RHR: Revolutionizing Cancer Treatment, with Dr. Chris Apfel

In this episode, we discuss:

• Dr. Apfel’s background and personal journey into cancer research
• The important first steps to take after a cancer diagnosis
• The SAGE Oncotest: Innovation in cancer treatment selection
• Why you should consider integrative oncology
• Promising innovations to know about

Show notes:

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Hey everybody Chris Kresser here, welcome to another episode of Revolution Health Radio. We live in the era of precision medicine, with many exciting innovations in diagnosis and treatment. Yet in many ways, cancer care lags behind. It remains pretty hit or miss, with only about a 30 percent chance of efficacy overall. There are new, relatively new diagnostic methods like genomic testing, but only one in four patients have actionable mutations to benefit from those therapies. And even if you are one of those one in four patients, the therapies aren’t guaranteed to work. So there’s really still quite a lot of room for improvement in cancer screening and treatment and follow up. And that’s why I’m really excited to welcome Dr. Chris Apfel. He is an MD, PhD, and MBA, a very highly educated guy who’s a physician, clinical researcher with over 100 published, peer reviewed papers, including a six factor clinical prediction model published in the New England Journal of Medicine that led to the development of the Apfel score, which is a clinical calculator used universally. He kind of wrote the textbook on this to predict the risk of postoperative nausea and vomiting. That was his original area of focus. But he became interested in cancer diagnosis and treatment when his father was diagnosed with lung cancer. He had already lost his mother to ovarian cancer. And when his dad was diagnosed with lung cancer, he opted to forego any therapy after having witnessed his wife really suffer from chemotherapy and just a sort of blunt instrument approach to treating her disease. And that drove Dr Apfel to want to find more effective means of diagnosing, or more specifically determining what treatments tumors would respond to, and thus increasing survival rates dramatically. So that really initiated a new effort. He left the clinical department at UCSF where he was, got an MBA from Wharton to complement his scientific education, and started SageMedic, a new company dedicated to this kind of precision cancer testing and optimizing the therapeutic approach based on the specific characteristics of the tumor. So I really enjoyed this conversation with Dr Apfel. I learned a lot. I wasn’t familiar with this test. It has the potential to be a game changer. Some of the most recent clinical data suggests it can roughly double the chances of a successful outcome, and it’s unlike any other test that’s available right now. So cancer continues to increase as a cause of death. I expect that will continue to be the case in the next several years, and so it’s more important than ever for us to have new tools to be able to increase our chances of overcoming it. So in this podcast, we talk about what the SAGE Oncotest is, how it works, what types of cancer it works for, how you can get the test if you have cancer, you or a friend or family member, what drugs or treatments the SAGE Oncotest tests for and some of the other new innovations on the screening and treatment side in the cancer world that Dr Apfel is excited about. Like I said, I learned a ton in this interview. I’m really excited to be aware of these tools now to recommend in my network, and I hope you learn a lot as well. So without further delay, let’s dive in.

Chris Kresser: Dr. Apfel, thank you for being here. It’s a pleasure to have you on the show.

Chris Apfel:  Thank you for having me.

Chris Kresser:  So I always love to start with just the guest’s personal story and background. I came to this work through my own struggle with chronic illness and also watching a grandparent struggle with a heart attack and all the consequences of that. And I know you have your own personal story as well. So what got you interested in cancer research in the first place?

