1. Astonishing Cancer Recoveries

[00:00:00.170] - Dr. Lemanne

I had a patient who came to me asking if there was anything that we could do for her advanced ovarian cancer. She'd had it for six or seven years, and the treatments weren't working anymore, so her doctor had recommended hospice. I took the case and wasn't sure exactly what I could do, but I reviewed what she already had, and we went back to one of the earliest treatments that she'd had, and I was hoping that perhaps some of the tumor would have regained some sensitivity to the first treatment. And lo and behold, it did. We gave her a little bit of her first treatment, and she got better. She felt a little bit better, and she was no longer in hospice. She was out hiking again.

[00:00:38.720] - Dr. Gordon

That's always a great day. When you say, I'm sorry, you're just going to have to be fired from hospice.

[00:00:45.870] - Dr. Lemanne

You have found your way to The Lemanne Gordon Podcast, where Docs Talk Shop. Happy eavesdropping. I'm Dr. Dawn Lemanne. I treat cancer patients.

[00:01:05.200] - Dr. Gordon

I'm Dr. Deborah Gordon. I work with aging patients.

[00:01:08.480] - Dr. Lemanne

We've both been practicing medicine a long time.

[00:01:11.220] - Dr. Gordon

A very long time. Should we tell them our secrets to

[00:01:15.520] - Dr. Lemanne

Staying healthy and vibrant for a very

[00:01:17.610] - Dr. Gordon

Long time, very long life.

[00:01:19.370] - Dr. Lemanne

And a good one.

[00:01:22.090] - Dr. Gordon

In our inaugural episode, Dr. Lemanne discusses four fascinating cases where patients with advanced cancer had unexpectedly good outcomes. You'll hear about two patients who started off in hospice but returned to fully active athletic lives. You'll also hear about a man who made medical history by becoming the first patient to fully recover from a supposedly fatal blood disorder and without using standard medical treatments. We also discuss a patient with advanced melanoma who managed to find his way to a cure via the back door. Along the way, we discuss how surgery can sometimes result in the spread of cancer and how science is working toward reducing the risk of that happening. Let's jump right into this discussion. One of the things I notice is that the difference in the practice of a primary care doc who people come in sometimes they have a bee in their bonnet about something, but oftentimes I just want to improve my general overall health, or I need to talk to somebody or who's going to renew my thyroid. And I am quite leisurely. I can feel relatively leisurely about addressing their issues. And every patient who walks in for you, you're on the hot seat.

[00:02:40.130] - Dr. Lemanne

Usually because I'm an oncologist, it's a life-threatening condition, and so we do have to get going. Yes, but speed isn't always the right move. I tell patients it's more important to do the right treatment than to do any treatment fast. Because if you do a treatment quickly because you just want to get something done, for instance, surgery is a big one. If you just hack that tumor out, you can do more harm than good. Sometimes, especially with certain breast cancers, it's much more important to give systemic or drug treatment upfront and see if you can get that tumor to shrink. That allows the surgeon to do a smaller operation. And sometimes that can be the difference between a big mess if you have a lot of positive margins left versus you get a nice clear rind of normal tissue around that tumor. So obviously you want the second outcome. And sometimes the only way to get that, or the best way to get that, is to give some kind of chemotherapy and or hormonal treatment or something else before you touch that with a

[00:03:41.460] - Dr. Gordon

Scalpel, getting everything all ready before you.

[00:03:44.230] - Dr. Lemanne

Move on it shrinking the tumor so that the operation is smaller.

[00:03:47.940] - Dr. Gordon

So there was an apocryphal risk associated with cancer surgery. That kind of the concept of dragging the tumor through normal tissue.

[00:03:57.870] - Dr. Lemanne

Oh, I'm so glad you brought this up. This is one of my favorite topics. Yes, an unskilled surgeon can and does drag cancer cells out of the incision and around to different parts of the open incision. And that happens a lot, or it used to happen a lot in the early days of laparoscopic surgery for bowel tumors. So surgeons swear up and down that they've got that licked, and let's hope that they do. But that was definitely a problem. And we would see tumors in the tract of the laparoscopic instrument, right?

[00:04:29.850] - Dr. Gordon

So the laparoscopics, when they don't cut open the whole belly.

