Localized Ewing tumor of bone: final results of the cooperative Ewing's Sarcoma Study CESS 86.
OBJECTIVE
Cooperative Ewing's Sarcoma Study (CESS) 86 aimed at improving event-free survival (EFS) in patients with high-risk localized Ewing tumor of bone.


METHODS
We analyzed 301 patients recruited from January 1986 to July 1991 (60% male; median age 15 years). Tumors of volume >100 mL and/or at central-axis sites qualified patients for "high risk" (HR, n = 241), and small extremity lesions for "standard risk" (SR, n = 52). Standard-risk patients received 12 courses of vincristine, cyclophosphamide, and doxorubicin alternating with actinomycin D (VACA); HR patients received ifosfamide instead of cyclophosphamide (VAIA). Tumor sites were pelvis (27%), other central axis (28%), femur (19%), or other extremity (26%). The initial tumor volume was <100 mL in 33% of cases and > or =100 mL in 67%. Local therapy was surgery (23%), surgery plus radiotherapy (49%), or radiotherapy alone (28%). Event-free survival rates were estimated by Kaplan-Meier analyses, comparisons were done by log-rank test, and risk factors were analyzed by Cox models.


RESULTS
On May 1, 1999 (median time under study, 133 months), the 10-year EFS was 0.52. Event-free survival did not differ between SR-VACA (0.52) and HR-VAIA (0.51, P =.92). Tumor volume of >200 mL (EFS, 0.36 v 0.63 for smaller tumors; P =.0001) and poor histologic response (EFS, 0.38 v 0.64 for good responders; P =.0007) had negative impacts on EFS. In multivariate analyses, small tumor volumes of <200 mL, good histologic response, and VAIA chemotherapy augured for fair outcome. Six of 301 patients (2%) died under treatment, and four patients (1.3%) developed second malignancies.


CONCLUSIONS
Fifty-two percent of CESS 86 patients survived after risk-adapted therapy. High-risk patients seem to have benefited from intensified treatment that incorporated ifosfamide.
Department of Pediatric Hematology/Oncology, University of Münster, Münster, Germany. michael.paulussen@uni-muenster.de
M
M
Paulussen
S
S
Ahrens
J
J
Dunst
W
W
Winkelmann
G U
GU
Exner
R
R
Kotz
G
G
Amann
B
B
Dockhorn-Dworniczak
D
D
Harms
S
S
Müller-Weihrich
K
K
Welte
B
B
Kornhuber
G
G
Janka-Schaub
U
U
Göbel
J
J
Treuner
P A
PA
Voûte
A
A
Zoubek
H
H
Gadner
H
H
Jürgens
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D017024:Chemotherapy, Adjuvant; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003609:Dactinomycin / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D012307:Risk Factors; D012512:Sarcoma, Ewing / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D016019:Survival Analysis; D016896:Treatment Outcome; D014750:Vincristine / Q000008:administration & dosage
D003609:Dactinomycin; D014750:Vincristine; D004317:Doxorubicin; D003520:Cyclophosphamide; D007069:Ifosfamide