Episode 276: Radiation Therapy for GI Cancer With Nina Sanford

Chadi sits down with Nina Sanford, MD, Chief of Gastrointestinal Radiation Oncology Service at UT Southwestern, to explore the evolving landscape of radiation therapy in upper and lower GI malignancies. They discuss how advances in systemic treatments are reshaping radiation strategies, current standards of care in colorectal, gastroesophageal, pancreatic cancers, and liver cancers, and the growing role of organ preservation and adaptive radiation in improving patient outcomes. Dr. Sanford also shares insights into emerging clinical trials, personalized treatment approaches, and what she is most excited about in the future of GI radiation oncology.

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Transcript

SPEAKER_00 0:12

It's Healthcare Unfiltered, and it's your host, Shadi Nabhan. Folks, thank you so much for coming to the show, and thank you for joining me on Healthcare Unfiltered. Today's podcast is with Dr. Nina Sanford from UT Southwestern talking about radiation oncology with a focus on GI cancers. A lot has a lot have happened in managing GI cancers, whether it's upper GI tumors, lower GI tumors, or hepatobiliary cancers and pancreatic tumors. But with that, with the changes of how we manage these diseases and how we manage these cancers systemically, it is important to ask the question how this affects radiation therapy, because historically, radiotherapy has been part of managing upper GI tumors, lower GI cancers, and so on, such as rectal cancer. So I've invited Dr. Nina Sanford to join me on the show to talk about radiotherapy across these GI tumors, current standards, what we do, and what she is looking forward to in the next couple of years from a research perspective. So join me as we discuss radiation therapy in various GI cancers with Dr. Nina Sanford. And folks, you can always subscribe to my show everywhere. You can listen to it on all platforms, and you can watch, like you're watching right now on YouTube, probably, or you're listening on Apple or Spotify, Amazon, SoundCloud, or anywhere you consume podcasts. You can follow me on Twitter, on Facebook, on TikTok, on Instagram, and always share your thoughts with me. And check out my books, Toxic Exposure: The True Story Behind the Monsanto Trials and the Search for Justice and the Cancer Journey, Understanding Diagnosis, Treatment, Recovery, and Prevention. And stay tuned for two more books coming out in 2026. Without further ado, Dr. Nina Sanford on Healthcare Unfiltered. Well, folks, I'm very excited because I finally get to have Dr. Nina Sanford on my Healthcare Unfiltered podcast. Nina, welcome to the show. Thank you so much for coming on the show.

SPEAKER_01 2:19

Thank you so much for having me. I'm excited.

SPEAKER_00 2:21

And we are taping this as we are both emerging, Nina in uh Dallas from an ice storm and in Chicago, where we had the high temperature a couple of days ago was probably minus five Fahrenheit. Um, but by the time this airs, hopefully the weather will be better and a bit springy. Um Nina, tell us a little bit about you and what you do and what got you into radiation oncology.

SPEAKER_01 2:44

Yeah, so I um so I'm a GI radiation oncologist. I'm here at UT Southwestern in Dallas, Texas, in the middle of this um ice storm. Um so I grew up in Boston, spent my whole life there, um, moved here after residency and have been here as my first attending job since 2018. Um, I treat GI cancers. Um, you know, how did I get into radiation oncology? I guess it wasn't like a like aha moment. Um just kind of all through medical school, I tried to have an open mind about things that I would like doing. And I think to be honest, I would have been happy in many different specialties. Probably I've been love being a medical oncologist as well. Um, but I happened to do a rotation um in the beginning of my fourth year. My mentor, Anthony D'Amico, just suggested I check it out. Um, and I just like the people, I like the variety of things that um they got to do, like week to week, day to day. Um decided to give it a go. And here I am in 2026.

