Kent Yip MRCP, FRCR, Presenter: Nothing to Disclose

Juliette Valentine MSc, Abstract Co-Author: Nothing to Disclose

James Stirling, Abstract Co-Author: Nothing to Disclose

Ian Simcock, Abstract Co-Author: Nothing to Disclose

N.Jane Taylor PHD, Abstract Co-Author: Nothing to Disclose

David John Collins BSC, BA, Abstract Co-Author: Nothing to Disclose

James A. D Arcy, Abstract Co-Author: Nothing to Disclose

Uma Patel, Abstract Co-Author: Nothing to Disclose

Andrew Gogbashian MD, FRCR, Abstract Co-Author: Nothing to Disclose

Peter Hoskin, Abstract Co-Author: Nothing to Disclose

Anwar Roshanali Padhani MD, Abstract Co-Author: Advisory Board, Acuitas Medical Ltd Advisory Board, Siemens AG Speakers Bureau, Siemens AG Researcher, Siemens AG Speakers Bureau, Johnson & Johnson

Roberto Alonzi MD, Abstract Co-Author: Nothing to Disclose

Hypoxia correction improves survival in patients treated with radiotherapy (RT) for some cancers. Previous studies have shown the presence of hypoxia in untreated prostate cancer (PCa) and hypoxia resolution following carbogen breathing. Androgen deprivation therapy (ADT) is normally given prior to RT. Because ADT is anti-angiogenic, its not known whether the use of carbogen gas will still be effective in correcting hypoxia post ADT. This study has assessed this during hypoxia modified RT.

50 men with high risk PCa took part in a phase II trial of prostate RT with hypoxia modification using carbogen gas and nicotinamide. 20 men also underwent serial mpMRI examination. 6 scans were carried out: 1st immediately prior to ADT (3 months pre RT); 2nd and 3rd (reproducibility pair) 1 week pre RT and 3 months into ADT; 4th, 5th and 6th at weeks 1, 3 and 7 of RT. The following sequences were carried out: T2-weighted; Dynamic Contrast Enhanced MRI; Intrinsic Susceptibility Contrast MRI (pre & post carbogen) and Diffusion Weighted MRI. Tumors were identified and outlined on the T2W & DW-MRI images on each scan for every time point. Voxel based calculations were performed to derive Ktrans, IAUGC60 and R2*. The extended Tofts’ Model was used for data fitting to calculate Ktrans. Percentage change in R2* compared to baseline values for each day was calculated.  

The changes in all the parameters are presented in table 1. Basal tumor R2* increased by 17% after 3 months of ADT compared to baseline. Carbogen administration caused a drop in delta R2* at all time points, by as much as 10%. Whole prostate Ktrans and IAUGC60 reduced after 3 months of ADT and then recovered during RT.

Reductions in blood flow and worsening in tumor hypoxia were seen after the 3 months of ADT. Despite this, tumors remained responsive to carbogen. The increase in blood supply during RT may explain the preservation of response to hypoxic modification.

The strategy of using carbogen to overcome intra-tumoral hypoxia remains valid for prostate cancer even with the prior use of ADT. Phase III testing of this hypoxia modification strategy can proceed, provided acceptable toxicity is confirmed in this phase II trial.

Yip, K, Valentine, J, Stirling, J, Simcock, I, Taylor, N, Collins, D, D Arcy, J, Patel, U, Gogbashian, A, Hoskin, P, Padhani, A, Alonzi, R, Hypoxia Modification during Prostate Radiotherapy. An Evaluation of Changes in the Tumor Microenvironment Using Multi-parametric MRI (mpMRI).  Radiological Society of North America 2014 Scientific Assembly and Annual Meeting, - ,Chicago IL. http://archive.rsna.org/2014/14016733.html