Demystifying radiotherapy in rectal cancer: Dr. Sanford (2021)

This is an automatically generated transcript.

Manju George 0:00
Hi everyone. Welcome to Doc talks. I’m Manju George, the scientific director of COLONTOWN. Today we have with us Dr. Nina Sanford. She got her medical degree from Harvard Medical School, and she did her internship in internal medicine at Brigham and Women’s and residency in radiation oncology at Harvard and Brigham and Women’s and Mass General. Now she is at, you know, UT Southwestern, and I met her last year at gi asco, and she’s been my go to person for all questions related to radiation oncology. So it’s such a pleasure to have you here with us, Nina. And welcome.

Dr. Nina Sanford 0:39
Thank you. I’m excited to be here, and I will go through the PowerPoint and then answer questions, and then, you know, we can definitely make this interactive as well. Alright, so I will be hopefully demystifying radiotherapy and rectal cancer.

Dr. Nina Sanford 1:04
Okay, so first, I’m just going to talk about some very basic things about radiation, before moving to more rectal cancer specific things. So first, what is therapeutic radiation? So for radiation oncologists, radiation is our you know, our tool. It’s our knife, our drug, and our goal is to selectively kill cancer cells. The most common type of radiation is high energy photons. However, charged particles ranging from electrons, which are very light to heavy particles, such as protons, can be used and radiation dose is measured in gray.

Dr. Nina Sanford 1:48
All right, so I just kind of want to go over if you see a radiation doctor, kind of your care path from beginning to end. So first, you know, you see them in consultation, they go over your history, and they make a recommendation. After that, there’s something called the simulation, where it’s kind of like the radiation planning process, also called sim or radiation planning. And for this, they do a CAT scan of you in the position you’re going to be treated in, usually for rectal cancer that’s either supine on your back or prone on your belly. When you’re on your belly, your bowel, for some patients, moves out of the treatment field. If you’re supine, your arms are over, usually on your chest, and your legs are straight. Usually we use a back lock bag for mobilization. That’s kind of like a bean bag, where you kind of suck the air out and it becomes firm. If you’re prone on your belly, then there’s something called a belly board that actually allows your belly to kind of fall forward, kind of under the treatment table. We do a CT scan, and we usually give intravenous and oral contrast. This is not specific to rectal cancer radiation, but we use different immobilization devices depending on the area of the body we’re treating. So if you’re getting head and neck radiation, you get a mask. And then usually, for rectal cancer radiation, kind of looks like more on the bottom, where you’re kind of in this back lock or bean bag that’s kept for you during the entire treatment duration, and you go in it every day for treatment. So after we acquire the CAT scan during the radiation simulation process, sometimes we fuse it to an a PET scan or an MRI to help us see things. So this is a head and neck plan, and they’re actually looking at the nerves in the area. This is on CAT scan, and you can see it better on MRI. So we fuse those things to do the radiation plan for rectal cancers, we also fuse with an MRI for certain cancers, we fuse with a PET scan. So what radiation oncologists do is that on every slice of the CAT scan we really outline both the areas that we want to treat. And here is in red for head and neck plan. It’s kind of the nodal bed. And then we also outline the areas we want to avoid. And here would be in yellow as a spinal cord. After we outline those areas, we give our plan to physics or dosimetry, and they make a plan. So what you see on the right is a radiation plan for head and neck cancer. And all the different colors refer to different dose levels, and they’re called isodose lines. And I tell my patients that this is kind of look like looking at a topographic map. So basically, the areas in yellow here are getting the highest dose, like they’re like the highest, you know, part of a mountain. And then as you go lower, depending on what you set your low dose, as these areas in blue are getting low dose, if we drag the kind of dose bar down to zero gray or one gray, you see pretty much the entire area here getting some radiation dose. And that’s important, that. Uh, you know, there are areas that are getting high doses, but you know, most of the areas that you’re treating in around it is getting some radiation dose as well. On the bottom is called a dose volume histogram, and it’s what we use to evaluate plans. On the x axis is basically different dose levels. And on the y axis is the percent of a certain structure getting that dose. And we look at those lines to make sure they meet our metrics for you know, what we think is safe, always, there are compromises. We want to make sure we’re covering our targets and minimizing dose to surrounding organs that we want to protect. And we do a lot of kind of going back and forth to find what we think is the optimal plan that, again, maximizes our target coverage and minimizes doses to critical structures around the area. There’s a QA which I won’t, you know, go into the details of, but basically, we have to make sure that, you know from very things that seem very rudimentary, like, when the machine is going around you, it like, doesn’t hit you. So there’s every plan that is done for it goes to the patient. We test it on a phantom. We do machine checks, just to make sure that, you know, in radiation oncology, like, like in most specialties, really, there’s, like, no room for error. So everything is very rigorously checked by many, many people. I’m very fortunate to work with really amazing physics and dosimetry that makes sure everything is safe and exactly how we want it to run before it gets to the patient. So treatment. This is a picture of like, I guess, the first radiation treatment in the 1950s it was a lot more crude, you know, just had them sit there and hope that it was treating the right area. Now, it’s a lot more sophisticated in that patients are put in mobilization devices. They’re measured to the millimeter of where they need to be. Basically, we need to make sure that the patient is in the right position in the device. The device is in the right position in on this kind of treatment table. So everything needs to be coordinated exactly right every day during treatment, depending on the type of radiation you get, you get daily films. So usually it’s X rays, and usually we line up to bone. Sometimes we can sometimes, if we really need to see soft tissue, we do more imaging that can help see the soft tissue, like for rectal cancer radiation, we want to see the bladder fill. So sometimes we’ll do what we call a cone beam CT to check the bladder fill. But generally we make sure that the bones are exactly lined up every day, and that’s a proxy for everything else lining up. And then after your treatment is over, we follow you along with your other providers, for two reasons, to make sure that to follow your cancer and to follow side effects as well. So now let’s get into more specific kind of rectal cancer. The more specific rectal cancer part, so I tell my patients that you know, you’ve probably heard of the term colorectal cancer as like, kind of one entity, and they are similar biologically and kind of embryologically. That’s why we can talk about mutation status in those that’s they’re all kind of the same. And a lot of the genomic testing is, you know, kind of the same family, but anatomically, they’re actually different. So I tell my patients when they think about colon, it’s kind of like your intestine in your belly that you kind of think about, whereas the rectum is this area at the end of the colon, before the anal canal that sits in the narrow pelvis. And that’s important because, because it sits in that narrow pelvis, which in males can be as narrow as like five centimeters. It can be harder to obtain negative margins at the time of surgery. Therefore, radiation can be more important in rectal cancer, and also along that route, local recurrence is more likely, and it’s also a lot more morbid. So basically, we really don’t want to have a local recurrence in rectal cancer. These are, these can be very, very tough to treat, and very, you know, really devastating for quality of life.

