Abstract：
OBJECTIVE: The source of tissue for genomic profiling of metastatic castration-resistant prostate cancer (mCRPC) is often limited to osseous metastases. To guide patient management, metastatic site selection and the technique for targeted bone biopsies are critical for identifying deleterious gene mutations. Our objective was to identify key parameters associated with successful large-panel DNA sequencing.
METHODS: We analyzed parameters for 243 men with progressing mCRPC who underwent 269 bone biopsies for genomic profiling between 2014 and 2018. Univariate and multivariate analyses were performed for clinical, imaging (bone scan; fluorodeoxyglucose [FDG] positron emission tomography [PET]; computed tomography [CT]; magnetic resonance imaging), and technical (biopsy site, number of samples, needle gauge) features associated with successful genomic profiling.
UNASSIGNED: Overall, 159 of 269 biopsies (59%) generated sufficient tumor material for a genomic profile. Seventy (26%) of the failures were histopathologically negative for mCRPC and 40 (15%) had insufficient tumor for genomic profiling. Of 199 mCRPC samples submitted for molecular testing, 159 (80%) yielded a genomic profile. On univariate analysis, PSA, serum acid phosphatase, number of biopsy samples, FDG PET positivity, CT attenuation, and CT morphology were significantly associated with genomic profiling success. On multivariate analysis, higher FDG maximum standardized uptake value (odds ratio [OR] 7.51, 95% confidence interval [CI] 3.01-18.78; p < 0.001), higher number of biopsy samples (OR 4.73, 95% CI 1.49-15.02; p = 0.008), and lower mean CT attenuation (OR 0.4, 95% CI 0.18-0.89; p = 0.025) were significantly associated with sequencing success.
CONCLUSIONS: In patients with mCRPC, bone biopsies from sites with metabolic activity and lower CT attenuation are associated with higher success rates for genomic profiling via a large-panel DNA sequencing platform.
RESULTS: We identified factors associated with successful genetic testing of bone tissue for patients with metastatic prostate cancer. Our findings may help in guiding the right scan technique and biopsy site for personalized treatment planning.
METHODS: We analyzed parameters for 243 men with progressing mCRPC who underwent 269 bone biopsies for genomic profiling between 2014 and 2018. Univariate and multivariate analyses were performed for clinical, imaging (bone scan; fluorodeoxyglucose [FDG] positron emission tomography [PET]; computed tomography [CT]; magnetic resonance imaging), and technical (biopsy site, number of samples, needle gauge) features associated with successful genomic profiling.
UNASSIGNED: Overall, 159 of 269 biopsies (59%) generated sufficient tumor material for a genomic profile. Seventy (26%) of the failures were histopathologically negative for mCRPC and 40 (15%) had insufficient tumor for genomic profiling. Of 199 mCRPC samples submitted for molecular testing, 159 (80%) yielded a genomic profile. On univariate analysis, PSA, serum acid phosphatase, number of biopsy samples, FDG PET positivity, CT attenuation, and CT morphology were significantly associated with genomic profiling success. On multivariate analysis, higher FDG maximum standardized uptake value (odds ratio [OR] 7.51, 95% confidence interval [CI] 3.01-18.78; p < 0.001), higher number of biopsy samples (OR 4.73, 95% CI 1.49-15.02; p = 0.008), and lower mean CT attenuation (OR 0.4, 95% CI 0.18-0.89; p = 0.025) were significantly associated with sequencing success.
CONCLUSIONS: In patients with mCRPC, bone biopsies from sites with metabolic activity and lower CT attenuation are associated with higher success rates for genomic profiling via a large-panel DNA sequencing platform.
RESULTS: We identified factors associated with successful genetic testing of bone tissue for patients with metastatic prostate cancer. Our findings may help in guiding the right scan technique and biopsy site for personalized treatment planning.
摘要：
目的：转移性去势抵抗性前列腺癌（mCRPC）基因组分析的组织来源通常仅限于骨转移。为了指导患者管理，转移部位选择和靶向骨活检技术对于识别有害基因突变至关重要.我们的目标是确定与成功的大型DNA测序相关的关键参数。
方法：我们分析了2014年至2018年期间接受269例骨活检的243例mCRPC进展男性的参数。单变量和多变量分析用于临床，成像（骨扫描;氟脱氧葡萄糖[FDG]正电子发射断层扫描[PET];计算机断层扫描[CT];磁共振成像），和技术(活检部位，样品数量,针规)与成功的基因组分析相关的特征。
■总的来说，269个活检中的159个(59%)为基因组谱产生了足够的肿瘤材料。70（26％）的失败是mCRPC的组织病理学阴性，40（15％）的肿瘤不足以进行基因组分析。在提交分子测试的199个mCRPC样品中，159（80％）产生了基因组谱。在单变量分析中，PSA,血清酸性磷酸酶，活检样本的数量，FDGPET阳性，CT衰减,和CT形态学与基因组分析成功显著相关。在多变量分析中，较高的FDG最大标准化摄取值(比值比[OR]7.51，95%置信区间[CI]3.01-18.78；p<0.001)，活检样本数量较高（OR4.73，95%CI1.49-15.02；p=0.008），和较低的平均CT衰减(OR0.4,95%CI0.18-0.89;p=0.025)与测序成功显著相关。
结论：在mCRPC患者中，来自具有代谢活动和较低CT衰减的部位的骨活检与通过大型DNA测序平台进行基因组谱分析的更高成功率相关.
结果：我们确定了与转移性前列腺癌患者骨组织基因检测成功相关的因素。我们的发现可能有助于指导正确的扫描技术和活检部位进行个性化的治疗计划。
方法：我们分析了2014年至2018年期间接受269例骨活检的243例mCRPC进展男性的参数。单变量和多变量分析用于临床，成像（骨扫描;氟脱氧葡萄糖[FDG]正电子发射断层扫描[PET];计算机断层扫描[CT];磁共振成像），和技术(活检部位，样品数量,针规)与成功的基因组分析相关的特征。
■总的来说，269个活检中的159个(59%)为基因组谱产生了足够的肿瘤材料。70（26％）的失败是mCRPC的组织病理学阴性，40（15％）的肿瘤不足以进行基因组分析。在提交分子测试的199个mCRPC样品中，159（80％）产生了基因组谱。在单变量分析中，PSA,血清酸性磷酸酶，活检样本的数量，FDGPET阳性，CT衰减,和CT形态学与基因组分析成功显著相关。在多变量分析中，较高的FDG最大标准化摄取值(比值比[OR]7.51，95%置信区间[CI]3.01-18.78；p<0.001)，活检样本数量较高（OR4.73，95%CI1.49-15.02；p=0.008），和较低的平均CT衰减(OR0.4,95%CI0.18-0.89;p=0.025)与测序成功显著相关。
结论：在mCRPC患者中，来自具有代谢活动和较低CT衰减的部位的骨活检与通过大型DNA测序平台进行基因组谱分析的更高成功率相关.
结果：我们确定了与转移性前列腺癌患者骨组织基因检测成功相关的因素。我们的发现可能有助于指导正确的扫描技术和活检部位进行个性化的治疗计划。
