Ewing sarcoma
Risk stratification for ES lacks consistency and a unified consensus for stratifying localized disease may enable reliable interpretation of international trials. European collaborative groups have used primary site, tumor volume, metastases and histologic response to stratify consolidation treatment, whereas the presence of metastatic disease alone is used in North America. Histologic response varies depending on the number and type of treatment cycles prior to local therapy and with a recent move towards pre surgical RT may no longer be as relevant.
Staging of ES has conventionally included a bone marrow biopsy. With the advent and familiarity of functional imaging in solid tumors, excellent correlation rates have been demonstrated between bone marrow biopsy and FDG-PET/CT in patients with ES.95-99 WB-MRI appears comparable to FDG-PET/CT and superior to bone scintigraphy, without requiring ionising radiation.88,100 In centers with access to these imaging modalities, it is possible to avoid an invasive bone marrow biopsy. Widespread acceptance for PET-CT or alternatively, WB-MRI as the standard for staging bone marrow will require prospective trials that incorporate large homogenous cohorts of patients with ES.
The role of high dose (HD) chemotherapy in ES remains controversial due to an overreliance on uncontrolled data.101-104 A randomized trial demonstrated consolidative HD chemotherapy using busulphan and melphalan (BuMel) confers a survival benefit in localized high-risk ES (large primary tumor, >200mls or poor response to induction VIDE chemotherapy) compared to standardized VIDE/VAI chemotherapy, with 3y EFS and overall survival of 69% vs. 56.7%(P =0.026), and 78% vs. 72.2% ( P =0.028) respectively.105 No benefit from BuMel, compared with conventional VAI with whole lung irradiation, was seen in patients with pulmonary metastases.106 Additional treosulfan and melphalan HD chemotherapy over standard VIDE induction/ VAC consolidation demonstrated no benefit in patients >14 years with primary metastatic ES.107 No randomized studies have been conducted in patients with recurrent or progressive disease in whom observational data indicates a potential greater benefit than seen in first line treatment.102,108
Debate often centers on choice of modality, sequence and timing forlocal control management . Combined modality treatment, favored in Europe, has resulted in excellent local control rates.66 There has been a move towards delivering RT pre-operatively aiming to reduce the impact of surgical fixation on the quality of RT and reducing the risk of late effects with lower doses, but at the risk of increasing wound complications which in turn compromise complex bone reconstructions.109 Complete resection of chest wall tumors appear superior to treatment with RT in improving survival.110 Sacral tumors demonstrate improved survival with definitive RT, compared to non-sacral pelvic tumors that do better with combined surgery and RT.64The role of surgery for patients with spinal ES has to be considered carefully. Spinal decompressive surgery (usually in an emergency setting) is usually intralesional increasing the risk of local recurrence whereas definitive RT is associated with better outcomes.111 Best practice is to tailor treatment for each patient individually with input from an expert multidisciplinary sarcoma panel.