Dr. Apfel’s Background and Personal Journey into Cancer Research

Chris Apfel:  Well thank you very much for asking. I have a medical background. I studied medicine way back in Germany and was very interested in clinical research. So my question was always what improves patient outcomes? So I’ve studied, run a lot of clinical trials and published over 100 peer reviewed papers and developed a clinical prediction model that is now textbook knowledge in the field of anesthesia and perioperative care. So that’s not oncology. And as a result of that, I basically got recruited to the US, and when a big paper came out on a 5000 patient study that we conducted in Europe and then was published in the New England Journal of Medicine, and I had some nice offers at the Cleveland Clinic, at Harvard and Stanford and and I chose the University of California in San Francisco because that’s actually one of the premier institutions that are really thinking of how can we really have global health and improved health for everybody? It’s a wonderful institution. And I continued my research there until my dad was diagnosed with lung cancer, and it was relatively clear he said to me, well, unless you can promise me the therapy is going to work, I don’t want it. And the background was that my mother has passed away from ovarian cancer. The conventional treatment, the chemotherapy basically destroyed her and made her miserable, even into her last months of life and it was actually only then that I realized even today, cancer treatment is largely hit or miss. We all like to believe the future is here now, but when one of your loved ones is affected, what you often realize is we’re still living in the past. And that struck me, and so, because I’ve also been an intensivist and in the ICU, if somebody has a sepsis, so a serious infection that is in the blood, we usually take the specimen, a blood specimen, we cultivate the germs, and then we put antibiotics on it to understand which one is the most effective treatment. And you really need to see what works best in order to understand what you want to give to the patient. And you can’t do this just with genomic testing, because that’s a very reductionistic approach. So the whole organism, like a bacterium, is basically more than the sum of its parts. And that’s actually especially true in the field of cancer. And the idea that what’s still the current standard of care is you take a biopsy, it’s thrown into formalin to preserve it. The tissue is then fixed and dead, and then you try to extract a molecule to predict which therapy would work, had you kept this tissue alive, and had you actually found it out. It’s a very indirect method. It has an appeal of mechanisms of certain molecular pathways. But in what way this is really relevant for that individual patient is not always clear. We call it, it’s called precision medicine, and it has led to the development of wonderful targeted therapies that actually have shown effectiveness for some patients, but unfortunately, only for a minority of patients. So unfortunately, according to the National Cancer Institute’s MATCH trial, the abbreviation for molecular choice, molecular analysis for therapeutic choice. According to the trial, only one out of four patients have so called actionable mutations. So have genetic alterations for which we have drugs that are more likely to work than others. And what we often forget is even then, the targeted therapy often doesn’t work. So this reductionistic approach ignores that the whole cell and the whole tumor is much more than the sum of its parts. It’s not just the DNA, it’s also the DNA expression, it’s a metabolomics, it’s a proteomics, it’s the extracellular matrix, it’s the micro environment of the tumor that all affects whether this tumor will respond to a certain therapy or not. And you cannot with no matter how much AI you throw on this, you cannot predict this with genomic testing. And so I was asking my oncologist, why can we not just take the patient specimen out, divide it up and test it in vitro to understand what would work best? And that’s actually when my journey started.

Chris Kresser:  Go for it, right? And you did. So before we talk a little bit more about what you developed with the SAGE Oncotest, let’s linger a bit more on the standard model of care for cancer. I believe, from the statistics I’ve seen, you’ve got, even in this era of precision medicine, you’ve got about a 30 percent chance of efficacy with treatment. And you also just highlighted some of the issues with focusing exclusively on genomic testing. Only one in four patients have actionable mutations that would even benefit from that therapy, and then the therapy itself may not work, even if you’re one of those lucky one in four patients. So what are some other challenges right now that somebody who’s diagnosed with cancer faces in the standard of care? And what are some of the strengths of the standard of care that we can take with us forward into a new generation of cancer diagnostics?

