Darrin Godin: Well, hello everyone and welcome to Talking Hope. I'm your host, Darrin Godin. Our guest today is Dr. Pashtoon Kasi, a gastrointestinal cancer specialist and the medical director of GI Medical Oncology for City of Hope Orange County. Dr. Kasi is one of the nation's leading experts in genomics of cancer and the development of personalized therapies. He practices at City of Hope Orange County's Lennar Foundation Cancer Center in Irvine, the most advanced comprehensive cancer center in Orange County, where he is part of an integrated team transforming cancer care and bringing new hope to patients and their families. Thank you for joining us today, Dr. Kasi, and welcome to Talking Hope.
Dr. Pashtoon Kasi: Thank you for having me.
Darrin Godin: Dr. Kasi, the American Cancer Society has reported a troubling increase in colon cancer and other cancers in people under 50. What do the people listening today need to know about colon cancer in America?
Dr. Pashtoon Kasi: As you pointed out, it is a troubling trend. Colon and rectal cancers are often lumped together as colorectal cancer, it is on the rise, especially in individuals who are in their twenties, thirties, forties, who wouldn't have met the guidelines for screening. But we are seeing increasingly incidence of rectal cancer in this young patient population.
Darrin Godin: Yeah, the statistics certainly are startling, as you said as well. Are there certain early warning signs or symptoms for colon cancer? And also/ what are you and your team currently working on for screening and early detection?
Dr. Pashtoon Kasi: Yeah. In addition to talking about symptoms, it is important to emphasize that the age, because of this troubling trend, has been moved from 50 years to 45 years, and then for some populations as early as forties, and even younger if somebody has a family history.
The troubling part is often colorectal cancer may or may not show symptoms until it's pretty advanced. That's why screening helps. However, in general, any kind of bleeding in your bowel movements, that is one common symptom that can happen in patients with rectal or colon cancer. Pain that does not go away. Often people can have aches and pains, but abdominal pain or symptoms that are persistent and growing worse, it should be a warning sign that you should talk to your primary care doctor or think about other signs. Change in the caliber of stool or the way the stool looks like or the way the bowel movements are or worsening constipation that is not temporary, but it's persistent, that it is getting worse. But those are in general some gastrointestinal symptoms. And often just weight loss that's unexpected. That is also something to be cautious about.
Darrin Godin: And what are you working on right now for screening and early detection?
Dr. Pashtoon Kasi: One growing area of research for early detection, and that's true for all cancers and in particular there's interest in colorectal cancer, is this growing field of liquid biopsies. So these are blood tests, simplistically. It's a misnomer since there's no biopsy being performed. But cancers, as they grow, they can shed their DNA in the bloodstream. That DNA can be detected through some of these tests. As one of my colleague calls this, there's a lot of “tumor trash” that can be detected in the bloodstream from DNA, RNA, protein, other things that can be detected by a simple blood draw. So these non-invasive blood tests are one area of growing interest. We were using a lot of these and still use it in a clinic on a day-to-day basis for patients with advanced or metastatic cancer to know what type of powers the cancer has, what mutation this colorectal cancer has. But then now they're kind of moving up the ladder to early detection and screening as well.
Darrin Godin: Is this a trial that's underway or is this an actual approved treatment already or approved test already?
Dr. Pashtoon Kasi: It's a great question. The liquid biopsies in the utility and what's commercially available and what's in vial is exponentially going up. There are commercially-available tests. I tell patients and caregivers there are two types of liquid biopsies that are available when you look at early detection, one that are cancer-specific. So for example, there are liquid biopsy tests that are only for patients for colorectal cancer. So the test is only meant for “normal” individuals, not patients whom we want to be screened for colorectal cancer. There are some that are commercially available.
Just a few weeks ago at our annual conference in oncology in San Francisco, there were several other tests or results that were reported out at City of Hope. Other collaborators and scientists have developed tests as well. So the good problem is there are many tests both commercially and academically available within City of Hope and as well as commercial partnerships that are options for patients with colon cancer.
The second type of blood tests, they often go by multi-cancer early detection assay, and as the name suggests, it's multi-cancer, meaning it's not going to just pick up signal from one cancer, but potentially is, as they say, like the holy grail of having a test that could pick up many cancers. So while colon cancer might be one of several dozens of other cancers that the test may pick up, you can imagine that the accuracy or how good the test is, its performance may vary and may be better for one cancer more than the other. Because it's not just about the cancer. The cancer has to be simplistically spilling out or spitting out the DNA or some content that the test is measuring into the bloodstream. And as they say, some cancers are high shedders, so any test is pretty good for them, and some cancers are low shedders, so the tests may not pick up and could be falsely negative. So we have to keep in mind the performance of the test, what the clinical question is, what the scenario is, as one size may not fit all.
