The long-term goal of this study is to develop a biomarker, measurable 10 days after radiotherapy (RT) or chemoradiotherapy (CRT), which is capable of estimating the probability of tumor control (TCP) at 12 months (m) in non-small cell lung carcinoma (NSCLC). Accelerated glucose transport is a hallmark of biochemical changes that occur with malignant cellular transformation. Cessation of glucose uptake in response to RT or CRT may be an early biochemical event that may be a sign for eventual cell death leading to tumor control. The glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) allows a measurement of glucose metabolic rate (MRglc) by quantitative 18F-FDG and positron emission tomography (PET). MRglc 10 days after RT or CRT may vary depending upon the presence or absence of residual tumor, and the amount of residual tumor. There may be a correlation between the levels of residual MRglc 10 days after RT or CRT, representing the amount of residual tumor, and the rate of subsequent clinical tumor control at 12 m. We propose an in vivo assay in which the rate of tumor control at 12 m will be correlated with the levels of residual MRglc 10 days after RT or CRT. MRglc will be measured with simplified kinetic method of 18F-FDG PET at the primary lesion before and 10 days after RT or CRT, and at 3, 6, and 12 m follow-up. Patients with medically inoperable stage I and II, and locally advanced stage III NSCLC will be accrued for this study. Tumor control is defined as (1) absence of regrowth by computed tomography (CT) and (2) absence of an increase in MRglc from the nadir value after RT or CRT.
Specific Aims of this study are: (1) To determine the levels of residual MRglc 10 days after RT or CRT and the rate of tumor control at 12 m at the corresponding levels of residual MRgtc, (2) To generate dose-response relationship between the gradient of residual MRglc and corresponding TCP from the above data, (3) To determine the level of residual MRglc that corresponds to the probability of tumor control (MRglc-TCP) >95% at 12 m, and (4) To plan for a phase II clinical study in which RT dose schedule and tumor volume for RT are guided by MRglc-TCP >95% with study endpoints of improved tumor control and survival over that of the current standard CRT or RT.
| Shusharina, Nadya; Cho, Joseph; Sharp, Gregory C et al. (2014) Correlation of (18)F-FDG avid volumes on pre-radiation therapy and post-radiation therapy FDG PET scans in recurrent lung cancer. Int J Radiat Oncol Biol Phys 89:137-44 |
| Choi, Noah C; Chun, Tristen T; Niemierko, Andrzej et al. (2013) Potential of 18F-FDG PET toward personalized radiotherapy or chemoradiotherapy in lung cancer. Eur J Nucl Med Mol Imaging 40:832-41 |
