Local control of Ewing sarcoma/peripheral primitive neuroectodermal tumour using multimodality treatment approach in children and adolescents in Johannesburg: a retrospective review

Background Ewing sarcoma and peripheral primitive neuroectodermal tumours (ES/pPNET) are aggressive bone and soft tissue malignancies that are most common in children and adolescents. The use of a multimodality treatment approach improves outcome especially following advancement in systemic chemotherapy. Local treatment strategies for local disease control continues to show promise in improving overall survival and local control rates in patients with localized disease. Objective The objective of this study was to determine the effectiveness of treatment in ES/pPNET by comparing surgery and radiotherapy in overall disease and event free survival. Materials and Methods This was a retrospective analysis of medical records of ES/pPNET patients treated in a public academic institution in Johannesburg. Records of fifty-four (54) patients with localized tumours treated from January 2000 to December 2015 were included in the study. Five-year overall survival and event-free survival as well as incidence of recurrence were estimated using the Kaplan-Meier for the analyzed cohorts. Cox regression models were used for analysis of prognostic factors and estimating odd ratios with 95% confidence intervals. Results The estimated 2-year and 5-year overall survival (OS) was 88.9% (95% CI: 0.7693 – 0.9485) and 77.7% (95% CI: 0.6400 – 0.8664) respectively. Based on the local treatment received, the 5-year OS was 73.3% for surgery only, 83.3% for radiotherapy only and 76.0% for patients that had both surgery and radiotherapy In total, 18 (33.3%) of the 54 patients experienced recurrence; isolated distant recurrence occurred in 15 patients, the commonest site being the lungs (55.6%), followed by the [vi] spine (14.8%) and the pelvis (14.8%). Combined local and distant recurrence occurred in 3 patients. The site of local recurrence in these three (3) was the pelvis. The estimated 5-year event free survival (EFS) for all patients was 65.8% (95% CI: 0.5130 – 0.7691). The estimated 5-year EFS was 63.6% (95% CI: 0.2042 – 0.8045) for surgery only, while for radiotherapy only, 66.7% (95% CI: 0.3771 – 0.8234) and for both surgery and radiotherapy 66.2% (95% CI: 0.4347 – 0.8149). No patient in this cohort of ES/pPNET had isolated local recurrence or failure following local treatment. Patients with tumour size ≥ 8cm are 2.54 times likely to have local or distant tumour recurrence compared to patients with tumours < 8cm (OR: 2.54, 95% CI: 1.05-6.13, p=0.019). Patients with high pretreatment lactose dehydrogenase (LDH) level (at diagnosis), had approximately 5 times increased odds of recurrence compared with those with normal LDH (OR: 4.59, 95% CI: 1.34-15.74, p=0.010). The factors associated with recurrence were tumour size (OR: 2.64, 95% CI 1.08-6.45) and LDH (OR: 4.01, 95% CI 1.15-13.99). For mortality, LDH level (p<0.001) and disease recurrence (p<0.001). Conclusion Overall disease control in ES/pPNET is comparable for patients treated with surgery or definitive radiotherapy with chemotherapy. The risk of local failure is commoner in patients treated with definitive radiotherapy than surgery. Although radiation therapy is frequently applied in unfavorable disease group, local control outcomes are good and in many cases similar to surgical treatment outcomes. Distant failures account for the majority of relapses in this disease; therefore there is need for better and improved systemic therapies for both local and distant disease control
A research report submitted in partial fulfilment of the requirement for the degree of Master of Medicine (MMed) in Radiation Oncology to the Faculty of Health Sciences, University of the Witwatersrand, School of Clinical Medicine, Johannesburg, 2023
Ewing Sarcoma, Tumour, Primitive neuroectodermal, Adolescents