The New Face of Colon Cancer: A Patient’s Story

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John Marshall, MD: Hey, everybody—John Marshall for Oncology Unscripted, and this session is all about a really big problem that I hate. It's changed my clinic. I really don't like anything about it. It is not what I signed up for. It is young people getting GI cancers. And, you know, the deal was that they were all supposed to be 60, 70, 80 years old with colon cancer, and now close to half of my clinic is under the age of 50. It's a totally different impact, a totally different disease.

There was a recent JAMA paper, which we are featuring, about the statistics around not just colorectal cancer but all GI cancers showing an increase.

And I am lucky enough to have, as one of those young patients, Chad Leo, who has taught me as much about this whole thing as I've taught him about the management of this. He was first diagnosed when he was age 42, and it was out of the blue. So, first, Chad, thank you for your willingness to jump onto this risky venture of Oncology Unscripted. Tell us a little bit about yourself and how they first found it—the sort of "out of the blue," something on your list that was never on your list before.

Chad Leo: Well, first let me say, Dr. Marshall, thank you very much for having me on here. You know, through this entire journey, I'm just overly grateful to be able to kind of give back and share my experience in the hopes that maybe it'll help other people my age—and, unfortunately, people even younger than me—that are being diagnosed with colon cancer.

So, when I was first diagnosed, I was going through some severe abdominal pains. I later found out that was sort of similar to the symptoms that other people diagnosed with colon cancer were going through as well. I was reluctant to really get it looked at, and as time went on, the symptoms progressed. Finally, I was convinced to go to the ER.

I think the way that doctors first saw me—they go, "He's 42, there's no way that this could be anything that severe"—and it was almost a detriment, to the point where I wasn’t fully examined to the extent of what should have been part of the full checkoffs that probably should have been done.

John Marshall, MD: So, what did they think it was? Just like constipation or something else?

Chad Leo: Yeah, their initial thought was that it's probably just Crohn's disease or some type of colitis. That was in my head—I was like, "Okay, that's probably what it is." And then a month later, I'm back in the ER again. The scans indicated that there was, in fact, a mass in my large intestine.

John Marshall, MD: Well, when I went to medical school a thousand years ago—you probably weren’t even born—we were taught that only older people got colon cancer, so it shouldn’t even be something we look at. There has been a growing message about young people getting the disease, but for a lot of folks, it's just not on their checkoff list. So, the patient doesn’t know to ask about it. The physicians are saying, “That can’t be that,” as you just said. To your knowledge, did you have any known risk factors? I mean, your family, your other medical issues—anything that would’ve teed you up for colon cancer?

Chad Leo: No, nothing would’ve indicated that—especially in my family history. I think I had a grandfather who had bladder cancer. My paternal grandmother had ovarian cancer, but nothing along the lines of colon cancer. It wasn’t on my radar. It wasn’t anything where I was directed to start getting screened early.

John Marshall, MD: One of the reasons I’m asking is that this paper we’re featuring lists the standard risk factors. We’ve got to look out for those people. Those people are kind of being followed—or they should be already—because they’re in that risk factor category. But most of my patients are more like you, where it’s just out of the blue. Very fit, obviously, otherwise very healthy, and then—out of the blue—with a diagnosis of colon cancer. So, message heard loud and clear that we’re sending out to the medical community with this discussion.

Tell me what it was like to—out of the blue at 42 years old—all of a sudden have colon cancer, surgery, chemo. How disruptive was all of that?

Chad Leo: It was a huge disruption. So, my job—I’m a detective with the DC Police Department—requires me to be very active. And so, going through the treatments meant that I had to take a break. I planned essentially to use my sick leave as much as possible just so I could focus on getting better.

All of these thoughts start going through your head at 42. I was single then. You start kind of thinking, “What have I done? What have I accomplished with my life?” That plays a heavy toll on your psyche.

Also, I think—being a little bit further removed from some of this—it pushed me to really take a look at my life and not take anything for granted.

John Marshall, MD: Yeah, I would rather you not have to have had that life stress to do that, but I hear you loud and clear.

Chad Leo: Neither would I. But I guess, you know, you’ve got to take everything with a grain of salt. There's always a silver lining to something, and I think that sort of mindset just kind of kept me going and just being hopeful. I think obviously having a terrific care team—such as yourself and the team you had with you—made a huge impact. I felt like my best interests were at heart.

