Understanding the Basics of the “C-word”: What Is Cancer?

[0:00:00]

Dr. Diane Reidy-Lagunes:  You have cancer, your wife has cancer, your baby girl has cancer. No doubt in this moment you feel the ceiling just caved in and for those of us who have heard those lines, we are gripped with fear. Fear of the intense treatments and the painful procedures. Fear of the uncertain future, fear for lack of control. Yet, there are moments in that storm when we realize we are not alone and that we can do this. Perhaps, when meeting a nurse or doc, perhaps when the plan is finally finalized, perhaps after receiving a fierce hug believing we will get through this. This is where we come in, we are on this journey with you. Let's talk about it, the C-word, cancer. What it is and what's coming.

[0:00:45]

Dr. Diane:  Hello, I'm Dr. Diane Reidy-Lagunes from Memorial Sloan Kettering Cancer Center and welcome to Cancer Straight Talk. We're bringing together national experts and patients fighting these diseases to have straightforward, evidence based conversations. Our mission is to educate and empower you and your family members to make the right decisions and live happier, healthier lives. For more information about the topics discussed here or to send your questions please visit us at mskcc.org/podcast. So here you are at ground zero, why me, why is this happening to me?  Today, we want to drill down to the basics, what is cancer? For that discussion, I am thrilled to have Dr. Matthew Matasar, besides being brilliant and talented and trained in that small college in Cambridge Massachusetts, he consistently gets spectacular ratings because he's loved and adored by both his patients and colleagues. Dr. Matasar, thanks so much for joining us and welcome to the show.

[0:01:48]

Dr. Matthew Matasar:  Thanks Diane.

[0:01:49]

Dr. Diane:  So Matt, let's start at the beginning and provide some statistics. The American Cancer Society estimates that in this year 2020, there will be 1.8 million new cancer cases, yet the good news is that mortality rate i.e., the number of patients that are passing away from the disease has declined by almost 30% when you look at statistics over the last 30 years. So it feels different, it feels like we're definitely doing something right. What's going on there?

[0:02:17]

Dr. Matthew:  So it can be hard for us to figure out what to do with these numbers and how they make sense to us. You could look at this either as a glass half full or glass half empty perspective, I guess. So if you're an optimist, you say, “Wow, despite all these new cancer diagnoses, we're doing something real and doing something important.” Is it that we're finding cancers earlier, so we're able to cure more patients, is it that our treatments are more effective or less toxic, are we really changing things with how we're treating cancer and it does feel like that. I think there's truth to that or you could be the pessimist and say, “Well, maybe just with all of the stuff that we do in medicine, with all the scans and all the testing and all the blood test that we do in the routine care of people, maybe were finding cancers too early or finding cancer don't even need to be found, and we're sort of inflating what the number of overall cancers out there and making it look like we're doing better when we're really not.”

[0:03:09]

Dr. Diane:  And I think that's the billion dollar question, what is cancer? A rose by another name right?

[0:03:15]

Dr. Matthew:  Yeah right.

[0:03:16]

Dr. Diane:  Like why would it be that we have so many different types of cancer and could you tell us a little bit of – just let's define it, what is it?

[0:03:23]

Dr. Matthew:  Your patient and your doctor, your surgeon, your primary care doctor says you have cancer, you need to go to Memorial Sloan Kettering or whatever, that can mean so many different things in so many different settings. Cancer with a capital C is this constellation of illnesses that are probably you know like a 1000 different illnesses, ranging from the slowest growing things to the fastest growing things and everything in between, what is it that they all have in common? I mean some cellular level, some fundamental scientific level, its disordered cell growth where the cells live too long and make copies of themselves and those copies live too long and they make copies and the copies make copies and these accumulate in some tissue of the body or other, overtime causing swelling or growth that eventually shows up on a scan or you feel in your body or is causing problems. But there's so many different types of cells and so many different ways that cells can go wrong, giving us this tremendous range of illnesses that we lump together as cancer.

