Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Research Institute for Future Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Cancer Res Treat. 2022 Jan;54(1):259-268. doi: 10.4143/crt.2021.010. Epub 2021 Apr 12.
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.
The study included 313 patients who received the first cycle chemotherapy with a CEDC (cisplatin+etoposide+doxorubicin+cyclophosphamide) 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.
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.
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.
本研究旨在确定首个化疗周期后中性粒细胞减少的程度是否可作为预测个体对化疗药物敏感性的替代标志物，从而影响神经母细胞瘤患者的治疗结果。
本研究纳入了 313 例接受 CEDC（顺铂+依托泊苷+多柔比星+环磷酰胺）方案化疗且具有绝对中性粒细胞计数（ANC）数据的患者。估计了进展和治疗相关死亡率（TRM）的累积发生率。为了确定与 ANC 相关的遗传变异，进行了全基因组关联研究（GWAS）。
将 ANC 为 32.5/μL 确定为截断值，以将患者分为进展预后良好和预后不良亚组。ANC 低值的患者进展累积发生率高于 ANC 高值的患者（p<0.001）。多变量分析表明，ANC 低值、年龄、骨髓受累和不良组织学是不良预后因素。关于 TRM，ANC 低值（ANC<51.0/μL）的患者 TRM 累积发生率高于 ANC 高值的患者（p=0.010）。在 GWAS 中，LPHN2 和 CRHR1 的单核苷酸多态性与 ANC 低值显著相关。
在神经母细胞瘤患者中，首个化疗周期后中性粒细胞减少的程度可用作预测个体对化疗药物敏感性的替代标志物。需要考虑根据中性粒细胞减少的程度调整治疗方案。