Important First Steps After Diagnosis

Chris Apfel:  Yeah, I think what’s really important is that if you have the diagnosis, you probably should take your life into your own hands. You cannot just rely on what’s been established. More often than not, you actually have to do something. So [my] first recommendation for anybody who has a diagnosis [is to] assemble a support structure. You most likely don’t have a medical background. All those technical terms don’t make sense to you. And the first time you hear this diagnosis, you are emotionally overwhelmed. You may not, most of this you may not understand and when you go home, you actually don’t, most people don’t remember exactly what was said, and it’s emotionally extremely stressful. My advice, number one, would be [to] develop a support structure. Have your partner, have your friends with you, and seek out patient advocacy groups, because you need to actually, basically understand what’s going on to kind of navigate the system. So there are brochures on your disease. You need to know what type of cancer this is, is there a certain subtype? What stage is it? What are the treatment options? And it reminds me of an advisor of ours, Dr. Archelle Georgiou, who has written a book titled Healthcare Choices. And she also has a wonderful podcast, Speak Up For Your Health. And what she says is you need to understand your condition, what are the alternatives of the treatment, what are the risks, what’s the experience, and also understand that it’s your body, it’s your health. So you may actually prioritize, for example, quality of life versus longevity or minimally or maximal invasive interventions very differently than anybody else. It’s your choice. It’s your decision. And you want to be able to understand how can you navigate the healthcare system? How can you communicate with your healthcare providers? What can they do? What can they not do? And this book also has very nice decision making tools at the end. So think through this, assemble a support structure with patient advocates. And then there’s one other thing that I actually would like to emphasize, get a second opinion. It’s actually a very interesting study by Dr. Snyderman and colleagues from the Memorial Sloan Kettering Cancer Center that actually has shown that if you actually look at second opinions, they can improve a patient’s outcome in roughly 23 to 57 percent of cases. It’s actually a pretty powerful study. And so that is, this would be the first step. Try to get your head around and try to understand it, because most likely than not, if you want the best possible outcome you want to be proactive and mindful about that. If you are in an early stage, you have a little melanoma, or you have a little lump in the breast, very often, with a surgical removal you could be cured, and you will know. So a chance to cut is a chance to cure, so to speak. In an early stage, stage one, cure rates are above 90 percent, 95 percent. We do exceptionally well in breast cancer. Actually, in one of the exceptions for the US healthcare system, in breast cancer, we actually outperform other Western countries, which is a surprise to me, but it has to do with the aggressive screening. So if it’s an early stage, you’re most likely fine. Unfortunately, our system is not set up for early screening. Even though there are now pan cancer screening tests, they’re not covered by insurance. People don’t know about it, and so very often you get diagnosis stage three, stage four, and you really need to be searching for what you can do in order if you want your outcome to be better than the average.

Dr. Chris Apfel joins Chris Kresser to discuss the SAGE Oncotest, a breakthrough in precision cancer care. Learn how personalized testing is doubling treatment success & improving outcomes. #CancerCare #Oncology #PrecisionMedicine #Chriskresser

Chris Kresser:  Yeah, I’m 100 percent in agreement with you. I’ve been involved as a patient, as a clinician, as a family member of the healthcare system for many, many years, and I’ve seen so many instances where people who were willing to advocate for themselves or perhaps advocate for a family member, had such a better outcome as a result of that, because, as you pointed out, nobody knows what their priorities, what a given person’s priorities are better than themselves. And oftentimes in the healthcare interaction, assumptions are made by the clinician perhaps has a certain perspective or a certain bias towards treating a certain way, being very aggressive, let’s say, and the patient, that may not be how they want to approach it. But without informed consent or without seeking other opinions, or without really understanding the full range of options, they just take that route because it’s what the doctor suggested, even though it wasn’t the best route in their particular situation. So I definitely agree with that. Let’s talk a little bit now about this SageMedic and the Oncotest, and going back to what your father’s oncologist said, or the question that you asked your father’s oncologist and what came of that.

The SAGE Oncotest: Innovation in Cancer Treatment Selection

Chris Apfel:  Right. So it was actually quite interesting, because I also have a biostatistical background. I looked into the literature trying to examine the biopsy, the fresh biopsy, and grow the tumor in vitro. That actually is not a new idea. That actually has been tried before 40 years ago. And interestingly, if you can actually grow the tumor that’s been kind of well established, and you put different drugs on it, you can actually say, with roughly 80 percent what works best. One of the challenges, why this has never become standard of care, was that it is very hard to grow the tumors. Very often you may not have proliferative material in the biopsy and actually in the majority of cases, those tumors, these ex vivo experiment didn’t grow. So if they grow, then you can actually measure which drug is best to inhibit the growth. But if they are basically very slow growing, or don’t grow at all, or get infected or die off, then you don’t have a result. And so what we said is there must be a way to have those results faster and not be dependent on the tumor growth. Because we don’t just want to inhibit that it’s growing and staying there, we actually want to succeed. We want to win this battle. We want to basically kill the tumor. We want a complete tumor response, and we want long-term survival. That’s actually what I would want to have. And so we developed a technique where we can actually get this biopsy shipped to us overnight. We create hundreds of micro tumors within one day. They are similar to the original tumor and then we drug them with often dozens of drugs to understand which drug or which drug combination is most effective in killing your cancer. And with this approach, we have a result back for you and the oncologist within seven to 10 days in over 90 percent of cases. And we have some data that suggests this can double the patient’s chance of a tumor response and significantly increase quality of life and survival.

