Fifty years of rhabdomyosarcoma studies on both sides of the pond and lessons learned

We review and summarize the highlights of almost five decades of cooperative group trials in rhabdomyosarcoma on both sides of the Atlantic, concentrating on chemotherapy regimens, what has been learned, and where remaining challenges are. The most important achievements have been to decrease or omit the dose of alkylator therapy for many patients, to clarify after much controversy that doxorubicin does not improve the outcome of patients even in the highest risk groups, and to show that high dose chemotherapy and stem cell rescue do not improve the outcome of the highest risk patients. In North America, vincristine/actinomycin/cyclophosphamide (VAC) remains an important part of therapy, whereas in Europe the alkylating agent of choice is ifosfamide. The highest risk patients, namely those with the poorest prognostic score, have had no improvement in outcome since the first cooperative group trial in 1972 and remain the greatest challenge. Philosophical differences between European and North American strategies still revolve somewhat around the total burden of therapy received, that is should certain groups of patients be spared aggressive local control in order to reduce late effects, recognizing that it is not possible to identify priori the children that can be cured with this approach exposing the whole population to a higher risk of relapse. Collaboration and joining resources may help answer some difficult questions.