A Systematic Overview of Radiation Therapy Effects in Hodgkin's Lymphoma

Abstract

A systematic review of radiation therapy trials in several tumour types was carried out by The Swedish Council of Technology Assessment in Health Care (SBU). The procedures for evaluation of the scientific literature are described separately (Acta Oncol 2003; 42: 357-365). This synthesis of the literature on radiation therapy for Hodgkin's lymphoma (HL) is based on data from 12 randomized trials and 2 meta-analyses. Data from 3 prospective studies, 29 retrospective studies and 58 other articles were also used. In total, 58 scientific articles are included, involving 27,280 patients. The results were compared with those of a similar overview from 1996 including 38,362 patients. The conclusions reached can be summarized thus: Solid scientific documentation shows that in patients with HL more than 80% in the early stages and 60-70% of younger patients in advanced stages of disease are now cured by the development of radiotherapy and combination chemotherapy. Long-term follow-up shows that after 15 to 20 years the mortality from HL in early and intermediate stages is exceeded by other causes of death, mostly secondary malignancies and cardiac deaths, especially myocardial infarction. Convincing data show that radiotherapy plays a major role in the development of solid cancers and cardiovascular disease, but no randomized trials have been performed. During the past decade increasing awareness of fatal long-term sequelae has fundamentally changed treatment strategies in early and intermediate stages. A thorough long-term follow-up is essential to evaluate the effects of the modifications of the therapy. In early stages of disease extended field irradiation is now replaced by short periods of chemotherapy followed by limited radiotherapy to decrease late sequelae. This approach is strongly supported by early reports from randomized trials. Final results cannot be fully evaluated for many years. The optimal radiation dose and volume after chemotherapy are not defined or if irradiation is needed at all. Several studies are under way. In intermediate stages two recently reported randomized trials indicate that combined modality therapy is preferable and that involved field could replace extended field irradiation. It is still too early to draw any firm conclusions. In advanced stages, there is no evidence of any survival benefit from additional radiotherapy. The role of radiotherapy in the case of residual tumour and bulky disease still remains controversial. There is no scientific support for improved survival with radiotherapy in conjunction with high-dose chemotherapy with stem-cell support. Radiotherapy as salvage treatment might be an alternative in late limited nodal recurrence after initial chemotherapy. However, the body of knowledge is small. The role of radiotherapy in the treatment of HL is decreasing.

Therapeutic radiation for lymphoma

“…44 Reductions in radiotherapy field sizes and treatment doses for HL and NHL have been made to address the known increased risks for second cancers and cardiac complications caused by radiotherapy. [45][46][47] It is only very recently, however, that epidemiology studies have shown associations between mesothelioma and radiation treatment for NHL and testicular cancer. 7,19 Travis et al 7 used SEER data through 2001, enhanced by data from other population-based registries in Canada and Europe, to identify 40,576 survivors of testicular cancer who were followed for second cancers.…”

Long‐term risk of cardiovascular disease in Hodgkin lymphoma survivors—Retrospective cohort analyses and a concept for prospective intervention

“…7,22,23 Two recent large cohort studies from the Netherlands and UK show an increased standardized mortality rate in CVD that is probably attributed to radiotherapy and adriamycin. 5,4 The UK study also found a significant relation to vincristin.…”

Treatment of Early Stage Hodgkin Lymphoma

“…It was not then until early 1960's when extended field RT (EF-RT) was adopted as standard of care for early stage HL. However, EF-RT was complicated by high relapse rates (Horwich, Specht & Ashley, 1997) and serious long-term side effects including pulmonary dysfunction, heart disease and secondary cancers (Gustavsson, Osterman & Cavallin-Stahl, 2003). Hence, in an attempt to lessen toxicity and improve treatment outcomes, several studies over the past 3 decades addressed those concerns through modifying the radiation field/dose and/or incorporating chemotherapy to RT.…”