SPEAKER_00 3:45

Well, um I'm I've we we talked before we went on the air on some of the videos that you broadcast, and they're very, very helpful and educational. So I know that you have a passion for teaching. Um, but what we decided to talk about is kind of a wide variety into radiation oncology across various GI cancers. And with a bit of twist into some of the new things are maybe happening, whether it's technology or trials and things of that nature. So let's start maybe with lower GI cancers. And um maybe rectal cancer is the one that is uh more common. What's happening there?

SPEAKER_01 4:22

Sure. Um, so yeah, so the management of rectal cancer has changed a lot in the past, I'd say, decade or so. Um I would say, you know, when I started and finished residency, it was more one size fits all for locally advanced rectal cancer based on the 2004 German rectal trial. Everyone got neoadjuvant long course chemoradiation, surgery, and adjuvant chemotherapy. Um I remember when I was a resident, um, there were some publications by this Brazilian surgeon, Dr. Habergama, that was pioneering organ preservation. Um and um people thought it was borderline insane to consider um organ preservation for an adenocarcinoma. And um, you know, they they they they thought it was potentially harmful to patients. And fast forward to 2026, and the pendulum has totally swung um in the direction of organ preservation. So I'd say it's gone from one size fits all in rectal cancer to um like 25 different options for patients. And I when I see a new patient, um I always tell them it's great to have options, but it can also be very confusing. Um I tell them to the best of our knowledge, all these different options have the same survival that we know of. You know, we we it would be you know unfair to offer them a someone who is otherwise healthy a treatment option with inferior survival. But what's different about the different uh treatments is really the toxicity and the long-term quality of life and also the treatment burden.

SPEAKER_00 5:57

Um are there patients with rectal cancer that you think do not need radiotherapy?

SPEAKER_01 6:04

Absolutely. Um it's all sort of a balance of toxicity and trade-off. Um so I think what we're moving towards is that for sort of lower risk rectal cancers is doing um one local treatment between surgery or radiation. So one or the other. We know that um a lot of these patients, when their cancer comes back, comes back, it's in the form of the distant recurrence. So chemotherapy is still very important for locally advanced rectal cancer. We know how much they are six months, doublet, triplet, um, but chemotherapy is important. But a lot of patients may not need surgery and radiation. So if that patient is um definitely going to surgery, either you know they um they qualify for an LAR, so they don't need a permanent colostomy, or they just don't want to have the burden of surveillance, anxiety of potentially um, you know, wondering if the cancer has come back, um, and they don't have really high risk features that make surgery more difficult, um, then some of those patients um can can can can not have radiation. And prospect trial is an important trial showing that that's feasible.

SPEAKER_00 7:10

Yeah, I remember uh this was maybe a couple of years now, prospect trial. Uh what are you seeing in the real world? Do you um maybe you can give us a bit of scenario on the prospect trial? And are you seeing people applying the prospect trial?

SPEAKER_01 7:22

So a couple of things. Um my patient practice tends to be skewed towards patients with more advanced disease. Um, about half my patients come from the community hospital, uh, Parkland Hospital in Dallas. And then these aren't early stage patients. They have large tumors, encroaching the mesorectal fascia. They have a lot of involved nodes. So a lot of them are getting trimodality therapy. Um, and also prospect trial, um, when that trial is initiated, um, organ preservation wasn't a thing. Um, so all those patients did go to surgery. Um, and now because that has become a trend so much in the US, a lot of these patients are still getting radiotherapy. Um, that being said, I think you know, for patients who really want to avoid radiation, they've had prior radiation, women who want to maintain their fertility, um, those are important patient populations to consider talking about. What would omission of radiation look like?

SPEAKER_00 8:15

Interesting. What should be what should what's what's intriguing you or exciting you in terms of uh in the next several years, in terms of what may change from a radiotherapy perspective for managing rectal cancer?

