Role of LD-ISRT in childhood and adolescent Hodgkin lymphoma

The use of LD-IFRT or ISRT in children with Hodgkin lymphoma may permit reduction in duration or intensity of chemotherapy and, as a result, dose-related toxicity of anthracyclines, alkylating agents, and bleomycin. This treatment may preserve cardiopulmonary and gonadal function and reduce the risk of subsequent leukemia.

Radiation has been used as an adjunct to multiagent chemotherapy in clinical trials for low-, intermediate-, and high-risk pediatric Hodgkin lymphoma. The goal is to reduce risk of relapse in initially involved sites that do not show sufficient early or end-of-therapy responses to treatment, with the intent of preventing toxicity associated with second-line therapy.Compared with chemotherapy alone, adjuvant radiation has, in most studies, produced a superior EFS for children with intermediate-risk and high-risk Hodgkin lymphoma who achieve a CR to multiagent chemotherapy. But it does not clearly improve OS because of the success of second-line therapy.[24] However, the intermediate-risk Hodgkin lymphoma study (AHOD0031 [NCT00025259]) did not show a benefit for IFRT in patients who achieved a rapid CR to chemotherapy (defined as >60% reduction in 2-dimensional tumor burden after two cycles and metabolic remission and >80% reduction after four cycles). The 4-year EFS rate was 87.9% for patients with rapid responses who were randomly assigned to IFRT versus 84.3% (P = .11) for patients with rapid responses who were not assigned to IFRT. The OS rate was 98.8% in both groups.[20] In a subset analysis of patients with anemia and bulky limited-stage disease, the EFS rate was 89.3% for patients with rapid early responses or complete remissions who received IFRT, compared with 77.9% for patients who did not receive IFRT (P = .019).[57][Level of evidence B1]Adjuvant radiation therapy may be associated with an increased risk of late effects or mortality.[58]

Radiation consolidation may facilitate local disease control in individuals with refractory or recurrent disease, especially in those who have limited or bulky sites of disease progression/recurrence or persistent disease that does not completely respond to chemotherapy.[59,60]

The radiation dose to breast, heart, thyroid, and lung tissue received by patients in contemporary COG trials is 55% to 85% lower than the dose received by survivors analyzed in the Childhood Cancer Survivors Study (CCSS). This finding should be considered when estimating the risk of late toxicity associated with modern radiation therapy.[61] However, a Stanford report identified a significant risk of breast cancer in children with Hodgkin lymphoma despite being treated with low-dose radiation therapy. The regimen used from 1970 to 1990 prescribed IFRT of 15 Gy to 25.5 Gy. At a median follow-up of 20.6 years, 18 of 110 children treated with radiation therapy in this dose range developed one or more subsequent malignant neoplasms, including 6 patients who developed breast carcinomas.[62]