Prognostic Factors and Patterns of Relapse in Ewing Sarcoma Patients Treated With Chemotherapy and R0 Resection

Abstract

PURPOSE/OBJECTIVE(S) To identify prognostic factors and patterns of relapse for patients with Ewing sarcoma (ES) who underwent chemotherapy and R0 resection without radiation therapy (RT). METHODS AND MATERIALS We reviewed the medical records of patients who underwent surgical resection at our institution between 2000 and 2013 for an initial diagnosis of ES. The associations of demographic and clinical factors with local control (LC) and patient outcome were determined by Cox regression. Time to events was measured from the time of surgery. Survival curves were estimated by the Kaplan-Meier method and compared by the log rank test. RESULTS A total of 66 patients (median age 19 years, range: 4–55) met the study criteria. The median follow-up was 5.6 years for living patients. In 43 patients (65%) for whom imaging studies were available, the median tumor volume reduction was 73% and at least partial response (PR) by RECIST was achieved in 17 patients (40%). At 5 years, LC was 78%, progression-free survival (PFS) was 59%, and overall survival (OS) was 65%. Poor histologic response (necrosis ≤ 95%) was an independent predictor of LC (HR=6.8, P=0.004), PFS (HR=5.2, P=0.008), and OS (HR=5.0, P=0.008). Metastasis on presentation was also an independent predictor of LC (HR=6.3, P=0.011), PFS (HR=6.8, P=0.002) and OS (HR=6.7, P=0.002). Radiologic PR was a predictor of PFS (HR=0.26, P=0.012) and post-chemotherapy tumor volume was associated with OS (HR=1.06, P=0.015). All deaths were preceded by distant relapse. Of the 8 initial local-only relapses, 5 (63%) were soon followed by distant relapse. Predictors of poor post-recurrence survival were time to recurrence <1 year (HR=11.5, P=0.002) and simultaneous local and distant relapse (HR=16.8, P=0.001). CONCLUSIONS Histologic and radiologic response to chemotherapy were independent predictors of outcome. Additional study is needed to determine the role of adjuvant RT for patients who have poor histologic response after R0 resection.

The relation of radiological tumor volume response to histological response and outcome in patients with localized Ewing Sarcoma

“…In our study, 41% of patients achieved adequate TVR during the early phase of induction therapy and 62% during late induction phase. These percentages are slightly better than the TVR reported by Pan et al , who examined 66 localized and metastatic EwS patients prior to surgery. Nearly 40% of patients achieved at least partial remission (PR) according to RECIST criteria.…”

“…Studies concerning radiological TVR and correlation with survival were performed in small patient cohorts and showed inconsistent results . In this respect, the large number of EwS patients included in our study is novel and adds to the available evidence.…”

“…Since HisRes has been identified as a prognostic factor, image‐based response might well correlate with HisRes . Previously published reports on imaging based tumor response cited only limited numbers of patients and focused more on response during late induction chemotherapy.…”

Pencil beam scanned protons for the treatment of patients with Ewing sarcoma

“…This hypothesis is however challenged by the results of the Texas group that reported the outcome of 66 patients treated with chemotherapy and surgery only with an R0 resection. 34 In this series, metastatic patients were 4.6 more likely to fail locally (P = 0.03) when compared to those with localized disease, which suggests that reseeding of the primary tumor by distant metastases could be an issue in a cancer with marked propensity for diffuse bone metastasis. 35,36 We acknowledge that the impact of stage at diagnosis on LC is controversial due to the available observational studies with conflicting results, mostly small and stemming from single institution, that usually report event-free or progression-free survival but rarely local events.…”

“…The latter study could suggest that radiation may not be the optimal LC strategy for metastatic patients. This hypothesis is however challenged by the results of the Texas group that reported the outcome of 66 patients treated with chemotherapy and surgery only with an R0 resection . In this series, metastatic patients were 4.6 more likely to fail locally ( P = 0.03) when compared to those with localized disease, which suggests that reseeding of the primary tumor by distant metastases could be an issue in a cancer with marked propensity for diffuse bone metastasis .…”