[0:04:20]

Dr. Diane:  So just to reiterate, cancer by definition is a proliferation of cells that's kind of a commonality where they're growing uncontrollably when they shouldn't be, but there's clearly lots of different reasons why those cells decide to divide uncontrollably. So what causes that to happen?  Because like you said there is blood cancer that you care for, there are solid tumor cancers that I care for. What do we know about that in the most basic elementary forms?

[0:04:46]

Dr. Matthew:  So what's the commonality, what's the common theme that tries to string all these different diseases together?  As you say it, it's uncontrolled or disordered cell growth and survival. What causes that?  Well, different cancers will have different causes, but fundamentally for the majority of cancers there is some change in the DNA, some change in the programming of that cell. Our DNA contains genes and those genes tell ourselves which proteins to make fundamentally that then dictates what that cell is going to do. And if there's mutations or alterations in the genetic code that can lead to changes and how that cell behaves including having it live longer than it's supposed to or having to make copies when it really shouldn't.

[0:05:25]

Dr. Diane:  So essentially what we're saying is that these cells got damaged and we believe now after centuries or many, many, many decades and years of further discovery that the damage of the cell occurred in the gene and that damage is called the mutation, but it's not usually just one mutation, there's a process that's going on there. So how does that happen?  Because I mean do we all get unlucky, we are in sun of lot, UV radiation, other things. We know smoking are potential causes of these cells getting damaged, but many of us have those exposures and yet don't develop these cancers.

[0:06:03]

Dr. Matthew:  Right and fundamentally, mutations are happening in everybody, every day. This is how we're built by our maker. Mutations, translocations, deletions these genetic changes are a fact of life and they happen spontaneously all the time, but our bodies are very good at weeding these bad cells out. Somebody once described it as even the very best of factories that weed out all the bad widgets coming down the line, but eventually some bad widget makes it through the factory. In our bodies when there's a bad widget coming out of the factory, that's a cancer cell that’s surviving all of our protective mechanisms at keeping that cancer from happening in the first place.

[0:06:38]

Dr. Diane:  Yeah and so when those genes get mutated, we also use that analogy of sometimes it's in a gene and that gene when it gets damaged essentially puts the gas pedal down and prevents it from coming up, but then there may be another damage that happens, sometimes a couple of years later, sometimes even 10 years later, and so another gas pedal gets pushed. And eventually it's almost like the game of bingo where you have so many of these genes and boom, the cancer develops. So it's extremely unsettling I would think for a patient's perspective to state that this is going on all the time, but I want to reiterate what you said before, this is a natural process that’s constantly going on in our bodies and our cells are supposed to recognize that damage and then clean themselves up. But yet for some reason they often can't or don't.

[0:07:26]

Dr. Matthew:  And it's that bingo card analogy that I think it really holds true because one mutation here, one mutation there that happened on daily basis, these don't lead to cancer. It's only when you get all of those chits and the diagonal on your card and then you're screaming bingo. It takes a very unlucky sequence of events for the vast majority of cancers, it's not just one genetic change. Cancers where one genetic change is enough to cause a cancer are super, super rare.

[0:07:51]

Dr. Diane:  The next question that often comes up after a patient has been diagnosed with cancer is, what stage am I at?  Can you tell us a little bit about the importance of the stage and how it helps us better define treatment?

[0:08:02]

Dr. Matthew:  When I'm meeting a patient for the first time, typically the first question is what is this illness that I have when you're talking about what is cancer like we just talked some about, I mean talk to them about their specific type of cancer and what it is and what it's like. And then the next question I have to say what it is, is where it is in the body and that's what we call stage, just a description of where it is in the body. And stage is important at some sort of philosophical level because it influences your prognosis, meaning how is this disease going to play out over the months and years to come and it's important because it can sometimes influence our choice of treatment. If it's found in certain stages, earlier stages, you may give certain treatments; if it's found at a more advanced age, you may use other treatment approaches. So it's important for the patient and understanding how it impacts their prognosis and it’s [Indiscernible] [0:08:50] their docs because it guides us in how best to treat them.