SPEAKER_01 8:29

Um So I'd say, you know, in terms of new data that's come out, um, we should have the results of um there's a large randomized trial out of Germany comparing the short course versus long course radiation um for organ preservation. And that's kind of been an ongoing question. You know, if you do short course radiation over a week, is that good enough to achieve complete response rates? So I think those results should come out um this year or next year. Um, you know, short course radiation has really fallen out for rectal cancer for with several trials, um, because the majority of data for organ preservation is long course heme radiation, but this trial is, I think, over 700 patients. So it should answer that more definitively. Um, the Janice trial, um, which is looking at full FOX versus full Therinox for um organ preservation intent, uh, completed enrollment uh this year. So it'll be a couple years until that reads out because it's a DFS endpoint, but that will be very important as well. Um, as a radiation college, what am I excited about for records? I think um this is general across all GI sites, but this um idea called adaptive radiation. Um I don't know if you've heard a little bit about that, but I think that's a good idea. Um, you know, traditionally when we make radiation plans, we make one plan at the outset, the simulation, right? Um, and that same plan is carried out the entire time. Whether that treatment is two weeks or five weeks, um, it's the exact same plan every single day. Um, you can imagine that um first the tumor is gonna change, um, the structure, the normal structures around the tumor are gonna change, everything's gonna change. So that plan is not gonna be precise as the treatment goes on. Um, you can also imagine that different tumors just respond differently to radiation. You know, we don't know the biology until we really start treating it. So some tumors may need more or less radiation. So, so-called adaptive radiation is changing the plan as the treatment as a patient's going through treatment. Um, and I think that idea will be critical for organ preservation to be successful in any GI site for a larger proportion of patients. Um, because probably we're either over-treating or under-treating a lot of patients, and we can probably get in that sweet spot of balancing response and toxicity if we do the so-called adaptive radiation. I think that'll be important in um rectal cancer. And I'm sure we'll talk about later esophagus cancer as well.

SPEAKER_00 10:59

I have to tell you, I always say this is this is precision oncology. It's not always about just the biomarker, the genomics, and the actual target. It's also about just simply giving the right dose for the right patient. That is precision oncology. So I yeah, I'm I I I love that. Let's go a bit higher. Colon cancer, traditionally, when I was in school, in residency, in fellowship, it was never recommended you give anybody with colon cancer radiation therapy. I'm assuming we're still there that no radiation therapy to the colon.

SPEAKER_01 11:30

It's it's um, yeah. I mean, I explained to patients that, you know, the colon tumors are easy to take out and and not leave anything behind. Um, so it's certainly not a standard. But if you have a very locally advanced colon cancer where you are concerned about an R1 resection, um, you usually start with chemotherapy, but there, if there is still a concern for margins on a case-by-case basis, we'll add pre-oper radiation as in rectal cancer. We actually it's not a standard, and I don't see any trials coming down the line.

SPEAKER_00 11:55

Right. Let's do upper GI because there's a lot happening there. My goodness.

SPEAKER_01 11:59

A lot happening, yeah. Um, okay, upper GI, I think of um esophagus, dejunction, and gastric. Right. Um, you know, I think there have been several positive trials in systemic therapy alongside negative trials in radiation therapy that, you know, they have shifted the standard landscape so that for many patients, radiation is no longer a standard of care. Um, obviously the biggest one are ESOPEC, which compared the cross-regimen, preoperative chemoradiation, to um perioperative chemotherapy. That was positive for peroperative chemotherapy. And then Matterhorn, which was presented at ASCO and then updated at ESMO, that looked at flot versus deflot, showed the addition of dervalumab, improved two-year EFS, which is their primary endpoint. And then at ESMO, they showed improved OS as well. Um, so that has become a standard of care as well for GGA, gastric, and a lot of extrapolating to esophagus as well. Um, that being said, um, you know, I think um there are still situations where we would recommend radiation for um esophagus, G-junction, gastric cancers. Um, and then there's also this idea of organ preservation, which I briefly mentioned about, but the data is a little bit different in esophagus cancer. So I'm happy to elaborate on those as well.

SPEAKER_00 13:14

Yes, please, please.

