Tandem High-Dose Chemotherapy Increases the Risk of Secondary Malignant Neoplasm in Pediatric Solid Tumors

Cancer Res Treat. 2024 Apr;56(2):642-651. doi: 10.4143/crt.2023.999. Epub 2023 Nov 24.

Abstract

Purpose: This study aimed to investigate the incidence and risk factors for secondary malignant neoplasms (SMN) in pediatric solid tumors, focusing on the effects of tandem high-dose chemotherapy (HDCT).

Materials and methods: Patients (aged < 19 years) diagnosed with or treated for pediatric solid tumors between 1994 and 2014 were retrospectively analyzed. The cumulative incidence of SMN was estimated using competing risk methods by considering death as a competing risk.

Results: A total of 1,435 patients (413 with brain tumors and 1,022 with extracranial solid tumors) were enrolled. Seventy-one patients developed 74 SMNs, with a 10-year and 20-year cumulative incidence of 2.680±0.002% and 10.193±0.024%, respectively. The types of SMN included carcinoma in 28 (37.8%), sarcoma in 24 (32.4%), and hematologic malignancy in 15 (20.3%) cases. Osteosarcoma and thyroid carcinoma were the most frequently diagnosed tumors. Multivariate analysis showed that radiotherapy (RT) > 2, 340 cGy, and tandem HDCT were significant risk factors for SMN development. The SMN types varied according to the primary tumor type; carcinoma was the most frequent SMN in brain tumors and neuroblastoma, whereas hematologic malignancy and sarcomas developed more frequently in patients with sarcoma and retinoblastoma, respectively.

Conclusion: The cumulative incidence of SMN in pediatric patients with solid tumors was considerably high, especially in patients who underwent tandem HDCT or in those who received RT > 2,340 cGy. Therefore, the treatment intensity should be optimized based on individual risk assessment and the long-term follow-up of pediatric cancer survivors.

Keywords: High-dose chemotherapy; Pediatric solid tumor; Radiation; Secondary malignant neoplasms.

MeSH terms

  • Bone Neoplasms*
  • Brain Neoplasms*
  • Carcinoma* / complications
  • Child
  • Hematologic Neoplasms* / complications
  • Humans
  • Incidence
  • Neoplasms, Second Primary* / diagnosis
  • Neoplasms, Second Primary* / epidemiology
  • Neoplasms, Second Primary* / etiology
  • Neuroblastoma*
  • Retrospective Studies
  • Risk Factors
  • Sarcoma* / drug therapy
  • Sarcoma* / epidemiology
  • Sarcoma* / etiology