The Treasury of Images: exploring the opportunities for diagnosing and treating prostate cancer

External beam radiotherapy (EBRT) is often used to treat prostate cancer (PCa). Technological developments in radiation delivery techniques allowed increasing the dose to the entire prostate gland thereby improving treatment outcome. Unfortunately these positive results come often at the cost of increased toxicity and local recurrences are still observed, mostly at the site of the primary tumor. New strategies to further enhance local control while maintaining an acceptable level of toxicity are thus needed.

An upcoming, more precise and accurate form of EBRT is stereotactic body radiotherapy (SBRT). This treatment technology is based on two principles: (1) precise 3D localization of the target (stereotaxis) by means of image guidance and (2) delivery of high doses of radiation in just a few treatment fractions (hypofractionation). Such hypofractionated treatment regimens could thus be used to biologically escalate the dose while maintaining current levels of toxicity. Furthermore, reducing the number of treatment fractions has several other advantages with respect to patient convenience, resources and costs as compared to the standard fractionation scheme. Alternatively, proton radiation therapy, which makes use of charged particles instead of photons, could also be an option to escalate the dose while improving treatment-related toxicity given the superior physical characteristics of protons. Instead of escalating the dose to the whole prostate gland, increasing the radiation dose only to the intraprostatic tumor nodule(s) (focal boosting) while keeping the exposure of surrounding tissues similar to treatment with a conventional, homogeneous dose to the prostate target volume, could be an ideal solution. Moreover, focal dose escalation may improve local disease control as local recurrences mostly occur at the site of the primary tumor location. Currently, this approach is being tested in several randomized phase III trials, including the FLAME trial in which our institute is participating.

Importantly, dose escalation, being conventional, biological or focal, requires accurate and precise delivery of the radiation dose. Hence, the performance of the imaging technique used for this purpose will be of crucial importance.

In this project we will investigate focal boosting strategies for the treatment of PCa making use of the latest technology in the field of radiation oncology, i.e. hypofractionated SBRT or proton therapy, thereby combining the potential advantages of the different dose escalation strategies to make a leap forward in the improvement of treatment outcome, both in terms of local tumor control and toxicity. To this end, a multicenter phase II study will be initiated to investigate the feasibility and safety of a simultaneous integrated focal SBRT boost to the macroscopic tumor in addition to whole gland prostate SBRT, called the hypo-FLAME study. In a translational side study, also the metabolic effect of this treatment regimen will be investigated, since there is emerging evidence that the metabolism plays a role in the response to radiation. As for proton therapy, an in-silico planning study on the potential benefit of focal boosting with this technique will be performed, striving at equal or better coverage of the focal boost regions and further reducing normal tissue toxicity. These results could serve as a sound base to decide on clinical trials in PCa patients in the future proton therapy center to be installed at UZ Leuven.

In order to safely implement and maximally benefit from these innovative treatment strategies the performance of multiparametric MRI for tumor volume delineation will be studied since - although an invaluable tool for the diagnosis and staging of PCa - its value in defining the exact location and boundaries of the intraprostatic tumor is still less obvious. More specific, we will develop an image registration pipeline based on 3D-printed patient-specific moulds and whole organ ex vivo MRI that will allow precise spatial, anatomical, functional and molecular correlation of in vivo MR images with histology from patients undergoing surgery.