Darrin Godin: Well, it certainly sounds promising, and the research that's being done here at City of Hope is helping to fuel those and move those potential screening options forward. Thank you for your work on that. I know one of your areas of expertise is neoadjuvant therapy. What exactly is that and how can it benefit patients with GI cancer?
Dr. Pashtoon Kasi: From a medical standpoint, to put it in layman terms, for a cancer, we do surgery first, and then whatever mop-up chemo or treatment might be done, it's referred to as adjuvant therapy. There's a paradigm shift happening for many reasons that it's probably better if we did the reverse sequence, meaning do the drugs and treatments first and then surgery later. When we do that in reverse order, it's called neoadjuvant therapy. And what's intriguing, especially in colorectal cancer in some of our work in this setting, is it's not just for colorectal cancer, it's also for skin cancers, other cancers for which immunotherapy is being used, which is drugs that take the break off your body, so your own body fights, the cancer, your own immune system, your own defense system fights the cancer.
There's a lot of intriguing data, especially in the last few years. There's something about the cancer still in the person. So that mothership where this process have started. When it's still in the body, the same drugs may work better. And we think that some of that could be because your body's already trying to fight the cancer, the so-called immune cells that are called T cells, they are in the lymph nodes that are containing the cancer. And by doing surgery first, where, simplistically, the goal is to remove the cancer, maybe that's not necessarily the best thing. Maybe attacking the cancer by unleashing the breaks off immune system before surgery happens, the same treatment, the exact same drug, the exact same dose, just the reverse order of things, is leading to at least 30-40% change in better outcomes.
So this concept, while it's not entirely new and we're not the first to report on this, but we've borrowed a page from some of our colleagues in melanoma, lung cancer, and one of our investigator-initiated trials was focusing on doing that for our patients with colorectal cancer to increase the proportion of people who can be cured.
Darrin Godin: Wow, that's really incredible. And so the promise for patients, as you mentioned, potentially curing their cancer. What other promise do you see for patients in this different way of treating them?
Dr. Pashtoon Kasi: I think it boils down to, if we can do and kill more cancer and downstage it before surgery, there'll be less reliance on chemotherapy. And pleasant things don't come to mind when people talk about chemotherapy. So if we could harness the power of the immune system to kill cancer, there could be less reliance on chemotherapy and also increasing the proportion of people who can be cured of this deadly disease, because even when it has not spread as soon as it hits a lymph node, even though that's something that the surgeon takes out, anywhere from 22% to a third, if not higher, these patients, they're not cured by standard of care surgery and adjuvant or mop-up chemo. So there's a huge unmet need to increase that number.
The other piece when it comes to rectal cancer, which is treated in some respects similar to colon cancer, but has the quality of life issue, because if it's close to a sphincter, then you may end up with a bag that might be permanent, which can be a big quality of life deterrent. If immunotherapy could potentially kill the cancer, then there is a term where we call it watch and wait, and as the term suggests, we just watch and wait and only do surgery if it's necessary. So not only is the goal in rectal cancer to cure more patients, but there is also a goal to help preserve the sphincter, not need the bag, which can be a big quality of life, and more important, again, it's important in every age group, but especially with the rise of colon and rectal cancer in young patient population, it's important that we not only focus on cure, but also focus on the long-term quality of life impact of any of our treatments in surgeries or chemotherapy might have.
Darrin Godin: Can you discuss the NEST trial that we're working on?
Dr. Pashtoon Kasi: Yeah. That's a term that we coined for a trial that we did neoadjuvant therapy for, and we had treated patients both which are responsive to immunotherapy, but more importantly, there's a huge subset of patients for which "commercially available" immunotherapy doesn't work, but newer immunotherapies that are second, third generation and their mechanism of action, different targets that they, again, work better when given before surgery. Again, there is promising work. Again, some of the trials that were at City of Hope as well, looking at the utility of these drugs in advanced or metastatic cancers, we kind of borrowed that page and took the idea of, if we know that immunotherapy could work better, what if we tried some of these newer drugs that are showing promise in metastatic or stage IV colon cancer and rectal cancer patients and try it before surgery? So that is, again, leading to a promising signal of more patients getting cured with no recurrences, which is begging the bigger question, can we now move forward with trials that could potentially challenge the current standard of care of surgery followed by mop-up chemo.
