More than 55,000 Americans will develop cancer of the head and neck (HN) this year accounting for nearly 3% of all cancers in the United States. These cancers are more common in men and in people over age 50. More than 85% of these cancers are related to tobacco and alcohol consumption. Despite aggressive surgery and radiotherapy (RT), which may result in significant functional loss, the survival rate of patients with head and neck cancer has remained relatively unchanged over the past three decades. The predictive indices based on tumor morphology or clinical characteristics are generally less accurate in defining outcome of response. Hence, there is an urgent need for a reliable predictor of early response in these tumors. Magnetic resonance spectroscopy (MRS) and imaging (MRI) can non-invasively identify specific metabolic patterns and tissue physiology that may be used as markers for predicting and monitoring early treatment response. Preliminary studies on 41 cases of non-Hodgkins Lymphomas and 12 cases of HN tumors indicate that 31p MRS can predict response prior to initiation of therapy. 1H MRS and MRI provides higher sensitivity and spatial resolution than 31p MRS and would thus facilitate studying smaller tumors and investigating heterogeneous tumor response. The overall goal for this proposal is to test the hypothesis that NMR spectroscopy and imaging can predict and monitor early response to treatment of head and neck tumors. This hypothesis will be tested with the following specific aims:
Aim 1 : To evaluate the utility of the PME/13 NTP ratio in predicting and detecting treatment response by 31p MRS, Aim 2: To determine if total choline (Cho) and lactate (Lac) levels can predict and monitor treatment response and Aim 3: To use physiological MRI parameters (T2, ADC and DCE) as predictors/monitors of local tumor response to chemotherapy and radiation therapy of HN tumors. 31p MRS studies will be performed using proton decoupled and NOE enhanced 3D CSI sequence. 1H MRS studies will be performed by implementing a selective multi-quantum coherence transfer pulse sequence (Sel-MQC), for detection of lactate (Lac) and total choline (TCho) on the clinical scanner. Standard MRI pulse sequences for implementing dynamic contrast enhanced (DCE), diffusion weighted imaging (DWI) and T2 weighted imaging (T2WI) imaging will be streamlined so that a complete examination consisting of 31p MRS or 1H MRS combined with DCE, DWI and T2WI can be implemented on human HN patients within one hour.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA102756-04
Application #
7249459
Study Section
Diagnostic Radiology Study Section (RNM)
Program Officer
Henderson, Lori A
Project Start
2004-06-01
Project End
2009-11-30
Budget Start
2007-06-01
Budget End
2009-11-30
Support Year
4
Fiscal Year
2007
Total Cost
$277,278
Indirect Cost
Name
University of Pennsylvania
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Chawla, S; Loevner, L A; Kim, S G et al. (2018) Dynamic Contrast-Enhanced MRI-Derived Intracellular Water Lifetime (? i ): A Prognostic Marker for Patients with Head and Neck Squamous Cell Carcinomas. AJNR Am J Neuroradiol 39:138-144
Chawla, Sanjeev; Kim, Sungheon; Dougherty, Lawrence et al. (2013) Pretreatment diffusion-weighted and dynamic contrast-enhanced MRI for prediction of local treatment response in squamous cell carcinomas of the head and neck. AJR Am J Roentgenol 200:35-43
Abdel Razek, Ahmed Abdel Khalek; Poptani, Harish (2013) MR spectrsocopy of head and neck cancer. Eur J Radiol 82:982-9
Delikatny, E James; Chawla, Sanjeev; Leung, Daniel-Joseph et al. (2011) MR-visible lipids and the tumor microenvironment. NMR Biomed 24:592-611
Chawla, S; Kim, S; Loevner, L A et al. (2011) Prediction of disease-free survival in patients with squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging. AJNR Am J Neuroradiol 32:778-84
Berrak, Su; Chawla, Sanjeev; Kim, Sungheon et al. (2011) Diffusion weighted imaging in predicting progression free survival in patients with squamous cell carcinomas of the head and neck treated with induction chemotherapy. Acad Radiol 18:1225-32
Kim, S; Loevner, L A; Quon, H et al. (2010) Prediction of response to chemoradiation therapy in squamous cell carcinomas of the head and neck using dynamic contrast-enhanced MR imaging. AJNR Am J Neuroradiol 31:262-8
Chawla, Sanjeev; Kim, Sungheon; Loevner, Laurie A et al. (2009) Proton and phosphorous MR spectroscopy in squamous cell carcinomas of the head and neck. Acad Radiol 16:1366-72
Mellon, Eric A; Lee, Seung-Cheol; Pickup, Stephen et al. (2009) Detection of lactate with a hadamard slice selected, selective multiple quantum coherence, chemical shift imaging sequence (HDMD-SelMQC-CSI) on a clinical MRI scanner: Application to tumors and muscle ischemia. Magn Reson Med 62:1404-13
Pickup, Stephen; Chawla, Sanjeev; Poptani, Harish (2009) Quantitative estimation of dynamic contrast enhanced MRI parameters in rat brain gliomas using a dual surface coil system. Acad Radiol 16:341-50

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