SPEAKER_01 13:16

Okay, so um you can tell me if I'm like getting way too much in the weeds.

SPEAKER_00 13:20

No, no, I think I think I think that I actually feel it's really important because there's so much happened in upper GI cancers, isovagal and GU junction and gastric standard of care have shifted over the past several years. And I think understanding where radiotherapy fits is so important.

SPEAKER_01 13:37

Okay, so I think the first thing I tell people is that I emphasize that ESOPEC and Matterhorn, those were for adenocarcinomas. So that was the only histology included in both of those trials. Um obviously adenocarcinoma is increasingly more common in the US, in the G junction. Squamous cell carcinomas are going down. Um, but I think sometimes you forget and just extrapolate it to anything in the upper GI. So if you have a squamous cell cancer, at least in 2026, um, cross regimen remains a standard of care. Um, those tumors tend to be more radiosensitive. And then um, you can add on adjuvant Nivolimab per checkmate 577 as well.

SPEAKER_00 14:16

Okay, so the cross regimen uh remains, and then but you were you were starting to comment about when you would actually do something different.

SPEAKER_01 14:24

Yeah, so yeah, so I was saying that for squamous cell cancers, um, pre-operative chemo radiation is still a standard of care. Um, and you can add on adjuvant Nivolamab for checkmate 577. So you can get that additional adjuvant immunotherapy as well. So squamous cell cancers, radiation is still a part of their care. Um, you know, I think the second one, um, you know, in addition to squamous cell cancers, would be if a patient is not a candidate for flot or deflot, if there's, you know, they have some sort of organ dysfunction that, you know, they can't get those chemotherapy agents. And one might say, you know, it is rare that a patient's a surgical candidate but can't get those chemotherapy regimens, but it does happen sometimes. Um, so if they cannot get flot or deflot, then there's another trial, the neo-agis trial, that provides equipoise between CROSS and ECF, which is another chemotherapy regimen. Um, and then the third bucket, which I think people have different opinions, is if you have a T2N0 cancer, these are not super common. Um, but you know, if a patient is it's incidentally found, um, they're not having symptoms, it is truly T2N0, then I think flawed or deflot is probably over-treatment. Um, their risk of systemic recurrence is going to be lower. And if you look at, you know, the forest charts from those papers, um, obviously those are not pre-planned analyses, but if you look at it, you see that the benefit to this intensified systemic therapy is really for those more node-positive tumors, those more advanced tumors. So I think if you have a true T2N0, cross is probably reasonable to discuss. Um, you have to remember also D flot. Um, it's perioperative dervalumat, but then dervalumab for a whole year after. So it is, it's pretty intensive. And you know, obviously we don't know how much that additional year is adding, in addition to the periop. And there's never going to be a trial comparing periop versus periop plus a year after because it's already been approved. Um, but it is a lot of treatment. And I think for a T2N0, um, then cross is something reasonable to consider. And then the other scenario would be you know, if a patient has had flawed or deflawed and you restage them and they haven't had a lot of response, um, if you're still concerned for an R1 resection, or you actually take them to surgery and pathologically they don't have a good response, um, then you might ask yourself, why am I going to give them the exact same chemotherapy again? Obviously, it's not a perfect switch to switch to local therapy, right? They're like dealing with different things, but it's something at least to consider, particularly if they have other risk features. So those are scenarios where I think it's still, you know, you should still consider um adding radiation.

SPEAKER_00 17:02

So in summary, for squim cell, we're still doing pre-op chemo RT, followed by surgery, followed by Nivolomab.

SPEAKER_01 17:11

If they don't have a complete response, exactly.

SPEAKER_00 17:12

If they don't have a complete response.

SPEAKER_01 17:14

Yeah.

SPEAKER_00 17:14

Um for aden OCA, um, few patients are getting RT because right now we're doing more systemic therapy plus surgery.