John Marshall, MD: Yeah. And did you tell the gang at work? Did they make accommodations? Did people try and help you? Or did you feel like you wanted to keep it quiet?

Chad Leo: I basically told my close friends and obviously my supervisors what was going on. Pretty much everybody from work was super supportive, and would reach out or come visit, and every once in a while send encouraging messages. I couldn’t have asked for a better support system.

John Marshall, MD: Yeah. So, you went through surgery, did some chemotherapy. We were in follow-up. You've been getting the fancy ctDNA test as well as scans. Describe a little bit about that, because you’ve had a rollercoaster there too.

Chad Leo: It was. The initial surgery I had was to remove the mass, and then I was affixed with a colostomy bag. And, you know, no pun intended—I don't know if we're allowed to curse on the podcast—but I won’t. Oh, okay, I’m getting a thumbs up. So, pun intended, it was a very shitty situation. That was a huge adjustment, where not only did I have a colostomy bag, but I had to learn how to do daily activities with that.

And just the sheer embarrassment of looking at myself in the mirror with this stoma poking out of my stomach. You still want to go out, still want to try to be somewhat normal, but then you have this colostomy bag. I remember at times meeting up with people, and you start to smell something, and you’re like, “I gotta go—it’s a leak or something.” So, I would limit my exposure with my friends to a few hours just because I didn’t know what could happen.

Once we got to a point where I was essentially no evidence of disease, I think I was kind of encouraging—or pushing—you to, like, “Hey, maybe we can look into getting this resection surgery.” So that was good to get to that point.

Then the follow-up tests and the blood tests post-surgery just kind of set up a platform, if you will, of, “Okay, let’s just keep banging out whatever the next steps are.”

John Marshall, MD: Yeah. I know we talked about the role of exercise. One of the big studies we featured in a previous episode was the dramatic impact that having a personal trainer had.

I don't know if I’ve shared this with you yet, but half the patients got a pamphlet that said, "Go exercise," and the other half were assigned a personal trainer. There was actually a survival delta between those. You're already very active, but when you talk about the ostomy—if we’re recommending exercise—an ostomy is exactly counter to that. It makes it very, very difficult to do the kind of physical activity that I know you like to do.

Chad Leo: Yeah, that was—so, I had started an intense workout routine before I even got diagnosed. So, to have the ostomy, basically, my exercise routine just consisted of lots of walking. Maybe just some push-ups. I tried hard not to do anything that would disrupt where the ostomy or the bag was, just because I was so self-conscious. I didn’t even want to go to the gym. I didn’t want to deal with the embarrassment of people seeing the colostomy bag.

But overall, I felt it was just important to stay active and move no matter what.

John Marshall, MD: Yeah. You're a few years out now. With each new scan, with each negative blood test, we’re a little bit further off. You know where we’re gonna be. All right.

And fingers crossed—we’ve had some nervous times still. You’ve got an audience of docs right now, all around the country, all around the world, other people in the industry. What sort of message would you like to share, given your experience? Is there anything you’d like us to hear about?

Chad Leo: I think most importantly—and you do a great job of this—it’s giving your patients hope. Giving someone like myself hope, even through the early stages where you feel like everything is at a loss. The way that you would say, “Hey, look, these are the steps that we’re going to take to try to get you to a point where you can hopefully live as much of a normal life as possible”—I think that’s one of the key things. Because if you have hope in your mind, who knows the benefits that provides the rest of your body? Your body may just continue to keep on fighting.Despite the chemo treatments or even the subsequent blood tests and scans that we go through afterward, you’re still clinging to that hope. Even though you get that little bit of anxiety every time a blood test or scan comes up.

Like I mentioned before, I know that I’m in good hands, and if something does come up, we’ll be able to treat it as early as possible and just give myself a better chance. Again, from my own personal experience, it’s about trying to live your life as normally as possible after going through an experience like that. You and your team have afforded me that ability.

John Marshall, MD: We’re happy to do it, and there are a lot of people out there who can do it well too.

