Second malignancies in patients with neuroblastoma: The effects of risk‐based therapy

Abstract

Background To investigate the incidence of second malignant neoplasms (SMN) for patients with neuroblastoma, we analyzed patients from the SEER database according to three treatment eras (1: 1973–1989, 2: 1990–1996, 3: 1997–2006) corresponding to the introduction of multi-agent chemotherapy, risk-based treatment, and stem cell transplant. Procedure The SEER database was mined for all patients with neuroblastoma or ganglioneuroblastoma. Cumulative incidence of SMN was calculated with death as a competing risk. A poisson regression model was used to estimate incidence rate ratios and 95% confidence intervals to compare the rates of SMN between patients in different Eras. Results The analytic cohort included 2,801 patients. Thirty-four patients developed a SMN, accounting for 1.2% of all patients. Of the patients who developed a SMN, 47.1% received radiation for their primary neuroblastoma. Fourteen of the SMN were carcinomas, and 10 were hematologic malignancies, with 6 cases of acute myelogenous leukemia. There was no difference in the incidence of SMN in Era 1 compared to Era 3 (p=0.48). The cumulative incidence of SMN at 30 years for high-risk patients was 10.44% (95% CI 3.98–20.52%) compared to 3.57% (95% CI 1.87–6.12%) for non-high-risk patients (p<0.001). Conclusions This study showed no increase in the incidence of SMNs for children treated in the most recent treatment era as compared to earlier Eras. However, as the risk for developing SMN does not plateau, the number of SMNs will likely continue to rise in the cohort of patients treated after 1996. Comprehensive follow-up care for these survivors will be important.

Neuroblastoma survivors are at increased risk for second malignancies: A report from the International Neuroblastoma Risk Group Project

“…Additionally, we demonstrate for the first time a markedly high prevalence of secondary AML in high- and intermediate-risk survivors within five years from their initial diagnosis of neuroblastoma, with SIRs of 106.8 and 127.7. The higher incidence of SMN in high-risk patients compared to intermediate- or low-risk patients was an expected finding and supports previous studies [6]. However, the high rate of AML observed in the intermediate-risk cohort of patients, who receive relatively low doses of alkylating agents and topoisomerase inhibitors, is surprising.…”

Overview and recent advances in the treatment of neuroblastoma

“…The types of second malignancies experienced by patients after therapy for high-risk neuroblastoma are broad, with the most common diagnoses including renal cell carcinoma, thyroid carcinoma, acute myeloid leukemia, sarcomas, and lymphoma. Hematologic malignancies tend to develop more rapidly than solid tumors after completion of neuroblastoma treatment [170]. Despite these risks, recurrence of disease still remains more likely than secondary malignancies, particularly in cases of high-risk neuroblastoma.…”

“…Between 2% and 7% of neuroblastoma survivors develop a second malignancy as a result of their therapy, with a cumulative 30-year incidence for high-risk patients of approximately 10% [170][171][172]. High-risk therapy, in particular, contains several known risk factors for secondary malignancies, including alkylating agents, topoisomerase II inhibitors, platinum compounds, and radiotherapy.…”

Genetic discoveries and treatment advances in neuroblastoma

“…However, outcome remains poor for patients classified as high-risk, with <50% achieving long-term survival. 1 High-risk survivors are at risk for significant treatment-related adverse events including subsequent malignancies, 2 emphasizing the critical need for more effective, less toxic treatments. In this review, we discuss recent progress in our understanding of the molecular underpinnings of the etiology and pathobiology of neuroblastoma.…”