SPEAKER_01 17:22

Correct. Yes, yes. I think that's the state. I mean, if you have a healthy patient who has a resectable tumor, you know, with esopec and matter horn, um, unless they're completely opposed to surgery, I think that the right thing is not for them flat or deflat.

SPEAKER_00 17:36

Sure. Um is it, I mean, obviously we always lump um esophageal, GE junction, and gastric in most studies. Is there anything unique for gastric specifically that you would do differently than isophageal cancer and GE junction? Or is it the management of these three organs the same?

SPEAKER_01 17:56

I think historically it's been because um we had the cross-trial that was for esophagus, sewer one and sewer two. And then sewer three and gastric was our always sort of perioperative chemotherapy. But now I think with these new studies, they're all kind of more bunched together. Um, we do look at the specific histology, though. You know, if we're they're more diffuse type, we think high-riskosystemic, treat more as a gastric, probably encourage chemotherapy more. If it's an intestinal type, um, we might consider local therapy a little bit more, just know it knowing patterns of recurrence. But I think now, you know, matter horn was actually just gastric in G junction, but people are extrapolating that up to the esophagus.

SPEAKER_00 18:35

Yeah.

SPEAKER_01 18:36

Um I think now they're actually more blended together.

SPEAKER_00 18:39

All right. Let's go now in between upper and lower GI to the pancreas.

SPEAKER_01 18:43

Yes. Um, yes, so pancreas, um, I think definitely is an area where um is definitely not one size fits all.

SPEAKER_00 18:53

Um I think um, yeah, let me think how to historically, historically, what what I've been taught back in the day, long time ago, um it was always obviously for in the early stage, the lucky ones who have the early stage. We we used to do the you know the surgery. Yeah. Uh and then you do chemotherapy or chemoradiation. And then there were some patients with locally advanced disease non-metastatic who would do chemoradiation, uh, and then followed by chemotherapy and so on. But radiation was always like kind of part of the treatment somewhere, either for locally advanced disease that is non-metastatic, or you would incorporate it somehow post-op or or pre-op. But uh I I I it's it's a bit all over for those of us who don't do that.

SPEAKER_01 19:50

Let me give you my framework for radiation and pancreas cancer. Um, okay, so the first thing is that a challenge for radiation oncology has been accruing to trials, um, and and and and and such that when the trials are complete, sometimes the standards of care have changed, particularly systemic therapy. Um, so I think the trial outcomes, particularly the form of baser randomized data, have not caught up to where we are now. But anyway, when I sort of explain radiation and pancreas cancer, um I try to explain that the indication for radiation is completely dependent on the resectability status of the tumor. Okay. So let's start with resectable cancers. These are cancers where um the surgeon looks at the tumor on the scan, and um he or she feels like it can be taken out without leaving anything behind. So there's like a plane between the tumor and the vessels and any critical organs that can't be sacrificed. Um, so in 2026, um, there's no standard role for radiation for most resectable cancers. Um, it's either upfront surgery or perioperative chemotherapy. Um, and there are two trials that are comparing those strategies. They finish recurring, so we'll get more information on that. Um, where we will think about adding radiation is dependent on the pathologic features at time of surgery. So, no standard role for radiation, but if there are high risk features for local recurrence over systemic recurrence, then we can think about adding post stop radiation. And that was based on a randomized trial that was presented last year that showed that suggested if there are more risk factors for local than distant recurrence, you can consider adding post-op radiation. So resectable cancers, no standard rule for radiation, but case by case basis, dependent on path features, if you're concerned about local recurrence. Borderline resectable, I think of the surgeon looks at the tumor and he or she says, I can probably take it out, but I'm probably going to leave behind at least my. Microscopic tumor, usually around the vessels. So the role of radiation in this setting is to facilitate an R0 resection. So it's basically the patient always starts with chemotherapy. And then we restage them. And if there's still concern for an R1 resection, then we'll recommend preoperative radiation. I'm happy to talk about the driven types as well. And then for locally advanced unresectable, it's completely different. So these are tumors that, you know, the surgeon looks at it and he or she's like, this can never come out because it is so encased by the vessels and it's just, it's a it's a probably never going to surgery type of case. Um in those situations, radiation is used as the only definitive treatment. So it's used as in place of surgery. So it's intended to hopefully eradicate macroscopic tumor. So that's how I sort of think about radiation therapy in those three settings resectable, borderline, and locally advanced. Um, and then we can obviously talk about the data for um each setting as well. Obviously, there are other settings like medically inoperable, metastatic, oligometastatic, but those are the three main buckets.

