达沙替尼治疗后通过18F-氟化物PET测量的去势抵抗性前列腺癌骨转移反应及其与无进展生存期的相关性：美国放射学会影像网络6687的结果
Castration-resistant prostate cancer bone metastasis response measured by 18F-fluoride PET after treatment with dasatinib and correlation with progression-free survival: results from American College of Radiology Imaging Network 6687.
作者信息
Yu Evan Y, Duan Fenghai, Muzi Mark, Deng Xuan, Chin Bennett B, Alumkal Joshi J, Taplin Mary-Ellen, Taub Jina M, Herman Ben, Higano Celestia S, Doot Robert K, Hartfeil Donna, Febbo Philip G, Mankoff David A
机构信息
University of Washington, Seattle, Washington
Department of Biostatistics and Center for Statistical Sciences, Brown University School of Public Health, Providence, Rhode Island.
出版信息
J Nucl Med. 2015 Mar;56(3):354-60. doi: 10.2967/jnumed.114.146936. Epub 2015 Jan 29.
UNLABELLED
(18)F-fluoride PET quantitatively images bone metabolism and may serve as a pharmacodynamic assessment for systemic therapy such as dasatinib, a potent SRC kinase inhibitor, with activity in bone.
METHODS
This was an imaging companion trial (American College of Radiology Imaging Network [ACRIN] 6687) to a multicenter metastatic castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT00918385). Men with bone metastatic CRPC underwent (18)F-fluoride PET before and 12 weeks after initiation of dasatinib (100 mg daily). Dynamic imaging was performed over a 15-cm field of view for trial assessments. The primary endpoint was to determine whether changes in (18)F-fluoride incorporation in tumor and normal bone occurred in response to dasatinib. Other endpoints included differential effect of dasatinib between (18)F-fluoride incorporation in tumor and normal bone, (18)F-fluoride transport in bone metastases, correlation with progression-free survival (PFS), prostate-specific antigen, and markers of bone turnover.
RESULTS
Eighteen participants enrolled, and 17 underwent interpretable baseline (18)F-fluoride PET imaging before initiation of dasatinib. Twelve of 17 patients underwent on-treatment PET imaging. Statistically significant changes in response to dasatinib were identified by the SUVmaxavg (average of maximum standardized uptake value [SUVmax] for up to 5 tumors within the dynamic field of view) in bone metastases (P = 0.0002), with a significant differential (18)F-fluoride PET response between tumor and normal bone (P < 0.0001). Changes in (18)F-fluoride incorporation in bone metastases had borderline correlation with PFS by SUVmaxavg (hazard ratio, 0.91; 95% confidence interval, 0.82-1.00; P = 0.056). Changes by SUVmaxavg correlated with bone alkaline phosphatase (P = 0.0014) but not prostate-specific antigen (P = 0.47).
CONCLUSION
This trial provides evidence of the ability (18)F-fluoride PET to delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PFS.
未标注
（18）F - 氟化物PET可对骨代谢进行定量成像，并可作为对如达沙替尼（一种有效的SRC激酶抑制剂，对骨有活性）等全身治疗的药效学评估。
方法
这是一项针对多中心转移性去势抵抗性前列腺癌（CRPC）组织生物标志物引导治疗试验（NCT00918385）的成像伴随试验（美国放射学会成像网络[ACRIN]6687）。骨转移性CRPC男性患者在开始使用达沙替尼（每日100毫克）之前和之后12周接受（18）F - 氟化物PET检查。在15厘米视野范围内进行动态成像以进行试验评估。主要终点是确定肿瘤和正常骨中（18）F - 氟化物摄取的变化是否因达沙替尼而发生。其他终点包括达沙替尼在肿瘤和正常骨中（18）F - 氟化物摄取之间的差异效应、骨转移灶中（18）F - 氟化物转运、与无进展生存期（PFS）、前列腺特异性抗原及骨转换标志物的相关性。
结果
18名参与者入组，17名在开始使用达沙替尼之前接受了可解读的基线（18）F - 氟化物PET成像。17名患者中有12名接受了治疗期间的PET成像。通过骨转移灶中SUVmaxavg（动态视野内多达5个肿瘤的最大标准化摄取值[SUVmax]的平均值）确定了对达沙替尼反应的统计学显著变化（P = 0.0002），肿瘤和正常骨之间存在显著的（18）F - 氟化物PET反应差异（P < 0.0001）。骨转移灶中（18）F - 氟化物摄取的变化通过SUVmaxavg与PFS有临界相关性（风险比，0.91；95%置信区间，0.82 - 1.00；P = 0.056）。SUVmaxavg的变化与骨碱性磷酸酶相关（P = 0.0014），但与前列腺特异性抗原无关（P = 0.47）。
结论
本试验提供了证据，证明（18）F - 氟化物PET能够描绘达沙替尼在CRPC骨转移中的治疗反应，与PFS有临界相关性。
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