Cancer Res Treat.  2024 Apr;56(2):642-651. 10.4143/crt.2023.999.

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

• Lim H
• Im M
• Seo ES
• Cho HW
• Ju HY
• Yoo KH
• Cho SY
• Kim JW
• Lim DH
• Sung KW
• Lee JW

• KMID: 2554353
• DOI: http://doi.org/10.4143/crt.2023.999

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.

Keyword

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

Figure

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  Fig. 1. Overall survival after secondary malignant neoplasm (SMN) development. Survival after an SMN diagnosis differed according to SMN type. Overall survival after SMN was highest in the carcinoma group.

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  Fig. 2. Risk factors of secondary malignant neoplasm (SMN) development. Clinical characteristics, including treatment modalities and diagnosis, were analyzed as risk factors of SMN. The SMN incidence was higher in patients who received radiotherapy (RT) exceeding 2,340 cGy or tandem high-dose chemotherapy (HDCT), or in those with confirmed cancer predisposition syndromes. Among chemotherapeutic (CTx) agents, the use of cyclophosphamide and ifosfamide were risk factors for SMN development.

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  Fig. 3. Cumulative incidences of secondary malignant neoplasm (SMN) according to tumor type. The incidence of SMN was higher in patients with extracranial solid tumors than in those with brain tumors, and the incidences are illustrated according to tumor type. IC-GCT, intracranial germ cell tumor.

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  Fig. 4. Secondary malignant neoplasm (SMN) type according to primary diagnosis. The SMN types were different according to primary tumor type. Carcinoma was the most frequent SMN in brain tumors and neuroblastomas, whereas hematologic malignancy (HM) and sarcoma frequently developed in patients with sarcoma and retinoblastoma, respectively.

Reference

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