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.