Chris Kresser:  Amazing. So it sounds like the innovation was around creating a plurality of the tumors rather than waiting for them to grow. You’re doing a bunch of micro tumors, and that allows you to do it much more quickly and not be dependent on the tumor growing as previous method was focused on.

Chris Apfel:  Yes, yes. That’s one of the interesting things, yes.

Chris Kresser:  And what, are there particular types of tumors that you tend to have more success with in this approach and types of tumors that tend to be more difficult or more resistant to this approach?

Chris Apfel:  So the beauty about our platform is that it is more or less tumor agnostic. So we can test triple negative breast cancers. We can test colorectal cancer. We can look at liver metastasis, just on a core needle biopsy. I have a strong interest in ovarian cancer, because my mother passed away from ovarian. So we do a lot in ovarian cancers. We have actually done stuff for glioblastoma. We also have done stuff for rare cancers or cancers of unknown origin. That’s actually where our platform really thrives, in particular when this is a late stage a metastatic or recurrent cancer or the therapy has stopped working, then you don’t wait. You don’t want to wait until it’s too late. You actually want to act now. Get a biopsy. See where we can get a biopsy to have that shipped to us, so that we can provide you with the options that are most likely to be effective for you.

Chris Kresser:  So let’s talk a little bit about those therapies. What kind of drugs are being tested, and are you also testing a combination of drugs, which, of course, some oncologists like like to do?

Chris Apfel:  Yes. And so we have, what we normally do is the following. And let me also take one step back. If you are diagnosed and you are scheduled for surgery, that’s actually the best opportunity to get a specimen to us, and you need to contact us ahead of time, because otherwise the specimen is thrown into formalin and the tissue is dead and can no longer be tested. So that needs to be arranged beforehand and that way you don’t need an extra biopsy, and you have plenty of material for testing. So I’ll give you one example. So let me walk you through ovarian cancer. There are, I would like to say roughly five to 10 chemotherapies that are more or less standard of care. Usually it’s a doublet therapy. We test the single compounds as well as a combination. But there are also so-called PARP inhibitors. And these PARP inhibitors are often given for maintenance, especially when the patient is BRCA one or two positive. And so we also take testing the PARP inhibitors. And then there are, some of the drugs are often pro drugs. So we test these drugs that are the active metabolites of that. And so we have the panel that is within the NCCN guidelines number one. That’s the first priority, because oncologists primarily are sort of bound to work within a framework, and the National Comprehensive Cancer Center Network, NCCN, has guidelines for oncologists which drugs to choose based on the tumor type or subtype. And so we test those first so that the oncologist can choose, I would like to say, can select the superior care within standard of care, because then it’s easier for the oncologist to implement it, number one. Number two, if there is a recurrence, we have an extended panel, these are usually another 12 patent drugs. But what we also do, and that’s actually has recently come up, we also look at repurposed drugs. It’s very interesting. There are drugs that are commonly used. Metformin is an example. Disulfiram is an example where we have seen. Lovastatin. So statins. There are repurposed drugs that are used for other purposes where your tumor may be very sensitive to. And that should not be a substitute. It should be an add on. It should be integrated into your care to maximize the chance that you get actually a complete response.

Chris Kresser:  That’s great, because I know several oncologists who are using those repurposed drugs with great success. So it’s great to hear that you test for them. So where does this test fit within like the healthcare system today in the United States, for example? If a cancer patient wants to get this test, does their oncologist need to order it? Can they request it through their oncologist? How would somebody go about getting it?

Chris Apfel:  Right. So it needs to be ordered by a physician. It could be your integrative oncologist, and we would need to get a specimen to our lab. So if you are scheduled for surgery, you speak with the, either the surgeon or your GP, or whoever is organizing this care, and that person can order the test. And then we will also communicate with the surgeon or the proceduralist how to get the specimen. Usually one should also involve pathology, it depends. But it’s ideal if the specimen is directly put during the surgery into the sterile tube, just to make sure that it is sterile. It needs to go through pathology anyway for regulatory purposes, but then that’s the easiest way. The other way is, let’s say you already had your surgery, or you are late stage, and you had already a biopsy, you already had the first and second line therapy, and it’s not working. You may have a lymph node that could be easily removed in your groin, in your axilla, or in your neck, or you may have some fluid collections. Ovarian cancer patients sometimes have so-called ascites which is fluid collection in the belly, and that can be drained and out of this drain that’s usually routine of care, we can get the specimen. If you have something else. Let’s say you have a glioblastoma, you may actually and there is new compression, you may need a re-operation. That’s another opportunity to get the specimen. Or if need be, you can have an exploratory procedure or a biopsy of a liver metastasis, and we can get the specimen as well.