One of the things that was fairly new when you were getting your chemo a few years ago was three months versus six months of chemotherapy. At a young age, you have a physical job, you need to be able to use your hands. The reason for three months versus six months was the cumulative neuropathy of oxaliplatin. We had those discussions about that. There are a lot of docs out there who might be listening in, who, as a young guy, might think, “You can take it because you're young,” and push it to the six months. But right now, one thing I’m glad about is your scans—you’re good. You’re good. And no neuropathy, or limited neuropathy.

Chad Leo: None that I can detect.

John Marshall, MD: And you’re a detective!

Chad Leo: Yes! I mean, I gotta do a lot of typing too. So, it’s important that everything works—at least where I can type. But yeah, I remember there was a point where I started feeling some neuropathy in my hands.

Subsequently, whatever happened after that, it has now since subsided.

John Marshall, MD: Chad, thank you so much for taking some time to discuss this with us.

We all hate this trend. It’s why there’s a big, important paper on this. You are the real kind of person who’s being affected by this. And for you to share all of this with us means a lot to us—and teaches us, as I said at the opening, maybe more lessons than we’ve ever taught you.

So, Chad Leo, thank you very much for joining me on Oncology Unscripted.

Chad Leo: Thank you so much, Dr. Marshall. It’s my pleasure.

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This transcript has been edited for clarity. 

The Rise of Young-Onset GI Cancers: Interview with Dr Thejus Jayakrishnan

John Marshall, MD: Hey everybody, John Marshall for Oncology Unscripted, and I promise there is no script anywhere in front of us right now. As you know, what we are focusing on this edition is: why are young people getting cancer all of a sudden? I thought we were supposed to be getting healthier.

We just blew up the EPA earlier this week, so I guess we're all going to die of cancer sooner rather than later, if that all works out to be true. But even before we blew up the EPA, some very, very smart people have been watching and monitoring this increase in young people getting colorectal cancer and other GI cancers.

And I am honored to be joined by the lead author of a very, very important review paper that looks at this.

That's been going on all around the world and in the United States. Thejas Jayakrishnan has just joined me today from the mecca of all knowledge—that would be Boston—at Dana-Farber. So, Thejas, thank you very much for joining us, and maybe give us a little bit of an introduction and a little bit about what drove you to put together this paper.

Thejus Jayakrishnan, MD: Thank you very much for the kind introduction. I am a gastrointestinal medical oncologist at Dana-Farber Cancer Institute, an instructor in medicine at Harvard Medical School and Brigham and Women's Hospital, and I work closely with the Dana-Farber Young-Onset Colorectal Cancer Center. I predominantly do clinical research and also translational work, trying to identify what are the biomarkers or molecular characteristics associated with young-onset GI cancers.

I finished my fellowship at Cleveland Clinic, and I had wonderful mentorship there with Dr. Khorana. I spent a lot of time during my fellowship trying to understand the molecular characteristics of young-onset GI cancer. It's mainly during the fellowship that I noticed there's increasing incidence, and the mentorship was helpful in getting me more attuned to recognizing those aspects and realizing some of the unique characteristics of this population. That led me to get involved in research related to the microbiome and metabolomics—trying to integrate different aspects of early-onset GI cancers. I've continued that work since moving to Dana-Farber Cancer Institute.

John Marshall, MD: I'm an old oncologist, right? And so, I didn’t sign up for a lot of my clinic being 20-, 30-, and 40-year-olds. Back then, they were all what we later found out to be Lynch syndrome patients and had genetic inherited syndromes, etc.

Nowadays, that’s not who all of these people are. They are very fit, very healthy, with no real strong risk factors that are showing up. And I think early on, people like the American Cancer Society and others were saying, “Oh, that’s just because they have bad behaviors,” or, “They have the wrong parents,” or something was causing it.

And I noticed that in your all's review, those things were mentioned again, but also, to your acknowledgment just now, we still really haven’t uncovered what the heck’s going on. Let me ask specifically—'cause I did a lot of work with our molecular database—we could not really find any clear next-gen sequence differences based on age. Have you guys got any more insight into the genetic piece of this?

Thejus Jayakrishnan, MD: Yeah, I mean, you're very right, Dr. Marshall. Genomically, we do not see a huge difference in early versus average onset. Certainly, there's a higher prevalence of germline predisposing syndromes in younger people, but that doesn't explain the increasing incidence over time.

