IN VIVO 31P MRS STUDIES OF NON-HODGKIN'S LYMPHOMA

描述（由申请人提供）：非霍奇金淋巴瘤（NHL）是美国第五大常见癌症类型，弥漫性大B细胞淋巴瘤（DLBCL）是其最常见的亚型。 直到最近，DLCBL是迅速和不可避免的致命的，但新的标准治疗与多药物免疫化疗组合使这种形式的癌症有可能治愈40%的患者。 对于大多数标准治疗失败的人来说，最后的希望在于更激进的治疗，如骨髓移植。 这些替代疗法风险更大，特别是对于那些已经因标准免疫化疗失败而虚弱的患者。 因此，对于那些标准治疗可能失败的患者，非常需要能够使肿瘤学家进行个体化治疗并立即开始根治性治疗的信息。 我们相信我们的非侵入性测量NHL肿瘤代谢的磁共振波谱（MRS）可以提供这一信息。 在以前的资助期间，我们已经获得了有希望的初步结果，表明磷酸乙醇胺（Etn-P）和磷酸胆碱（Cho-P）的治疗前代谢比，通过三磷酸核苷酸（NTP）的肿瘤含量进行标准化，可以灵敏地和特异性地预测DLBCL的治疗失败。 我们的多中心研究的第一个目的是检验我们的假设，即[Etn-P + Cho-P]/NTP比值与DLBCL的治疗结果显著相关。 除了证实我们以前的结果与31 P MRS在1.5 T场强在一个独立的样本的患者，我们还试图通过研究DLBCL肿瘤的代谢与31 P在3.0 T扩展这些结果，也调查绝对胆碱水平DLBCL与31 P和1H在1.5 T和3.0 T。我们的第二个目的是随访初步迹象，即[Etn-P + Cho-P]/NTP比值与治疗结果之间的相关性的意义广泛适用于所有形式的NHL，而不仅仅是DLBCL亚型。 我们将通过积累足够的患者来独立分析每个亚型，使用最直接适用于当代临床环境的1.5T方法来实现这一目标。 这项拟议中的研究是引导定向治疗临床试验的最后一步，也是MRS转化研究前所未有的项目的高潮。

DESCRIPTION (provided by applicant): Non-Hodgkin's lymphoma (NHL) is the fifth most common type of cancer in the United States, and diffuse large B cell lymphoma (DLBCL) is its most common subtype. Until recently DLCBL was rapidly and inevitably fatal, but the new standard of treatment with multi-drug immuno-chemotherapy combinations makes this form of cancer potentially curable in 40% of patients. The last hope for the majority for whom standard treatment will fail lies in more radical therapies such as bone marrow transplant. These alternate treatments are more risky, especially for patients already weakened by a failed attempt at standard immuno-chemotherapy. There is thus a great need for information that could allow oncologists to individualize treatment and immediately begin radical therapy in those for whom standard treatment is likely to fail. We believe our non-invasive measurement of NHL tumor metabolism with magnetic resonance spectroscopy (MRS) can provide this information. During previous periods of grant support, we have obtained promising initial results showing that the pre-treatment metabolic ratio of phosphoethanolamine (Etn-P) and phosphocholine (Cho-P), normalized by the tumor content of nucleotide triphosphates (NTP), can sensitively and specifically predict treatment failure in DLBCL. The first aim for our multi-center study is to test our hypothesis that the [Etn-P + Cho-P]/NTP ratio is significantly correlated with treatment outcome in DLBCL. In addition to confirming our previous results with 31P MRS at the 1.5T field strength in an independent sample of patients, we also seek to extend these findings by studying the metabolism of DLBCL tumors with 31P at 3.0T, and also investigating absolute choline levels in DLBCL with 31P and 1H at both 1.5T and 3.0T. Our second aim is to follow up on initial indications that the significance of the correlation between the [Etn-P + Cho-P]/NTP ratio and treatment outcome is widely applicable to all forms of NHL and not merely the DLBCL subtype. We will approach this aim by accruing sufficient patients to analyze each subtype independently, using the 1.5T methods that are most directly applicable to the contemporary clinical environment. The proposed research is the final step leading a directed-therapy clinical trial and the culmination of an unprecedented program of translational research in MRS.