PREDICTING OUTCOME OF EXPERIMENTAL THERAPY IN LYMPHOMAS BY 31P & 1H MRS

预测 31 岁前淋巴瘤实验治疗的结果

基本信息

批准号：
8097398
负责人：
Fernando Arias-Mendoza
金额：
$ 16.98万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2013-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8097398
关键词：
Academic Medical Centers Achievement Adverse effects Aftercare Antineoplastic Agents Area B-Lymphocytes Back Biopsy Cancer Patient Chemistry Choline Clinical Combination Drug Therapy Data Diffuse Disease Disease-Free Survival Dose Doxorubicin Early Diagnosis Follicular Lymphoma Funding Goals Human Hydrogen Individual Investigational Therapies Lead Lymphoma Magnetic Resonance Spectroscopy Malignant Lymph Node Neoplasm Malignant Neoplasms Measurement Measures Metabolic Methodology Methods Modality Molecular Needles New York Non-Hodgkin&apos s Lymphoma Outcome Patient Care Patients Pharmaceutical Preparations Phosphorus Phosphorylcholine Predictive Value Public Health Recording of previous events Reporting Research Research Personnel Research Project Grants Research Proposals Schedule Staging Study of magnetics Sum Techniques Technology Technology Transfer Testing Therapeutic Time Toxic effect Translational Research Treatment outcome Universities Variant Visit Work base cohort cost economic impact follow-up imaging modality in vivo large cell Diffuse non-Hodgkin&apos s lymphoma magnetic field molecular marker novel nucleoside triphosphate phosphoethanolamine prevent programs public health relevance response standard care success therapy outcome treatment response tumor wasting

项目摘要

DESCRIPTION (provided by applicant): We recently have demonstrated that in vivo phosphorus magnetic resonance spectroscopy (31P MRS) provide metabolic signatures that predict treatment outcomes to standard treatment in non Hodgkin's lymphomas (NHL).1-9 The goal of the present proposal is to extend these results and demonstrate the value of 31P and hydrogen (1H) MRS at 3.0 Tesla acquired non-invasively and during the same visit in providing metabolic signatures to predict clinical outcome in NHL patients undergoing non-standard (experimental) treatment. If successful, these methods can be used to individually tailor the new treatments available for lymphoma patients with a potential increase in therapeutic success rates. Thus, the central aim of this proposal is to determine if the metabolic profiles determined non-invasively by in vivo 31P and 1H MRS are an independent a priori predictor of tumor therapy outcome in NHL patients, whom are going to receive non-standard therapy. Our clinical colleagues agree that successful achievement of this aim would help guide the use of more aggressive and novel therapies after a lymphoma patient has shown to be unresponsive to standard therapies. With the initial demonstration of our hypothesis in this proposal, we plan its extension into a multi-center research proposal aiming to accrue a larger patient cohort to formally validate the initial results. We believe that the expenses of the present proposal and its extension into a multi-center study are justified by the potential utility and economic impact of the results; namely to be able to tailor-fit novel therapies to the metabolic profile of an individual patient. We plan to study tumor areas of 30 non Hodgkin's lymphoma patients using noninvasive 31P and 1H MRS technology at 3.0 Tesla before and during the course of receiving non-standard therapy. We will follow-up the patients clinically to correlate the MRS results with objective measures of their therapeutic outcome namely long-term response to treatment and disease-free survival. In addition, the same tumor area of ten of these patients will be studied using 31P MRS at 1.5 Tesla before receiving therapy so a comparison factor can be found between the two magnetic field strengths. In this way, the data obtained at 1.5 Tesla can be compared with the data obtained at 3.0 Tesla. PUBLIC HEALTH RELEVANCE: In a previous work, we studied the chemistry of the tumors of patients with non-Hodgkin's lymphoma (a form of cancer of the lymph nodes) with a method called magnetic resonance spectroscopy that is non-invasive (meaning that it does not need x-rays, biopsies or needles). In the previous work, the chemistry of the tumors that we studied allowed us to predict if the tumor was going to respond to the drugs commonly given to treat the disease before the patients were treated. In the present work, we want to extend our findings by studying non-Hodgkin's lymphoma patients that already received the commonly given anti-cancer drugs and their tumor either failed to respond to treatment (the tumor did not go away) or came back once again, and that are now scheduled to receive non-standard (experimental) drugs. If we are successful, the non-invasive study of the chemistry of the tumors will allow us to predict and to follow-up whether or not the tumor is responding to the non-standard (experimental) treatment as we have predicted the response to standard treatment. This research will impact public health by identifying in advance if the patients with lymphoma will or will not respond to the newer treatment allowing doctors to tailor-fit the treatment on these patients by avoiding ineffective treatments preventing side-effects, waste of money, and waste of valuable time.

