The Intergoup Rhabdomyosarcoma Study (IRS) Group was established in 1972 by 3 pediatric cooperative cancer study groups. There have so far been 5 major trials, I–V. Survival after treatment of rhabdomyosarcoma at all sites has improved from 25% in 1970 to 70% in 1991 due to their work (Crist, J Clin Oncol, 1990; Maurer, Cancer, 1988; Wharam, Ophthalmology, 1987). The IRS found that favorable prognostic factors include
- Undetectable distant metastases at diagnosis
- Primary sites in the orbit and nonparameningeal head/neck and genitourinary nonbladder/prostate regions
- Grossly complete surgical removal of localized tumor at the time of diagnosis
- Embryonal/botryoid histology
- Tumor size < or = 5 cm
- Age younger than 10 years at diagnosis
Protocol V studied reducing exposure to cyclophosphamide and radiation therapy (RT) in patients at low risk while adding new, active agents such as topotecan or irinotecan to the standard therapy of vincristine, actinomycin D, and cyclophosphamide (VAC) plus XRT for patients with unfavorable histology or advanced disease. Bone marrow/stem cell reconstitution has not been included because this strategy has thus far failed to improve survival rates of patients with metastases at diagnosis (Raney, J Pediatr Hematol Oncol 2001).