Treatment Approach for Children and Adolescents with Hodgkin Lymphoma
In the last decade, two major pediatric trials [9,21] have evaluated the utility of LD-IFRT in the treatment of Hodgkin lymphoma. A trial of the former Children's Cancer Group (CCG) for children and adolescents with Hodgkin lymphoma compared outcome in patients who achieved an initial CR with chemotherapy followed by LD-IFRT or no further therapy. CR was defined as an absence of residual tumor or residual tumor that showed a reduction in size of 70% or more since diagnosis and a change from gallium positivity to gallium negativity for initial gallium-positive lesions. Patients received risk-adapted chemotherapy (stages I-III, COPP/ABV; stage IV, more intensive therapy). The EFS for the 829 eligible patients was 85% at 5 years. CR was obtained in 83% of patients. Five hundred-one patients were randomized to receive LD-IFRT or no further therapy. In an as-treated analysis, 3-year EFS was 93% � 1.7% for patients receiving LD-IFRT, and 85% � 2.3% for patients receiving no further therapy. Three-year survival for patients treated with and without LD-IFRT was 98% and 99%, respectively.
In 1995, the GPOH initiated a study to assess the effect on EFS and OS of eliminating radiation for all patients achieving complete resolution of disease following chemotherapy. Radiation dose was determined by extent of disease reduction following completion of chemotherapy. Twenty-three percent of patients achieved a CR, defined as complete resolution of all disease. Sixty-two percent of patients achieved a PR (>75% but <95% disease reduction) and received 20 Gy of radiation (30 Gy if <75% disease reduction). More relapses occurred in patients who achieved a CR and received no radiation (21/222, 9.5%) than in patients who achieved a PR and received radiation (43/758, 5.7%). Overall EFS was 92% for patients receiving radiation and 88% for those receiving no radiation (P = .05). For patients with stage IA, IB, and IIA Hodgkin lymphoma who achieved a CR after chemotherapy, EFS was 97%, which is similar to the EFS of 94% in patients achieving a PR who then received radiation therapy. For all other patients, however, EFS after CR to chemotherapy was 79%, compared with 91% for patients who achieved a PR and then received radiation therapy (P = .01). For both groups, survival was 97%.[21,26] In both the German GPOH-95 and CCG-5942 studies, the benefit of radiation therapy on EFS was greater in patients with advanced-stage disease at presentation.
In an attempt to decrease long-term toxicity, the POG used a dose-dense, early response-based treatment approach with ABVE-PC and 21 Gy of radiation to involved regions for intermediate- and high-risk Hodgkin lymphoma patients.[Level of evidence: 1iiDi] Those with a rapid early response ([RER] 50% or more reduction of sum of the products of perpendicular diameters of lesions) had three cycles of chemotherapy, then received radiation therapy. Slow early responders (SER) had two additional cycles of chemotherapy before radiation therapy. The 5-year EFS was 84% for intermediate-risk and 85% for high-risk Hodgkin lymphoma patients with no difference in outcomes for RER versus SER patients. Patients with large mediastinal masses had a lower EFS (80%) versus those without (91%). Stage IV patients had a 77.8% EFS versus 92% for all others. These patients were also randomly assigned to receive or to not receive dexrazoxane. Patients who received dexrazoxane had more hematologic and pulmonary toxicity. The dose-dense application of ABVE-PC allowed 63% of patients (RER) to have less chemotherapy exposure. Further follow-up will be needed to determine if long-term toxicities differ between those receiving three versus five cycles of ABVE-PC.