Age, Gender and Temporal Trends in Solid Tumor As Second Primary Malignancy Risk after De Novo Myelodysplastic Syndrome: A SEER Database Analysis

Introduction: Myelodysplastic syndromes (MDS), a group of blood disorders characterized by abnormal development of blood cells, are associated with an increased risk of second primary malignancy (SPM), primarily secondary hematological malignancy. Various studies have also established an increased incidence of secondary solid tumors after de novo MDS, a term used to describe MDS that occurs without a known cause. In this population-based cohort study, we aim to understand the influence of age, temporal trends, and gender on solid tumor SPM development in patients with de novo MDS.

Methods: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 17 database registry, a comprehensive source of cancer incidence and survival data in the United States, we identified a cohort of patients diagnosed with de novo MDS (Site and Morphology Site recode ICD-O-3 2023 Revision Expanded) between 2000 and 2021. We analyzed the incidence of solid tumor SPM using SEER*Stat Multiple Primary- Standardized Incidence Ratio (MP-SIR) session stratified by age group at MDS diagnosis (<60, 60-69, >70), gender (male, female) and year of diagnosis of MDS (2000-2005, 2006-2010, 2011-2015 and 2016-2020). Standardized incidence ratios (SIRs) were calculated to compare observed and expected development rates of solid tumor SPM development.

Results: Among 52,686 de novo MDS patients, 7,423 patients developed SPM. Of 7,423 patients, 3,272 patients developed solid tumors as SPM. There is a significant difference in the overall risk of these solid tumor SPMs among MDS patients compared with the United States general population (SIR: 1.05, 95 % CI [1.01-1.09]). SIRs for these solid tumor SPMs decreased with increasing age of MDS diagnosis (SIRs: <60 years: 1.39, 95% CI [1.25-1.53]; 60-69 years: 1.12, 95% CI [1.04-1.20]; ≥70 years: 0.98, 95% CI [0.94-1.03]). A modest increase in these solid tumor SPMs SIRs was observed over time, with the highest rates in the most recent diagnostic period (SIRs: 2000-2005: 0.95, 95% CI [0.88-1.10]; 2006-2010: 1.02, 95% CI [0.96-1.08]; 2011-2015: 1.12, 95% CI [1.05-1.2]; 2016-2020: 1.16, 95% CI [1.06-1.27]). A slightly higher SIR of these solid tumor SPMs was seen in females compared to males (SIRs: male: 1.04, 95% CI [1.00-1.09]; female: 1.06, 95% CI [1.01-1.12]).

Conclusion: Our study found that younger age at MDS diagnosis, female gender, and more recent diagnosis year is associated with a greater incidence of solid tumor SPM in patients with de novo MDS. These insights can inspire the development of personalized surveillance protocols, facilitating early detection and intervention for SPM. There is a need for further research to understand the underlying mechanism for up-trending SIR for secondary solid tumors SPM in patients with de novo MDS.

No relevant conflicts of interest to declare.