Beyond Classical Hodgkin Lymphoma: Long-Term Risks and Secondary Cancers-Insights from the Texas Cancer Registry
Authors: Hassanain Hala , Burns Ethan A , Mathur Sunil , Choksi Darshil , Gentille Sanchez Cesar Giancarlo , Hu Chih-Chi Andrew , Hanh Mai , Yuen Carrie , Shah Shilpan S. , Ganguly Siddhartha , Pingali Sai Ravi Kiran 
Published: December 2024

Objectives:
Classical Hodgkin lymphoma (cHL) is a highly curable cancer, but outcomes remain poorer for older patients despite advances in novel therapies. Moreover, patients cured often die from other causes as opposed to their primary disease. However, less is known about non-cHL mortality events in the older patient population diagnosed with cHL, which comprises 20% of the cHL population. Identifying non-cHL causes of death may further improve long-term outcomes in older patients with cHL. The objective of this study is to examine secondary causes of death in cHL patients, through utilization of the Texas Cancer Registry (TCR)1.
Methods:
Patients ≥65 years with cHL and available follow-up data were collected from the TCR from 1995-2017 and analyzed. Patients were divided into the following eras: 1995-2002, 2003-2010, and 2011-2017. Specific mortality rates and non-cHL causes of death were recorded and classified as second cancers, cardiovascular events, neurologic events, and “others”. Likelihood ratios and cox-proportional hazard models with 95% confidence intervals (CI) were used to compare covariates. Overall survival (OS) and was assessed using Kaplan-Meier methodology and p-values&lt;0.05 were considered statistically significant.
Results:
There were 1,033 patients included: 386 (37.4%) in 1995-2002, 336 (32.5%) in 2003-2010, and 311 (30.1%) in 2011-2017, with a median age of 74 (65-97) years. There were 835 (80.8%) deaths, of which 420 (50.3%) were not attributed to cHL. Of these, there were 113 (26.4%) cardiac causes, with the most common cause being coronary artery disease (27.0%). There was a total of 67 (15.9%) second cancers; of second cancers, there were 9 (13.4%) hematologic cancers and 58 (86.5%) solid organ cancers. The most common solid cancer were lung cancer (40%), colon cancer (19.0%), and prostate cancer (10.0%). The 3rd most common cause of non-cHL deaths were neurologic with 60 (14.3%) events, of which 45% were attributed to stroke. “Other” deaths included 46 (24.5%) respiratory events and 34 (18.4%) infections. Median time to reported death event was six months (95% CI 4.87, 7.13) for cHL, 34 months (95% CI 16.53, 51.47) for cardiovascular events, 58 (95% CI 51.13, 64.88) months for second cancers, and 96 months (95% CI 63.24, 128.76) for neurologic events (p&lt;0.001). Chemotherapy and radiation therapies did not impact the risk of cardiovascular mortality (HR 1.04 [95% CI 0.85, 1.23], p=0.685) or second cancers (HR 1.07 [95% CI 0.83, 1.38], 95% CI 0.60], p=0.60), respectively.
Conclusion:
In older patients, a high proportion of deaths following cHL treatment are non-cHL related, with 15.9% second cancers. The application of chemotherapy and radiation did not impact the risk of non-cHL death. Close clinical monitoring even after successful treatment of cHL is needed to identify early predictors of cardiovascular and neurologic events, and to identify second malignancies.
References:
1.Cancer incidence data have been provided by the Texas Cancer Registry, Cancer Epidemiology and Surveillance Branch, Texas Department of State Health Services, 1100 West 49th Street, Austin, TX 78756, https://www.dshs.texas.gov/tcr/.