[00:04:31.830] - Dr. Lemanne

Key hole surgery, right. And they put in a little tube with light and instruments, instruments and a little telescope and get to work through a smaller incision.

[00:04:41.950] - Dr. Gordon

And they really can drag cancer cells back along the track.

[00:04:45.400] - Dr. Lemanne

But there is something much more insidious about cancer surgery. And this has been studied at podunk research facilities. Harvard MIT. So I just mentioned that because it's not woo, we can go look it up. We'll put some of the links in our notes. But just the act of injuring tissue anywhere in the body stimulates an immune response that says, hey, everybody, Joe's been wounded, or Josephine's been wounded. Everybody who needs to who's associated with this wound, please wake up, start dividing and growing and filling in the wound so that it heals. And that's great for the actual wound, such as a surgical incision. But the problem is that this is an immune signal from the immune system. The immune system gets very upset with this. And the immune system signal is chemical. It goes through the bloodstream, all the lymphatics, everywhere in the body. And wherever there are dormant metastatic cancer cells, that signal reaches those cells as well. And they wake up and they say, oh, we're supposed to wake up and grow. Okay. And so what you see is about some of these studies at MIT in conjunction with a French research group, I believe, at the past year institute, but I'd have to look that up.

[00:05:57.160] - Dr. Lemanne

The main author is a surgeon named Patrice. Forget. It's spelled “forget”. We'll put the link in our show notes. These studies showed that about 18 months after any kind of surgery, including breast cancer surgery or breast reconstruction surgery, you would see a bloom of metastases in a certain proportion of patients that was eventually statistically traced back to that incision in that particular immune response. Now, there are ways to block that response. So NSAIDs, Betablockers, Viagra and Cialis and some European doctors have even used the flu vaccine to kind of counter the immunological responses to this particular type of injury at surgery. And again, it's not just cancer surgery. Of course, cancer patients tend to have cancer surgery. So that's an easy place to look at this, but any kind of surgery. So I worry about patients who've had cancer who are going to have a big dental procedure, for instance. Should we be worried about that? Should we be pretreating them with some of these drugs that can block that particular type of immune response? And I think the answer is a very big maybe. It depends. There are side effects. So you want to take everything into account.

[00:07:05.590] - Dr. Gordon

I want to generalize that a little bit in two ways. One is, does that include injury? So if somebody falls down and just tears open their skin or cuts themselves or breaks their ankle, is that also stimulate latent metastases to grow?

[00:07:20.400] - Dr. Lemanne

That's not been directly tested, but I would say that probably yes. It's the act of injury. It's not who does the injury or why the injury came about. It is the active tissue injury that stimulates that particular immune response. Illnesses may do that. Getting the flu or a COVID or something may also or some other infection may predispose to development of a cancer that's already present to the stimulation of a dormant cancer.

[00:07:44.530] - Dr. Gordon

And just to clarify about that, you were referring to that dormant cancer as possibly being unidentified preexisting metastases. But isn't it also true that going through our lifetime, we all probably have little cancers that our own immune system handles and we never really know about them?

[00:08:01.680] - Dr. Lemanne

That's absolutely true. So you want to keep your immune system in good shape and you don't want to overstimulate the immune system. Remember, it is the immune system's alarm response that seems to trigger the outgrowth of previously dormant metastases. So it's not good to overly stimulate the immune system either, at least to stimulate it in the wrong way.

[00:08:21.740] - Dr. Gordon

So you're saying if you are going to have some cosmetic surgery, maybe you shouldn't have six in one year.

[00:08:28.450] - Dr. Lemanne

I would say it depends on the reasons for the cosmetic surgery and all of that has to be put in the mix. But when you do an operation, when you have an operation, you're probably incurring some risk of cancer. You're certainly incurring risk if you're having general anesthesia of dementia and other neurodegenerative problems later in life, there is always a risk. So one would not undertake surgery lightly.

[00:08:52.580] - Dr. Gordon

Because the immune cells are going to pitch in and contribute to the recovery. And in so doing, some of them might take a path astray down a malignant route.

