Chapters Transcript Video Evolving Evidence in Radiation Oncology Back to Symposium All right, thank you very much for giving me the opportunity to talk. Unfortunately my voice is also failing a bit now as well um so gonna go through some of the evolving evidence in radiation oncology and I don't have any financial disclosures so the topics just very briefly kind of evolution of some of the technology with radiation, uh, rectal spacers not very new but increasing utilization and it is pertinent to some of the other data I'll show you. Um, we'll talk about proton therapy, specifically for prostate cancer, adaptive radiation therapy, as well as SBRT or stereotactic radiation for renal cell. So there's been a very big evolution in terms of the quality of radiation, the techniques, the technology that we're able to achieve. So of course the primary goal always the same treat what we need to protect the tissues that are nearby. When we're doing radiation planning, we do usually CT often MRI, especially for prostate cancer. This is the simulation or radiation planning session. We need to develop an individualized radiation plan for every patient and, uh, typically we'll use image guided radiation or IDRT at least when we're doing, um, external beam treatment. So for radiation techniques there's been a big evolution started with 3D radiation. Just kind of coming from different angles. The pictures at the bottom are color wash images, so basically just shooting front to back, side to side, where all the beams intersect is where the dose is the highest, so that's the red. Then we move to IMRT or intensity modulated radiation. Now we have multiple different beams from different directions. They're shielding within the head of the machine that's modulating or moving to help shape the radiation dose as well. VA is basically where when you're laying on the treatment table and the machines rotating around patients and again that shielding is kind of moving in and out and so that gives us a better dose drop off. The SBRT is the stereotactic approach we use this for large dose per treatments and this again allows for a very rapid dose drop off from high to low very quickly. So radiation, um, planning fractionation. The dose per treatment. And so, uh, we could go at different speeds. The way I describe it to my patients is we're kind of walking, jogging or sprinting. And so, um, we're moving as a community to more and more hypo fractionation. SBRT is being utilized increasingly both in the definitive setting and in particular for oligo metastatic or, uh, select metastatic cases. So rectal spacers, not new, but you're gonna see a lot of your patients who are getting treated for prostate cancer getting them. These are, um, at least a Fox chase inserted by our wonderful urology team transperineal approach to create a temporary space. There's, um, 3 of the more common brand names that I put here. Uh, 2 of them are gels. One is a biodegradable. Balloon implant. So basically they're creating a gap or space. So the red um dash line is basically our enlargement or our what we call planning target volume. So basically it's a circumferential enlargement in terms of uh around the prostate of what we're targeting during our treatments so you could see in the image that the spacer actually creates that nice space or gap so that way the high dose radiation or our target. I, um, within the spacer itself and not the anterior rectal wall. And then you could see on the MRI image very nicely the spacer as well. So for um in the hyperfractionation study I'm gonna go through this pretty quickly but I put a lot of words just because I knew what voice was failing so you could uh see some of the details there but essentially this was mostly low intermediate risk uh patients they were looking to at the dose symmetry can we improve dose to the rectum and then also looking at acute side effects. And so essentially, basically everybody had a dramatic reduction in terms of the dose symmetry to the rectum. Uh, in the spacer group there's only 3% of patients compared to about 14% that experience grade 2 or higher QGI side effects. Um, I don't know how well you could read that table, but basically there's, uh, no significant difference in terms of the quality of life in all. that are looking there all acute GI toxicity resolved at 6 months and there's no, uh, grade 3 or higher toxicity in either arms if we want to look at patients that where there's longer data, we have it from conventional fractionation very similar patient population. Um, looking again at dossymmetry as well as, um, acute effects, but they followed patients out for more than 3 years. So rectal dose was reduced at 3 years there was no grade 2 or higher rectal toxicity versus, uh, 4 patients or 6% in the control arm. Bowel, uh, quality of life scores favored the spacer patients. There was no difference in terms of urinary toxicity. Um, or quality of life measures, uh, for sexual function changes there's also no difference but if on the subset analysis they looked at patients who had good sexual function to begin with and, um, having a spacer did have improvements in terms of their continued sexual function after so, um, you know, rectal spacers are something that for our prostate patients we discussed with all of them it's something that we're utilizing increasingly. And um very excuse me um common procedure that our patients will have done so just to go on to proton therapy, very different, um, the radiation treatment that we most typically use is via linear accelerator using high dose photons. Protons are hydrogen atoms heavy um charged particles. The dose distribution is different. Um, photons deliver most of their doughs pretty close to the surface. Protons kind of do it all at once and create this rag peak. You could spread out the rag peak, um, and ideally have your tumor kind of located between that, um, spread out Bragg peak and protect the tissue behind it. Um, cellular damage kind of differs. Phons create a lot of single strand, um, DNA breaks versus. The protons are gonna have more double stranded complex cellular injury which is harder for the cells to recover. So some of the potential advantages are, well, if we could reduce the dose to the organs that are nearby we can therefore reduce some of the toxicity as well to those adjacent organs at risk. Um, there's a lower integral or overall radiation dose to the patients, so even though the risk of developing a second cancer is low, maybe we can make that even better. Um, because the relative biologic effectiveness of the proton therapy, um, just the way that the the physics and the, um, biology is, we would expect it to be at least as good as photons, maybe better, but potential disadvantages is that there, um, excuse me, there can be disadvantages, uh, in terms of the way that the dose is distributed. There is like a. Intensity modulated proton therapy that can overcome that. There's also greater uncertainties in the effectiveness kind of right at the end of that rag peak. And so if you have your bra that end of the rag peak kind of ending right near the anterior rectal wall, well then that is gonna be associated with higher rates potentially of toxicity, uh, much