Cooperative trial CWS-91 for localized soft tissue sarcoma in children, adolescents, and young adults.
OBJECTIVE
To improve risk-adapted therapy for localized childhood soft tissue sarcoma within an international multicenter setting.


METHODS
Four hundred forty-one patients younger than 21 years with localized rhabdomyosarcoma and rhabdomyosarcoma-like tumors (ie, extraosseous tumors of the Ewing family, synovial sarcoma, and undifferentiated sarcoma) were eligible. Therapy was stratified according to postsurgical stage, histology, and tumor site. In unresectable tumors, treatment was further adapted depending on response to induction chemotherapy, TN classification, tumor size and second-look surgery. A novel five-drug combination of etoposide, vincristine, dactinomycin, ifosfamide, and doxorubicin (EVAIA) was evaluated for high-risk patients, but cumulative chemotherapy dosage and treatment duration were reduced for the remaining individuals as compared with that of the previous trial CWS-86. Hyperfractionated accelerated radiotherapy (HART) was recommended at doses of either 32 or 48 Gy.


RESULTS
At a median follow-up of 8 years, 5-year event-free survival (EFS) and overall (OS) survival for the entire cohort was 63% +/- 4% and 73% +/- 4%, respectively (all survival rates in this abstract are calculated and displayed with +/-95% CI). EFS/OS rates by histology were 60% +/- 5%/72% +/- 5% in rhabdomyosarcoma, 62% +/- 10%/69% +/- 10% for Ewing tumors of soft tissues, 84% +/- 12%/90% +/- 10% for synovial sarcoma, and 67% +/- 38%/83% +/- 30% for undifferentiated sarcoma, respectively. Response to one cycle of the five-drug combination EVAIA was similar to that of the four-drug combination VAIA used in CWS-86. Two hundred twelve patients with rhabdomyosarcoma underwent radiation (EFS, 66% +/- 6%); 53 of those patients had a favorable risk profile and received 32 Gy of HART (EFS, 73% +/- 12%). TN classification, tumor site, tumor size, histology, and age were prognostic in univariate analysis.


CONCLUSIONS
Improved risk stratification enabled decreased therapy intensity for selected patients without compromising survival. Intensified chemotherapy with EVAIA did not improve outcome of localized high-risk rhabdomyosarcoma.
Dantonello
Tobias M
TM
Olgahospital, Pediatrics 5 (Oncology, Hematology, and Immunology), and Katharinenhospital, Department of Radiotherapy, Klinikum Stuttgart, Germany. tobias.dantonello@olgahospital-stuttgart.de
Int-Veen
Christoph
C
Harms
Dieter
D
Leuschner
Ivo
I
Schmidt
Bernhard F
BF
Herbst
Manfred
M
Juergens
Heribert
H
Scheel-Walter
Hans-Gerhard
HG
Bielack
Stefan S
SS
Klingebiel
Thomas
T
Dickerhoff
Roswitha
R
Kirsch
Sylvia
S
Brecht
Ines
I
Schmelzle
Rainer
R
Greulich
Michael
M
Gadner
Helmut
H
Greiner
Jeanette
J
Marky
Ildiko
I
Treuner
Joern
J
Koscielniak
Ewa
E
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D003131:Combined Modality Therapy; D003609:Dactinomycin / Q000008:administration & dosage; D019583:Dose Fractionation, Radiation; D004317:Doxorubicin / Q000008:administration & dosage; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D012208:Rhabdomyosarcoma / Q000628:therapy; D012509:Sarcoma / Q000628:therapy*; D012512:Sarcoma, Ewing / Q000628:therapy; D013584:Sarcoma, Synovial / Q000628:therapy; D012983:Soft Tissue Neoplasms / Q000628:therapy*; D014750:Vincristine / Q000008:administration & dosage; D055815:Young Adult
D003609:Dactinomycin; D014750:Vincristine; D005047:Etoposide; D004317:Doxorubicin; D007069:Ifosfamide