The first large multi-institutional trial in children and adolescents less than 21 years of age with rhabdomyosarcoma (RMS) and undifferentiated soft-tissue sarcoma (UDS) was planned by members of the Children’s Cancer Study Group A (CCSGA) in North America, under the leadership of Denman Hammond, MD, Group Chairman, and led by Ruth M. Heyn, MD. This study included pediatric oncologists in the United States and Canada and was composed of physicians specializing in surgery, pathology, radiation oncology, hematology/oncology, and statisticians. The rationale and results were published in two successive articles. The first part of the study, opened in 1967, was to answer this randomized question: would the addition of chemotherapy with dactinomycin (actinomycin D, denoted by A) and vincristine (VA) to surgery (S) and radiation therapy (RT) for patients with newly diagnosed RMS and UDS who had undergone complete removal of localized disease result in a more favorable outcome, compared to those who underwent only local therapy without VA chemotherapy? Finding a statistically significant improvement in disease-free survival with the addition of VA led to the conclusion that all young patients with RMS and UDS should receive chemotherapy for 1 year along with local treatments (Heyn et al. 1974). The second part of the study, later amended to include oral cyclophosphamide (C, collectively called VAC), opened in 1970 for patients with localized disease, grossly removed, with pathologically demonstrable microscopic residual tumor, patients with localized disease and grossly visible tumor after biopsy or subtotal resection, and those with distant metastases at diagnosis. The results were 3-year survival rates of 70.8%, 43.2%, and 27.2%, respectively (Heyn et al. 1977). The addition of C to VA did not result in a significantly improved survival rate compared to patients with the same amounts of residual disease in the first study (Heyn et al. 1974).