SPEAKER_00 23:08

Sure. Anything happening on the hepatocellular? Uh I know there was obviously, you know, some data, you know, on yttrium labeled and type of therapies, but external radiotherapy does ever give into the liver?

SPEAKER_01 23:24

Yeah, so it does. Um, so I guess, you know, when I think of HCC, sort of like a thousand-foot overview is that there are many local modalities, probably more than in any GI cancer. You know, you have TACE, one of the earliest ones, Y90, ablation, of course, surgery, and then SBRT. Of all of those, SBRT is actually the newest one out of all of them. Um, so just for that sort of temporal reason, um, the data, I keep saying that the data hasn't caught up to I think what we can do in 2026 with SBRT. The second challenge is that there is just a ton of variation globally in terms of access, what we can do, what we can't do. I don't know and say globally, like across the US, there's a ton of variation. And, you know, at ASCO GI, um, you know, I was on a panel and it was uh myself, um, someone in IR from from Northwestern, um, someone from California, someone from Italy, and someone from uh Spain. So global panel.

SPEAKER_00 24:20

Global.

SPEAKER_01 24:21

Global panel. Um, and you could see that there was just a lot of variation in practice. Um, so those things I think make HCC very challenging. Um, and and I think make uh you know creating an algorithm for HTC very challenging as well. Um, that being said, I think in 2026, there are a few scenarios where I think um external beam radiation in the form of SBRT mostly has has good data for. Um the first is early stage ACC. Um, small tumors in favorable locations away from the subgent bowel, um, radiation can give very high local control rates, um, I would say upwards of 95%. Um, and and it can be used when ablation isn't feasible for larger tumors near the dome, when RFA isn't feasible, or when patients just want something non-invasive. So a small tumor in a favorable location, SBRT is curative. Um, there's a randomized trial comparing SBRT to RFA that showed better local control with SBRT. Obviously, there's some caveats to that, but it, you know, anyone who um treats APCC knows if you have a small tumor, you can hit it hard, your your the likelihood of cure is very, very high. Um, the second scenario, which I'd like to see more data on, is bridging and downseging to transplant. Still, Y90 is the most commonly used treatment, um, but some centers like Toronto are using more SBRT with good outcomes as well. So I think that is coming down the line, but I think there is good some data supporting that. Um, the third one is sort of these large tumors. Um, so you have sort of one dominant tumor, um, particularly those with vessels involved, like macrovascular invasion. Um, I think that is an area where SBRT can be preferentially used over other treatments when it's involving the vessels. Um, and it's really one of the only local modalities that can really conformly treat the tumor and tumor thrombus while respecting uninvolved liver. Um, and then we have a large randomized trial showing that that is safe and efficacious. Um, and then the fourth, which you know, I recently did a little video on my little YouTube channel, is that um palliative radiation um is really underutilized in GI cancers. And there was a randomized trial showing just one dose of eight-gray to very large liver uh burden disease, even the whole liver can offer um can offer pain relief. So I think there are settings where um external beam radiation um has good data supporting it. Um, but hope, but hopefully there'll be better data coming down the line.

SPEAKER_00 26:52

Nina, you just alluded a little bit about ASCO GI. Was there anything across all of these tumors from a radiation oncology perspective that piqued your interest at ASCO GI specifically, or was it like just uh, you know, just part of the ongoing studies and so on? Nothing necessarily has will change what you offer patients from as a radiation oncologist based on ESCO GI data?