more expensive in terms of cost and so this is older analysis but the best I could find, basically showing proton therapy is at least twice as expensive. Availability is certainly, um, not an issue locally, but Something that comes up more on the national level, um, something I get asked about very often Fox Chase, we do not have a proton center here, but, um, gonna show you some data that looked at protons versus photons for prostate cancer that essentially, um, in this observational study showed no difference in terms of GI toxicity, GU toxicity at 6 months, 1 year and 2 year end points. The, um, most recent and kind of the best data I think that's currently out there is from the particual trial. This is a randomized multi-center phase 3 study. Again, low or intermediate risk prostate patients, uh, they only got radiation. There was no hormone therapy associated with it. We only treated our patients that were enrolled only received treatment to the prostate and the seminal vesicles. There was no, um, treatment to the pelvic lymphatics, and patients could get treated either with conventional or moderately hyperfractionated dose. So stratifications listed, um, looking, again, they randomized about 450 men, either proton or IMRT and they looked at, um, multiple secondary outcomes and time points going for 5 years. Uh, this was a very well balanced study. About half the patients got the rectal spacers, uh, a little bit more than 50% are intermediate risk disease. And so ultimately from an efficacy standpoint there was no difference in terms of biochemical recurrence rates, um, local recurrence or distant metastases, so protons, photons equally effective, um, from the quality of life standpoint there was no difference in GU incontinence, bowel toxicity, sexual quality of life. And so my thoughts on this is that this confirms that with modern radiation techniques, um, and with modern planning we have excellent outcomes very favorable 5 year quality of life outcomes. It's unclear how this results would apply to high risk patients, especially those that would require notal treatment. It adds confidence when I tell my patients that based on available data that. Um, protons are, you know, equally as effective as photons. Um, and it does beg the question whether there's gonna be an impact in terms of future reimbursement as well. Adaptive radiation therapy, um, we first started doing at Fox Chase in 2023 and since then there's been increasing number of patients that we've been treating, um, for a variety of sites essentially what it is is doing treatment plan modification in real time. This may be related to the tumor's response to treatment. The position of the target, the tumor itself, um, or the position of the normal tissues replanting and quality assurance are done while the patient's on the treatment table for every single fraction or radiation treatment and the potential is that we could get better coverage of our targets so again meeting those primary goals and um hopefully superior normal tissue radiation dose. So patients get their typical CT and for prostate MR stimulation. We do the treatment planning. patient comes in for their set up, so we do pre-treatment imaging that image guided radiation, see how everything aligns, and then we see how our initial plan would actually look on the patient with that current anatomy and the position that there are and um then a second plan is created. Uh, basically, a comparison is done to see which one is better. If the replan is better, then we go with that adaptive or replan treatment and the patient gets their treatment right then and there. Um, so in this example, this is a prostate cancer patient that's being treated. I don't expect anyone to be able to read those, but on the side, these are the types of information that's given out. It's, um, we get data regarding our target coverage and so in this example here, this patient's target coverage was actually not as good if we were to use the, um, previously our original plan. Uh, on their current positioning, but on the replan, uh, it's improved. Additionally, on the replan or the adapted plan, the dose to the organs at risk, mainly the rectum were improved. Um, so in this example, um, typically our patients who are getting the adaptive radiation for prostate cancer, they will get space or view, um, which you could see a little bit beneath some of the, um, the color wash and some of the, the lines there as well as fiduciial markers, and that helps with the algorithm of, um, the software. And so we can then make adjustments and even without adaptive planning we can make some adjustments based on anatomic positions but we could also then account for other changes such as um variations in bladder filling and so we can now say, OK, things have moved around or adjusted and we could adjust our plan accordingly to it. And so the adaptive radiation again allows for real-time assessment and planning. It can be utilized for many different cancer types. We could do it for many different types of fractionation. Um, it is time and labor intensive. The patient has to be able to lay on the table for instead of a standard 15 minute appointment, 30 to 40 minutes depending on the specific treatment, and it also gives us the opportunity to do novel techniques, maybe a focal boost to say part of the prostate. Other, um, if we're treating kidney things like that we're able to, um, hopefully dose escalate because we also have a higher level of confidence about where our normal tissues are. uh, adaptive radiation can also be used very nicely for renal cell carcinoma for SBRT typically or historically we would say, uh, renal cell carcinomas are resistant to radiation. So they were not really utilized in the definitive setting or radiation wasn't really utilized in the definitive setting, but SBRT is becoming increasingly utilized as a way of doing noninvasive nephro responding, uh, nephron sparing treatments for those patients who either are high risk, opt against, um, surgery or not are not candidates for surgery, um, so there's been several recent studies that have demonstrated that we can have high rates of local control. There we go, um, so there's a multi-institutional meta-analysis that was done that showed 5.5% year of local, um, 5.5% local failure rate, so 94.5% local control. There's only one grade 4 toxicity, no grade 3 or higher events, and a meta-analysis that was recently. Published as well, um, this had over 800 patients and excellent local control rates again 94% with favorable 5 year progression free and overall survival. Uh, different fractionation options that could be utilized, uh, SPRT is typically up to only 5 fractions. That's gonna depend on. The proximity to normal tissues as well as the tumor size, um, so within the past two years there's actually been several uh publications that have um tried to develop practice guidelines recommendations as well so I'm just over my time uh thank you for your attention and the opportunity to speak today. Thanks. Created by Related Presenters Randi Cohen, MD, MS Director of Radiation Oncology, Fox Chase Cancer Center – East Norriton,Associate Professor, Department of Radiation Oncology, Fox Chase Cancer Center
