EARLY ASSESSMENT OF CYTOSTATIC DRUG RESPONSE

描述：（改编自提案）在癌症治疗过程中早期评估治疗反应的非侵入性成像技术将具有直接的临床影响。早期评估与涉及细胞抑制剂（与细胞溶解药物相反）的较新的生物治疗特别相关，其中治疗反应的评估通常需要数周至数月。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）扫描出现显著变化之前，往往需要长时间的观察。这影响了基于“疾病进展时间”的治疗反应评估，以及基于“生存”的治疗反应评估。此外，这些标准（临床终点）在个别患者的临床管理中提供的预后信息很少。本提案的具体目的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，以评估对细胞抑制剂（SU101， PDGF受体拮抗剂）的治疗反应。这是一项针对10例首次复发的高级别恶性脑肿瘤（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，肿瘤的增殖或代谢活性的降低是否发生在早期（在一个或两个疗程的治疗后），而这些患者随后被证实符合标准标准的治疗反应？本研究旨在评估由[124I]标记的碘脱氧尿苷（IUdR） PET成像评估的肿瘤增殖变化，或由[18F]标记的氟脱氧葡萄糖（FDG）测量的肿瘤代谢变化，是否有可能建立一个定义早期治疗反应的新标准。

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.