Speaker 1 9:35
So how’s radiation given in rectal cancer?

Dr. Nina Sanford 9:39
So I’ll go through some of the major studies in rectal cancer. There have been a lot of studies, but I’ll kind of go over the major one. So the a big one that was now almost 20 years ago is the German rectal study. So prior to this, surgery was actually used first, and radiation was given after surgery. Okay, that was kind of the trend in a lot of different cancers to operate first and then kind of clean up with surgery, with radiation and chemo after this trial compared doing radiation before surgery versus radiation after surgery, it found that doing radiation before surgery reduced the local failure rate; increased the rate of sphincter sparing surgery. You can imagine that because you’re downsizing the tumor, and there were less toxicities, both acute and late. So after this trial, in 2004 pre op chemo radiation became the standard of care. So this was a very important trial, because it really shifted the practice from post op to pre op radiation. A lot of patients also ask about short course versus long course chemo radiation. So long course chemo radiation was studied first. This is generally about 50 gray and 25 fractions. That’s five weeks of treatment, and that’s given with concurrent 5fu or Capecitabene, which is the oral form of five Fu. Short Course radiation is 25 gray and five fractions no chemotherapy, and it’s completed in one week. So it’s given every day. You might say that, well, a short course half the dose of long course radiation, because 25 is half of 50. The answer is no, because when your fraction sizes are bigger, so short courses five gray per fraction the biologically effective dose. So how, how powerful that dose is in your body is more. So the biologic effective dose of short course is not half that of long course, but it’s a little bit less. There have been two trials that showed equivalent outcomes and decreased toxicity with short course radiation. However, short course is really underutilized in the United States. I think a study a couple years ago showed that this was about 1% of all treatments. This has changed with COVID, so it has definitely picked up with COVID when, you know people don’t want to be people really didn’t want to be coming here for five weeks and increasing their exposure. Also, the way that radiation oncologists are paid has been per treatment or per visit. So there’s been a financial incentive to do longer treatment courses as well. There will be bundled payments in radiation, where patients or where providers are paid per kind of treatment course. So sorry. So you know, for, you know, for what it is, I feel confident that with the changes in bundled payments, there will also be more short course radiation. So total neoadjuvant therapy is also a emerging paradigm, or I shouldn’t even say emerging. It’s a currently being practiced paradigm in rectal cancer. So what does it mean? It means putting all of the chemo, radiation and chemo, prior to surgery. So it’s neoadjuvant, means before, in total, I guess, means everything, so basically everything before surgery. So what are the advantages of this one? Is it increases the ability to complete chemotherapy. So it can be hard to do chemotherapy after surgery. If you do all of it up front, then the likelihood that a patient is going to complete all of it is higher for more advanced tumors. It provides early elimination of micro metastatic disease before taking them to surgery, which is what we do in other cancer sites like pancreas cancer, where there is a really high risk of metastatic disease, it provides maximal down staging of the primary tumor, which potentially could allow for organ preservation or sphincter preservation if they’re getting surgery, also allows for earlier stoma reversal. So because they’re not getting chemotherapy after then, really after the surgery, if they have a temporary ostomy that can be reversed in a couple of months. There are many trials evaluating this. I’d say probably one of the largest is the NRG gi 002, which looks at eight cycles of FOLFOX radiation and Capecitobine followed by surgery. And they’re testing additional agents to be given with Capecitobine, such as a PARP inhibitor or immunotherapy. I’ll talk about this a little bit more, but the uptake of total neoadjuvant therapy has been very high, and for many centers, it really is now the standard of care for locally advanced rectal cancer. There is some controversy about whether or not to do chemotherapy first or chemo radiation first, and there are differing opinions and kind of pros and cons to both. And I think the decision really has to be individualized to that patient, their symptoms and what their goals are. So I’ll go over a trial that I think really has changed practice over the last year. This was presented at ASCO last year. This was a rapid trial which looked at short course radiation, followed by chemotherapy and then surgery, versus more the traditional long course chemo, radiation, surgery and adjuvant chemotherapy in high risk rectal cancer. So the primary endpoint was disease related treatment failure. That was a composite endpoint, including distant meds, local, regional failure, a new primary cancer or treatment related death. They had a lot of secondary endpoints as well. This is just to show that it was a pretty large trial with actually 920 patients randomized close to 1000 patients. So in terms of the results, there were no differences in surgical complications between short versus long course, they noticed that with short course radiation, most more patients had a pathologic complete response, which means that at the time of surgery, there was no tumor left over that is most likely