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

Abstract

Background Magnetic resonance imaging (MRI) is the modality of choice for local staging and response evaluation of Ewing sarcoma (EwS). Aim of this study was to determine the relevance of tumor volume response (TVR) in relation to histological response (HisRes) and survival, in order to evaluate if early modification of chemotherapy might be indicated in patients with inadequate TVR. Methods Three dimensional (3D)‐tumor volume data at diagnosis, during early induction phase (1‐3 courses of chemotherapy; n = 195) and/or late induction phase (4‐6 courses; n = 175) from 241 localized patients were retrospectively analyzed. A distinction was made between adequate response (reduction ≥67%) and inadequate response (reduction <67% or progression). Correlations between TVR, HisRes, event free survival (EFS), and overall survival (OS) were analyzed using chi‐square tests, log‐rank tests, and the Cox‐regression model. Results Early adequate TVR, noted in 41% of patients, did not correlate with EFS (P = 0.92) or OS (P = 0.38). During late induction phase 62% of patients showed an adequate TVR. EFS for patients with late adequate TVR was better (78%) than for those with inadequate late TVR (61%) (P = 0.01); OS was 80% and 69% (P = 0.26), respectively. No correlation was found between TVR and HisRes. Multivariate analysis showed that poor HisRes, pelvic location and late inadequate TVR were associated with poor outcome. Conclusions Early inadequate TVR does not predict adverse outcome; therefore, changing the treatment to second line chemotherapy is not indicated in case of inadequate early TVR. Late adequate TVR and good HisRes correlate with better EFS; patients with late inadequate TVR might benefit from augmented therapy.

Pediatric Rhabdomyosarcomas: Three-Dimensional Radiological Assessments after Induction Chemotherapy Predict Survival Better than One-Dimensional and Two-Dimensional Measurements

“…Our data are also consistent with several studies conducted on other pediatric malignancies, in which initial response to chemotherapy was found to predict outcome in Ewing sarcoma [ 5 ], osteosarcoma [ 6 ], Hodgkin’s lymphoma [ 7 ], and neuroblastoma [ 8 ]. 3D measurements have proved more sensitive than the 1D-RECIST or the 2D-WHO in predicting clinical outcome in adult gastrointestinal stromal tumors [ 27 ], lung cancer [ 28 ] and pediatric Ewing sarcoma [ 19 ].…”

“…Most patients are diagnosed with unresectable lesions, however, and initially receive neoadjuvant chemotherapy [ 3 ]. Early response to chemotherapy, assessed from changes in tumor size on computed tomography (CT) or magnetic resonance imaging (MRI), has recently emerged as a significant prognostic factor in many pediatric cancers, including Ewing sarcoma, osteosarcoma, neuroblastoma, and Hodgkin’s lymphoma [ 4 , 5 , 6 , 7 , 8 ]. Assuming that response to induction therapy is an outcome predictor in RMS as well, the European pediatric Soft-Tissue Sarcoma Study Group (EpSSG) currently tailors subsequent treatments based on early radiological response, including chemotherapy-induced changes in patients identified as poor responders [ 2 ].…”

Comparison of local control and survival outcomes between surgical and non-surgical local therapy on pelvic Ewing’s sarcoma patients: a meta-analysis

“…Thus, it is important to assess the chemotherapeutic respond after surgical procedure to guide patient’s prognosis and the postsurgical treatment. However, it remains a challenge to evaluate the chemotherapy respond before the surgery ( 32 ). The radiographic respond is one of noninvasive assessment methods of the chemotherapeutic respond.…”

Magnetic resonance biomarkers in radiation oncology: The report of AAPM Task Group 294

“…For example, within the lung it is generally appreciated that change in tumor volume reflect therapeutic response 11 . In contrast, in Ewing sarcoma — the second most common malignant bone in pediatrics and young adults — inadequate early change in tumor volume following chemotherapy is not predictive of adverse outcome while late volumetric change with histologic response was demonstrated to have higher correlation with event free survival 12 . With the increasing use of targeted and immunotherapies it is unclear what anatomic changes will occur and how well they correlate with response to therapy.…”

“… 11 In contrast, in Ewing sarcoma — the second most common malignant bone in pediatrics and young adults — inadequate early change in tumor volume following chemotherapy is not predictive of adverse outcome while late volumetric change with histologic response was demonstrated to have higher correlation with event free survival. 12 With the increasing use of targeted and immunotherapies it is unclear what anatomic changes will occur and how well they correlate with response to therapy. Additional investigation is therefore required before this biomarker can be used as a surrogate endpoint (i.e., Type 2).…”