Evaluation of MRI Apparent Diffusion Coefficient (ADC) Mapping As a Predictive Biological Marker in Potentially Personalized and Genetically Targeted Approach in the Radiation Therapy Treatment of Carcinoma Prostate

Abstract

Non-invasive MRI ADC value mapping has a potential to identify less responsive volume and permits itself for repeated scanning due to lack of radiation exposure. Since it reflects the extent of apoptosis in the tumor tissue, recognisable early in the course of radiotherapy, it has the potential to become predictive model of response and consequently, help modulate dose of radiotherapy. Since ADC is also a marker of apoptosis, it also serves as a genomic marker which can be evaluated dynamically within areas of the entire tumor. In the present study, MRI ADC is evaluated before start of radiotherapy, after 1st, 5th, 10th, and 15th fractions of radiation and changes were analysed. ADC was measured by “segmentation technique” to understand ADC changes in different parts of prostate carcinoma Vis a Vis the entire tumor. ADC was measured in 0.23 cm2 area in 12 segments of the prostate at the upper, mid and lower levels (totally 36 segments for each MRI).This technique was expected to increase the “sensitivity” of estimation, which otherwise would be averaged out when entire tumor value is considered. Normal tissue changes in 12 segments and entire tumor ADC values at each level were also measured. Data was analysed using Friedman’s Rank Test for multiple comparisons. This is an analysis of 4 patients who underwent radical radiotherapy for prostate carcinoma. There was no significant change in ADC values in 48hrs of starting treatment (p=0.14). However, there was a significant change over time in prostate tumor segment ADC values (p=0.03) during first 15 fractions of IMRT/IGRT. This change was maximum at 10th fraction (p=0.01). The results suggest trend in ADC values during radiotherapy could help in developing a predictive 3D apoptotic model for radiation response. The results from this methodology indicate that there are volumes and sub-volumes of “more sensitive” differential response in carcinoma prostate, which may help in selecting the appropriate patients and/or sub-volumes for dose modification in future.