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Cancer Research and Treatment > Accepted Articles
doi: https://doi.org/10.4143/crt.2021.010    [Accepted]
Absolute Neutrophil Count after the First Chemotherapy Cycle as a Surrogate Marker for Treatment Outcomes in Patients with Neuroblastoma
Ji Won Lee1, Joon Seol Bae2, Jin Ho Kim3, Hee Won Cho1, Hee Young Ju1, Keon Hee Yoo1, Hong Hoe Koo4, Sook-young Woo4, Seonwoo Kim4, Ki Woong Sung1
1Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
2Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
3Clinical Precision Medicine Center, Seoul National University Bundang Hospital, Seongnam, Korea
4Statistics and Data Center, Research Institute for Future Medicine, Samsung Medical Center, Seoul, Korea
Correspondence  Ki Woong Sung ,Tel: 82-2-3410-3529, Fax: 82-2-3410-0043, Email: kwsped@skku.edu
Received: January 4, 2021;  Accepted: April 8, 2021.  Published online: April 12, 2021.
*Ji Won Lee and Joon Seol Bae contributed equally to this work.
ABSTRACT
Purpose
We performed this study to determine whether the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker of individual susceptibility to chemotherapeutic agents affecting treatment outcome in patients with neuroblastoma.
Materials and Methods
The study included 313 patients who received the first cycle chemotherapy with a CEDC regimen and had absolute neutrophil count (ANC) data available. The cumulative incidences of progression and treatment-related mortality (TRM) were estimated. To identify genetic variations associated with the ANC, a genome-wide association study (GWAS) was performed.
Results
An ANC of 32.5/µL was determined as the cutoff point to categorize patients into the good and poor prognosis subgroups in terms of progression. Patients with a high nadir ANC had a higher cumulative incidence of progression than those with a low nadir ANC (p < 0.001). In multivariate analysis, high nadir ANC, age, bone marrow involvement, and unfavorable histology were poor prognostic factors. With regard to the TRM, patients with a low nadir ANC (ANC < 51.0/µL) had a higher cumulative incidence of TRM than those with a high nadir ANC (p=0.010). In GWAS, single-nucleotide polymorphisms of LPHN2 and CRHR1 were significantly associated with the nadir ANC.
Conclusion
In neuroblastoma patients, the degree of neutropenia after the first chemotherapy cycle can be used as a surrogate marker to predict an individual’s susceptibility to chemotherapeutic agents. Tailoring of treatment based on the degree of neutropenia needs to be considered.
Key words: Neuroblastoma, Neutropenia, Treatment outcome, Germline, Genome-wide association study
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