Avoiding RT Possible in Some Early-Stage Hodgkin Lymphoma Patients?

Early-stage classical Hodgkin lymphoma is a highly treatable and usually curable malignancy. Because of the high cure rate, reducing toxicity is a primary concern. One idea for doing so is a subject of ongoing research: is elimination of all radiotherapy (RT) in many of these patients a possibility?

In a talk at the 11^th Annual National Comprehensive Cancer Network (NCCN) Hematologic Malignancies Congress, Ranjana H. Advani, MD, of the Stanford Cancer Institute in California, discussed the state of that research, and whether reducing or eliminating RT completely is feasible.

“I think we’re in an era where somehow all RT is [considered] bad,” she said, though this is at least somewhat a holdover from earlier eras when much more toxic RT modalities were used. Extensive RT used decades ago was first honed down to extended field RT, which has been further whittled into involved field (IFRT) and involved site RT (ISRT).

The transition to the more targeted IFRT, according to one study, yielded a 63% reduction in relative risk of breast cancer. Long-term data on ISRT has not yet matured, but that work is currently underway.

The current regimens used to treat early-stage classical Hodgkin lymphoma are generally very effective, with 12-year freedom from progression and overall survival rates well above 90%. Combined modality regimens with chemotherapy and RT have often shown 10- or 12-year survival of 94% and higher. “How do we improve on something that was doing well?” Advani asked. “Can risk-adapted strategies be used to omit RT?”

To answer the question, there is first a need to define patients by risk. Early-stage patients who are deemed favorable have a cure rate of over 90%, and the primary goal for these patients is to reduce toxicity. For unfavorable-risk patients, the cure rate is between 80% and 85%, and the goal is to both increase efficacy and to do so with any increase in toxicity. Unfavorable risk refers to those early-stage patients with certain risk factors, including large mediastinal mass, extranodal lesions, at least three nodal sites, or other factors.

“Can favorable patients get less treatment?” Advani asked. “Can unfavorable patients get more treatment? How can we select patients for chemotherapy alone?”

An effective method to stratify patients by risk, she said, is by using positron emission tomography (PET) scans and the Deauville scale, which runs from 1 to 5. In one retrospective analysis conducted at MD Anderson Cancer Center in Houston, patients with a Deauville score of more than 2 had a worse outcome than others. 

There is some prospective data on using that scale to avoid RT, though it has not conclusively shown this approach is successful. The UK NCRI RAPID trial had patients undergo a PET scan after 3 cycles of chemotherapy; those with a score above 2 went on to receive RT, while those with lower scores were randomized to either no further treatment or RT. There was a 5% to 7% progression-free survival advantage with RT over no further treatment. Advani said the difference is relatively small, but it is hard to claim that chemotherapy alone is noninferior to the combined therapy.

In another study, the EORTC H10 trial, chemotherapy alone was again compared with chemotherapy combined with RT. Though differences were not large and outcomes were generally good, the superiority of chemotherapy alone could not be demonstrated.

Other trials have used a Deauville score of 3 rather than 2 as a cutoff, which Advani said could help save more people from undergoing RT. The Alliance study and others, which are testing these same concepts in patients with bulky stage I and II disease, are ongoing and will yield data soon.

“Where are we?” Advani asked. “The prognosis is excellent,” though there does appear to be slightly higher failure rate with chemotherapy alone than when RT is incorporated. In younger patients, when both the risk of breast cancer and fertility concerns are paramount, the idea of eliminating RT may be more attractive. “I think it is a balance of efficacy vs long-term outcome,” Advani said. “Early-stage Hodgkin lymphoma is highly curable. It’s an opportunity to move away from traditional therapies by incorporating some of these newer concepts.”