Abstract

Title

Role of 22q12 translocation as a predictor of metastasis and decreased survival in Ewing sarcoma

Authors

BARBARA GUERRIERI1, Chiara Mattioli1, Mauro Loi1, Daniela Greto1, Michele Ganovelli1, Giulio Frosini1, Victoria Lorenzetti1, Cecilia Cerbai1, Domenico Andrea Campanacci2, Giuliana Roselli3, Annarita Palomba4, Angela Tamburini5, Lorenzo Livi1

Authors Affiliations

1University of Florence, Radiation Oncology Unit, Florence, Italy; 2University of Florence, Department of Orthopaedic Oncology and Reconstructive Surgery, Florence, Italy; 3University of Florence, Azienda Ospedaliera Universitaria Careggi, Florence, Italy; 4University of Florence, Section of Pathological Anatomy, Department of Health Sciences, Florence, Italy; 5Meyer University Children's Hospital, Division of Pediatric Oncology/Hematology, Florence, Italy

Purpose or Objective

Ewing sarcoma (EWS) is a rare malignancy with a high metastatic potential. The most common genetic abnormality is 22q12 translocation, found in 90% of cases. However, the prognostic role of chromosomal abnormalities as driver factors in the clinical course of the disease is still investigational. Here we present a retrospective analysis on the outcome of non-metastatic Ewing patients treated with neoadjuvant chemotherapy followed by local treatment.

Materials and Methods

We present a retrospective review of cases treated in our institution from April 2002  to July 2019. Presence of 22q11 rearrangement was detected with Fluorescent in situ hybridization (FISH). We performed a statistical analysis to assess the predictive correlation of clinical and genetical features on Distant Metastasis-Free Survival (DMFS) and Overall Survival (OS).

Results

Data from 27 non-metastatic EWS patients were included. Skeletal and extraskeletal disease was observed in 20 (74%) and 7 (26 %) patients, respectively; 22q12 translocation was present in 22 cases (81%), while lack of translocation was found in 5 cases (19%). Primary tumor location affected the trunk in 48% of cases (n=13) and the limbs in 52% of cases (n=14). All patients received upfront chemotherapy according to the ISG/SSGIII and the ISG/AIEOP-EWS1 protocol in 18 (66%) and 9 (34%) cases, respectively, followed by local treatment of the primary tumor. Surgery was performed in 24 patients (88%), resulting in a 87% R0 resection rate (n=21): a Picci grade 3 complete response was observed in 20% (n=5) of tumor specimens. Preoperative or postoperative irradiation was delivered in 5 (19%) and 7 (26%) cases, respectively, while 3 (11%) patients received definitive radiotherapy to a dose of 54 Gy in 36 fractions. Total Lung Irradiation (TLI) delivering 15 Gy in 10 fractions was performed in 4 patients (15%). After a median follow-up of 23 months (range 9-73 months), metastatic relapse occurred in 9 patients and 4 patients died of disease. DMFS was 96% at 1 year and 73% at 2 years; OS was 96% at 1 and 2 years. Absence of 22q12 translocation was the only feature significantly associated with impaired DMFS (median 18 months versus not reached, p=0.005) and OS (median not reached, p=0.038).



Conclusion

Based on data from our experience, lack of 22q12 translocation showed a correlation with DMFS and OS in non-metastatic EWS. Giving its potentially prognostic role, assessment of 22q11 rearrangement could be useful for treatment personalization. However, further prospective studies are needed to confirm these results.