Prognostic role of bone erosion in orbital RMS: a report from the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG)

Abstract

Background: Orbital rhabdomyosarcoma (RMS) is often limited to the orbital cavity and has a favorable prognosis. In some cases, the tumor can erode the orbital bone and behave as a parameningeal RMS (PM-RMS); thus, it is treated more intensively. However, the current protocols do not provide any guidance on how to consider different grades of bone erosion (BE) that can vary widely, hampering a uniform classification and the subsequent treatment assignment. With the aim of clarifying the role of BE as a risk factor, we analyzed patients with orbital RMS included in the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG) protocol.

Methods: We retrospectively analyzed the radiological reports of 199 patients with orbital RMS (PM or not) and defined three grades of BE: minimal (thinning of the bone), moderate (focal bone lysis), and extensive (complete cortical destruction).

Results: BE was present in 55 of the 199 (27.6%) patients, which was classified as minimal in 27, moderate in 7, and extensive in 21. Tumors with extensive BE were more frequently large (>5 cm, p = 0.0008) and invasive (T2, p = 0.001). With a median follow-up of 70.4 months (range = 7.1-167.7), a total of 183 patients are alive, with 5-year event-free survival (EFS) and overall survival (OS) rates of 76% (95%CI = 69.2-81.3) and 92% (95%CI = 86.7-94.8), respectively. Patients without any BE had better OS (95% vs. 81%, p = 0.001), but not EFS. Patients with no/minimal/moderate BE had better EFS and OS compared with patients with extensive BE [EFS of 78.1 (95%CI = 71.1-83.5) vs. 57.1 (95%CI = 33.8-74.9), p = 0.0114, respectively, and OS of 94.0 (95%CI = 89.2-96.8) vs. 71.1 (95%CI = 46.6-85.9), p < 0.0001, respectively]. Events and metastatic relapses (in all cases CNS/meningeal) were more frequent in patients with extensive BE.

Conclusions: Only those patients with orbital RMS and extensive BE should be considered as PM and should be treated accordingly.

Keywords: RMS; bone erosion; orbital tumor; parameningeal; pediatric rhabdomyosarcoma.

Figure 1

Example of a patient affected by rhabdomyosarcoma (RMS) with no bone erosion (BE). The patient underwent orbital CT scan and MRI at staging. (A) Bone window axial reconstruction of the CT did not show BE (yellow arrows). (B) Axial T2-weighted image of magnetic resonance confirmed right-side orbital mass (yellow asterisk).

Figure 2

Example of a patient with orbital rhabdomyosarcoma (RMS) and minimal bone erosion (BE). (A, B) MRI images showed left orbital tumor on T2-weighted coronal plane (yellow asterisk) (A) and minimal grade of BE on the axial fat-saturated T2-weighted image (green arrow) (B).

Figure 3

Example of a patient with orbital rhabdomyosarcoma (RMS) and moderate bone erosion (BE). CT scan and MRI were performed at staging. (A) Bone window coronal reconstruction of the CT scan showed moderate grade of BE (orange arrow). (B) Coronal fat-saturated T2-weighted image of magnetic resonance well demonstrated a right orbital tumor (yellow asterisk).

Figure 4

Example of a patient with orbital rhabdomyosarcoma (RMS) and extensive bone erosion (BE). (A, B) MRI showed left orbital mass on the coronal plane fat-saturated T2-weighted image (yellow asterisk) (A) and an extensive grade of BE on the axial T1 fat-saturated post-contrast sequence (blue arrow) (B).

Figure 5

Event-free survival (A) and overall survival (B) by bone erosion.

Figure 6

(A) Event-free survival (EFS) by level of bone erosion (BE): extensive (5-year EFS = 78.1%, 95%CI = 71.1–83.5) versus no/minimal/moderate (5-year EFS = 57.1%, 95%CI = 33.8–74.9, p = 0.01). (B) Overall survival (OS) by level of BE: extensive (5-year OS = 94%, 95%CI = 89.2–96.8) versus no/minimal/moderate (5-year OS = 71.1%, 95%CI = 46.6–85.9, p < 0.0001).