attributed to patients in the short course arm getting chemotherapy before surgery as well. In terms of the primary outcomes, they found that patients getting short course and chemo had lower rates of distant metastases. However, there is no significant difference in local regional failure or overall survival. So to me, this trial really shows that short course radiation, chemotherapy and surgery is is a is a standard of care now and I think it remains to be seen, you know, comparing short course versus long course with chemo up front. This wasn’t really a trial comparing short versus long course TNT, because the long course arm had chemo after surgery, but it really brought in the short course in chemo as a standard of care and even since this trial, I’ve definitely seen this used more and more as nonoperative management, I know, is definitely a topic that a lot of people are interested in. So it’s actually not a new concept. It was actually really introduced probably a couple decades ago, in the early 2000s maybe even before in the original pioneer was a female surgeon from Brazil, Dr Habr-Gama. And I actually remember when I was a resident, which was not that long ago, and people really thought she was crazy, and this wasn’t that long ago. You know, they brought up her papers when we’re kind of disparaging to her, actually, and that is like changed so much in the last five years. So basically, non operative management, as the name suggests, is omission of surgery for patients who have a complete response that is determined by endoscopy and MRI. So this is an example that I got from this reference on the station as a tumor, and then they get whatever treatment they get, and then after they have no more tumor. It may be particularly attractive for young patients. You can avoid a permanent class mean distal tumors, along with other side effects from surgery. Close surveillance is needed, especially the first two years. Generally, these patients should be surveilled every three months for the first two years, and there are a lot of ongoing trials assessing kind of different regimens for this. A big study that was presented also last year is the Opra study, looking at organ preservation in rectal cancer. That’s what Opra stands for. And this study looked at doing either chemo radiation first or chemotherapy first, and then the preliminary findings found that there was no difference in cancer outcomes, but starting with chemo radiation actually was associated with higher rates of organ preservation of 59% versus 43% and they hypothesized that the time from radiation, just because radiation takes time to work, allowed for a more robust response. But I’m sure there’ll be a lot more will come out when the study is published. So I have to say something about chemotherapy, even though this is this is a talk about radiation, because distant mets remains the predominant form of failure. But six months of five fu based multiagent chemo with either FOLFOX or CAPOX, that’s five Fu and oxaliplatin, or Capecitabine and oxaliplatin is the standard of care. This is actually extrapolated from that MOSAIC colon cancer trial. So just kind of on an off topic, I think it’s very interesting that in colon cancer, there is a lot of studies, you know, going from six months to three months of chemo in rectal cancer. We got our chemotherapy from colon cancer. But, you know, we’re talking about escalation of chemo, and, you know, I It’s, I think it’s an interesting issue, but immunotherapy is very hot in cancer. Thus far, it’s really shown to be most effective in mismatch repair deficient colorectal tumors. I put this innate trial here. This is a trial that. We have at UT Southwestern combining radiation and immunotherapy and short course radiation and rectal cancer, there is an emerging role of circulating tumor DNA in colorectal cancer, which may be able to guide adjuvant therapy. And then the prodigious 23 study showed that neoadjuvant, FOLFIRINOX improved disease free survival and metastas free survival compared to FOLFOX. So in practice, FOLFIRINOX is used for the healthiest, really metastatic patients. I’d say most providers aren’t using it for locally advanced setting as a standard of care quite yet, just because increased toxicity, and they really want to save the irinotecan in case a second line therapy is used. So there are, like so many treatment options for rectal cancer. I totally understand that it can be very confusing for patients with all the treatment options. The key trends, I would say, I don’t know if this is a trend, but it’s a reality, is that there’s a lot of heterogeneity between centers and experts. Adoption of total neoadjuvant therapy is very high. There is growing interest in non operative management, but I think that really is best limited centers with expertise and use of short course radiation is finally increasing. So what we do here at UT Southwestern is that we were actually very early adopters of short course radiation as far back as 2015 so we feel very comfortable doing that. Our most common regimen is short course radiation and three to six months of chemo and then surgery, kind of like the rapido study, non op is really per patient request, and for specific cases, we do have an upcoming trial looking at that fewer patients are getting long course chemo radiation. We also do intraoperative radiation. A lot of that is for recurrent rectal cancers that can really be very invasive, involving the pelvic sidewall, in the pre sacral area, where it’s hard to get negative margin. So we do actually interop radiation for those cases. I have to put a plug in for this trial that we’re recruiting at here on the PI is my colleague, Dr Aguilera. So this is a trial looking at short course