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从骨转移灶获取去势抵抗性前列腺癌组织用于分子分析

Castration-Resistant Prostate Cancer Tissue Acquisition From Bone Metastases for Molecular Analyses.

作者信息

Lorente David, Omlin Aurelius, Zafeiriou Zafeiris, Nava-Rodrigues Daniel, Pérez-López Raquel, Pezaro Carmel, Mehra Niven, Sheridan Elizabeth, Figueiredo Ines, Riisnaes Ruth, Miranda Susana, Crespo Mateus, Flohr Penny, Mateo Joaquín, Altavilla Amelia, Ferraldeschi Roberta, Bianchini Diletta, Attard Gerhardt, Tunariu Nina, de Bono Johann

机构信息

Prostate Cancer Targeted Therapy Group and Drug Development Unit, The Royal Marsden National Health Services Foundation Trust and The Institute of Cancer Research, Sutton, UK.

Oncohematology Department, Kantonsspital St. Gallen, St. Gallen, Switzerland.

出版信息

Clin Genitourin Cancer. 2016 Dec;14(6):485-493. doi: 10.1016/j.clgc.2016.04.016. Epub 2016 May 5.

Abstract

BACKGROUND

The urgent need for castration-resistant prostate cancer molecular characterization to guide treatment has been constrained by the disease's predilection to metastasize primarily to bone. We hypothesized that the use of clinical and imaging criteria could maximize tissue acquisition from bone marrow biopsies (BMBs). We aimed to develop a score for the selection of patients undergoing BMB.

MATERIALS AND METHODS

A total of 115 BMBs were performed in 101 patients: 57 were included in a derivation set and 58 were used as the validation set. The clinical and laboratory data and prebiopsy computed tomography parameters (Hounsfield units [HUs]) were determined. A score for the prediction of biopsy positivity was developed from logistic regression analysis of the derivation set and tested in the validation set.

RESULTS

Of the 115 biopsy specimens, 75 (62.5%) were positive; 35 (61.4%) in the test set and 40 (69%) in the validation set. On univariable analysis, hemoglobin (P = .019), lactate dehydrogenase (P = .003), prostate-specific antigen (P = .005), and mean HUs (P = .004) were selected. A score based on the LDH level (≥ 225 IU/L) and mean HUs (≥ 125) was developed in multivariate analysis and was associated with BMB positivity in the validation set (odds ratio, 5.1; 95% confidence interval, 1.9%-13.4%; P = .001). The area under the curve of the score was 0.79 in the test set and 0.77 in the validation set.

CONCLUSION

BMB of the iliac crest is a feasible technique for obtaining tumor tissue for genomic analysis in patients with castration-resistant prostate cancer metastatic to the bone. A signature based on the mean HUs and LDH level can predict a positive yield with acceptable internal validity. Prospective studies of independent cohorts are needed to establish the external validity of the score.

摘要

背景

去势抵抗性前列腺癌分子特征对指导治疗的迫切需求因该疾病主要倾向于转移至骨而受到限制。我们推测,使用临床和影像学标准可使骨髓活检(BMB)获取的组织最大化。我们旨在制定一个用于选择接受BMB患者的评分系统。

材料与方法

对101例患者进行了总共115次BMB:57例纳入推导集,58例用作验证集。确定了临床和实验室数据以及活检前计算机断层扫描参数(亨氏单位[HU])。通过对推导集进行逻辑回归分析制定了活检阳性预测评分,并在验证集中进行了测试。

结果

115份活检标本中,75份(62.5%)为阳性;测试集中35份(61.4%),验证集中40份(69%)。单变量分析时,选择了血红蛋白(P = 0.019)、乳酸脱氢酶(P = 0.003)、前列腺特异性抗原(P = 0.005)和平均HU(P = 0.004)。多变量分析中,基于乳酸脱氢酶水平(≥225 IU/L)和平均HU(≥125)制定了一个评分,该评分与验证集中BMB阳性相关(比值比,5.1;95%置信区间,1.9% - 13.4%;P = 0.001)。该评分在测试集中的曲线下面积为0.79,在验证集中为0.77。

结论

对于骨转移的去势抵抗性前列腺癌患者,髂嵴BMB是获取肿瘤组织进行基因组分析的可行技术。基于平均HU和乳酸脱氢酶水平的特征可预测阳性产出,且内部效度可接受。需要对独立队列进行前瞻性研究以确立该评分的外部效度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/317a/5132155/0f11f4625fc4/gr1.jpg

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