Changes in the incidence of second malignant neoplasms in neuroblastoma over time: An updated SEER database analysis.

Abstract

10040 Background: To investigate changes in the incidence of second malignant neoplasms (SMN) for patients with neuroblastoma in the era of anti-GD2 immunotherapy, we analyzed patients from the SEER database according to four treatment eras (1: 1975–1989, 2: 1990–1996, 3: 1997–2010, 4: 2011–2018) corresponding to the introduction of multi-agent chemotherapy, risk-based treatment, stem cell transplant, and GD2-directed immunotherapy. We hypothesized that while the GD2-directed immunotherapy would not increase the incidence of SMNs for patients with neuroblastoma, the standardization of tandem autologous transplant would. Methods: The SEER database was assessed for patients younger than 30 years of age with neuroblastoma (ICD-O-3 9500) or ganglioneuroblastoma (ICD-O-3 9490). Patient demographic information and characteristics were assessed, including age at diagnosis, sex, race, histology, year of diagnosis, and extent of disease. Data about delivery of chemotherapy or radiotherapy were collected when available. Statistics including the cumulative incidence of SMN, standardized incidence ratios (SIRs), and rates of SMNs between patients in different eras were calculated. Results: The analytic cohort included 4,491 patients. Eighty-four patients (1.9%) developed a SMN with a median latency of 10 years. The SIR of all SMNs was 5.5 (95% CI 4.4-9.0). The majority of SMNs were hematologic (n=23; SIR 18.5, 95% CI 11.7-87.0), followed by kidney cancer (n=14; SIR 28, 95% CI 15.2-309.1) and thyroid cancer (n=12; SIR 11.2, 95% CI 5.8-58.6). Patients who developed a SMN were more likely to have received radiation than those who did not (39.3% versus 24.7%; p=0.002). There was no significant difference in median age, sex, race, or ethnicity between patients who did or did not develop a SMN. The cumulative incidence of SMN at 30 years from diagnosis for high-risk patients was 4.1% (95% CI 2.63-5.56) compared to 1.6% (95% CI 1.07-2.12) in non-high-risk patients. There was a trend toward increasing SIRs over time; in Era 1: the SIR was 3.4, with a 95% CI 2.2-7.0; in Era 2: the SIR was 3.2, with a 95% CI 1.4-9.9; in Era 3: the SIR was 8.7, with a 95% CI 6.3-20.3; and in Era 4: 9.2, 95% CI 4.8-42.1. Conclusions: High-risk neuroblastoma patients continue to suffer from high rates of SMNs compared to non-high risk neuroblastoma patients in the current era of GD2-directed immunotherapy. Using standardized incidence ratios, there is a trend toward increasing rates of SMNs in our cohort compared to the general population. This increase may be due to the continued addition of cytotoxic therapy. Ongoing monitoring and research into treatment-associated toxicities is needed for neuroblastoma survivors in the modern era of therapy.