“When patients come in with Hodgkin lymphoma, especially, the provider is likely to say, ‘You’re lucky. This is a highly curable type,’” says Michael Roth, MD, the director of the Childhood Cancer Survivorship Program at University of Texas MD Anderson Cancer Center in Houston. What a doctor may not say is that HL also leads to very high incidences of later-in-life diseases, particularly when patients are children when diagnosed. “We now know that obtaining a cure for lymphoma isn’t enough,” says Dr. Roth. “You also have to maximize patients’ quality of life over the long term.”
Early Curative Treatments for Lymphoma Raised the Risk for Other Diseases
For years, the standard of care for treating HL was to use a combination of radiation and chemotherapy, a one-two punch that blasted cancer cells and could also have a seriously destructive impact on surrounding healthy cells. “We took a bazooka approach, but that approach increased the risk for a host of medical complications, including cardiac issues, lung disease, infertility, secondary blood cancers, thyroid cancer, and breast cancer,” says Lisa Roth, MD, the director of the adolescent and young adult lymphoma program at NewYork–Presbyterian and Weill Cornell Medicine in New York City. For instance, doctors now believe that breast tissue in girls and teenagers may be especially sensitive to radiation. “We’ve found that breast cancer is prevalent in lymphoma patients who received radiation at a young age,” says Dr. Lisa Roth. This unexpected fallout has led to a major shift in the management of Hodgkin lymphoma — one that calls for less radiation, when possible, as well as targeted treatments that harness the body’s immune system to attack only tumor cells and leave healthy cells in peace.
Monitoring Long-Term Effects on the Heart
It’s heartbreaking enough for any child to get a cancer diagnosis, but survivors of HL who are diagnosed as children or teens are especially prone to serious heart conditions as adults. One study from 2015 found that HL patients have a four- to sixfold increased incidence of congestive heart disease or heart failure compared with the general population. (1) They are also more likely to develop valve abnormalities and have heart attacks in their thirties, forties, and fifties. “These survivors are getting diseases of the elderly at an earlier stage,” says Michael Roth. “The chemotherapy and radiation to the chest appear to be speeding up the aging process in organs more targeted by those treatments, like the heart.” A class of chemotherapy drugs known as anthracyclines, which include drugs such as doxorubicin (Adriamycin) and eprubicin (Ellence), is also now known to be cardio toxic. (2) “Anthracyclines trigger the release of free oxygen that damages cells, including heart cells,” says Michael Roth. Along with his MD Anderson colleagues, he is investigating whether first giving patients a cardio-protective drug known as dexrazoxane (Zinecard) before chemotherapy can head off heart problems later. “The data is still coming in, but the early evidence is promising,” he says. Findings like these have spawned an emerging field known as cardio-oncology, which aims to reduce the unhealthy heart effects produced by so many cancer treatments. “Monitoring these problems is an important part of cancer survivorship,” says Michael Roth. “Years ago, we didn’t know the side effects of being exposed to radiation and chemotherapy. Now we are trying to take action on the back end, by doing regular screenings — including echocardiograms and EKGS — on these patients who were treated back in the ’70s and ’80s.” The goal? “To try to catch abnormalities early on.” Patients in MD Anderson’s Childhood Cancer Survivorship Program come back regularly, and are given screenings based on how much radiation they received, or their age during treatment, or any number of factors,” says Michael Roth. “For Hodgkin lymphoma, this kind of postcancer follow-up is now the standard of care.” RELATED: CAR T Cell Therapy Enhances the Human Immune Response to Cancer
The Future of Care: Avoid Doing Damage in the First Place
For young patients getting a diagnosis of Hodgkin lymphoma now, oncologists are offering more targeted, individualized treatments. “When we do use radiation, we use lower doses,” says Lisa Roth. “And the technology has gotten much better at allowing us to home in on just the areas that need the radiation, rather than hitting healthy tissue.” Many patients no longer get radiation at all. Often, they begin with chemo. If scans at the halfway point show that they’re responding quickly and their tumors are shrinking, they may forgo radiation — and the dangers that come with it. Doctors are also looking beyond chemotherapy to immunotherapy, which enhances a patient’s own immune response to a tumor. One example: Antibodies from a patient’s immune system might be used to pummel certain proteins on the surface of cancer cells. “We’ve seen encouraging responses with an immunotherapy drug called pembrolizumab (Keytruda), which is what’s called a checkpoint inhibitor,” Lisa Roth explains. “It works by changing the interaction between the tumor and the immune system so that the latter can fight the cancer cells more effectively.” (3) Meanwhile, a trial at MD Anderson is looking at subbing in a new drug for the chemotherapy agent bleomycin, which has been shown to cause lung damage. They are trying a medication known as brentuximab. (4) “It’s an antibody that targets a protein on the surface of tumor cells, and is safer for the lungs,” MD Anderson’s Michael Roth explains. Another new treatment, known as CAR T cell therapy (CAR stands for chimeric antigen receptor), has shown promise in treating acute leukemia as well as non-Hodgkin lymphoma. “Basically, we take out a patient’s immune system, edit it so that it will target tumor cells, then put it back into the body,” says Michael Roth. Of course, researchers still don’t know if immunotherapy will produce side effects in 10, 20, or 50 years’ time. “We will have to do that surveillance, too,” Michael Roth admits. Still, he says, “there’s hope to be seen. Some of the changes we’ve made — decreasing radiation, limiting chemotherapy doses, using more targeted therapies — are already resulting in patients living longer — with a better quality of life. It’s not just about curing the cancer anymore.”