Darrin Godin: Thank you, Dr. Kasi. I'm interested in hearing how you were drawn to become a physician and what really drew you to focusing in on oncology and cancer care?
Dr. Pashtoon Kasi: I would say, for me, a lot of my decisions have been punctuated by mentors and colleagues and education and people that, serendipitously, that you meet over the years, at least growing up. Both of my parents are physicians. My father is a pathologist and my mother is a gynecologist, and her clinic actually was in our home at the front of our homes. Physically, we grew up with an environment surrounded by healthcare and patient care. While there was no pressure to consider medicine as a field, you are drawn to it by seeing so much value and science and patient care that is to it.
But then later on, oncology, like I said, during my residency at University of Pittsburgh, one of my first clinics that I was just randomly assigned to was outpatient oncology. And I think there's a lot of cool science and great healthcare and people getting cured, vaccines, immunotherapy, a lot of this that you don't get to hear or see on the inpatient or the hospital side of things because often that's for emergencies and other issues and you don't necessarily see a balanced opinion of what oncology or cancer care can do. So what was potentially possible in the outpatient setting in the cancer center helped me choose oncology as a career. And then during fellowship at Mayo Clinic in Rochester, Minnesota, that's kind of home to a lot of treatments for colorectal cancer. A lot of these drugs and treatments have been founded there. So again, punctuated by mentors who led the field, it kind of shapes your career choices.
Darrin Godin: Well, you're here now at City of Hope, and as a physician and a scientist, what do you think sets City of Hope apart? What does being here allow you to do for patients that might be difficult to do or might be difficult to find elsewhere
Dr. Pashtoon Kasi: I think a couple of things that are very important for any oncologist providing care to a patient with cancer is ability to provide two real-time multidisciplinary care where everything is under one roof and available real-time. For colorectal cancer, there's no cancer that's more multidisciplinary in terms of orchestrating the timing of treatment, even, and the best sense of curing the cancer is the first time round. So it's important that a multidisciplinary team is making those decision real time not in a sequential or discordant fashion. So that is one key, that you see it be in live action every single day.
The second piece is access to novel therapies and trials. Due to multiple reasons, trials sometimes in some places can take, you'll be lucky if it opens within a year. You would imagine that patients sometimes wonder, "Why is it taking so long for a treatment that you said would be available at your center?" And sometimes you would be surprised some of these things, you'd be lucky if it opens within a year. So at City of Hope, one thing that's really sets it apart is access to the multiplicity and also their focus on making sure that these opening of trials, running of trials are very efficient so that we have more options for our patients. In our national guidelines, a statement that I strongly believe in says, "The best management of a patient with cancer lies in a clinical trial," but if you can't offer clinical trials, that's a defeated statement.
So that's one thing that I find it of extreme value to not only be able to provide trials, but with City of Hope's network of two sites in California, and also partnering with our sites in Chicago, Atlanta, and Phoenix, we have developed now a model where I, as an investigator, could start a trial here in Orange County, but draw in on expertise and have it physically also be an option for patients who might be able to go to Chicago, Atlanta, and Phoenix, but may or may not be able to come and travel to California. So that is something that is very unique, and to see it further grow is very heartening.
Darrin Godin: And I am preaching to the choir when I talked to you about the amount of trials that are underway at City of Hope, more than 800 cancer-specific clinical trials, that's a great deal of research happening right here at our organization that is transforming, not just locally, but across the country, cancer care for patients. What does the concept of hope mean to you, Dr. Kasi?
Dr. Pashtoon Kasi: I would say, for a patient or caregiver or family, because cancer is a devastating diagnosis that's not affecting just the individual, but also the whole family, and while every single life is important, it has even more devastating consequences when it's a 30-year-old, 40-year-old. I think it's all about cure. So we always talk about how much longer a treatment may help control the cancer, different terms being used about how much shrinkage may happen, or something called progression-free survival, duration response, at the end of the day, all what really should matter is can your treatment cure? So that's the most important thing that comes to my mind when anybody mentions hope.
Darrin Godin: Thank you, Dr. Kasi. We're so happy to have you today, and thank you for your time. We appreciate that. City of Hope is top five ranked cancer care in the nation right here in Orange County. In the hands of the nation's leading physicians, scientists, and researchers, cancer loses and life wins. Visit cityofhope.org/oc for more information or call us at (877) 541-4673. I'm Darrin Godin. Thank you for joining us on Talking Hope and we'll see you next time.