Radiotherapy and high-dose chemotherapy in advanced Ewing's tumors.
BACKGROUND
Ewing's tumors are sensitive to radio- and chemotherapy. Patients with multifocal disease suffer a poor prognosis. Patients presenting primary bone marrow involvement or bone metastases at diagnosis herald a 3-year disease-free survival below 15%. The European Intergroup Cooperative Ewing's Sarcoma Study (EICESS) has established the following indications for high-dose therapy in advanced Ewing's tumors: Patients with primary multifocal bone disease, patients with early (< 2 years after diagnosis) or multifocal relapse.


METHODS
As of 1987, 83 patients have been treated in the EICESS group, 39 of them at the transplant center in Düsseldorf, who have been analyzed here. All individuals received 4 courses of induction chemotherapy with EVAJA and stem cell collection after course 3 and 4. Consolidation radiotherapy of the involved bone compartments was administered in a hyperfractionated regimen 2 times 1.6 Gy per day, up to 22.4 Gy simultaneously to course 5 and 22.4 Gy to course 6 of chemotherapy. The myeloablative chemotherapy consisted of melphalan and etoposide (ME) in combination with 12 Gy TBI (Hyper-ME) or Double-ME with whole lung irradiation up to 18 Gy (without TBI).


RESULTS
The survival probability at 40 months was 31% (44% DOD; 15% DOC). Pelvic infiltration did not reach prognostic relevance in this cohort. Radiotherapy encompassed 75% of the bone marrow at maximum (average 20%). Engraftment was not affected by radiotherapy.


CONCLUSIONS
High-dose chemotherapy can improve outcome in poor prognostic advanced Ewing's tumors. The disease itself remains the main problem. The expected engraftment problems after intensive radiotherapy in large volumes of bone marrow can be overcome by stem cell reinfusion.
Pape
H
H
Department of Radiotherapy and Radiation Oncology, University of Düsseldorf.
Laws
H J
HJ
Burdach
S
S
van Kaik
B
B
Glag
M
M
Gripp
S
S
Wittkamp
M
M
Jürgens
H
H
Göbel
U
U
Schmitt
G
G
D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D019046:Bone Marrow Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D001859:Bone Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D002648:Child; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D008297:Male; D020360:Neoadjuvant Therapy; D009378:Neoplasms, Multiple Primary / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy; D011379:Prognosis; D012512:Sarcoma, Ewing / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy*; D015996:Survival Rate