While radiation therapy is an effective treatment for patients with early-stage favorable Hodgkin lymphoma, it also poses a risk of long-term toxicity to the surrounding organs and tissue. In a study recently published in JAMA Network Open, a team of researchers led by first author Chelsea Pinnix, MD, PhD, of MD Anderson Cancer Center, found that combined modality therapy consisting of ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine) and contemporary radiation therapy (RT) demonstrated efficacy in this patient population while limiting radiation doses to at-risk organs. In this interview with i3 Health, Dr. Pinnix explains the significance of the study's findings and shares advice for members of the cancer care team using RT to treat patients with early-stage favorable Hodgkin lymphoma.
What are some of the most challenging aspects of treating patients with early-stage favorable Hodgkin lymphoma?
Chelsea Pinnix, MD, PhD: Patients with early-stage favorable Hodgkin lymphoma have exceptional outcomes. For oncologists, the true challenge is to identify the optimal therapy to use, one which is associated with both a high cure rate and limited long-term toxicity. We do not want the therapy to be more toxic than the disease itself. Combined modality therapy with doxorubicin-based chemotherapy followed by RT has been the standard of care for early-stage favorable Hodgkin lymphoma for many years. However, historic radiation fields and approaches have resulted in significant long-term side effects, including secondary cancers and cardiac toxicity. These outdated, extensive RT fields encompassed sites of disease involvement as well as neighboring nodal basins and therefore were associated with extensive normal tissue exposure.
Thankfully, the RT approaches from several decades ago are not the techniques that we use today: just as the cell phone has evolved, so has radiation! The goal of RT is to reduce the risk of Hodgkin lymphoma relapse. The greatest risk for relapse is in the lymph nodes that were initially involved at diagnosis; therefore, modern RT field design incorporates only the nodes that were involved at diagnosis. Moreover, we have several tools at our disposal to provide optimal RT delivery while minimizing exposure to normal, uninvolved tissues. This includes deep inspiration breath hold (DIBH), intensity-modulated RT (IMRT), proton therapy, and the use of an incline board for breast sparing.
Can you comment on the significance of your findings regarding modern RT doses to organs in patients with early-stage favorable Hodgkin lymphoma?
Dr. Pinnix: In our single institutional study of early-stage favorable Hodgkin lymphoma, we treated our patients according to the standard therapy established by the German Hodgkin Study Group (GHSG) for this patient population: two cycles of chemotherapy consisting of ABVD and 20 Gy of involved-site RT. With an involved-site approach, the radiation oncologist aims to restrict the RT field to the lymph nodes that were involved at the time of diagnosis; there is no role for treating neighboring lymph nodes or nodal regions that were not identified as harboring disease on the baseline positron emission tomography (PET)/computed tomography (CT) scan. With this involved-site approach, we show that the undesired radiation exposure to critical organs is exceedingly low.
For instance, long-term cardiac survivorship studies have identified a mean heart dose of 5 Gy or higher as a potential threshold dose for the development of long-term cardiac morbidity. We observed a mean heart dose of 0.8 Gy for the patients in our study, and no patient had a mean heart dose that exceeded 5 Gy. Breast exposure among the female patients in the study was also negligible, with a mean dose of less than 0.2 Gy for these patients.
What further research needs to be done regarding RT doses to organs at risk in patients with early-stage favorable Hodgkin lymphoma?
Dr. Pinnix: There is still a lot of work to be done in the survivorship arena regarding radiation therapy. In the past, we did not use CT-based planning for RT delivery. Therefore, survivorship studies that have evaluated the impact of RT doses on long-term toxicity have been based on estimates of the dose delivered to a specific organ. Going forward, we need to examine the effect of radiation dose on normal tissues that receive specific radiation doses. Our colleagues in the Childhood Cancer Survivor's Group (CCSS) have already initiated this important work.
Do you have any words of advice for members of the cancer care team treating patients with early-stage favorable Hodgkin lymphoma?
Dr. Pinnix: For radiation oncologists and community medical oncologists who treat these patients, we would recommend being incredibly mindful of the risks and benefits of various treatment approaches and making personalized patient decisions. The patient's initial PET/CT scan has the most impact on the potential involved-site RT field and will vary from patient to patient. This scan should be reviewed by a multidisciplinary team at diagnosis and should guide treatment decisions. It is helpful to have a radiation oncologist provide insight into the expected normal tissue exposure with an involved-site approach. At MD Anderson, we approach these patients in a multidisciplinary way in order to identify the treatment with the optimal risk/benefit ratio for each patient.
For oncologists who administer radiation to this patient population, we would advocate for taking extreme measures to limit normal tissue doses. At times, I and my colleagues, Dr. Bouthaina Dabaja, Dr. Jillian Gunther, Dr. Penny Fang, and Dr. Susan Wu, have been known to be a bit obsessive regarding limiting doses to normal tissues in these patients because we want to provide as much benefit from radiation with as little risk as possible. Most radiation oncologists are more accustomed to treating solid tumor patients with doses of 50-70 Gy; therefore, a treatment of 20 Gy may seem very straightforward. However, we recommend going the extra mile to limit the RT dose to normal tissues as much as possible. This often requires being thoughtful about patient setup, spending time to contour all of the normal structures that should be avoided, and delineating the involved-site target volumes appropriately. Furthermore, during plan evaluation, assess the low RT doses and work with your dosimetrist to limit these low doses to the optimal extent. Ultimately, the goal is to limit the radiation footprint as much as possible, because toxicity won't be caused by radiation in an area that did not receive it.
About Dr. Pinnix
Chelsea Pinnix, MD, PhD, is an Associate Professor of Radiation Oncology at the University of Texas MD Anderson Cancer Center, where she is also Residency Program Director for the Department of Radiation Oncology. She specializes in the use of radiation therapy for patients with Hodgkin and non-Hodgkin lymphoma. Dr. Pinnix serves on several committees, including as Radiation Oncology Chair of the Southwest Oncology Group (SWOG) Myeloma Committee and Council Member of the International Lymphoma Radiation Oncology Group (ILROG).Her research focuses on developing novel strategies for incorporating radiation in the treatment of lymphoma, minimizing toxicity to normal tissue, and managing radiation-association toxicity. She has authored or coauthored numerous publications in peer-reviewed journals.
For More Information
Pinnix CC, Gunther JR, Fang P, et al (2020). Assessment of radiation doses delivered to organs at risk among patients with early-stage favorable Hodgkin lymphoma treated with contemporary radiation therapy. JAMA Netw Open,3(9)e2013935. DOI:10.1001/jamanetworkopen.2020.13935
Bates JE, Howell RM, Liu Q, et al (2019). Therapy-related cardiac risk in childhood cancer survivors: an analysis of the Childhood Cancer Survivor Study. J Clin Oncol, 37(13)1090-1101. DOI:10.1200/JCO.18.01764
Transcript edited for clarity. Any views expressed above are the speaker's own and do not necessarily represent those of i3 Health.