[0:08:54]

Dr. Diane:  I'd like to emphasize when you in your world, of blood cancers, because I know your type, stage IV in general, patient says, “I have stage IV,” it's as if patients have this reaction like “Oh that's the worst kind, that's a bad thing.” Can you talk a little bit about that in your world and then I'll share in my world, because I do think the implications of what stage IV means is like you said, by definition it's where is the cancer located and its normally in another place distant from where it started, but doesn’t necessarily have as bad of a implication as I think traditionally people think of, is that true in your world?

[0:09:29]

Dr. Matthew:  In lymphoma, stage – well, first to say, lymphoma is not one disease, there’s 105 different types of lymphoma which is why I have a day job. And these diseases range again from very slow growing to very fast growing, diseases that tend to present with early stage or advanced stage disease. But stage IV for lymphoma means not just cancer in the lymph nodes, but some other part of the body such as the bone marrow or the blood stream. And it's common to find many types of lymphoma not only in the lymph nodes. And it's not all that prognostically important or meaningful for a lot of cancers. Indeed for many of the slow growing non-Hodgkin lymphomas which are quite common, patients may present with stage IV disease and yet be perfectly fine, have no symptoms, have very little lymphoma in their body, need no treatment for years, decades or forever. So stage at some level is just a geographic description of what you're seeing and where you're seeing it in the body. It doesn't necessarily, in lymphoma at least, tell you a lot about what that disease is doing or what you need to do about it.

[0:10:30]

Dr. Diane:  And I do think that's super important to emphasize because in my disease or diseases, it does become important, because often if the cancer spreads to a different place in the body, surgery may be trickier to help, in terms of being a curative therapy, but there are exceptions to that. So for example in our colon cancer patients where its metastasized only to the liver, we can often resect both the colon, primary and the liver metastasis for cure, but if it's traveled or metastasized to other locations, it's very hard to state that surgery will help improve outcome and/or lead to a curative intent. So I think that the idea of stage IV in certain types of diseases can be helpful, but I think we do need to be cautious on sort of the implications of what that means because patient is here and if it's like, “Oh, that's the worst kind, I'm in a lot of trouble,” and like you said many of my patients can live for many years with stage IV disease even without surgery, so we have to be careful of defining that.

[0:11:26]

Dr. Matthew:  And that's why I always advise my patients and friends and family members if they are going through this journey to say not just what is my stage, but how is that important for me, what does that tell you as my doctor about what it means to take care of me, it's more than just a number.

[0:11:39]

Dr. Diane:  Often our first line of therapy, our first string players are the so-called traditional chemotherapies. And we both in your world and my world will see some major tumor shrinkage sometimes, but how could it be that these cancers can shrink sometimes quite dramatically and then start to grow again, what's going on there?

[0:11:56]

Dr. Matthew:  I know how frustrating it is for us as physicians and for patient going through this process, it can be such a roller coaster. I think at some level it tells us that cancer cells are not identical copies of each other. We have this image of cancer as exact mirror image cells, one cell and then it is perfect copies and then perfect copies again and these perfect copies accumulating. We're increasingly understanding that cancer is not just perfect copies of one bad cell and there's a lot of other changes that can happen during the copying process which is imperfect. So you end up with a lot of cells, but they may have differences amongst one another. And the treatments may work for 99% of those cells, but maybe some small group of those cells develop some additional mutation that made them resistant. So it looks like the cancer is all dying because the majority of the cells are dying, but there some cells that are resistant for whatever biological reasons from additional mutations or changes that allows them to survive that chemotherapy and grow over time making it seem like the cancer shrinks and then grows.

[0:12:58]

Dr. Diane:  And so our second line therapies can often be yet again chemo, but there are other treatments as well, what are those different therapies and why don't we think about targeted approaches or less toxic approaches and why focus on these traditional chemotherapies often, particular in your disease?

