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仍是迅速且不可避免地致命的，但多药免疫化疗联合治疗的新标准使这种癌症在40%的患者中有可能治愈。对于大多数标准治疗失败的人来说，最后的希望在于骨髓移植等更激进的治疗方法。这些替代疗法风险更大，尤其是对那些因标准免疫化疗失败而身体虚弱的患者。因此，对信息的需求很大，这些信息可以使肿瘤学家对那些标准治疗可能失败的患者进行个体化治疗，并立即开始根治性治疗。我们相信我们使用磁共振波谱（MRS）对NHL肿瘤代谢的无创测量可以提供这些信息。在之前的拨款支持期间，我们已经获得了令人鼓舞的初步结果，表明治疗前磷酸乙醇胺（Etn-P）和磷酸胆碱（Cho-P）的代谢比，通过肿瘤中三磷酸核苷酸（NTP）的含量归一化，可以敏感和特异性地预测DLBCL的治疗失败。我们的多中心研究的第一个目的是验证我们的假设，即[Etn-P + Cho-P]/NTP比值与DLBCL的治疗结果显著相关。除了在独立的患者样本中用1.5T场强下的31P MRS证实我们之前的结果外，我们还试图通过研究3.0T下31P的DLBCL肿瘤的代谢，以及研究1.5T和3.0T下31P和1H的DLBCL的绝对胆碱水平来扩展这些发现。我们的第二个目标是追踪初步迹象，表明[Etn-P + Cho-P]/NTP比值与治疗结果之间的相关性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。这项拟议的研究是引导定向治疗临床试验的最后一步，也是核磁共振史无前例的转化研究项目的高潮。

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.