Chris Kresser:  Okay, so multiple options there. What has been the response that you’ve received in the professional community? I know sometimes there’s resistance to innovation or skepticism. It seems to me that this is a very welcome innovation, given what it offers and in terms of cancer diagnosis, but I’m just curious what that’s been like.

Chris Apfel:  So it’s exceptionally welcome and appreciated by surgeons, cancer surgeons, surgical oncologists. They understand the limitations. In particular, gynosurgeons know about these limitations of genomic testing, and because gynosurgeons in this country often also do the chemotherapy, and they often are then faced with these difficulties, what now, they are more open to send tissue to you and especially when we are talking about a later stage. The traditional I would like to say oncologists that are more, I would like to say, boxed into the standard treatment paradigms of genomic chemotherapy or genomic testing with target therapies, or let’s add some immunotherapy, they are usually very strongly minded towards what’s covered by insurance and what’s considered standard of care. And if it’s outside of this realm, a patient really needs to speak up for herself in order to get it done. And sometimes it requires that the patient is looking for different oncologists. And at the end of the day, it’s your own life, and you have to speak up for your health.

Integrative Oncology

Chris Kresser:  Yes, this is what we were talking about before, being your own advocate. And I think that’s true in so many areas of medicine, but particularly in cancer where the stakes are very high and it’s important that people understand that there are these limitations. I think most clinicians have a good heart and are doing it for the right reason, but they often are victims of the system as well. They perhaps feel bound to a certain standard of care, or they’ve just become accustomed to doing things in a certain way. They maybe don’t have as much time as they should have to stay current with the research, and abreast of all the newest diagnostic procedures and treatment. And so, as you’ve said, when it’s your life that you’re, that’s at stake, or the life of a family member, it really pays off to ask a lot of questions and even be willing to step outside of the current model to find the right path forward.

Chris Apfel:  Right and as you mentioned, stepping out of the current model, one thing that I would also recommend, and I think you’ll probably like that comment is, consider an integrative oncologist. So I, for example, have had some contact with Dr. LaValley, and he is an integrative oncologist who actually has really a depth of expertise in terms of which repurposed drugs or alternative treatments can work through which pathway. So I like him a lot. The other thing is, many major, I would like to say, academic centers now have integrated oncologists. There is, for example, a very interesting talk from Dr. Lorenzo Cohen, who is originally, who is at the MD Anderson Cancer Center. And he gave a talk at the Moffitt Cancer Center at some point, and he talked and quoted a study from, I think it was Dr. Barbara Anderson, from Ohio State. And she and the title is something like psychological interventions, or impact on psychological interventions on patients with breast cancer. And what she was doing is, I think she looked at over 200 patients, the randomized control trial, and she looked at over 200 patients who had breast cancer surgery and lymph node resection. So basically regional stage, and she was showing that with stress reduction, mood improvement, exercise, plant-based diet and treatment adherence, she could double the chance of, or can reduce, could actually cut the risk of recurrence and death by half.

Chris Kresser:  I believe it.

Chris Apfel:  So if that would be a drug, it would be a billion dollar drug. And it’s something that multiple, it would be the biggest blockbuster. But there is stress reduction, exercise, plant-based diet. There is no money in it. There is no industry behind it. And so there is a lot you can do on your own by thinking about how what you can do for your own health to strengthen your immune system through exercise and to avoid junk food. If you think about that, in infusion centers, very often they offer candies and other stuff that is high glucose that cause glucose spikes. And we know that sugar loves glucose. The system is sometimes so anachronistic you need to put it into your own hands.