[0:13:17]

Dr. Matthew:  So when I'm talking for the first time with one of my patients about treatment, I even take a step further back and I say what are the types of things that doctors do for patients when they are doing a diagnosis of cancer, and I’ll speak about the three general things that we have. We have surgery, you've got a lump and the surgeon just sucks it out. We have radiation therapy, you have a problem spot causing problems, you shine a beam on it to burn it and we have medicines that go through the whole body or at least from your nose to your toes and hopefully killing cancer cells wherever they are. Those medical therapies consist of a variety of different stuff under that sort of category. Traditional chemotherapy what we call cytotoxic or cell killing chemotherapy medicines, this is traditional chemo.

And we have other medicines, things that we call targeted therapies which are meant to target specific enzymes or pathways, key signals within these cancer cells that we think allow them to live or to grow or to not die. And then we have treatments that address cancer not by targeting pathways or just generically killing dividing cells, but rather by enhancing the immune system's ability to kill cancer cells for us, the so called immunotherapies. So we have these different buckets to choose from, targeted therapy, chemotherapy, immunotherapy. How do we as oncologists know to give recommendations for one or the other and why do we start with chemo when in some ways it's more toxic at least in the short term?  And here, it's about sort of what you think about is what are you trying to accomplish as a doctor, what are your goals?  And many types of cancer, both in solid tumors settings as well as in blood cancers, our goal can be cure.

And when it's not cured, it can be very long lasting remissions and wonderfully prolonged measures of control of these illnesses. And that's achieved with chemotherapy more often than not, there's very few settings where we think we can cure a cancer with medicines other than chemotherapy medicines. So we go with what's most proven and most effective particularly when we are reaching for a cure. It's in those other settings where the goal may not be cure, the goal may be to prolong life, to improve life, to alleviate suffering, to let people live successfully and feel good despite having to coexist with their cancer. There, there's more of a role and a rationale for using less toxic, more sustainable, more targeted therapies and chemotherapy with the short term pain for long term gain may not have the same rationale.

[0:15:44]

Dr. Diane:  As long as possible and as well as possible.

[0:15:46]

Dr. Matthew:  That's the mantra.

[0:15:47]

Dr. Diane:  Tell me about integrative medicine. We, in the west could learn from those in the east and vice versa and what is the role of nutrition alternative medicines and other therapies that may not have been studied as well as these traditional medicines but may play a role?

[0:16:05]

Dr. Matthew:  These are adjunctive things that patients can and often do receive that can ease the course of their care along with what it is that you and I are prescribing and recommending. And there's good evidence for a lot of this. We know that acupuncture can alleviate a lot of side effects of treatments and symptoms from cancer. Fatigue, hiccups, nausea, pain, these are all symptoms and side effects that there's pretty good evidence, western style evidence that acupuncture can alleviate. Nutrition has tremendous importance both in terms of maintaining your energy and your sense of wellness, but in also making sure that your health is good enough to sustain the kind of life you want and to be able to receive the treatments that we need to prescribe to prolong and improve life. The important thing is to understand that not all integrative approaches are good, just like not all medical approaches are good.

And it's a matter of trying to understand what the goals are, what are you trying to accomplish and what are the tools available to you. Is it acupuncture, is it chemotherapy, is it steroids, is it radiation, is it a hug, right. There's so many tools available to us as doctors and understanding how to put them together in your care of the patient is what makes this an art and not just a science.

[0:17:19]

Dr. Diane:  Absolutely. So talking about that science, talk to me little bit about clinical trials, that's what you do every day helping our patients of today and tomorrow.

[0:17:27]

Dr. Matthew:  Speaking about clinical trials as a thing is like talking about cancer.

[0:17:30]

Dr. Diane:  That’s right.

[0:17:31]

Dr. Matthew:  Right?  It’s like it's not just one thing people. And people will come to you with very clear and sometimes quite misguided understandings about what it means to be on a clinical trial. Some people think that a clinical trial means I'm going to be a guinea pig and you're going to test some medicine on me, that's just a string of letters and numbers that's been given to four rhesus monkeys and macaque. And I'm going to be the first human being ever to get this instead of getting something that is going to cure me.

