Adding Radiation to Chemotherapy May Improve Outcomes in Early-Stage Hodgkin Lymphoma
Combined data from five randomized clinical trials appear to suggest that combined radiation therapy and chemotherapy for patients with early-stage Hodgkin lymphoma decreases the risk of relapse and increases overall survival compared with chemotherapy alone. However, these data are insufficient to draw firm conclusions that could be used to definitely inform therapy. Also, these data do not address the known risks of radiation therapy, which include late-term organ damage and second cancers.
Cochrane Database of Systematic Reviews, published online February 16, 2011 (see the journal abstract).
The combination of radiation therapy and chemotherapy is currently a standard treatment for some stages of Hodgkin lymphoma. However, radiation therapy can cause late side effects in survivors. Since patients with Hodgkin lymphoma tend to be young at the time of treatment, many survivors have decades of life after treatment in which late side effects could occur. These side effects include second cancers, most commonly breast cancer in young women who receive radiation therapy to the chest.
Given the long-term effects of radiation therapy, some researchers have questioned its use in patients with early-stage disease, suggesting that treatment with chemotherapy alone could result in comparable or even better long-term survival. Individual clinical trials testing chemotherapy alone against chemotherapy plus radiation therapy have included relatively small numbers of patients. Therefore, the authors combined data from several trials—called a meta-analysis—to learn what this kind of analysis would say about omitting radiation therapy in patients with early-stage Hodgkin lymphoma.
Researchers from the Cochrane Haematological Malignancies Group combined data from 1,245 patients enrolled in five randomized trials. Each trial had compared outcomes among patients treated with six cycles of chemotherapy alone with those among patients treated with six cycles of chemotherapy plus radiation therapy.
The earliest trial included in the study was started in the 1970s. The most recent trial recruited patients between 1998 and 2004. In all five trials, patients had stage I or stage II disease. Median follow-up for the trials ranged between 2 and 11.4 years.
Patients who received the combination of radiation therapy and chemotherapy lived longer than patients who received chemotherapy alone. The authors estimated that one life would be saved for every 11 to 55 patients treated with combination therapy instead of with chemotherapy alone. Patients who received combination therapy also had a lower risk of relapse. For every six patients treated with combination therapy instead of chemotherapy alone, the authors estimated, one relapse would be prevented.
During the trials, patients receiving either treatment experienced similar side effects. However, “long-term adverse effects such as secondary malignancies…can occur later than the reported observation times of the discussed trials,” explained the authors. This long lag time makes it impossible to determine from the available data if deaths due to late side effects differ between the two groups.
The lack of long-term data on second cancers and other late effects is a major limitation of this study, explained Dr. Richard Little, an investigator with NCI’s Division of Cancer Treatment and Diagnosis. “The conclusions of this study should be viewed with circumspection, particularly for younger patients,” he said.
“There is up to a 1 percent yearly incidence of secondary cancers from radiation therapy,” he continued. “Hopefully modern radiation techniques will reduce this incidence, but long-term data are not available. The fact remains that the majority of patients are cured with chemotherapy alone. Consigning all patients to receive chemotherapy and radiation therapy results in overtreatment for most, thus exposing them to unnecessary risk.”
Ongoing clinical trials are testing whether positron emission tomography (PET) scans, which measure the metabolic activity of cancer cells, can be used to determine if some patients with early-stage Hodgkin lymphoma can safely skip radiation therapy.
“The trend in clinical trials for early-stage Hodgkin lymphoma is towards using PET not only to risk stratify for radiation therapy, but also to reduce therapy for those who appear to get an early cure,” said Dr. Little.