Utilization of Radiotherapy in Pediatric Hodgkin Lymphoma after ABVD: A Systematic Review

Abstract

<h3>Purpose/Objective(s)</h3> Doxorubicin/hydroxydaunorubicin, bleomycin, vinblastine and dacarbazine (ABVD) chemotherapy with or without radiotherapy (RT) is widely used for the management of adult Hodgkin lymphoma (HL); however, data are more limited for pediatric HL (pHL). The use of RT in conjunction with ABVD in pHL is even more uncertain. Considering the ABVD backbone is currently being used in several North American cooperative group studies that include pHL, and that many Latin America centers commonly use ABVD outside a clinical trial, we conducted a systematic review of studies to inform us about the role of RT following ABVD in pHL. <h3>Materials/Methods</h3> A PubMed search was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Articles in English reporting survival outcomes, by risk group, of pediatric patients treated with ABVD ± RT were analyzed. Data were arranged by study design, patient age range, number of patients, risk group, number of ABVD cycles, response assessment with computed tomography (CT) and/or positron emission tomography (PET), RT approach, and survival outcomes. Results were stratified by risk group. <h3>Results</h3> The PubMed search generated 89 abstracts. 7 articles met inclusion criteria. Outcomes for both limited (low- and intermediate-risk groups) and advanced (high-risk group) disease were each specified in 6 articles. Chemotherapy consisted of 4-6 cycles in limited disease, and mostly 6 cycles in advanced disease. RT indications and interim imaging were heterogeneous. For limited disease: 2 studies recommended RT for all patients; 1 only if slow or incomplete response (PET evaluation); 1 if slow or incomplete response for adolescents and young adults, or incomplete response for children (PET or CT); 1 if bulky disease or slow response (PET or CT); and 1 if incomplete response. For advanced disease: 1 study reported RT in all patients; 1 only if bulky disease; 1 if incomplete response; 1 if slow or incomplete response (PET); 1 if bulky disease or slow response (PET or CT); and 1 did not use RT for stages IIIA2 to IV after 8 cycles of ABVD, but did use RT in stages IIIA1 after 6 cycles. Radiation doses ranged between 20 and 40 Gy. Event-free survival (EFS) and overall survival (OS) at 4-10 years ranged from 84%-100%, and 93%-100% in limited disease. In patients with advanced disease, EFS ranged from 50%-84.4% and OS from 75%-95.3%. In studies where a limited RT approach was used, RT was used between 9% and 40% of patients. <h3>Conclusion</h3> Based on the systematic review of pHL treated with ABVD ± RT, the data suggest that RT may be safely limited to cases of slow or incomplete response. This approach could spare RT for more than half of patients and still achieve favorable outcomes, particularly for those with limited-stage disease. More prospective pediatric trials with ABVD are needed to define the optimal RT strategy in pHL worldwide and with imaging availability in mind.