Intrapatient 16α-[18F]Fluoro-17β-Estradiol PET Heterogeneity as a Prognostic Factor for Endocrine Therapy Response and Survival in Patients with Estrogen Receptor–Positive Metastatic Breast Cancer

Jasper J.L. van Geel, Jasmine Moustaquim, Jorianne Boers, Sjoerd G. Elias, Esther M.M. Smeets, Jelijn J. Knip, Andor W.J.M. Glaudemans, Erik F.J. de Vries, Geke A.P. Hospers, Michel van Kruchten, Marcel Stokkel, Daniela E. Oprea-Lager, Willemien C. Menke-van der Houven van Oordt, Elisabeth G.E. de Vries, Carolina P. Schröder
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Abstract

Intrapatient heterogeneity of estrogen receptor (ER) expression on 16α-[18F]fluoro-17β-estradiol ([18F]FES) PET is related to outcome in patients with ER-positive metastatic breast cancer (MBC), but a validated and practical method to support clinical decision-making is lacking. Therefore, the [18F]FES PET heterogeneity score (i.e., percentage of [18F]FES-positive metastases) was validated as a prognostic factor for endocrine therapy response and survival in a large cohort of patients with newly diagnosed MBC. Furthermore, we explored 2 less laborious methods to predict the [18F]FES PET heterogeneity score. Methods: Patients with ER-positive MBC included in the IMPACT-MBC study, who received baseline [18F]FES and [18F]FDG PET and first-line endocrine therapy, were included in this subanalysis. ER homogeneous (100% [18F]FES-positive lesions) and ER heterogeneous (both [18F]FES-positive and [18F]FES-negative lesions) MBC was distinguished by manual segmentation of all lesions on [18F]FES PET and related to progression-free survival (PFS) and overall survival (OS). In addition, the positive predictive value of the visual assessment and the 5-largest-lesions assessment to predict homogeneous MBC in all lesions on [18F]FES PET was determined. Results: From the 102 MBC patients eligible for the present retrospective subanalysis, 46 had ER homogeneous MBC and 56 had ER heterogeneous MBC. Differences were found between ER homogeneous and ER heterogeneous MBC for median PFS (19.8 vs. 15.0 mo; hazard ratio, 0.63; 95% CI, 0.41–0.96; P = 0.03) and median OS (62.5 vs. 34.7 mo; hazard ratio, 0.65; 95% CI, 0.38–1.08; P = 0.09). Twenty-one (38%) of 61 patients with ER homogeneous MBC by visual analysis and 37 (45%) of 83 patients with ER homogeneous MBC by the 5-largest-lesions method had ER heterogeneous MBC by manual segmentation of all lesions on [18F]FES PET (positive predictive value, 0.66 and 0.55, respectively). Conclusion: Patients with ER-positive homogeneous MBC showed a trend toward superior PFS and OS compared with patients with ER heterogeneous MBC. This analysis confirmed and validated the prognostic value of the [18F]FES PET heterogeneity score for endocrine therapy response and survival in a large cohort of MBC patients. The less laborious visual and 5-largest-lesions methods were inferior compared with assessment based on the [18F]FES PET heterogeneity score in all lesions.

16α-[18F]氟-17β-雌二醇PET异质性是雌激素受体阳性转移性乳腺癌患者内分泌治疗反应和生存的预后因素
16α-[18F]氟-17β-雌二醇([18F]FES) PET上雌激素受体(ER)表达的患者内部异质性与ER阳性转移性乳腺癌(MBC)患者的预后有关,但缺乏一种有效且实用的方法来支持临床决策。因此,在一大批新诊断的MBC患者中,[18F]FES PET异质性评分(即[18F]FES阳性转移灶的百分比)被证实是内分泌治疗反应和生存的预后因素。此外,我们还探索了两种不太费力的方法来预测[18F]FES PET异质性评分。方法:纳入IMPACT-MBC研究的er阳性MBC患者,接受基线[18F]FES和[18F]FDG PET和一线内分泌治疗,纳入本亚分析。ER均质性(100% [18F]FES阳性病变)和ER异质性([18F]FES阳性和[18F]FES阴性病变)MBC通过对[18F]FES PET上所有病变的人工分割来区分,并与无进展生存期(PFS)和总生存期(OS)相关。此外,我们还确定了[18F]FES PET上所有病变的视觉评估和5个最大病变评估预测均质性MBC的阳性预测值。结果:在102例符合回顾性亚分析的MBC患者中,46例为ER均质MBC, 56例为ER异质MBC。ER同质和ER异质MBC在中位PFS方面存在差异(19.8 vs 15.0月;风险比0.63;95% ci, 0.41-0.96;P = 0.03)和中位OS (62.5 vs. 34.7个月;风险比0.65;95% ci, 0.38-1.08;P = 0.09)。61例目视分析ER均质性MBC患者中有21例(38%),83例5大病灶法ER均质性MBC患者中有37例(45%)在[18F]FES PET上对所有病灶进行人工分割后发现ER均质性MBC(阳性预测值分别为0.66和0.55)。结论:与ER异质性MBC患者相比,ER阳性的同质MBC患者有更高的PFS和OS的趋势。该分析证实并验证了[18F]FES PET异质性评分在一大批MBC患者中对内分泌治疗反应和生存的预后价值。与基于[18F]FES PET异质性评分的所有病变评估相比,省力的目视法和5大病变法的评估效果较差。
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