SPEAKER_01 27:14

I don't think there is, you know, to be honest, I don't think there's any practicing practice-changing studies um involving radiation at ASCO GI this year. Um there's some exciting sort of concepts coming down the line. Yeah. Um, but I don't think there is anything that is like a takeaway that has since changed my practice.

SPEAKER_00 27:33

So a couple of things I just have to ask you as we wrap up a little bit. Uh this was very, very helpful. I mean, I I hope folks are listening to this and viewing this and just getting like almost this like you know crash course of where radiotherapy is applying GI cancers. But a couple of things, uh as you and I know, um NGS is happening across all of these GI tumors right now. I mean, it's just you know, what you do with the data is a different story. Uh is the radiation oncology world moving towards if I give you an NGS panel, for example, for somebody, whether it's colon, pancreas, or upper GI tumors, you'll be able to tell me, I don't know, A, this will be radioresistant, B, this could be radiosensitive, C, you know what, I should probably give lower dose, higher dose. You know, are we moving towards this way where, or are there studies happening? Because I, as an outsider, I want to see that.

SPEAKER_01 28:26

That is the goal. I don't, I don't think we're at I think medical oncology is way ahead of us in terms of um, you know, molecular subtyping. Um, I think for radiation oncology, probably the biomarkers will not just be the tumor markers, but maybe things like radiomics or some more data in that sphere. Um, than sort of what I mentioned earlier, just looking at adaptive change throughout treatment. Um, but that is the goal, you know, like um to really individualize radiation towards a specific tumor. So I think that's coming on the pipeline. I don't think that's going to be um very imminent. Um, but but but hopefully in the future. Definitely agree.

SPEAKER_00 29:04

Anything, anything you'd want to share with the viewers and listeners on proton therapy? Every time I have a radiational color on my show, I have to ask this question.

SPEAKER_01 29:12

Um yeah, so I um yeah, so I think protons, um, so a couple main points. Um, you know, I train at a place of protons. Um, you know, I published a retrospective uh study comparing protons versus photons in HCC. Um, you know, what I like to tell so the goal of protons, of course, is that they have little to no exit dose, so that the goal is to spare normal tissue. Um that's the rationale behind protons. They're not more powerful than photons. So the actual dose to the tumor is the same. It's not like carbon or other heavy ions that actually are more potent. It's just uh better normal tissue sparing. Um, what I like to tell patients is that it is one of many tools uh radiation oncologists have to make treatment more precise. Um, and what are the other tools? So I mentioned adaptive radiation, you know, I mentioned um, you know, you I have mentioned, but using different imaging techniques like MRI to better see the tumor. Um, because the whole goal is to be as precise as possible with your target and to treat the smallest target you can while covering the target and treating as less normal tissue as possible. So protons is one modality. Um, just being knowing anatomy really well, um, and and just being judicious with your target volumes is is also very important. Um, you know, I have seen cases where protons just don't make sense because you're treating the whole posterior fossa, right? So, like, yes, you can say you're using protons, but you can also use two beams like they did 30 years ago and accomplish the same thing, right? Um, motion management is very important as well, right? Like tumors in the diaphragm or in the lung are going to move a lot. So you need to either decrease that motion or track that motion. So those are sort of less um, you know, less, less sexy tools, but but just as efficacious as using protons. So, you know, when I think about protons, I tell patients that um it really is dependent on that exact scenario if protons are helpful at all. So I first say, you know, why are we doing protons in your case, right? So like what is the rationale? What organs are in the area? What are we trying to miss? What are we trying to avoid? What are we trying to target, right? Um, so that's the first thing. What is the rationale if you're even doing it? Then two, I say, what is the data supporting it? Do you have a randomized trial? Do you have a retrospective series? Do you have a phase two randomized trial? What's the endpoint of that trial? Is it survival? Is it toxicity? And then I try to put all that together and say, well, in your case, does it make sense? And then I also take into account how much are you gonna have to travel for protons? You know, how much are you gonna have to pay out of pocket, if any? I try to put all those things together. Um, it's it's something that can be very helpful in some scenarios, um, but in others just doesn't make sense.