radiation with a CD 40 agonist, which is immunotherapy. So patients get that agent during radiation, and during FOLFOX chemotherapy, the randomized get that, or just our standard, which is short course radiation, chemo, and then they get surgery after, so we need to talk about toxicities of radiation. This is a very important topic that has been that I’m glad is getting more and more attention to. So the first thing to know about radiation is that side effects of radiation are really directly related to the target location. The exception of that is fatigue. Most patients do get fatigue, and that’s sort of a systemic symptom. But I tell patients that you will not have hair loss on your head from the radiation, and you will not be radioactive. Those are kind of like two commonly asked questions. So this is a patient plan. I just want to show the organs where we treat, I mean near our target volume. So first of all, the patient’s tumor is circled here in red on the left, the kind of light purple ends up being our target volume. And the reason it’s a bit bigger is that we include where there could be lymph nodes hiding, and then the bladder is in yellow above and below the tumor in brown is the rectum, the large bowel is in pink, and then this purple up front is a small bowel. So those are all the organs kind of in the area that we treat. We treat with a bladder full. I know that was one of the questions. You can see that even for this patient, when our bladder is full, it actually pushes a small bowel up and out of the treatment field, whereas, if we’re empty, it could fall down and be closer to our treatment field. So we treat with bladder fall. So this is our consent form, and I’ll go over the main things in details, but basically, we divide up side effects of radiation into acute or late acute is during or shortly after radiation, and late is three months plus after radiation, so three months years and decades after. So the most common toxicities during acute, acutely or during radiation, are diarrhea, bladder irritation, proctitis, which is inflammation of the bowel and anal canal, skin changes, also called radiation dermatitis, fatigue and patients can also be at increased risk of yeast infections. And here I already I put in kind of our most common treatment recommendations for those symptoms, I would say that the degree that patients get. These symptoms depends on where their tumor is. So if it’s a very distal tumor and we’re really treating the anal canal and the skin around that area, these symptoms tend to be more severe. If it’s an upper rectal tumor and we’re really not getting the anal canal or the skin, those treatments tend to be more easily tolerated. The other thing is short course versus long course. So I would say that my patients during short course radiation really don’t have any of these symptoms for a variety of reasons. Sometimes they can get diarrhea about two weeks after the treatment is over. But really, the radiation goes by pretty fast for short course five days, the total dose ends up being a little bit lower that they don’t really notice much of these symptoms. So I’m going to divide toxic, late toxicities of radiation into several different kind of body systems. So the first is gastrointestinal. This is a lot of these are uncommon. One difficult part about talking about these symptoms is that it’s conflated with surgery and chemotherapy. So really teasing apart the individual contributions of radiation itself can be a little bit tough. So permanent bowel habit changes, and I say uncommon would be severe, permanent bowel habit changes. So, you know, feeling like you have to go to the bathroom all the time, incomplete emptying. It’s rare for radiation itself to cause that. For incontinence, I tell patients that if they weren’t having incontinence before radiation, it’d be very unlikely for radiation to cause incontinence. The dose we go to is just lower than the tolerance of the nerves. Now, if they were having already incontinence before radiation started, I also say it could be unlikely that radiation will fix the incontinence, because usually the nerve damage is lasting. Obviously, if they’re getting a permanent ostomy, then you know that that, that part, you know, is less relevant. But I usually tell a patient, you know, if they have an upper tumor, upper rectal tumor, they’re getting an LAR it’s unlikely for them to be incontinent after from the radiation. Bowel obstruction would be due to adhesions from the radiation, and that’s also uncommon. Patients also ask a lot about musculoskeletal side effects of radiation, so So fractures. So I found a study, I think this was 2012 looking at post operative imaging of patients who got chemo radiation, about vibrant patients at medium follow up of three and a half years, about 7% develop a sacral insufficiency fracture. So this was caught on imaging. It doesn’t mean that all of them were clinically, you know, causing a lot of problems. I’m sure some of them were a lot of these were radiographic findings age greater than 60, which probably correlates to menopausal status, female sex and history of osteoporosis had increased risk in terms of risk reduction from the patient perspective, management of osteoporosis, such as with bisphosphonates, can be helpful, as well as weight bearing exercises. And I think there was a question about getting a baseline DEXA scan, which I think is a good idea. From our perspective, we are looking at doses to bone marrow and trying to minimize those doses, both for risk of osteoporosis and for suppressed marrow function in the long term. Usually, I’d say, like 99% of these are managed on operatively with physical therapy and you know, most of these end up healing on their own.