[0:17:55]

Dr. Diane:  The tails pops out or something.

[0:17:57]

Dr. Matthew:  Yeah right or you know my skin turns blue. There's a lot of different types of clinical trials in different settings. One way to think about it is are you testing a medicine that's already been FDA approved and evaluated as a treatment and you're now trying to figure out is it useful in other situations?

[0:18:13]

Dr. Diane:  In a new disease.

[0:18:14]

Dr. Matthew:  In a new disease or in a different what we call line of therapy, meaning it's been approved after other treatments have failed. Maybe it could be tested before the treatments have failed or in combination with medicines that has not been combined with before to see if we can make one plus one equals three. So if you add a newer medicine to a traditional medicine, can you do better? There are some trials that are randomized, meaning that there is some coin getting flipped in a computer somewhere and if it comes up heads, you're going to get treatment A and if it comes up tails, you’re going to get treatment B. Randomized trials are good when you’d be okay with either coin side. You have to be okay as the doctor and as the patient understand that both of those coin flips are good treatments for your illness.

[0:18:55]

Dr. Diane:  Talk to us just a little bit about that, because I think patients get really worried that one of those flip of the coins maybe a placebo and now you're not getting treatment and does that potentially have the risk of hurting them?  I think many of our trials as, you know, have something called crossover, but talk to us a little bit about those trials and what that means?

[0:19:13]

Dr. Matthew:  So there's – whenever you're discussing about a placebo controlled trial, you know you're going to have to have a nuanced conversation and do a lot of teaching from our side of the desk. A placebo means that there's a medicine being given that doesn't have any actual anti-cancer property, it's a fake. And there's a number of situations where a placebo makes perfectly good sense and I'll give examples for my world in lymphoma. So there's a very standard chemotherapy program for a very common type of lymphoma, an aggressive lymphoma called diffuse large cell lymphoma and there's a very standard chemo program that has been around longer than I've been oncologist, the name of which is called R-CHOP, it doesn't matter, it's just a chemotherapy program that cures many, but not all.

If you're trying to do better than R-CHOP, you may want to try adding an additional medicine to it, but if you give everybody that additional medicine, it's going to be hard to know what would have happened without it in that group of patients. So half made it R-CHOP with the new medicine and half will get R-CHOP without the new medicine and with a placebo instead. R-CHOP is the standard, if you don't participate in that trial you're going to get R-CHOP. If you do part in the trial, you're going to get R-CHOP or R-CHOP plus the new medicine.

[0:20:22]

Dr. Diane:  So the care is not compromised, you're getting standard of care, it's just you may also be getting an additional therapy that may or may not work.

[0:20:28]

Dr. Matthew:  Exactly. It's either standard of care or standard of care plus. There are other situations where you may not be doing standard of care plus, but you may be designing the trial as you say with crossover, where you start by getting either the new medicine or the placebo and you watch these patients typically very, very carefully at the early part of the study to see is whatever they're receiving working. If it's working, awesome, steady she goes, continue doing whatever it is you're doing. And if it's not working then you find out were they getting the real medicine or were they getting the placebo?  And if they were getting the placebo and the placebo is not working as it often does not, not always, if they're getting placebo and it is not working, then they crossover, meaning okay now we're going to give you the active medicine and see if it works this time. Patients in this kind of trial are guaranteed to have access to that medicine. They just may not get it at first, they may get it if they're receiving the placebo and the disease is progressing nonetheless. Whenever we're writing these studies, there's this major ethical burden on us, as doctors. We write these studies because we want to help our patients. The study is a means to an end right?

The purpose of the study is to help our patients. The purpose is not to do the study and if the study is going to put patients at any risk of not having a good thing happen, then why would we write the study, why would we participate in the study, why would we offer the study to our patients? There's no reason and in fact you have to believe that you're doing the right thing for the patient for the study even to open at your center. There's a lot of ethical checks and balances along the way to make sure that everybody agrees that this is the right thing to do for the patients. Studies are a treatment, they're a tool and for patients who need access to newer treatments because maybe the standard treatments we have right now are good, but not good enough. They can be an important tool by trying to improve that one person's outcomes.

