Biology and therapy of pediatric rhabdomyosarcoma.
OBJECTIVE
To review key developments in biology and therapy of rhabdomyosarcoma (RMS) since the early 1970s.


METHODS
The literature regarding biology, therapy, and late effects of therapy through March 1995 was reviewed.


RESULTS
The two major histiotypes, embryonal and alveolar, are characterized by specific genetic abnormalities that provide clues to mechanisms of tumor induction. Alveolar tumors, for example, often possess a chromosomal translocation [t(2;13)(q35;q14)] that fuses the PAX3 gene in band 2q35 with the FKHR gene in band 13q14, creating a novel chimeric protein that could inappropriately activate normal targets of the PAX3 gene product, thereby contributing to tumorigenesis. Recognition of prognostically important patient groups primarily identified by tumor extent, site, and histology, and development of effective risk-based multimodal therapy in randomized trials, have increased long-term survival in RMS from 25% in 1970 to more than 70% in current studies. The most significant recent gain in therapeutic results was realized in patients with gross residual tumor after biopsy.


CONCLUSIONS
Contemporary risk-based therapy cures more than two thirds of children with RMS while minimizing acute and late effects. Increased dose-intensity of known effective agents with hematopoietic growth factor support, new agents, and hyperfractionated irradiation are being evaluated in hopes of further improving therapy. Recent discovery of novel genetic features in this tumor should lead to better methods of diagnosis and risk assessment, and ultimately to identification of molecular targets for specific treatment.
Pappo
A S
AS
Department of Hematology/Oncology, St Jude Children's Research Hospital, Memphis, TN 38101, USA.
Shapiro
D N
DN
Crist
W M
WM
Maurer
H M
HM
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002882:Chromosomes, Human, Pair 13; D002889:Chromosomes, Human, Pair 2; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D004268:DNA-Binding Proteins / Q000235:genetics; D006801:Humans; D007223:Infant; D009367:Neoplasm Staging; D000072041:PAX3 Transcription Factor; D051761:Paired Box Transcription Factors; D011379:Prognosis; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014157:Transcription Factors; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D000072041:PAX3 Transcription Factor; C489409:PAX3 protein, human; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; C068686:Pax3 protein, mouse