Individualizing therapy for patients using the latest imaging techniques

What is new in the treatment of prostate cancer and what methods are you using at Johns Hopkins? Prostate cancer in the United States is primarily managed by one of two methods: radiation therapy or surgery. The number of surgeries being used for prostate cancer is diminishing as the therapies in the radiation field have improved substantially within the context of a greater number of cures with reduced side effects. The most important advances being employed right now for prostate cancer are what are called tomographic redelivered radiations. That is, we can image the prostate every day before we treat so we know exactly where it is located any given day. That enables us to give high doses to (the prostate cancer), while giving minimal or no doses to other tissues. Before, you would use somewhat less of a dose because you would be a little less precise. With this technique there has been a reduction in the side effects. How quantifiable is the benefit of this new technique? The quantification of that in terms of the side effects is well described by us as well as other institutions in the US. One of the most important side effects we worry about is rectal injury from radiation. This technology has reduced that to about half, so that’s a substantial improvement in the quality of life of the patients. There’s been another paper showing that the higher doses of radiation we can now apply, in randomized clinical trials have been proven to be much more effective in controlling the cancer than previously. I think the next important evolution in the field is to combine biologic imaging with radiation, because right now the standard is that we treat everybody basically the same, with few variations. But we know that some patients do better than others, so with the use of biological imaging – that is to say, PET scans, MRI scans – we can image the cancer frequently throughout the course of the therapy and more easily decide who needs a higher dose, who might actually need a lower dose of radiation, what parts of the prostate might require greater doses. The goal is to individualize the care that we are now delivering. What other methods of treating prostate cancer are being developed at Johns Hopkins? I think the last important component that we have worked on a great deal is the integration of other kinds of cancer therapeutics with radiation in prostate cancer in particular. This has been on multiple levels. The one that we are most excited about is the evolution about a way to deliver RNA (ribonucleic acid). Specific RNAs can target the repair machinery of the cell, because when a cancer cell is irradiated, it has an ability to try and repair the damage that I have inflicted and therefore they die at a reduced level. So we’ve developed a way to target that repair machinery so that with the same dose of radiation we will kill about seven times more cells. We’ve done this both in vitro, in the culture dish, also in animals, and now we’re starting a clinical trial. Can you tell us more about this technology? We at Johns Hopkins have developed a common cold virus, and were able to engineer this virus in such a way that it can only get inside prostate cancer cells, which is exclusive to other cells in the body. It can only deliver this RNA to cells that make a substance called PSA (Prostate Specific Antibody) so even if it gets into a cell that it’s not supposed to, unless that cell makes this PSA, this RNA cannot be produced. It’s targeted specifically to the prostate cells, and when that RNA is produced, it will target the repair machinery, keep it from working. It’s a kind of «smart bomb,» if you will. We have clinical trials now. How do your methods differ from what a patient gets in a general hospital? Most patients don’t receive the very precisely delivered radiation at the doses that we give, not so much due to technological limitations, although that is part of the reason, but it’s the balance of the large team that is necessary to deliver that care. Without that, it really can’t be done safely. Can you forecast what radiation oncology is going to look like in 10 years’ time? Radiation oncology over the next 10 years will be a larger specialty because it will be based on the newest biology-based imaging and profiling of tumors, so we know exactly what the different patients have in their cancers that will predict which therapies they are most likely to respond to.