Patterns of Care and Outcomes of Early Stage I-II Hodgkin Lymphoma Treated with or without Radiation Therapy

Purpose: To evaluate trends in radiation therapy utilization in early-stage classic Hodgkin Lymphoma (cHL) and analyze the impact on overall survival (OS).

Methodology: The National Cancer Database (NCDB) was queried to identify all patients between the ages of 18-60 diagnosed with Stage IA-IIB cHL between 2004 and 2017 and treated with multiagent chemotherapy only or chemotherapy and radiation therapy (combined modality therapy, CMT). Clinical characteristics and demographics were identified; differences were evaluated using T and χ2 testing. Predictors of receipt of radiotherapy were identified using univariable and multivariable logistic regression. Overall survival (OS) was calculated using a Kaplan-Meier estimator, before and after adjustment with inverse probability of treatment weighting. Stepwise Cox proportional hazards modeling was used to identify covariates associated with increased risk of death.

Results: We identified 23,103 early-stage cHL patients between 2004 and 2017, during which RT utilization decreased from 63% to 39%. Patients received either chemotherapy only (n=11,907) or CMT (n=11,196). On multivariable analysis (MVA), patients were less likely to receive CMT if they were stage IB, IIA or IIB compared to IA (OR 0.75, 0.71, 0.56, respectively, all p< 0.001), diagnosed after 2008 (OR 0.85, p=0.01), age < 40 (OR 0.91, p< 0.03), Black race compared to White (OR 0.76, p< 0.001), had Medicare or no insurance (OR 0.74 and 0.62, respectively, p< 0.001), resided >50 miles from treatment facility (OR 0.72, p< 0.001), lived in the US South compared to Northeast (OR 0.86, p=0.04), or had lymphocyte-depleted cHL compared to nodular sclerosing cHL (0.36, p< 0.001). Patients were more likely to receive CMT if they had lymphocyte-rich (OR 1.3, p=0.02), lived in the US Midwest (OR 1.2, p=0.02) or West (OR 1.2, p=0.01). With a median follow-up of 6.0 years, the 5-year OS for CMT versus chemotherapy only were 97.0% and 93.2%, respectively (p < 0.001), with 10-year OS of 93.5% and 88.4%, respectively (p < 0.001); this difference remained significant after cohort balancing. Factors associated with increased risk for death on MVA included treatment with chemotherapy only vs CMT (OR 2.1, p< 0.001), lymphocyte-depleted histology (OR 2.5, p< 0.001), Charlson comorbidity index score of 1+ (OR 1.6, p< 0.001) and Medicaid (OR 1.7, p< 0.001), Medicare (OR 2.9, p< 0.001) or no insurance (OR 1.8, p< 0.001) compared to private insurance. Annual income >$63,000 was associated with decreased risk of death (OR 0.55, p< 0.001).

Conclusions: CMT with the inclusion of radiation therapy is associated with improved OS compared to chemotherapy alone in early stage cHL. Concerningly, RT utilization decreased precipitously during the study period, particularly among at-risk patient groups including Black race, uninsured or of lower socioeconomic status. Further evaluation is warranted to identify factors underlying disparities in RT receipt.

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