title: 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 (Era 1: 1973-1989, Era 2: 1990-1996, and Era 3: 1997-2006) corresponding to the introduction of multi-agent chemotherapy, risk-based treatment, and stem cell transplant.
  
  
  METHODS
  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 six 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.
authors.affiliation: Departments of Pediatrics, University of Chicago, Chicago, Illinois.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Applebaum
authors.forename: Tara O
authors.initials: TO
authors.lastname: Henderson
authors.forename: Sang Mee
authors.initials: SM
authors.lastname: Lee
authors.forename: Navin
authors.initials: N
authors.lastname: Pinto
authors.forename: Samuel L
authors.initials: SL
authors.lastname: Volchenboum
authors.forename: Susan L
authors.initials: SL
authors.lastname: Cohn
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D009367:Neoplasm Staging; D016609:Neoplasms, Second Primary / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D009447:Neuroblastoma / Q000150:complications* / Q000401:mortality / Q000532:radiotherapy; D011379:Prognosis; D011832:Radiation Injuries / Q000453:epidemiology* / Q000209:etiology / Q000401:mortality; D011878:Radiotherapy / Q000009:adverse effects*; D012307:Risk Factors; D018426:SEER Program; D015996:Survival Rate; D055815:Young Adult
keywords: SEER; late effects; neuroblastoma; second malignancies