Results of a retrospective study of the treatment patterns and outcomes of a cohort of children and young adults with relapsed/refractory Hodgkin lymphoma showed high 5-year rates of freedom from local failure and overall survival (OS) in patients receiving moderate-dose salvage radiation therapy. The finding of this study were published in Radiotherapy and Oncology.
Although the majority of children and young adults diagnosed with Hodgkin lymphoma respond well to frontline therapy, progression of primary disease or disease recurrence occurs in approximately 15% of these patients. While second-line treatment often involves systemic therapy with novel agents followed by high-dose chemotherapy and autologous hematopoietic cell transplantation (AHCT), the use of curative-intent radiation therapy in this population remains controversial. In addition, the limited number of patients with Hodgkin lymphoma treated in the salvage setting is an impediment to the prospective investigation of salvage treatments in this population.
This retrospective study included 46 children and young adults with progressive or relapsed Hodgkin lymphoma treated with curative-intent salvage radiation therapy at St Jude Children’s Research Hospital between March 2000 and December 2015.
The median patient age was 16.5 years and 17.5 years at diagnosis and first treatment failure, respectively. At initial diagnosis, 70% and 72% of patients presented with advanced disease and nodular sclerosing histologic variant, respectively. Nearly all patients (96%) had lymph node involvement as part of initial failure, whereas 26% of patients had both nodal and extranodal disease as sites of initial failure. In addition, 17% of patients had involvement of a site distinct from those identified at diagnosis. The median dose of initial radiation therapy (for those patients receiving upfront radiation therapy) was 25.5 Gy, and the median dose of salvage radiation therapy was 30.6 Gy.
Salvage radiation therapy followed AHCT in patients with high-risk disease (80% of patients) or salvage chemotherapy in patients with low-risk disease. For the 70% of patients who had received upfront radiation therapy, salvage radiation therapy was typically administered to sites involved at the time of treatment failure, whereas all sites of initial disease were typically targeted with salvage radiation therapy for the patients who did not received radiation therapy as part of their upfront treatment regimen. Median follow-up following administration of salvage radiation therapy was 3.8 years.
Treatment outcomes for these patients included a 5-year cumulative incidence of local failure rate following salvage radiation therapy of 17.7% (95% CI, 8.2–30.2%), a 5-year freedom from subsequent treatment failure rate of 80.1% (95% CI, 69.2–92.6%), and a 5-year OS rate of 88.5% (95% CI, 79.5–98.6%).
Of the clinicopathologic characteristics evaluated, only male sex (P =.049) and inadequate response to salvage systemic therapy (P =.048) were significantly associated with local failure after salvage radiation therapy.
Interestingly, all 9 patients who did not undergo AHCT achieved durable tumor control following salvage therapy.
“These findings support the notion that not all patients who experience disease relapse after frontline therapy require AHCT, particularly if their response to initial salvage therapy is adequate and time to recurrence is long,” the study authors commented.
They also noted that “a salvage treatment paradigm of intensive chemotherapy and moderate-dose RT limited to sites of refractory disease, with or without AHCT, provides durable local control and encouraging long-term survival outcomes.”
Grade 3 or higher toxicities occurring >3 months following salvage radiation therapy included pulmonary (8.7%; and grade 5 pulmonary toxicity in 2 patients), cardiac (6.5%), gastrointestinal (2.2%), and other (2.2%). Second malignancies occurred in 4.3% of patients but were considered to be outside the primary or salvage radiation fields.
The study authors concluded that “these data contribute to the growing pediatric literature highlighting the role of salvage radiation therapy and reaffirm the importance of large, risk-stratified, prospective trials specific to relapsed/refractory Hodgkin lymphoma.”
- Tinkle CL, Williams NL, Wu H, et al. Treatment patterns and disease outcomes for pediatric patients with refractory or recurrent Hodgkin lymphoma treated with curative-intent salvage radiotherapy. Radiother Oncol. 2019;134:89-95.