SPEAKER_00 31:58

That's amazing. Um, look, I um we could talk for hours. This is really very, very, very helpful. Is there anything that you want to share with viewers and listeners I completely overlooked and I did not mention or discussed?

SPEAKER_01 32:09

Um I think, you know, you you had mentioned, you know, things that I'm excited about in the future for radiation. Um so I mentioned one adaptive radiation. Um I think that will be absolutely necessary to maximize the potential of GI radiotherapy, particularly in the form of organ preservation. Um, I think we need better trials and better endpoints. This is something I've talked a lot about. Um, I think our trials, you know, being designed to show a massive overall survival benefit is not gonna happen for a local modality. So I do appreciate that. I think people are recognizing um other benefits of radiation in terms of quality of life, in terms of treatment burden, in terms of things like that. Um, I like that I saw the FDA put out a notice that they're um encouraging Bayesian design trials in oncology. And um, you know, obviously we can talk a little more about that, but I think the frequentest trial design really does hurt radiation oncology because we really only have one chance for really any trial. And if you get it wrong, you don't miss, you don't make the P equals 0.05. That is doomed forever, right? We don't have 20 I.O. trials like medical oncology does. So I really hope that actually happens, particularly in the quad group level. Um, what else? I have like obviously a lot of thoughts. Um, you know, we didn't talk a whole lot about radiation drug combos. Um, it's not my full area of expertise, but I think we are moving beyond just sort of the philosophy of it to hopefully, you know, knowing more about specific dose, fractionation, timing, you know, target volume, and how to really interface that with the best drugs, looking at local effects versus systemic immune responses. Um I would like to see more funding for radiation oncology trials, um, for sure. I mean, I think we um that is an area that um, you know, we're lacking for, you know, for a lot of different reasons. But hopefully, you know, that that that that may change in the near future. Obviously, I have a lot more thoughts. But I think those are the main things in terms of radiation oncology and GI radiation oncology.

SPEAKER_00 34:08

Well, congratulations. I mean, you guys are doing amazing. And I I say I learn so much every time I have one of my uh fellow colleagues from radiation oncology because it was always an enigma. And uh honestly, in medical oncology, even in training, we never got so much exposure. You do a rotation a month here, a month there, but you never really dig deep. So it's always in abstracts and in papers that we read versus kind of roll up your sleeves and and and do a few things. So um would love to have you back to talk. I mean, there's so many other things. I mean, radio like you know, radio ligands, and and we we didn't talk about so many other aspects of uh radio pharmaceuticals. I mean, this is a completely new, not new, but a different field that we even didn't even touch on.

SPEAKER_01 34:52

Yep.

SPEAKER_00 34:53

Yeah.

unknown 34:53

Dr.

SPEAKER_00 34:54

Nina Sanford on Healthcare Unfiltered, thank you so much for joining me.

SPEAKER_01 34:57

My absolute pleasure. Thanks for having me.

SPEAKER_00 35:07

Okay, folks, thank you so much for joining. And thank you, Dr. Sanford, for coming on Healthcare Unfiltered. I appreciate your thoughtful commentary and educating us about all things radiotherapy in all GI cancers. Well, most GI cancers, obviously. We can't cover all of them on one podcast episode. Folks, subscribe to the show, write a brief review, share it with your friends and colleagues, and comment. Let me know what you think, and join the conversation. And before I let you go, I'm gonna leave you with the saying by a Lebanese poet Khalil Jibran. He once said, Yesterday is but today's memory and tomorrow is today's dream. Until next time, take care of that.