描述（由申请人提供）：我们最近证明，体内磷磁共振光谱（31p MRS）提供了代谢特征，可预测非霍奇金淋巴瘤（NHL）标准治疗的治疗结果。1-9本提案的目标是为了扩展这些结果并证明了3.0特斯拉的31p和氢（1H）MRS的值，在提供代谢特征以预测接受非标准（实验）治疗的NHL患者的临床结果时，在同一访问期间获得了非侵入性。如果成功，这些方法可用于单独调整可用于淋巴瘤患者可用的新疗法，其治疗成功率可能会增加。因此，该提案的核心目的是确定由体内31p和1H MRS非侵袭性确定的代谢谱是否是独立的NHL患者肿瘤治疗结果的先验预测指标，NHL患者将接受非标准疗法。我们的临床同事一致认为，在淋巴瘤患者对标准疗法无反应后，成功实现这一目标将有助于指导使用更具侵略性和新颖的疗法。在本提案中我们的假设最初证明了我们的假设，我们计划将其扩展为一项多中心研究建议，旨在积累较大的患者队列以正式验证初始结果。我们认为，本提案的费用及其扩展到多中心研究是合理的，这是结果的潜在效用和经济影响；也就是说，能够为单个患者的代谢特征量身定制新型疗法。我们计划使用非侵入性31p和1H MRS技术在接受非标准疗法之前和期间研究30名非Hodgkin淋巴瘤患者的肿瘤区域。我们将在临床上跟进患者，以将MRS结果与其治疗结果的客观度量相关联，即对治疗和无疾病生存的长期反应。此外，在接受治疗之前，将使用31p MRS使用31p MRS研究这些患者的相同肿瘤区域，以便在两个磁场强度之间发现比较因子。这样，可以将以1.5特斯拉以1.5的数据与3.0特斯拉获得的数据进行比较。公共卫生相关性：在先前的工作中，我们研究了非霍奇金淋巴瘤患者的肿瘤（一种淋巴结癌），其方法称为无创磁共振光谱，该方法是非侵入性的（这意味着它确实确实如此不需要X射线，活检或针）。在先前的工作中，我们研究的肿瘤的化学性能使我们能够预测肿瘤是否会在治疗患者之前对通常治疗该疾病的药物反应。在目前的工作中，我们希望通过研究已经接受过通常给予过抗癌药物的非霍奇金淋巴瘤患者来扩展我们的发现，其肿瘤要么无法对治疗做出反应（肿瘤没有消失）或再次回来，现在计划接受非标准（实验）药物。如果我们成功，那么对肿瘤化学的非侵入性研究将使我们能够预测和随访肿瘤是否对非标准（实验）治疗做出反应，因为我们已经预测了对标准的反应治疗。这项研究将通过事先确定淋巴瘤患者是否会或不会对新的治疗做出反应，从而影响公共卫生，从而使医生可以通过避免无效治疗来防止副作用，浪费金钱和浪费来量身定制这些患者的治疗方法。宝贵的时间。