[0:22:31]

Dr. Diane:  Absolutely. It's also very brave thing for them to do, because as you said we're absolutely hoping and expecting that some good outcomes would come about, but there are risks there, so we're always grateful for those that enroll in clinical trials that can help us better understand the disease as well as you said.

[0:22:46]

Dr. Matthew:  Yes, it’s tremendously brave.

[0:22:48]

Dr. Diane:  Last question, could you share a story of a patient that inspired you?  I'm sure you've been doing this for a long time as have I since we've trained together. Every one of our patients leaves that indelible mark, but some can often last an impression, that's the one that you carry with you. Any stories like that you want to share?

[0:23:03]

Dr. Matthew:  Yeah, I mean talking about the bravery of clinical trials makes me think, there is a patient that I've been taking care of now for years. When I first met her, she was a young woman, she was a sophomore in college and been diagnosed with Hodgkin lymphoma which is a rare, but curable form of cancer. And her primary care doctor that had diagnosed her, I'm sure jinxed her and told her, “Oh you've got the good cancer, it's going to be alright.” And indeed her good cancer was anything but – and the standard treatment that we use that cures many, but not all failed her. The second, third, fourth treatments failed and failed and failed. We went through together 12 consecutive different treatments for her Hodgkin lymphoma and during this entire journey, her disease never went into remission once and she was very, very sick from her Hodgkin lymphoma, as sick as can be.

And her parents with whom she was living at the time were dismayed by how sick their daughter was, this woman that they loved and were tired of seeing treatments fail and of disappointment, wanted her to say enough was enough and to talk about ending life with dignity and transitioning to comfort care and to hospice. And she wasn't having it and she knew that there was another clinical trial here that she was eligible for that worked differently than the treatment she had received previously. And she wanted to come and give it a go and her parents just didn't have it in them to bring her and couldn't and wouldn't. But she insisted and she literally hitchhiked to clinic that day to come because her parents wouldn’t bring her in to sign onto a study. And this was one of the studies we talked about earlier with letters and numbers and a new medicine and it turns out that I didn't know at the time, but she was actually only the second person in the world with Hodgkin lymphoma to receive this medicine.

We had no way to know if it would help. This is a medicine that has since become known as Nivolumab and has since become FDA approved as a treatment for Hodgkin lymphoma after chemotherapies have failed. And she received the medicine, she very quickly went into her first ever remission. She received the medicine for years in a complete remission because we were afraid to stop it, because we didn't know what would happen. We eventually did stop the medicine because she'd been in remission for very, very long and she's now been off of that medicine for years in an ongoing remission and what we believe this must be a cure because there's no other explanation. She's living a wonderful life, she has way more hair than I ever will. She travels. It’s the closer thing as I've ever had in my practice to a miracle and it gives me chills still to think of it, but it's not a miracle.

We do have these stories and good things do happen in our field. And it goes back to those numbers, you know we are changing cancer. Good things are happening in the clinic, we're able to do things we've never been able to do before for our patients and as an oncologist, it's such a tremendous time of optimism for me on behalf of my patients and it really is inspiring.

[0:26:08]

Dr. Diane:  Amen, thank you so much. Many thanks to Dr. Matthew Matasar for joining me today. As we go with our future podcasts, we will be getting down to the nuts and bolts of chemotherapy, surgery, targeted therapies, the role of exercise and much, much more. So stay tuned. Thank you for listening to Cancer Straight Talk for Memorial Sloan Kettering Cancer Center.

For more information or to send us any questions you may have, please visit mskcc.org/podcast. Help other people find this helpful resource by rating and reviewing this podcast at Apple Podcasts or wherever you listen to your podcasts. These episodes are for you but are not intended to be a medical substitute. Please remember to consult your doctor with any questions you have regarding medical conditions. I am Dr. Diane Reidy-Lagunes, onward and upward.

[Audio Ends] [00:27:08]