Treatment strategies to reduce radiotherapy late effects in children

Abstract

Late effects of treatment are an important cause of morbidity and mortality in childhood cancer survivors. The use of radiotherapy has been implicated as a risk factor for the development of many late complications. Several strategies have been employed in pediatric oncology to minimize the late effects of radiotherapy. These have included (1) omitting or delaying radiotherapy until the child is older, (2) decreasing radiotherapy doses and volumes by incorporating chemotherapy in the treatment regimen, (3) alteration of radiotherapy fractionation, (4) use of novel techniques to spare or minimize radiation dose to surrounding normal tissues, and (5) elimination of radiotherapy in favorable subsets of patients. In infants with brain tumors, delaying radiotherapy and giving chemotherapy until the child is 3 years old was a popular approach three to four decades ago with limited success with respect to tumor control. With the advent of modern radiotherapy technology, younger patients are now able to be treated with conformal techniques and reasonable neurotoxicity. Using chemotherapy to reduce doses of radiation therapy has been employed in standard-risk medulloblastoma, intracranial germinoma, Hodgkin lymphoma, and Wilms' tumor. Likewise, the use of chemotherapy to reduce radiotherapy volumes has been employed in intracranial germinoma, Hodgkin lymphoma, and neuroblastoma and for the boost portion of treatments for rhabdomyosarcoma and Ewing sarcoma. There are a few phase III trials comparing conventional and hyperfractionated radiotherapy, but none of them have shown superiority of one over the other in terms of tumor control and late effects. Current protocols are testing the omission of radiotherapy in the most favorable subset of patients with Hodgkin lymphoma and Wilms' tumor. Intensity-modulated radiation therapy is currently used in many children in developed nations. Proton therapy is available in a few centers; clinical results of treatment are accumulating regarding the effectiveness and long-term toxicity of this radiation modality. © 2012 Springer-Verlag Berlin Heidelberg.