Risk Of Solid Subsequent Malignant Neoplasms (SMNs) With Extended Follow-Up Of Childhood Hodgkin Lymphoma (HL) Survivors Is Comparable To The Risk In Known High-Risk Groups Within The General Population: Report From The Late Effects Study Group (LESG)

Background We describe the pattern and incidence of SMNs with 10 additional years of follow-up of an international cohort (Bhatia, N Engl J Med, 1996; Bhatia, J Clin Oncol, 2003) of children with HL diagnosed between 1955 and 1986 at age 16 y or younger. Methods Medical record review was used to identify SMNs, define vital status and describe therapeutic exposures. Pathology reports served to validate SMNs. Cumulative incidence (CI) utilized competing risk methods. Standardized incidence ratio (SIR) and absolute excess risk (AER/10,000 p-y) utilized age-, gender- and year-matched rates in the general population. Cox regression techniques (using calendar time as time scale) identified predictors of SMN risk. Results The cohort included 1023 patients diagnosed with HL at a median age of 11 y, and followed for a median of 26.8 y (IQR, 16.4-33.7). Eighty-nine percent had received radiation, either alone (22%), or in combination with chemotherapy (67%). Alkylating agent (AA) score was defined as follows: 1 AA for 6 m = AA score of 1; 2 AA for 6 m or 1 AA for 12 m = AA score of 2, etc. The AA score was 1-2 for 54% and 3+ for 16%; 30% did not receive AA. A total of 188 solid SMNs developed in 139 patients (breast [54], thyroid [24], lung [11], colorectal [11], bone [8], other malignancies [80]. Table summarizes SIR (95%CI), CI, and AER by attained age. The cohort was at an 11.1-fold increased risk of developing solid SMNs (excluding non-melanoma skin cancers) compared with the general population (95% CI, 9.4-13.0). CI of solid SMNs was 25.2% at 40 y from HL diagnosis (Fig 1). Among patients aged ≥40 y, 79% of total AER was attributable to breast, thyroid, colorectal and lung SMNs (Table). Thirty-seven patients developed >1 solid SMN; the cumulative incidence of the 2nd SMN was 19.6% at 10 years from diagnosis of the 1st SMN. Breast Cancer: Females (n=41) had a 20.9-fold increased risk, and males (n=3) a 45.8-fold increased risk c/w general population. Age at HL of 10-16 y vs. Conclusion In this cohort of HL survivors with 20,344 p-y of follow-up, the greatest excess risk of SMNs among those > 40 y was attributable to breast, thyroid, colorectal and lung SMNs. Observed risks for the most common SMNs were comparable to or greater than known high-risk groups within the general population. Disclosures: No relevant conflicts of interest to declare.