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根据发热性中性粒细胞减少的风险来选择患者进行培非格司亭的一级预防性使用是否合适?

Is it appropriate to select patients for primary prophylactic use of pegfilgrastim based on the risk of febrile neutropenia?

作者信息

Narui Kazutaka, Ishikawa Takashi, Takashima Ikumi, Kashiwabara Kosuke, Uemura Yukari, Kikawa Yuichiro, Taira Naruto, Mukai Hirofumi

机构信息

Department of Breast and Thyroid Surgery, Yokohama City University Medical Center, 4-57 Urafune-Cho, Minami-Ku, Yokohama, Kanagawa, 232-0024, Japan.

Department of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan.

出版信息

Support Care Cancer. 2025 May 7;33(6):456. doi: 10.1007/s00520-025-09514-6.

Abstract

BACKGROUND

Febrile neutropenia (FN), a major hematologic adverse event in perioperative chemotherapy for breast cancer, is more prevalent among Asian populations than Caucasians. Hematopoietic growth factor guidelines recommend pegfilgrastim for primary prophylaxis based on chemotherapy regimen and patient risk factors. We verified the appropriateness of these guidelines for patient selection.

METHODS

The CSPOR-BC FN study, a prospective multicenter study conducted in Japan from 2015 to 2017, included 477 patients surveyed for FN (≥ 37.5 ℃ and grade 4 neutropenia). Cutoff values for age and pre-treatment neutrophil count as risk factors were determined.

RESULTS

The incidence of FN was 28.7% (N = 137). The regimen (TC), age (≥ 65), low pre-treatment neutrophil count, and no primary prophylaxis with pegfilgrastim were significant FN risk factors. Logistic regression determined age ≥ 65 as a significant risk factor (odds ratio, OR = 2.24; 95% confidence interval, CI: 1.34-3.75). However, sensitivity, specificity, and area under the curve (AUC) of receiver operating characteristic (ROC) curve for FN cutoff at 65 were 28.4%, 83.8%, and 0.5195, respectively, indicating low discriminative ability. Similarly, pre-treatment neutrophil count at 1000/μl remained a risk factor (OR = 0.8, 95% CI: 0.67-0.95), even with the ROC-optimized cutoff of 2436/μl. The sensitivity, specificity, and AUC were 27.6%, 83.8%, and 0.5561, respectively, indicating a limited ability to differentiate.

CONCLUSION

These results indicate that the current approach to select patients for primary prophylactic use of pegfilgrastim by evaluating existing FN risk factors may not be appropriate for individual patient assessment.

摘要

背景

发热性中性粒细胞减少症(FN)是乳腺癌围手术期化疗中的一种主要血液学不良事件,在亚洲人群中比高加索人群更为普遍。造血生长因子指南根据化疗方案和患者风险因素推荐聚乙二醇化重组人粒细胞刺激因子用于一级预防。我们验证了这些指南在患者选择方面的适用性。

方法

CSPOR-BC FN研究是一项于2015年至2017年在日本进行的前瞻性多中心研究,纳入了477名接受FN调查的患者(体温≥37.5℃且中性粒细胞减少4级)。确定了作为风险因素的年龄和治疗前中性粒细胞计数的临界值。

结果

FN的发生率为28.7%(N = 137)。化疗方案(TC)、年龄(≥65岁)、治疗前中性粒细胞计数低以及未使用聚乙二醇化重组人粒细胞刺激因子进行一级预防是FN的显著风险因素。逻辑回归确定年龄≥65岁是一个显著风险因素(优势比,OR = 2.24;95%置信区间,CI:1.34 - 3.75)。然而,以65岁为FN临界值的受试者工作特征(ROC)曲线的敏感性、特异性和曲线下面积(AUC)分别为28.4%、83.8%和0.5195,表明判别能力较低。同样,即使将ROC优化后的临界值设为2436/μl,治疗前中性粒细胞计数为1000/μl仍是一个风险因素(OR = 0.8,95% CI:0.67 - 0.95)。其敏感性、特异性和AUC分别为27.6%、83.8%和0.5561,表明区分能力有限。

结论

这些结果表明,目前通过评估现有FN风险因素来选择患者进行聚乙二醇化重组人粒细胞刺激因子一级预防的方法可能不适用于个体患者评估。

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