Dr. Nina Sanford 28:45
Secondary malignancy is a very scary side effect of radiation. And you know, I hate when I meet a patient and tell them that, you know, we’re trying to use radiation to cure your cancer, but it can also cause a cancer, but, but unfortunately, that’s a reality. It’s radiation dose dependent, age dependent, much more likely in our young patients and target location dependent, meaning, if you get radiation of the pelvis, any secondary cancer would be in the pelvis. It’d be indirectly in that area that you treated. With the exception of blood cancers like leukemia and myelodysplastic syndrome, they can be increased with radiation as well. The good thing is that there have been a couple studies on secondary malignancies, specific to rectal cancer and the absolute risk. And these studies actually showed no increased risk above the population level. I think there certainly is an absolute increased risk. It’s likely quite small, but certainly you know not nothing. I know you’re having an expert talk about sexual health after and I would definitely defer to her. But there are, you know, a couple things specific to radiation that I did want to bring up so radiation can and I divide into women and men. So in women, radiation can cause a lot of unwanted side effects, vaginal dryness, thinning, stenosis or shortening, dyspareunia, which means painful intercourse, bleeding and also injury to the bladder or bowel or bowel, infertility and sudden menopause. And also kind of relate to all those things, psychosocial effects on the picture on the right, you can see that basically it’s a picture of vaginal stenosis. So before treatment, the vagina is open, and after it can really scar down and close. Fortunately, that can almost be completely preventable with vaginal dilator. So, you know, it kind of looks like, I guess, a tampon. We tell patients, patients to use the largest size that’s comfortable to start four to six weeks after pelvic radiation is over, daily. But I tell patients three times a week is probably fine 15 to 30 minutes with a water based lubricant, and the most critical, critical time to use this is for about a year after treatment is over with this, you’re really breaking up the fibrosis, and it essentially, completely prevents it, because you’re, you know, actively breaking up the scar tissue. So this is super important, you know, unfortunately, I’ve seen patients who have recurrences or for whatnot, and didn’t have didn’t use vaginal dilators and weren’t instructed about them, and unfortunately, they cannot have sexual intercourse. They cannot get cervical exams. And it’s and it’s really very, very tough. So fertility in women is also an important topic, particularly as our patients are, unfortunately getting younger. So radiation of pet impacts fertility in multiple ways. One is hormonal dysfunction, ovarian dysfunction and uterine dysfunction. Unfortunately, with the doses that we use for GI cancers, the risk of infertility and in women is about 100% the dose needed to cause infertility is very, very low, and even with procedures and you can’t really prevent internal scatter radiation, so the risk of infertility, unfortunately, is very, very high. Pregnancy after radiation can be possible, and a lot of these are other cancers, but can be associated with poor outcomes. So I tell patients that if they are considering having children in the future, egg harvesting is a good option. Or, you know, egg harvesting and embryo freezing, unfortunately, that does take some time to do chemo. So, yes, radiation, you know, doesn’t cause infertility alone. Unfortunately, chemotherapy, to do can also cause infertility. Fortunately, a lot of the agents that are really high risk are not used in rectal or colorectal cancer. And then really we’re looking at 5FU, which, fortunately, is lower risk in terms of infertility. So I think this is actually my last slide. So for men, or second to last slide, the risk of infertility is lower about one in five. So I tell men that they probably will be able to have children. They should sperm bank if they’re considering having children. Fortunately, for men, it’s a lot easier to sperm bank than for women to egg harvest. There’s often a fee associated with preserving, preserving the sperm, unfortunately. But most my men, my male patients, have have been able to do that. Who who wish to it can really be done literally, in between the time you do the radiation planning and the radiation treatment start, you can do a couple sperm making sessions in terms of sexual side effects and erectile dysfunction. There’s little data on the effect of radiotherapy alone in rectal cancer, because most of these patients are getting surgery. I think as we have more patients who get non operative management, it’ll be really important to follow these patients long term to see what their long term side effects are. In prostate cancer, where there is a lot more data, because a lot of those patients are getting radiation alone, the risk of erectile dysfunction is about 40% with radiation alone. However, the dose in prostate cancer is much higher than rectal about two times, and the location is a little bit different as well. There is a high rate of sexual dysfunction from rectal cancer surgery. And I asked one of our surgeons this very recently, and that person quoted to me 1% and I was a little bit surprised by that estimate. So I actually looked it up, and it’s quite a bit higher. Studies suggest that it can be as high as 50 to 70% erectile dysfunction, and that is mostly due to injury to the nerves with surgery, you can see that these sacral nerves control a lot of sexual function in men, and these are these can be injured with surgery. This abstract I have, are these results. Here is from another paper, and it shows that ll and D, which stands for lateral lymph node dissection, also increases the risk of erectile dysfunction, so it actually can be quite high after surgery, which I was a little bit surprised to see, actually. So I think that’s actually all I have. I happy to answer any questions, or I can go through the questions,