Chris Kresser:  Yeah, it’s backwards. Yeah. I had Dr. Lise Alschuler as a guest on my show. She’s a professor of clinical medicine at University of Arizona, and is on the faculty of Arizona Center for Integrative Medicine. She’s an integrative oncologist, and we chatted a lot about these topics, and there’s so much that people can do and evidence based interventions too. A lot of times people who are entrenched in the dominant paradigm will just sort of scoff at these integrative interventions and claim that there’s no evidence behind them. But that’s not true. The study you cited is one of many studies that support these diet and lifestyle interventions. It’s generally best to combine them with other standard methods of care, and you get the best outcomes that way. But again, this really boils down to personal choice. We all have a right to choose what path we want to take based on our values and our worldview, and it’s really important to know what the options are, so that you can make an informed choice. Dr. Apfel, I wanted to ask you just before we finish up, any other medical innovations, either on the diagnostic side or the therapeutic side that you’re tracking right now that are promising cancer care?

Promising Innovations to Know About

Chris Apfel:  Yeah, I think there are two I would like to say. There is screening, there is now a pan cancer screening test from Grail. And if you think about that, we are currently screening for breast cancer, for colorectal cancer, for melanoma, perhaps some of them, and then prostate perhaps, and even their PSA is not a good marker. There is now the Galleri test that can actually detect a wide range of cancers at a much earlier stage. And if you keep in mind that if you’re in stage one or stage two, your survival is 80 percent. If you’re at stage three or four, your survival may be below 20 percent. So you really want to catch it early, because the tumor actually takes about 10 to 20 years to grow. Most tumors, not all of them. And so, you really want to, if you are, let’s say, at my age, I’m now above 60, the chance that there would be something in my body that may become relevant in five to 10 years, that chance is already five percent. So I have made it for me, I’m paying out of pocket, and I’m doing this once every five years. I’m not paranoid about this every year. And then the other alternative is complement and alternate that within whole body MRI. Not going crazy on it, just looking, just checking that for early detection. And then there is the other part is when you, if you are diagnosed, if this treatment doesn’t work, or something like that, the number one, I think, the next biggest innovation is SageMedics ability to really understand which therapy can work best for your body or for your cancer, actually. And then once you have that, and you have the selection, there is a liquid biopsy test from, for example, Signatera or Personalis, where you can actually test for minimal residual disease. You can actually see whether now once you have those treatment options, you can actually see how your body is responding to it, and you can react much faster than with any imaging results. So those are the, I would like to say, the three main areas that I find interesting. Screening, early screening, in asymptomatic people above 60, or if you have any other reason why your risk should be increased, that’s one part. The second part is, if you are diagnosed, make sure a fresh specimen comes to Sage. Do also be active in your lifestyle changes, in exercise, nutrition, relaxation techniques. Consider integrative oncology, and then once you have your treatment, make sure you have your finger on the pulse whether the treatment is working.

Chris Kresser:  And that’s where the liquid biopsy comes in.

Chris Apfel:  Yeah.

Chris Kresser:  This has been fascinating. I’m really excited to learn about this Oncotest and be able to recommend it to patients and the providers in our network. Where can people learn more about the tests, Dr Apfel?

Chris Apfel:  Yes. So it’s at SageMedic.com. Sage is S-a-g-e, like the person you are talking to or the plant. SageMedic.com. Not medical, just one word, SageMedic.com. And there’s also a phone number you can call and get further information. And I can also provide you with some other information that provides you an overview of what we are doing in our, how our solution works.

Chris Kresser:  Great. And this would be a good resource if a patient is interested in this test, and their provider’s maybe not familiar with it, but open minded and willing to learn more, there’s a section on the website for physicians, I see.

Chris Apfel:  Right. It might be best if you, for example, contact us to kind of see where are you in your journey. Does it make sense? And we could then help you to kind of figure out, is there, can we get a specimen from somewhere and when? Then once you’re armed with that information, then go to your oncologist or to your other physician to get it prescribed, and we can help you with that as well.

Chris Kresser:  Yeah, that’s a great recommendation. Just minimize the friction and the number of steps and make it as easy as possible for them to buy in. Great, well thank you so much for your time, Dr. Apfel. I really enjoyed this conversation. I know that our listeners are going to be excited to learn about this just to increase the options and increase the likelihood of surviving what can be a challenging and life threatening diagnosis. So thank you for your work in this field, and thanks everyone for listening. Send your questions to ChrisKresser.com/podcastquestion.