SAN FRANCISCO—Radiation therapy for treatment of patients with early-stage Hodgkin's disease appears to have long-term survival benefits compared with patients not treated with radiation, researchers reported here at the American Society for Radiation Oncology Annual Meeting (Abstract CT-08).
In the study, after 10 years about 84 percent of patients who underwent radiation therapy at the start of their treatment regimen were alive compared with 76 percent of those who did not undergo the therapy, a difference that translates to a 49 percent relative risk reduction that was highly significant, said Rahul R. Parikh, MD, Director of Proton Beam Therapy at Mount Sinai Health System in New York.
The timing of the radiation therapy also appeared to make a significant difference, he said. At 10 years, 84 percent of patients who had been treated with radiation within 30 days of diagnosis were alive compared with 78 percent of patients who received radiation therapy more than 30 days after diagnosis.
In the study, “we have identified specific factors—socioeconomic differences, insurance status, and facility type—associated with underutilization of radiation therapy which may be targeted to improve access to care,” he said. “This is the largest contemporary dataset of patients with early-stage Hodgkin's disease.”
The researchers accessed the National Cancer Data Base and identified 41,420 patients diagnosed with Stages I-II Hodgkin lymphoma from 1998 to 2011. The median follow-up was 6.4 years; the median age of the patients was 37, with a range of 18 to 90.
Of the patients in the study, 20,897 did not receive radiation therapy—about 51 percent of the patients. There were 20,523 patients who received radiation at a median dose of 30.6 Gy as part of the combined-modality therapy. The patient population was about evenly divided by sex; more than 80 percent were white and about 10 percent were black. A little more than one-third of the population was age 30 or younger, and approximately 25 percent were over age 50.
“The standard of care for Stage I-II Hodgkin lymphoma has been combined-modality therapy of chemotherapy followed by consolidation radiation therapy,” Parikh said. “Multiple randomized trials have found that use of radiation has resulted in tumor control and progression-free survival.
A meta-analysis that included 1,245 patients found a substantial survival benefit with radiation in reducing the risk of mortality by 60 percent; and a SEER study that included 12,247 patients found that combined-modality therapy resulted in a five-year overall survival benefit with radiation therapy in which 87 percent of patients receiving radiation survived, compared with 76 percent of patients who didn't receive radiation.”
He said that despite these results, beginning in the 2004-2006 period there has been a declining use of radiation therapy to the point that less than half of Hodgkin patients receive radiation therapy. In 1998, 56 percent of patients with Hodgkin lymphoma underwent radiation therapy, but in 2011 the radiation utilization in these patients had dropped to 41 percent of the total.
“The main reason given for not using radiation was that radiation was not part of the planned initial treatment strategy,” Parikh said.
There may be several reasons for that decline in use, explained Karen Winkfield, MD, Director of Hematologic Radiation Oncology at Massachusetts General Hospital Cancer Center/Harvard Medical School.
“There are already randomized clinical trials that show the benefit of using radiation therapy in early-stage Hodgkin lymphoma, but the hard thing with randomized controlled trials is that sometimes you might not have a long enough time to show a clear overall survival benefit. Additionally, the number of patients in the randomized controlled trial is often small.
“The issue has been that many of the large studies used very large radiation fields, which is really not what we are doing today, and in fact the survival curves crossed after 12 years because of some of the late toxicities of radiation therapy—at least that's what they are saying,” she said.
Another problem perceived with randomized controlled trials is that they have a homogeneous population that may not, in fact, represent the population of patients seen in the clinic, she added. “This study, though, is the largest cohort of patients being looked at to actually show that radiation therapy does indeed provide not only progression-free survival, which everyone acknowledges, but also overall survival.”
The study also indicated that socioeconomic status, education level, and other non-medical factors may influence which patients receive optimal treatment, Winkfield said. For example, the report showed that 24.3 percent of the population studied did not have medical insurance—and they represented just 17.2 percent of the patients who underwent radiation therapy. People with lower education attainment and lower levels of household income were also less likely to receive radiation therapy.
These differences, she said, “speak to the issue of access—”This is a snapshot of what happens in the real world. That is why this is, for me, a very compelling study: There are large numbers of patients; it represents more than 75 percent of the patients being treated in the United States and it shows what happens. I think this is a great study.
“I hope it will renew and re-invigorate the discussions among colleagues. For me, it highlights the need for radiation oncologists being at the table. At the Massachusetts General Hospital Cancer Center we have developed a multidisciplinary team for Hodgkin's lymphoma,” she said. “It is critically important to have discussions between the medical oncologist and the radiation oncologist, and also to allow the patients to be involved in their care.”
Parikh said that when all the parameters and variables were scrutinized with an eye toward what determined an overall survival benefit, he found a correlation with age—patients 40 or younger were likely to do better, and white race was likely to increase the overall survival benefit.
But when it came to treatment, the use of radiation oncology provided a 54 percent reduction in the risk of mortality; the timing of when to receive radiation therapy resulted in a significant 16 percent reduction in the risk of mortality if patients were treated within 30 days of diagnosis.