Manju George 35:50
Yeah, thank you, Nina. This is amazing. And thank you for the slide, absolutely. So maybe we can go through the list of questions people have.

Speaker 2 36:08
Is it recommended to do long course radiation instead of short course? Or does it matter? Yeah,

Dr. Nina Sanford 36:17
so that’s a super, really good question. So almost all the studies in watch and wait are using long course that are published have used long course chemo radiation. As I said, the total dose is higher. So I would say that if you polled many providers now, they would say, if you want to do watch and wait, they’d probably recommend long course over short course, just because that’s what the data show. There are multiple studies now opening looking at short course radiation and watching weight, including one from Wash U where they published some preliminary results or presented some preliminary results maybe one to two years ago, and they looked really, really promising. The decision really has to be individualized to the to the patient’s tumor. If it’s a really big tumor, then they’ll probably need a little bit more radiation dose. If it’s like a smaller t2 and one early t3 tumor, then maybe less dose is fine. But right now I see the standard, and I think what most people would agree with is that for watch and wait long course is probably preferable. But that’s a great question, and not fully answered as of yet.

Speaker 3 37:32
I see okay. One last question is, if you do radiation for your rectal cancer, is it correct that if there’s a reoccurrence in that local area, we cannot do radiation again?

Dr. Nina Sanford 37:49
Yeah so that’s a really good question too. It depends. So a couple of things. So if the cancer already got the full dose of radiation and it grew back. It tells us that that cancer may not be as sensitive to radiation. So it tells us something biologically about the cancer, that radiation may not be as effective in terms of whether or not you can do re irradiation. It depends on how long it was from the prior radiation, if it was like, a year six months ago, I think a lot of people would be hesitant to do re irradiation. And to be honest, a lot of those instances are like, you know, recurrences at the anastomosis that probably can be taken out surgically. If they were, you know, got treated 10 years ago and are having a recurrence, and the surgeon is concerned about margins. Then we have done re irradiation in those settings. Then this is a situation where the interop radiation might be helpful, because then you’re really avoiding dose to a lot of the surrounding organs and really getting where the concern is for the high risk margin. So I’ve we’ve treated plenty of rectal recurrences here with re irradiation, so it has to just be made on a case by case basis. Great.

Speaker 3 39:08
Thank you so much. Yeah, that’s all my questions.

Manju George 39:12
Nina, one question I have is about, so you said that you in your center. You have been doing short course from 2015 right? So do you have some data from your place about people having done watch and wait? What is your personal opinion?

Dr. Nina Sanford 39:29
So we’ve done short course with surgery. We haven’t done a lot of short course with watch and wait. So hopefully we have a trial coming for that, but we’ve been very much believers in short course radiation, so hopefully we’ll have some more data out on that.

Manju George 39:44
Okay, thank you. So maybe then we can look at these questions. I kind of wanted, after you go through the questions, to talk a little bit about, you know, boosters and our, you know, extra dose to lymph nodes, those kind of special things that you do for rectal cancer, which is not really standard of care, right?

Dr. Nina Sanford 40:02
Okay, should I just go from the top? Then I guess. Okay, so why do some ride on say to have bladder full, and others say doesn’t matter. So bladder full pushes a small bowel out of the treatment field, we do bladder full for all of our rectal cancer patients, a difficulty of it, which I definitely experience, is the is a variability day to day. So you’re asking patients to drink two bottles of water, 30-45, minutes for treatment. But really their bladder filling depends on how much water they had, like the night before, or, you know, when they urinated. So one difficulty of that could just be the day to day variation. So I could imagine, if there’s a patient whose anatomy, like is really doesn’t matter with the bladder, or they just don’t have a lot of bowel and they’re having a lot of variability in their daily feeling that it’s possible that, you know, their clinician could just say, Don’t worry about it, because that’s not going to really help you, and it’s causing a lot of you of, you know, difficulty adhering to, you know, the daily treatment protocol. But we do bladder full for everyone. Okay, what is being done to radiate the tumor and spare the surrounding tissues and organs? So that is, like the crux of our job. So I would say a lot is being done to do that. And basically, you know, when we do the treatment planning, we outline exactly what we want to treat and what we don’t want to treat, and the way we arrange our beams, and have, you know, weight, the different beams and the angles and whatnot, really maximizes dose to the tumors and minimizes to the surrounding organs as much as we can. It’s always a trade off, as I was saying. So we don’t, you know, we can never get to zero dose to the surrounding organs, but, yeah, that’s definitely very important to us. You know, interesting to see what the connection from radiation to LARs is. So Lars, is lower anterior rectal syndrome, and it refers to kind of long term toxicities due to sphincter preserving surgeries or lower anterior resection. So I would say, you know, if you look at those symptoms as a whole, those are generally like incontinence or increased bowel frequency, you know, diarrhea, constipation, having a lot of gas. I’d say radiation most likely worsens those symptoms, just because radiation can cause some of those symptoms as well. I always tell patients that if they’re having those symptoms long term, you know, Lars is sort of a diagnosis of exclusion. So it’s kind of saying, you know, if we ruled out everything else, and it’s probably large because you had sort of had radiation, but be sure to get worked up for other things. Even I’ve seen patients after radiation be diagnosed with inflammatory bowel disease or irritable bowel syndrome or bacterial overgrowth, or, you know, something unexpected. So if you’re having, particularly if these symptoms kind of come on suddenly and you weren’t having on them before, definitely get worked up to make sure that, you know, we’re not missing something. For just saying, this is Lars and and whatnot. Is there any way to protect the females, other females, other parts during radiation? That is a good question. So some places use put in a vaginal dilator, actually during treatment, to spare the anterior vaginal wall. So that is something daily that can be done. I would say that, you know, because the ovaries are so sensitive to radiation, you know, we generally don’t do surgeries to, you know, ovarian transposition, to move the ovaries. A lot of it depends on where the tumor is. So for upper rectal tumors, we’re really not getting that much of the vagina anyway. But I would say that in terms of reducing long term side effects using the vaginal dilator after radiation is probably like the most important thing, what can we do to make sure our internal organs and muscles that were exposed to radiation can be more flexible and move better? That is a good question, because I do have patients after radiation that just kind of feel stiffer and weaker in their kind of large pelvic muscles. There’s really no magic bullet to preventing that. I would say exercise and stretching is very, very important, particularly for our older patients. We have a great pm and our team that if that can evaluate patients, so I tell patients that they’re having symptoms that they’re concerned about, at least be evaluated by pm and our because they can do very kind of specific testing, looking at muscle strength and pressure and all those things, at least get a baseline evaluation, and then they can also help with some exercise too.

