PET to Measure Breast Cancer Bone Metastasis Response

描述(申请人提供)：骨是乳腺癌常见的转移部位。虽然乳腺癌很少被“治愈”，但骨性占优势的乳腺癌患者比内脏受累的患者预后更好，而且可能会有更长的生存期。这些患者受益于越来越多的有效治疗方法；然而，由于难以评估疗效，治疗的选择受到阻碍。在回顾性研究中，我们已经表明，系列FDG PET可以测量骨转移对治疗的反应，FDG摄取的变化可以预测进展时间(TTP)，FDG摄取的水平可以预测骨骼相关事件(SRE)的可能性，如骨折。我们还使用了18F-氟化物PET来评估肿瘤对邻近转移的1块骨的影响，结果表明，从氟化物PET获得的骨转移行为的信息与FDG PET是不同的，也是互补的。我们现在建议将这些初步研究扩展到对接受系统治疗的骨显性乳腺癌患者进行FDG和氟化物PET的更大规模的前瞻性研究。我们的目标是(1)以患者预后为金标准，前瞻性地验证FDG和氟化物PET作为衡量骨转移治疗疗效的指标；(2)结合使用定量FDG PET/CT和氟化物PET来测量转移部位及邻近骨的体内生物学特性，目的是预测骨骼事件的风险，并将PET措施与通过活组织检查材料体外检测的肿瘤特征相关联；以及(3)使用氟化物PET来衡量双膦酸类化合物对骨转换的早期影响，以更好地了解这些几乎被普遍用于乳腺癌转移治疗的制剂的体内效果。这些研究的结果将是经患者结果验证的成像方法，用于在临床试验和临床实践中测量乳腺癌骨转移反应，并指导适当的早期干预以预防骨骼事件。

DESCRIPTION (provided by applicant): Bone is a common site of metastasis for breast cancer. Although rarely "cured" of breast cancer, patients with bone-dominant breast cancer have a more favorable prognosis than patients with visceral involvement and may have prolonged survival. These patients benefit from an increasing array of effective therapies; however, the choice of therapy is hampered by the difficulty of assessing response. We have shown, in retrospective studies, that serial FDG PET can measure bone metastasis response to therapy, that changes in FDG uptake with treatment predict time-to-progression (TTP), and that the level of FDG uptake predicts the likelihood of skeletal-related events (SRE), such as fracture. We have also used 18F-fluoride PET to assess tumor effect on the1 bone adjacent to metastases and have shown that the information gained on bone metastasis behavior from fluoride PET is distinct from and complementary to FDG PET. We now propose to extend these preliminary studies to a larger prospective study of FDG and fluoride PET in patients with bone-dominant breast cancer undergoing systemic therapy. Our aims are (1) to prospectively validate FDG and fluoride PET as measures of bone metastasis response to therapy with patient outcome as the gold standard, (2) to measure the in vivo biology of metastatic sites and adjacent bone using a combination of quantitative FDG PET/CT and fluoride PET with the goal of predicting the risk of a skeletal event and also to relate PET measures to tumor characteristics measured by in vitro assay of biopsy material, and (3) to measure the early effect of bisphosphonates on bone turnover using fluoride PET to better understand the in vivo effect of these agents, which are almost universally used in treating breast cancer metastases. The result of these investigations will be imaging methods, validated by patient outcome, for measuring breast cancer bone metastasis response in clinical trials and clinical practice and for directing appropriate early interventions to prevent skeletal events.