The vast majority of these cancers are sporadic, meaning they are not inherited-type syndromes. We do see certain subsets of early-onset GI cancers—for instance, early-onset cholangiocarcinoma—where there’s a higher prevalence of FGFR2 fusion. That has been described and is a targetable mutation in cholangiocarcinoma.

In pancreatic cancers, there’s a higher prevalence of not having the KRAS mutation in early cancers, but having other targetable mutations like IDH1. But again, that’s not a standard targeted therapy in pancreatic cancer. These are still very small percentages.

So, what we really see is also the fact that most patients with young-onset GI cancers present with more aggressive disease. There’s a higher prevalence of, say, signet ring cell cancers or poorly differentiated cancers across the different early-onset GI cancers. A lot of patients present with stage IV disease at diagnosis, which could be partly from delays in diagnosis. But then, we also see higher prevalences of these aggressive variants.

Even with aggressive treatments—younger people, you can imagine, don’t have a lot of comorbidities that may prevent them from getting intensive treatments—we do not see a proportionate improvement in the outcomes. So, there's definitely more molecular factors at play that we need to understand better.

John Marshall, MD: Yeah. So, bad cancers—not necessarily better cancers. Yes, they're younger, and you can beat ’em up more, but that doesn't necessarily mean it's translating into improved outcomes for those patients.

Let’s sort of talk a little bit about current theories as to why. One of the things that only recently—in the last three to five years—that I recognized is that for colon cancer, and it's not necessarily the other GI cancers, instead of the normal sort of 40% right, 60% left, we're seeing this very high percentage of rectosigmoid tumors.

And so, I've been sort of thinking, this must be some sort of microbiome issue. My God, I hope it’s not Starbucks. And I hope it's not bourbon, because then I'm just gonna get it too—those are like my two favorite things.

But, you know, some people are looking at exercise, antibiotic use, or other kinds of components. Microplastics—people are out there.

Thejus Jayakrishnan, MD: Absolutely.

John Marshall, MD: If you had to put a quarter down right now and bet, what do you think the common sort of theme or molecular pathway that’s causing this would be? What would you say?

Thejus Jayakrishnan, MD: I think it is an interaction between environmental factors and the microbiome. That’s what a lot of our studies are trying to do—like a deconvolution—to understand how much one component is contributing.

We definitely have seen an increase in obesity over the last 40 years. Childhood obesity is increasing, and it has been shown that early exposure to adult and maternal obesity can be a risk factor for early-onset GI cancers. But, you are right. I do see a lot of people who do not have these risk factors, so there have to be other factors as well. Physical activity correlates—lower levels of physical activity are associated with higher risk for these types of cancers. But again, we see people who are athletes who do develop early-onset GI cancers.

I do think that exposures play a role. Dietary patterns have changed over time. We see associations with Western-style dietary patterns, which include higher intake of processed meat and sugar-sweetened beverages. Even if someone may not have obesity or metabolic syndromes, they may still have higher exposure to unhealthy diets. Another common factor that connects all of this is microplastics. There are actually studies that have shown microplastic exposures in experimental models lead to higher rates of growth of colon cancers.

There's also synergism between high-fat diet and microplastics, which has been demonstrated in experimental models. We need more epidemiological data and tissue-based analyses to really understand how this may be contributing.

Studies—including ones I’ve been involved in—do show differences in microbiome characteristics, both tissue-based microbiome and stool microbiome, in early-onset versus average-onset GI cancers.

Now, some of it could be associated with the development of cancer, but there are unique differences. We have also identified that these microbiome differences correlate with the metabolites in the body. So, there are a lot of connections between exposures, microbiome alterations, and metabolic changes in the body.

What we are trying to do—through the young-onset colorectal cancer cohort—is prospectively collect tissue, blood, and stool from young-onset patients, along with exposomal data. That includes dietary exposure, physical activity, and other lifestyle factors. We’re really trying to integrate that to understand how different factors may be interacting with one another in the development of cancer.

John Marshall, MD: Part of the reason we're focusing on your great paper is that we don’t have widespread awareness in primary care and urgent care clinics that young people can get cancers. Our screening is not well established. We did drop it to 45 for colon, but we don’t screen for cholangio. We don’t screen for pancreatic.

So, we need to think about: is it enough of a problem that we need to begin shifting screening?

On one level, you’re trying to figure out who’s getting it and why, so we can intervene and reverse whatever it is that’s causing it.