Manju George 44:52
What is PMNR?

Dr. Nina Sanford 44:58
statistical medicine and rehab. So it’s a specialty that basically specializes in, you know, helping patients recover from symptoms, whether it’s radiation, whether it’s from trauma, whether from surgery. And there within pmnr, there are physicians that actually specialize in, like pelvic floor therapy, which can be very, very helpful. – What is the prevalence of hip and lower back muscular fibrosis after radiation? How can we manage Is there any risk to hip and spinal joints and discs? That is a good question. I actually do not know the number prevalence of muscular fibrosis, but I can look that up and get back to you on that wrist to hip and spinal joints, and just, I would say, fortunately, we’re below, really a lot of the you know, we we try to avoid the femoral heads during radiation. And, you know, we’re really at the lower end of the disc and the vertebral bodies the hips, probably is some of what I was talking about before, about kind of the sacral insufficiency fractures, which we’re trying to minimize by limiting the dose of the bone marrow. Risk of osteoporosis. – Can a DEXA scan be done prior to radiation? You get a baseline so your risk of osteoporosis depends kind of on your baseline risk of osteoporosis as well. I don’t have an exact number of how radiation would increase that risk, but if you are at risk for osteoporosis, I think a baseline DEXA scan is just a great idea, and to get on a bisphosphonate if, if you’re, you know, you have osteopenia or osteoporosis, how much, oh, a similar radiation and large syndrome. – Has there been studies of hyperbaric treatment that show healing? Good question. So I have had a couple of patients that have gone hyperbaric oxygen therapy. So the thought is that giving, like, high doses of oxygen can, can, can cause healing from radiation. My patients who have had that done have had really large, like open wounds, and a lot of those are in anal cancer patients that had really large wounds after after anal cancer treatment and their tumor disappeared. And actually, HBO did help their their wound healing in the in that respect, I have also, I guess, not had personal experience, but known of patients who had HBO hyperbaric oxygen after more kind of colitis, like injury. So I think it could help. I think we are don’t have a lot of studies, at least from a randomized fashion. Looking at HBO, it is an intensive treatment, so usually it’s about 30 treatments, and they might do that more than one. So it’s definitely a time commitment. Fortunately, the cases of patients that I have had getting HBO, have been covered by insurance, so that is at least good. – During radiation, my colon adhered to my vaginal wall, requiring an unexpected repair during La surgery. So radiation can cause adhesions, especially if you had prior surgery in that area with short course radiation, I’ve changed that outcome. So potentially, because the radiation dose is lower, also the timing from radiation to surgery can also affect the degree of fibrosis, but it really depends on, you know, kind of those factors, and whether or not you might have had adhesions beforehand for whatever reason. But potentially the short course radiation could have been less toxic. — I’d like to know why proton beam radiation isn’t used motor cancer. Very good question. So protons are a heavy particle, a heavy charged particle. Their benefit over photons or X rays is in their dose fall off. So basically they enter the target and then they have no exit dose. So in terms of the strength of the radiation, it’s not more effective in killing the cancer cells. It’s actually the same, same effectiveness, but it could be less toxic. So it’s really the sparing normal organs where it could be helpful. The reason why so it’s it’s been approved for a lot of pediatric cancers and also cancers of the central nervous system in the brain and spine. The reason why it hasn’t been used a lot in rectal cancer is because when we make a radiation plan for rectal cancer, we aren’t being very tight with our margins. We really want to treat the tumor, and actually a pretty generous area around it, so we’re treating where all the lymph nodes could be. So you know, the actual treatment volume isn’t just the tumor itself. And the other part is, we know your bowel moves, your bladder moves, so we have to account for all that motion. And. So there probably is not really a net benefit of proton therapy in rectal cancer. And the other part is, our dose is not super high right now, so I So, I think for all those reasons, it hasn’t been, you know, rectal cancer hasn’t been a disease site where protons has probably, would probably be the most useful

Manju George 50:22
Nina, can I ask a question? So basically, what you mean by that answer is that, like, for example, with the central nervous system tumors or and things like that, the proton beam is really focused on the tumor, whereas with rectal cancer, your aim is to not only get the tumor but also whatever might have spilled outside.

