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

Daniela Di Carlo; Giulia Fichera; Veronique Minard-Colin; Beatrice Coppadoro; Daniel Orbach; Alison Cameron; Monica Albiac Ramos; Myriam Ben Arush; Johannes H M Merks; Gianni Bisogno

doi:10.3389/fonc.2024.1497193

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

Front Oncol. 2024 Dec 12:14:1497193. doi: 10.3389/fonc.2024.1497193. eCollection 2024.

Authors

Daniela Di Carlo^{1

2}, Giulia Fichera³, Veronique Minard-Colin⁴, Beatrice Coppadoro⁵, Daniel Orbach⁶, Alison Cameron⁷, Monica Albiac Ramos⁸, Myriam Ben Arush⁹, Johannes H M Merks^{10

11}, Gianni Bisogno^{1

2}

Affiliations

¹ Department of Women's and Children's Health, University of Padova, Padova, Italy.
² Pediatric Hematology-Oncology Division, University Hospital of Padova, Padova, Italy.
³ Pediatric Radiology Unit, University Hospital of Padova, Padova, Italy.
⁴ Department of Pediatric and Adolescent Oncology, Institut national de la santé et de la recherche médicale (INSERM) U1015, Gustave Roussy, Université Paris-Saclay, Villejuif, France.
⁵ Hematology Oncology Division, Department of Women's and Children's Health, University of Padova, Padova, Italy.
⁶ Soins, Innovation, Recherche, en oncologie de l'Enfant, de l'aDOlescent et de l'adulte jeune (SIREDO) Oncology Centre (Care, Innovation and Research for Children, Adolescents and Young Adults with Cancer), Pitié Salpêtrière (PSL) University, Institut Curie, Paris, France.
⁷ FRCR-Bristol Haematology and Oncology Centre, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom.
⁸ Department of Radiation Oncology, Hospital Vall d'Hebron, Barcelona, Spain.
⁹ Joan and Sanford Weill Pediatric Hematology Oncology and Bone Marrow Transplantation Division, Ruth Rappaport Children's Hospital, Haifa, Israel.
¹⁰ Princess Máxima Center for Pediatric Oncology, Utrecht, Netherlands.
¹¹ Division of Imaging and Oncology, University Medical Center Utrecht, Utrecht University, Utrecht, Netherlands.

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.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Fondazione Città della Speranza, Italy, has funded the RMS2005 trial management, and Alice’s Arc (alicesarc.org), a children’s cancer charity focusing on rhabdomyosarcoma, United Kingdom, has funded data management and statistical processing for current analyses. Open Access funding provided by Università degli Studi di Padova | University of Padua, Open Science Committee.