Dr. Ann S. LaCasce Photo courtesy of Sam Ogden
Dr. John P. Leonard
Session Chair Ann S. LaCasce, MD, of the Dana-Farber Cancer Institute, said the session will be a case-based format, with the presenters discussing high- and low-risk cases of Hodgkin lymphoma in adolescents and young adults.
“The session will focus on the differences between how treatment is approached depending on whether patients are being treated by adult or pediatric oncologists,” she said. “Patients aged 15 to 24 years are often seen by oncologists who treat adults when they are diagnosed, but they may also be treated by pediatric oncologists. The approaches can be quite different depending on where the patients are treated.”
Other presenters during the session include John P. Leonard, MD, of Weill Cornell Medical Center, New York–Presbyterian Hospital, who will discuss the adult approach to the cases; Kara M. Kelly, MD, of Roswell Park Cancer Institute, who will address the pediatric approach; and David C. Hodgson, MD, MPH, FRCPC, of Princess Margaret Cancer Centre, in Canada, who will talk about the contrasting radiation therapy approaches to Hodgkin lymphoma.
Dr. LaCasce said that presenters “will consider the differences in the chemotherapy backbone for these patients, the differences in the way that radiation may or may not be used depending on the situation, and the long-term toxicity of treatment.”
Both the pediatric and adult oncologists, she said, “have been innovative in how they design studies and have had great outcomes. We are figuring out how to work together. We want to work on long-term survival so that these patients are not dealing with heart disease and secondary cancers in 30 years.”
Hodgkin lymphoma is among the most curable forms of childhood cancer. However, although the 5-year survival rates for children and adolescents with Hodgkin lymphoma is approximately 98%, long-term overall survival can decline from delayed effects of therapy.
Radiation therapy is associated with an increased risk for late mortality; second malignancy; cardiac, endocrine, and pulmonary dysfunction; and abnormality in growth. Researchers are working to develop strategies that can maintain survival and avoid long-term morbidity of therapy. These strategies are often different than those used in an adult population.
Both adult and pediatric oncologists are now using less radiation for younger patients, given the significant toxicity associated with high radiation doses. Dr. Hodgson will discuss the novel techniques in radiation, such as fixed-field intensity-modulated radiation therapy, response-based radiation therapy, use of 3D CT-based radiation therapy planning, and volumetric image guidance, which are strategies than can reduce the radiation dose to normal tissue and decrease later adverse effects.
Dr. Hodgson was lead author of the International Lymphoma Radiation Oncology Group treatment guideline for pediatric Hodgkin lymphoma.1 The guideline, issued in March 2015, describes methods for identifying target volumes for radiation therapy and how to implement the concept of involved site radiation therapy to define radiation target volumes and limit the dose to normal organs at risk. To accurately assess the extent and location of disease, both contrast-enhanced CT and fluorodeoxyglucose-PET (FDG-PET) are required.
The guideline outlines how evaluation of response to chemotherapy influences the targeting of the lymphoma and the volume of normal tissue treated by using the capacity to fuse CT and FDG-PET images taken before and after chemotherapy to CT imaging taken for radiation therapy planning.
According to Dr. Hodgson, the guideline has the potential “to reduce the radiation therapy breast dose by about 80% and the heart dose by about 65% for an adolescent girl with Hodgkin lymphoma. This shift is more personalized treatment planning tailored to the individual patient’s disease and will optimize risk–benefit considerations for our patients and reduce the likelihood that they will suffer late effects from radiation therapy.”
Appropriate selection of a treatment regimen to avoid late toxicities will be a major point of discussion of the cases during the session. Clinical trials are investigating promising new therapies, such as brentuximab vedotin and new checkpoint inhibitor drugs targeting PD-1.
“We want to use the best drugs upfront so that we can avoid using radiation as much as possible and reduce the toxicity associated with some of the standard chemotherapy drugs,” Dr. LaCasce said. “Clinical trials with this younger population are looking at combining brentuximab vedotin with currently used chemotherapy regimens, and we hope to test PD-1 inhibitors in the future.”
Dr. Kelly has written that establishment of a standard of care approach to management of Hodgkin lymphoma in children and adolescents is “complicated by the recognition that long-term overall survival declines in part from delayed effects of therapy and that there continue to be subgroups of patients at risk for relapse for which prognostic criteria cannot adequately define.”2
This challenge, she said, has brought various strategies that are intended to identify the best balance between maintaining overall survival and avoiding long-term morbidity of therapy, “often representing strategies quite different than those used for adults with Hodgkin lymphoma.”
Targeted therapies have been introduced in both the frontline and relapsed settings, she said, but there remain significant barriers “in the development of new combination therapies, necessitating collaborative studies across pediatric Hodgkin lymphoma consortia and in conjunction with adult groups for the adolescent and young adult population with Hodgkin lymphoma,” she said.