[00:09:03.880] - Dr. Lemanne

No, not the immune cells so much. The immune cells elaborate messages, chemical messages, and these go all over the body and they say, everybody wake up. And that's great for the cells that are right next to the injury. They do need to divide and multiply and replenish the Earth, and then they need to stop growing. And normal cells know how to do that. They have all of their brake signaling, as in brakes on a car. They have all of their brake signaling working well. And when the wood is healed and the tissue is normal again, they stop growing. Cancer cells don't stop growing. They don't have brakes ever. Their brakes are broken. If somehow somebody's managed to lull them into a dormant state, you do not want to wake those dragons.

[00:09:50.430] - Dr. Gordon

Isn't that one of the problems with people using growth hormone therapies, which I know have been used in the past for resolving things like degenerative arthritis, but that they could stimulate growth in cells that you really don't want to grow?

[00:10:06.200] - Dr. Lemanne

Parts of the growth hormone pathway, in particular IGF One and IGF One receptors, have been directly linked to cancer risk. So there's a family of people in South America who have a condition that's called laron dwarfism and they inherit a defective or a differently working I'm going to call it that a differently working IGF One receptor, such that IGF One signaling is greatly dampened. And what you get with that is you get short stature because IGF One is part of the human growth hormone pathway and you also get resistance to cancer. Almost none of these people ever die of cancer. And they're also, even though they're a little bit obese, if you look at their photographs, you'll see this. They don't develop diabetes. So it's kind of an interesting way of studying the effects of locking the IGF One signaling pathway. And yes, I think we know that people with excess of human growth hormone disease from a pituitary adenoma I'm blanking on the name of that syndrome, but you'll think of it too.

[00:11:06.810] - Dr. Gordon

Is that acromegaly?

[00:11:08.160] - Dr. Lemanne

Acromegaly. Thank you. Yes. So we know that they have an increased risk of diabetes and cancer as well as a few other things. So that speaks to your point about the human growth hormone pathway.

[00:11:19.590] - Dr. Gordon

It's so interesting to see it intersect in other areas. So in the setting of cancer, sometimes you're the pilot in somebody's cancer treatment and sometimes you end up being the copilot.

[00:11:32.030] - Dr. Lemanne

In what way?

[00:11:32.960] - Dr. Gordon

Oh, the observer of some patient perhaps calling their own shots for a treatment that confounds you and surprises you and where you don't expect to see a good recovery, such as the character in.

[00:11:44.850] - Dr. Lemanne

The oh, I see what you're getting at. Okay. You're talking about patients who decline standard therapy and go their own route and then have an excellent outcome. Probably.

[00:11:57.860] - Dr. Gordon

Sometimes they don't.

[00:11:59.830] - Dr. Lemanne

Most times they don't. And this is really interesting. Sometimes they do. Again, it's very rare. And how rare? So you're asking me to talk about Glenn Sabin, with whom I wrote a book.

[00:12:12.840] - Dr. Gordon

Right. So you can name him, be very public.

[00:12:15.640] - Dr. Lemanne

He has a website about his story. He has a book that he and I wrote about his story. He has a business that he's built about his story. So he's very, very public and welcomes discussion.

[00:12:28.550] - Dr. Gordon

How did you happen to meet him?

[00:12:30.060] - Dr. Lemanne

I read his blog online about ten years ago now. So I called him up and I kind of grilled him. I said, well, do you have your records? Are your doctors keeping track of all this? And we talked for about 2 hours, and I thought, well, this guy sounds like maybe he's onto something, that maybe he is doing a little bit better than we think. So I asked him to send me all his records, and he sent me a couple of boxes full of records, all his bone marrow biopsies and his doctor's notes.

[00:12:56.030] - Dr. Gordon

And what he was writing about was.

[00:12:58.170] - Dr. Lemanne

His struggle with oh, chronic lymphocytic leukemia. Thank you. Yes, he had a diagnosis of chronic lymphocytic leukemia when he was 28. Isn't that typically very young? Yes, and that was very unusual. He had his spleen removed because it was enlarged at that point. But that's all the treatment that he had that was standard. Thereafter, his doctors at Harvard and Johns Hopkins, again, not backwaters, advised him to go for chemotherapy and various other things. And he declined. And he got sick a couple of times in the 20-year course. I met him when he was about approaching 50, I think. So about 20 years into this, he was maybe 48. He had managed to avoid doing any standard therapy, but that last year, after I met him, he started getting worse. His lymphocyte count was rising.

