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Secondary malignant neoplasms after osteosarcoma: early onset and cumulative alkylating agent dose dependency

 Seung Hyun Kim  ;  Kyoo-Ho Shin  ;  Sang Ok Seok  ;  Yong Jin Cho  ;  Jae Kyoung Noh  ;  Jin-Suck Suh  ;  Woo-Ick Yang 
 Annals of Surgical Oncology, Vol.22(3) : 859-865, 2015 
Journal Title
 Annals of Surgical Oncology 
Issue Date
PURPOSE: To analyze the impacts of chemotherapeutic agent exposures on the development of secondary malignant neoplasms (SMP) after osteosarcoma. METHODS: Of 132 patients who had been treated for high-grade extremity osteosarcoma from September 1992 to September 2008, 90 survivors were retrospectively reviewed. Fifty-eight of the survivors received a doublet of doxorubicin (ADR) and cisplatin (DDP), and 32 received a triplet of ADR, DDP, and ifosfamide (Ifos). On the basis of the dose distributions in the study cohort, the association between SMN and the cumulative dose of each agent was evaluated. RESULTS: After a mean of 13.1 years of follow-up, six SMNs were noted, three in each regimen. There were no SMNs among 42 patients who died of osteosarcoma. In Kaplan-Meier estimates, the triplet regimen group showed a higher cumulative incidence and shorter latency for SMNs than the doublet group (log rank P = 0.032). Fifteen years' cumulative incidence of SMNs in the triplet and doublet regimen group was 9.4 and 3.8%, respectively. In the independent t test, the mean latency to SMN in the triplet group (3.7 ± 1.3 years) was shorter than that in the double group (13.1 ± 2.8 years) (P = 0.017). In Cox regression, the alkylating agent score (AAS) [hazard ratio (HR) = 2.459, P = 0.015] and DDP (HR = 1.779, P = 0.046) showed a significant relationship with SMNs, whereas ADR (HR = 0.896, P = 0.664) and Ifos (HR = 3.694, P = 0.119) did not. AAS was also significant after adjusting for ADR and DDP (HR = 3.319, P = 0.020). CONCLUSIONS: High cumulative AAS is an independent risk factor for SMN and its early-onset development after osteosarcoma.
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1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
김승현(Kim, Seung Hyun)
노재경(Roh, Jae Kyung)
서진석(Suh, Jin Suck) ORCID logo https://orcid.org/0000-0001-9455-9240
신규호(Shin, Kyoo Ho)
양우익(Yang, Woo Ick) ORCID logo https://orcid.org/0000-0002-6084-5019
조용진(Cho, Yong Jin)
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