Incidence, risk factors, and survival of secondary primary CNS tumors following hematologic malignancies: A population-based SEER study (2000-2022).

Abstract

e19047 Background: Survivors of hematologic malignancies face an increased risk of secondary cancers, but the incidence and outcomes of primary central nervous system (CNS) tumors following hematologic malignancies remain poorly defined. Methods: Using the SEER 17 registries (2000–2022), we identified 830,018 patients with a first primary hematologic malignancy. Of these, 813 (0.1%) subsequently developed a primary CNS tumor. For comparison, a cohort of 122,270 patients with a first primary CNS tumor and no prior malignancy was constructed. We evaluated demographics, incidence, survival, temporal trends, and risk stratification by clinical and demographic factors. Standardized incidence ratios (SIRs) were calculated to compare secondary CNS tumor risk against the general population. Results: Patients with secondary CNS tumors were older at hematologic diagnosis, more frequently male (64%) and White (90%), and most commonly presented with nodal NHL (31%) or CLL (19%). Their CNS tumors predominantly arose in the brain (95%), with a median latency of 4.5 years, peaking within the first 5 years. Survival after secondary CNS tumor diagnosis was extremely poor (median OS: 6 months; 85% mortality). Even after adjustment for age, sex, race, and income, secondary CNS tumors conferred the worst overall survival, though cancer-specific survival was paradoxically higher than for primary CNS tumors without prior malignancy. The risk of secondary CNS tumors was significantly elevated compared with the general population (SIR = 1.17), rising sharply over time and peaking in 2022 (SIR = 8.57). Risk was highest among Asian/Pacific Islanders (SIR = 3.98), Black patients (SIR = 1.47), females (SIR = 1.55), adolescents (ages 15–19, SIR = 4.32), and those diagnosed within the first year after hematologic malignancy (SIR = 4.29). Extranodal NHL (SIR = 3.96) and acute lymphocytic leukemia carried the strongest associations, whereas Hodgkin lymphoma, CLL, and myeloma were associated with reduced risk. Radiation (SIR = 2.22) and chemotherapy (SIR = 1.36) significantly amplified risk. Anatomically, excess risks were profound for brain regions including cerebrum (SIR = 136.88), frontal (SIR = 105.51), temporal (SIR = 121.32), and parietal lobes (SIR = 102.05), with overlapping brain lesions (SIR = 208.76) showing the highest excess. Conclusions: Survivors of hematologic malignancies, particularly those with extranodal NHL, ALL, or prior radiation/chemotherapy, are at significantly elevated risk for aggressive secondary CNS tumors with dismal survival outcomes. These findings highlight the need for heightened surveillance, risk-adapted follow-up, and future studies on prevention and early detection strategies in this vulnerable population.