Proton Therapy in Hodgkin Lymphoma Yields Favorable Acute Toxicity Profile

Hodgkin lymphoma patients treated with consolidative proton therapy after chemotherapy had “excellent” early relapse-free survival rates and no early grade 3 radiation-related toxicities, according to a study published in the Annals of Oncology.

The study investigated early outcomes for 138 patients diagnosed with Hodgkin lymphoma and treated with chemotherapy, followed by consolidative proton therapy, between June 2008 and August 2015. Those with relapsed or refractory disease were excluded.

The patients were enrolled on several institutional review board–approved protocols: the University of Florida outcomes tracking protocol (n = 39), the University of Pennsylvania adult or pediatric proton registry (n = 54), and the Proton Collaborative Group registry (n = 45).

“When you’re dealing with a disease as rare as Hodgkin lymphoma, where radiation is being used less because of concern over long-term toxicity, you really need to pool these resources to get sufficient numbers,” said study lead investigator Bradford. S. Hoppe, MD, MPH, of the University of Florida College of Medicine in Gainesville.

The National Cancer Institute estimates 8,260 new cases of Hodgkin lymphoma will be diagnosed in the United States during 2017.

Describing the well-established link between radiation dose to organs and late toxicity, the study authors noted proton therapy can reduce dosage-and damage-to organs, and potentially lower the risk of late side effects for Hodgkin lymphoma survivors, who are likely to develop a grade 3 or higher toxicity within 30 years of treatment. Late side effects include cardiovascular problems and secondary cancers.

Patients in the study ranged in age from 6 to 57; the median age was 20 years. Overall, 42% were pediatric (≤ 18 years) and 93% were younger than 40 years. Females (62%) outnumbered males (38%). Stage distribution was 73% with I/II disease and 27% with III/IV disease.

Patients who received proton therapy as part of first-line therapy were primarily “those with the highest risk of developing late toxicities,” including younger patients, female patients, and patients with bulky mediastinal disease adjacent to the lung, heart, and breasts.

Most patients had mediastinal involvement (96%) and bulky disease (57%), and 37% had B symptoms.

The median dose was 21 Gy(RBE) in pediatric patients (range, 15–36 Gy[RBE]) and 30.6 Gy(RBE) in adult patients (range, 20–45 Gy[RBE]).

Results showed a 3-year relapse-free survival rate of 92% for all patients: 96% for adults and 87% for pediatric patients (P = .18). Patients with a partial response at the end of chemotherapy-as evaluated by positron emission tomography (PET)/CT-had worse 3-year progression-free survival (78% vs 94% for other patients; P = .0034).

No grade 3 radiation-related toxicities and “no clinically meaningful pneumonitis” developed in the cohort during the follow-up period, which had a median of 32 months (range, 5–92 months).

“This study shows Hodgkin lymphoma is a great place for using proton therapy,” Hoppe said. “Young adults and adolescents would benefit the most, along with pediatric patients.”

The study also “demonstrated that we’ve got similar relapse-free survival with proton therapy as you would get with regular x-ray radiation...and furthermore demonstrated low rates of acute toxicity,” said Hoppe. “We need to look at a lot of follow-up data, over decades, to demonstrate reduction in long-term complications.”