Treatment Patterns and Intensity Differ between Pediatric and Adult Centers in AYA with Hodgkin's Lymphoma but Result in Equivalent Outcomes: A Population-Based Study Using the IMPACT Cohort
Authors: Gupta Sumit , Baxter Nancy , Pole Jason , Nagamuthu Chenthila , Lau Cindy , Sutradhar Rinku , Nathan Paul 
Published: October 2019

Abstract
Background: Hodgkin's lymphoma (HL) is one of the most common cancers in adolescents and young adults (AYA). Unlike acute lymphoblastic leukemia, few studies have compared AYA HL outcomes between pediatric and adult centers, or pediatric and adult protocols. Recently, a comparison of AYA (17-21 years) treated on a pediatric COG trial vs. an adult ECOG trial demonstrated superior survival in AYA treated on the pediatric trial, but other studies have not demonstrated a treatment center disparity. None of these studies were population-based. We therefore compared treatment patterns, intensity, and outcomes between AYA HL treated at pediatric vs. adult centers using a population-based clinical database.
Methods: The IMPACT Cohort comprises all Ontario, Canada AYA aged 15-21 years diagnosed with one of six common cancers (including HL) between 1992-2012. Detailed demographic, disease, treatment, and outcome data were collected through chart abstraction and validated by content experts. Locus of cancer care (pediatric vs. adult cancer center vs. adult community hospital) was based on where the majority of therapy was delivered in the first three months after diagnosis. Linkage to population-based health administrative data identified additional cancer events (second cancers, relapse, death). The treatment modalities received [radiation vs. chemotherapy vs. combined modality treatment (CMT)] were compared by locus of care, as were cumulative doses of doxorubicin, bleomycin, and radiation. Predictors of CMT (vs. chemotherapy only) were examined using logistic regression. Event-free (EFS) and overall survival (OS) were determined using Kaplan-Meier methods. The impact of locus of care on EFS and OS was determined using multivariable Cox proportional hazard models, adjusting for demographic, disease, and treatment variables. Events included disease progression, relapse, death, and second malignancies.
Results: Among 954 AYA with HL, 711 (74.5%) received therapy at an adult center (adult regional cancer center or community hospital). The proportion of AYA with limited stage disease did not vary between pediatric centers [90/221 (40.7%)] and adult centers [172/456 (37.7%); p=0.45]. While AYA treated at pediatric centers were more likely to receive radiation, radiation doses were higher at both adult cancer centers and adult community hospitals, as were cumulative doses of doxorubicin and bleomycin (Table 1). When adjusted for age, stage, and histology, AYA treated at pediatric centers were significantly more likely to receive CMT rather than chemotherapy alone as compared to AYA at adult cancer centers [odds ratio (OR) 5.0; 95% confidence interval (CI) 3.0-8.4; p<0.0001] or adult community hospitals (OR 3.9, CI 2.2-7.0; p<0.0001). 5-year EFS and OS for the cohort were 83.0%±1.2% and 94.9%±0.7%. 10-year EFS and OS were 81.1%±1.3% and 92.6%±7.4%. In multivariable analyses, CMT was associated with superior EFS as compared to chemotherapy alone [hazard ratio (HR) 0.68; CI 0.50-0.93; p=0.02] but was not significantly associated with OS. Despite the significant differences in treatment modality and treatment intensity between pediatric and adult centers, locus of care was not significantly associated with either EFS or OS in either univariate or multivariable analyses (Table 2).
Conclusions: In this large, population-based cohort, survival outcomes did not differ between AYA treated at pediatric vs. adult centers. However, treatment intensity patterns varied, with AYA treated at a pediatric center more likely to receive radiation (though at lower doses) but exposed to lower cumulative chemotherapy doses. These results imply that acute toxicities and the types and cumulative burden of late effects may differ by locus of care. Given equivalent outcomes, these results also suggest that a proportion of AYA are being over-treated. Future analyses will study these hypotheses.

Disclosures
No relevant conflicts of interest to declare.