Trends in Utilization of Radiation in the Treatment of Pediatric Hodgkin Lymphoma

Hodgkin’s lymphoma (HL) is a curable form of pediatric cancer. Late effects from treatment are a concern. Radiation therapy (RT) can be associated with toxicity, including secondary malignant neoplasms (SMN). Pediatric protocols have attempted to decrease RT dose or eliminate RT due to toxicity. Here we evaluate characteristics associated with utilization of RT for pediatric HL, their effects on outcomes and development of SMN. The SEER database was queried for patients diagnosed with HL at ages 0-19 years from 1973-2012. Patient factors were assessed in regards to utilization of RT. Cause specific (CSS) and overall survival (OS) were calculated. Observed-to-expected ratios (O/E) were calculated for secondary tumor sites, comparing the development of cancer to incidence rates for the general population. P<0.05 was used to determine significance. 6572 patients were identified. 83.8% of patients were white, 52.4% male, and 54.7% of patients received RT. Use of RT decreased by decade from 71.5% between 1973 and 1979, 62.7% in the 1980s, 52.1% in the 1990s, to 49.9% in patients treated after 2010. The lowest yearly rate was 39.1% in 2012. RT use increased with age; 35% for those under 4, 50.3% from 5-9 years, 55.5% for those 10-19 years. No difference existed in RT use by sex (males 55.2% vs females 54.2%). Black patients (49.3%) were less likely to receive RT compared to whites (52.9%) and others (52.2%). 90% of patients were from metropolitan areas, with no difference in delivery of RT in metropolitan areas (54.8%) vs nonmetropolitan areas (54.4%). 332 SMNs (O/E 5.87) occurred. RT patients developed 240 SMNs (O/E 6.50) compared with 81 SMNs (O/E 4.81) in patients without RT (P<0.05). RT patients had higher rates of salivary gland, digestive, respiratory, soft tissue, breast, and hematologic cancers compared to patients not receiving RT. Females were at higher risk for all SMNs and solid tumors. For the entire cohort, 10 year CSS and OS were significantly improved for those treated with RT (92.7%, 90.6%) compared to those who did not receive RT (90%, 87.3%). By decade, CSS and OS were significantly improved in RT patients in the 1970s and 1980s. OS and CSS were also improved in the RT cohort in the 1990s and 2000s, though not significantly. Six hundred thirteen patients died from cancer, including 451 from HL and 162 from SMNs. The next leading cause of death was diseases of the heart (76). Use of radiation therapy for pediatric Hodgkin’s lymphoma has decreased over time. A benefit to CSS and OS for patients treated with radiation is present regardless of decade of diagnosis. Improved chemotherapy and increased OS in HL has diminished this relative difference to the point it is no longer significant. SMN is the second leading cause of mortality in this cohort and is more common in females treated with RT.