Justine M. Kahn1, Kara M. Kelly2, Qinglin Pei3, Debra L. Friedman4, Frank Keller5, Rizvan Bush6, Smita Bhatia7, Tara O. Henderson8, Cindy L. Schwartz9, Sharon M. Castellino5
1Columbia University Medical Center, New York, New York, USA,2Roswell Park Comprehensive Cancer Center, Buffalo, New York, USA,3Children‘s Oncology Group, Statistics & Data Center, University of Florida, Gainesville, Florida, USA,4Vanderbilt University School of Medicine, Nashville, Tennessee, USA,5Emory University, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia, USA,6Children's Oncology Group, Statistics and Data Center, Monrovia, California, USA,7University of Alabama at Birmingham, Birmingham, Alabama, USA,8University of Chicago Comer Children's Hospital, Chicago, Illinois, USA,9Children's Hospital of Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
Background: Population-based studies in the U.S. and analyses of adult cooperative group trials have reported inferior outcomes in adolescent/young adults (AYAs) with Hodgkin lymphoma (HL). While 15 years (y) is the lower age threshold for delineating AYA cancer outcomes in most countries, recent guidance from the American Society of Clinical Oncology and Friends of Cancer Research calls for including children ≥12y on late phase trials. We examined outcomes by age category (<12y or ≥12y; <15y or ≥15y) in children and adolescents receiving response-based therapy for HL.
Methods: This was a pooled analysis of individual patient-level data from three COG Phase 3 trials for intermediate low, and high-risk HL (AHOD0031, AHOD0431, AHOD0831). Five-year event free survival (EFS) and overall survival (OS) were estimated by age category via Kaplan Meier method. Cox regression models examined the influence of age on EFS and OS, adjusted for demographics, histology, Ann Arbor stage, B symptoms, bulk, study, and radiation therapy (RT).
Results: Median follow-up was 6.9 years. We included 2071 of 2155 patients (1 – 21y) enrolled on COG HL trials in the U.S. or Canada between 2002 and 2012. Mean age was 14.6y (±3.5) with 54% ≥15y (N = 1121) and 81% ≥12y (N = 1684). In unadjusted analyses, patients ≥15y had statistically significantly worse EFS than those < 15y (80% vs. 85%, p = 0.02). A difference in EFS was also noted in those ≥12y vs. <12y (81% vs. 87%, p = 0.0503). OS was significantly worse in patients ≥15y (95% v. 98%, p = 0.006), but did not differ in <12y vs. ≥12y (99% v. 97%, p = 0.14). In multivariable models, older age was an independent predictor of EFS in both age categories (Table), and patients <15y had significantly worse OS.
Conclusions: In patients treated for HL with response-based therapy on contemporary COG trials, adolescents ≥12y had worse EFS than younger groups. This suggests that in HL, age ≥12y defines a high risk cohort who may benefit from therapy escalation and/or inclusion in late phase trials of novel agents.