EARLY ASSESSMENT OF CYTOSTATIC DRUG RESPONSE

描述：(改编自该提案)在癌症治疗过程早期评估治疗反应的非侵入性成像技术将立即产生临床效果。早期评估与涉及细胞抑制药物(与细胞溶解药物相反)的较新生物治疗特别相关，在这些药物中，治疗反应的评估通常需要数周至数月的时间。也就是说，在患者的临床状态或磁共振(MR)或计算机断层扫描(CT)出现显著变化之前，通常需要长时间的观察。这对基于“疾病进展时间”的治疗反应评估和基于“存活率”的治疗反应产生影响。此外，这些标准(临床终点)提供的预后信息很少，对个别患者的临床管理有用。该建议的具体目标是将无创正电子发射断层扫描(PET)成像与标准临床和MR/CT标准进行比较，以评估对细胞抑制药物(PDGF受体拮抗剂SU101)的治疗反应。这是一项针对10名首次复发的高级别恶性脑瘤(多形性胶质母细胞瘤)患者的初步研究。更广泛的目标是解决在细胞抑制药物治疗过程中早期成像肿瘤增殖活性(和/或葡萄糖代谢)的变化是否具有预后价值。也就是说，肿瘤增殖或代谢活性的下降是否发生在随后被标准标准确认为治疗有效的患者的早期(经过一到两个疗程)？这项应用建议评估通过[124I]标记的碘脱氧尿苷(IUdR)PET成像评估的肿瘤增殖的变化或通过[18F]标记的氟脱氧葡萄糖(FDG)测量的肿瘤代谢的变化是否具有建立定义早期治疗反应的新标准的潜力。

DESCRIPTION: (adapted from the proposal) A non-invasive imaging technique to assess treatment response early in the course of cancer therapy would have immediate clinical impact. Early assessment is particularly relevant to the newer biological treatments involving cytostatic (in contrast to cytolytic) drugs, where the evaluation of treatment response is often protracted over weeks to months. Namely, a long period of observation is often required before there are significant changes in the patient`s clinical status or in the magnetic resonance (MR) or computerized tomographic (CT) scans. This impacts on the assessment of treatment response based on `time to progression of disease`, and on treatment response based on `survival`. Furthermore, these criteria (clinical end points) provide little prognostic information that is useful in the clinical management of individual patients. The specific objective of this proposal is to compare noninvasive positron emission tomographic (PET) imaging to standard clinical and MR/CT criteria for evaluating treatment response to a cytostatic drug (SU101, a PDGF receptor antagonist). This is a pilot study of 10 patients with high grade, malignant brain tumors (glioblastoma multiforme) at time of first relapse. The broader objective is to address whether imaging a change in tumor proliferative activity (and/or glucose metabolism) early in the course of treatment with cytostatic drugs has prognostic value. Namely, does a decrease in the proliferative or metabolic activity of tumors occur early (after one or two course of therapy) in patients that are subsequently confirmed to be treatment responsive by standard criteria? This application proposes to evaluate whether a change in tumor proliferation assessed by [124I]-labeled iododeoxyuridine (IUdR) PET imaging {or a change in tumor metabolism measured by [18F]-labeled fluorodeoxyglucose (FDG) has potential for establishing a new criterion for defining early treatment response.