Radiation Therapy Can Still Be Used Safely in Combined Modality Approaches in Patients With Hodgkin's Lymphoma

Abstract

In this issue of theJournalofClinicalOncology, Heidenreich et al 1 provide important information that further quantifies the cardiovascular risks associated with wide-field, high-dose radiation that was once used in the management of Hodgkin’s lymphoma. Their study suggests that Hodgkin’s lymphoma survivors who were treated with older radiation techniques are at high risk for heart disease and may therefore benefit from screening for cardiovascular disease. However, it is important to note that the results of this study may not be extrapolated to modern-day radiation treatments. Clinical trials have indicated that modern-day radiation therapy can be delivered safely and offers significant advantages in preventing disease recurrence. Therefore, these data should not influence decisions to use radiation treatment in the combined modality treatment of Hodgkin’s lymphoma. Unfortunately, it will take another generation of cured patients with Hodgkin’s lymphoma treated with these current radiation techniques before reports on radiation-induced cardiac toxicities become part of a historical background. The cardiovascular injury results presented in the Heidenreich et al 1 study needs to be understood in its appropriate historical context. The use of a radical approach of radiation therapy, which was pioneered in Stanford University in the 1960s by Henry Kaplan and Saul Rosenberg, offered patients with Hodgkin’s lymphoma the first hope for cure. 2 To compensate for the lack of systemic treatment, which became available in the early 1970s, radiation therapy utilized large fields that treated the entire lymphatic system to relatively high radiation dosages. Oftentimes, the entire heart was included in a component of the radiation fields, and much higher biologic doses were delivered compared with contemporary treatment. The cure rate of patients with Hodgkin’s lymphoma was further increased after the addition of chemotherapy combinations like MOPP (mechlorethamine, vincristine, procarbazine, and prednisone). 3 However, the toxicities from combining both modalities were significant. Many of the patients studied in the Heidenreich et al 1 report were treated in such a fashion. The realization of the high toxicity, including increased rates of cardiovascular injury and development of second malignancies, led to several randomized trials that shifted the practice of both medical and radiation oncologists. The toxic chemotherapy regimen, MOPP, was replaced by ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine), which was found to be an equivalent, but less toxic, regimen. This was based on a study that compares six to eight cycles of MOPP with six to eight cycles of ABVD or to alternating ABVD and MOPP for 12 cylces. 4 Radiation oncologists also began a series of studies aimed at minimizing the toxicity of radiation therapy treatment. German Hodgkin’s Lymphoma Study Group (GHLSG) HD8 showed in a randomized trial that reducing the treatment volume from extended- to involved-field radiation therapy (IFRT), when combined with chemotherapy, is as effective as extended-field radiotherapy. 5 Furthermore, the long-term results of the European Organisation for Research and Treatment of Cancer (EORTC) H7 trial also showed that in combined-modality treatment (CMT), IFRT could safely replace subtotal nodal radiation for patients with clinical stage I and II Hodgkin’s lymphoma. 6