvant radiotherapy and resection mode remained as independent prognostic factors. Conclusions: Total en bloc resection can significantly improve PFS for primary spinal ES/pPNETs and adjuvant radiotherapy was a favorable factor for PFS. Total en bloc resection and adjuvant radiotherapy considerably improve OS for patients with primary spinal ES/pPNETs.

Keywords: Ewing sarcoma; primitive neuroectodermal tumors; prognostic factor; spinal; survival.

Figure 1

A case labeled as spinal canal type because the maximal diameter of the tumor was located in the spinal canal. Preoperative T1-weighted (A) and T2-weighted (B) images revealed a tumor at the T10–12 level. Contrast-enhanced sagittal (C) and coronary (D) images revealed that the tumor showed heterogeneous enhancement. Postoperative X-ray showed sound reconstruction by a 3D printed microporous titanium vertebral body and posterior screw-rod system. Anterior-posterior view (E). Lateral view (F). Postoperative computed tomographic scan of the thoracic spine 1 year after surgery showing excellent spinal fusion and the absence of tumor recurrence. Coronal section image (G). Sagittal section image (H).

Figure 2

A case labeled as vertebral type because the maximal diameter of the tumor was located in the vertebral body and accessory. Preoperative T1-weighted (A) and T2-weighted (B) images revealed a tumor at the T1 level. Contrast-enhanced sagittal (C) image revealed that the tumor showed significant homogeneous enhancement. Postoperative radiograph of the thoracic spine after surgery showing that the reconstructed thoracic spine was well-maintained. Anterior-posterior view (D). Lateral view (E).

Figure 3

A case of primary intradural ES/pPNET at the C3–C5 level. Images obtained 14 months after the first surgery (A,B) showed no tumor local recurrence at the C3–5 level (lack of preoperative MRI examination findings), but they did show multiple metastases in the spinal canal through the cerebrospinal fluid (C–F).

Figure 4

Histopathological, immunohistochemical, and cytogenetic examination of ES/pPNET. Light microscopy showed a highly cellular ES/pPNET tumor consisting of undifferentiated, small, round cells with frequent mitoses (A) (hematoxylin–eosin × 400). Immunohistochemical staining showed positivity for CD99 (×100) (B). Microphotograph showing immunohistochemical staining of FLI-1 (C). The representative FISH result using EWSR1 (22q12) dual color break apart rearrangement probe (Vysis). Tumor cells of the ES/pPNET displayed one fusion (yellow signal), and the simultaneous split pattern of one orange and one green signal, being indicative of a rearrangement of one copy of the EWSR1 gene (D).

Figure 5

Kaplan–Meier curves of progression-free survival and overall survival. Kaplan–Meier curves of progression-free survival for resection mode (A). Kaplan–Meier curves of progression-free survival for patients treated with radiotherapy and without radiotherapy (B). Kaplan–Meier curves of overall survival for resection mode (C). Kaplan–Meier curves of overall survival for patients treated with radiotherapy and without radiotherapy (D).