A big “next step” in targeting radiation therapy within the prostate?

In February this year we noticed the abstract of a paper about “The use of dynamic contrast-enhanced (DCE) imaging for delineation of prostate tumors” and the use of “probability mapping” to assist in the treatment planning process.

At the time, frankly, we weren’t entirely sure we understood the premise. (Have a look at the abstract of this paper by Korporaal et al. and see what you think.) Biomedical science can get complicated fast, and if you don’t “get” new terminology it can be difficult to “get” the underlying idea.

Luckily, the authors of the original paper decided it was worth providing a less esoteric explanation of their research concept in “Beyond the Abstract” on the UroToday web site.

What Korporaal and his colleagues have done is to develop a highly sophisticated method for relating the probability of the presence of a tumor (as shown using dynamically contrast-enhanced CT scanning or DCE-CT) to the intensity of the radiation therapy delivered to highly defined volumes of tissue within the prostate. At least in theory, the very highest levels of radiation could be delivered with extreme accuracy to the portions of the prostate shown to have the very highest probabilities of the presence of cancer.

What this process may allow — assuming that the process can be refined and automated — is focal radiation therapy within the prostate that goes way beyond the current idea of “treating only the tumor we can see.” One of the problems inherent in current imaging of the prostate is that CT scans and MRI scans and even more sophisticated combination scanning techniques can not always tell the radiation team with absolute confidence what is a tumor and what is not. As a consequence, the goal of most current forms of radiation treatment — from intensity-modulated techniques (IMRT and IGRT) to stereotactic body radiation (CyberKnife and RapidArc) to proton beam radiation (PBRT) to brachytherapy and even to high-intensity focused ultrasound (HIFU) — is usually to maximize radiation to the whole prostate while minimizing the overlap of radiation of tissues that are outside the prostate.

The possibility that we could actually link the dose of radiation delivered to a specified volume of tissue within the prostate, based on the probability that cancer occurs within that highly defined volume of tissue entirely changes the way in which radiation might be used to treat prostate cancer in the future.

The image on the right (which we hope we will be forgiven for reproducing from the UroToday web site) illustrates the way in which DCE-CT shows the probability of the presence of a tumor in three different planes. The data used to construct these images can also be combined to provide a three-dimensional probability map of the presence of cancerous tissue within the prostate.

Basically, what DCE-CT does is show blood flow and blood vessel leakage within the tissues being imaged. We know that tumor regions within the prostate are typically characterized by increased blood flow and increased blood leakage (illustrated by the red areas in the image) by comparison with healthy prostate tissue (the blue areas). But (and it’s a big “but”) there is overlap between the blood flow and leakage values of healthy and tumorous prostate tissue. This means we can never be completely sure whether a specific region in the prostate is tumor or not. But we can assign a probability to the likelihood that a specific volume contains cancerous tissue or not. So clearly the large red areas in this image have a very high probability of being cancerous and the large blue areas have a very low probability. By associating the amount of radiation delivered to specific volumes of tissue to the probability that that volume of tissue is cancerous, we can take the “intensity modulation” of the radiation therapy to a highly sophisticated and customizable level.

If it proves possible to combine this type of probability mapping and radiation delivery with the use of fiducial marker systems like Calypso and stereotactic body radiation systems like CyberKnife radiation, we may really be on the road to highly targetable radiation therapy for localized prostate cancer, in which the ability to optimize high dose therapy to the tumor can be combined with the ability to minimize radiation of healthy tissue.

It is also possible that the principle of probability-based radiation planning outlined by Korporaal et al. using DCE-CT can be based on other forms of digital imaging technique. We suspect that there will be “more to come” on this topic in the not too distant future.

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