Thejus Jayakrishnan, MD: Mm-hmm.

John Marshall, MD: On the other end, from a public health perspective, we’re trying to say: should we be looking more aggressively, as a healthcare system, at a time when our system is already stretched to the nines?

But let’s go one other place. You’re 42 years old, and now you’ve got stage III GI cancer. You have to work to pay for your insurance. It’s disruptive, because none of our treatments are easy.

Talk a little bit about the impact of cancer for a 40-year-old versus what we all signed up for, which was a bunch of 70-year-olds.

Thejus Jayakrishnan, MD: Yeah, you know, that’s what makes it even tougher to manage. A lot of the people that you diagnose with this cancer are at a stage where they have a growing family. They may have recently gotten married or had kids or just started a new job.

They’re gradually progressing in their careers when they’re faced with this diagnosis. Many of the young patients I see don’t have previous exposure to the healthcare system. So now they’re going back and forth to the hospital for biopsies, chemotherapy, managing complications—and it’s all new to them. That’s combined with other life stressors—managing a career, a family, everything. So, we do see higher psychosocial distress.

John Marshall, MD: I gotta throw this in. You know, 70-year-olds don’t complain about any side effects, but 40-year-olds complain about every single side effect that we cause. It’s always interesting to say, yeah, you're young, you're tough—but they list them all—whereas that 70-year-old is just used to feeling that way.

Thejus Jayakrishnan, MD: That’s also something that’s part of our research—trying to figure out if there’s a biological mechanism that may be responsible for a higher risk of toxicity. But it definitely impacts the ability to deliver the treatments we want to. We do want to give intense treatments, but then you see significant side effects, whether it's nausea, vomiting, or even neuropathy from oxaliplatin.

And then, we have to think about long-term side effects—even in curable colon cancer, where you have to receive adjuvant, postoperative chemotherapy to decrease the chance of recurrence. But then you’re faced with having to deal with some of these side effects.

Even post-surgical complications, like low anterior resection syndrome after rectal cancer surgery, can have a big impact on quality of life. So, there are a lot of considerations there.

John Marshall, MD: You know, part of it—being the end of July—is we’ve got our brand-new fellows coming in, and we’re teaching them as much as we can.

I think when it comes to young people, for example, young patients, we often say, “We want to be very aggressive.”

Thejus Jayakrishnan, MD: Mm-hmm.

John Marshall, MD: But I keep trying to swing us away from that word. Being more effective is really what we want. And this young group—I was thinking mostly around colorectal, but it’s true in other diseases too—there’s increasing interest in organ preservation, avoiding radiation. These are the kinds of strategies we’re using because if you’re going to have this problem and you’re going to survive it for the next 30 or 40 years, we want to optimize your quality of life.

I know your center does a lot of this. We do a lot of this. It’s less easy to do as a generalist or someone out there who doesn’t feel quite as comfortable, but I know we’re all out there to help them and offer advice to try and optimize that patient’s quality of life—to be the most effective, not necessarily the most aggressive.

Thejus Jayakrishnan, MD: Yes, totally agree. With the PROSPECT trial and the OPRA trial in rectal cancer, we have more evidence that we could potentially avoid radiation or help a portion of people avoid surgery altogether for rectal cancer.

Over time, I think we will see increased adoption of these approaches. There are also studies looking at early-stage rectal cancers—T1, T2—whether we can use chemotherapy or chemoradiation and avoid surgery in those subsets of patients.

There are newer immune checkpoint inhibitor combinations coming up. So whether those translate into opportunities for non-operative management in microsatellite-unstable tumors remains to be seen.

And can we develop effective immunotherapies for microsatellite-stable rectal cancer that can also help us avoid the risks of some of these other treatment modalities?

John Marshall, MD: I can’t thank you enough for taking the time. I know you’re busy—I know we’re all busy—but this is such an important topic. Your paper got the appropriate big national recognition—on news channels and the like.

I just wanted to make sure that our audience also had a little bit deeper dive on this issue, because we’re the ones that are going to be meeting these people across the exam room table from us.

And we want you to know out there as much as we know, so that we can make it a little easier on all those folks out there. Thejus, again, thank you very much.

And for Oncology Unscripted, this is John Marshall. Thanks for joining.

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This transcript has been lightly edited for clarity.