Dr. Nina Sanford 50:41
Exactly because, at least for, you know, for in the pre op setting, you know, our goal is not to kill the whole tumor, because they’re going to take it out with surgery. It’s really, actually to what we call sterilize the margin, so the area around where the surgeon takes that, we want to make sure there’s no microscopic disease there. So you don’t want to just target the tumor. That would not be that would not be effective. Whereas, if you had or not, you if someone had a tumor in their brain, and it was like right against the optic nerves, which control vision, well then you’re looking at like, millimeters of precision where you really don’t want to have any dose in the nerves, and you just want to get to the tumor. And that’s an instance where protons could potentially be more effective.

Manju George 51:24
I want to ask one more related question. Oh, we’re really running close to time. So the other main question was, like, people have this question, like, colon cancer doesn’t need radiation. Why does rectal cancer need radiation?

Dr. Nina Sanford 51:37
yeah, so good question. So that goes back into anatomy. So even though they’re similar biologically, colon cancer, it’s just much easier to obtain negative margins. You know, they can, they usually get surgery first. And you know, there aren’t even that many studies. So now there are some looking at chemotherapy before surgery, because usually you just can take it out, and you want to get the pathologic diagnosis right away. So just has to be it just has to do with where the colon cancers are, and they’re usually in the belly, and it’s just easier to take out. I, you know, I have had patients who have colon cancers that are like invading the abdominal wall. And then, actually, I have done pre op radiation for those patients. Because I say, you know, this is like a rectal cancer where we’re concerned about margins, and the surgeon doesn’t want to do like a big, you know, anterior abdominal wall resection with the tumor. So, hey, let’s do some radiation, and maybe even let’s give some chemo up front so that the surgeon can get negative margins. So kind of taking a rectal cancer approach to it, but it’s really just the anatomy of it that changes the recommendation,and then I usually also tell them about the peritoneal reflection part.

Dr. Nina Sanford 52:47
So the peritoneal reflection is basically a anaconca landmark, where that generally separates the rectum and the colon so basically, above the peritoneal reflection, we think of as colon cancers. Below the peritoneal reflection, we think of as rectal cancers. Technically, if something is straddling the peritoneal reflection, we should treat it as a rectal cancer. That being said, we know that upper rectal cancers have lower risk of recurrence than lower rectal cancers for all those anatomical reasons. So this is kind of a separate topic, but for upper rectal cancers, there are studies looking at omission of radiation, such as a prospect trial. So you know, it’s really more of a continuum, like everything is than black and white. That is an important anatomical landmark. So thank you for bringing that up that you can see on MRI. — Is there such a thing as targeted radiation that is different from just radiation? So I’d say all radiation is targeted. But as I was saying, for rectal cancer radiation, we do need to be a little bit more broad in treating a whole area, if you have a recurrence and the whole area has been treated, then sometimes we’ll just target the area of recurrence to try to spare other tissues. — Does the position in which people get radiation depend on the location of the tumor? Does it change the side effect profile? So the answer is yes. So if someone has a very upper rectal tumor, then there’s no reason to treat like the whole anal canal, or really any of the anal canal. If the tumor is more distal, then we do need to extend the treatment field into the anal canal. Also, the size of the tumor may determine, you know, our treatment volumes. I’ve had very, very large tumors, and you’re looking at a larger treatment volume, the size of the tumor and what nodes are. Nulls also determines what nodes you may need to cover, which may extend or decrease your radiation treatment field, rates of recurrence local and distance between short course and long course. So the rapid o study is. Actually good to look at this. So unfortunately, distant Mets still are the predominant form of failure for patients with locally advanced rectal cancer. That’s around 25 to 30% so because of that, we always need to be looking at better systemic agents, local occurrence, fortunately, is low. So I’d say it’s under 10% more closer to 5% and the studies don’t show any difference between Long and Short Course radiation.

Manju George 55:28
Okay. Thank you very much. So basically, that means that for people considering long course and short course, they should really worry about the local recurrence. They should actually be worried about systemic recurrence, which the radiation doesn’t affect anyways,

Dr. Nina Sanford 55:40
Exactly.

Manju George 55:41
Thank you so much. This was very good, and I’m sure after people watch it, they’ll have more questions, and then I’ll email you.

Dr. Nina Sanford 55:50
Yeah, email me. You know, I should have included my email, so when you send it out, just include my email to to patients. I’m always happy to, you know, chat one on one, or or answer questions by email too. So you know, you know my email, so just, you know, send it on the link too. That’s totally fine,

Speaker 4 56:07
Thank you so much. This was, this was great.