[00:13:48.730] - Dr. Gordon

So that's a white blood cell.

[00:13:50.760] - Dr. Lemanne

White blood cell.

[00:13:51.880] - Dr. Gordon

Most numerous of the white blood cells.

[00:13:54.490] - Dr. Lemanne

There were too many of those types of white blood cells in his blood. That can be a harbinger of poor prognosis, and eventually death. This disease is considered fatal. There have been, until Glenn Sabin, no cases reported in the medical literature of a durable response. In other words, the disease goes away and doesn't come back without any special treatment. He started getting worse around ten years ago. I became friends with him. I really liked him. He's a very interesting man. Very honest, open, affable, charming, and he is very, very proactive, which I admired very much. So he and I became friends. I said, you need to write a book about this. And he said, I don't want to write a book. I don't like writing. And I said, okay, well, you need to write a book, so I'm going to write your book. And we made a deal, and I wrote his book. He told me his story, brought me all the records, and I tried to make it interesting.

[00:14:44.520] - Dr. Gordon

You did? I think that's a good read, that book.

[00:14:46.920] - Dr. Lemanne

Well, thank you. I went to a bookstore, and I never read fiction. I'm not like you. You read fiction all the time.

[00:14:52.750] - Dr. Gordon

I do.

[00:14:53.400] - Dr. Lemanne

And I thought, well, people have got to be interested in this. So I walked up to the bookstore clerk and I said, what is the best selling fiction book? And he took me over to something by Dan Brown. It was about the Mona Lisa something, and it was a murder mystery. And so I started reading this book, and I thought, well, this is okay. And what I noticed about it was that the chapters were really short, like two pages, maybe even less one and a half pages, and they all ended on a big cliffhanger. I can do that. So I wrote really short chapters.

[00:15:22.330] - Dr. Gordon

Maybe you should teach writing in your spare time.

[00:15:24.980] - Dr. Lemanne

Yeah. So I tried to end everything on a cliffhanger, and then we had to wait for his blood counts. His case is the only case in the literature. I want to give people a sense of how rare this is. Don't do this at home, because this is a fairly common cancer, the most common leukemia. It's still a rare disease. It's in the rare diseases, orphan disease and rare disease category at the NCI, but it's the most common leukemia. He got worse and worse. He then changed his treatment around a little bit. He used some herbal preparations. I'm not going to name them here. If people want to read the book, they can. But we were careful not to put his protocol into the book because we didn't want people to use it and die. I did write a paper, which is published in the peer reviewed literature now on his case, and we'll put a link to that in our show notes as well. And if people want to know a little bit more about the details of his case from a physician's perspective, they can read about that there. To make a long story a little bit shorter, he eventually pushed his leukemia completely out of his bone marrow.

[00:16:29.700] - Dr. Lemanne

His Harvard doctors did multiple bone marrow biopsies. It was gone. It has stayed gone over the past ten years. We don't know why. But he was very, very determined to find a way through this without using standard therapy, if possible. He was open to standard therapy, which I want to point out, if he had to have it. But he was lucky enough to find a way out of this himself. Maybe it was just something in his own biology, and nobody else has this biology. One has to think about that before recommending this path to any other.

[00:17:05.340] - Dr. Gordon

Right. He already had an atypical form affecting him so young, of a rare cancer. So he was already probably in a category of one situation, right?

[00:17:16.490] - Dr. Lemanne

Yes. Most people with CLL are a little bit elderly, 50 and over, and so.

[00:17:22.260] - Dr. Gordon

Often other things become part of their management. And he chose a particular diet plan which, number one, would not have been, in general, your recommendation about a diet plan to a cancer patient. Correct me if I'm wrong. And number two, right now there is a cultural thought that, gee, cancer feeds on sugar sometimes. Definitely true. And the ketogenic diet is the be all and end all of cancer diet. So it was neither that nor what I think you would conventionally recommend. But his diet was his diet was.

[00:17:55.690] - Dr. Lemanne

On the vegetarian side. He did eat fish. He occasionally ate pizza with cheese on it. He admits to that.

[00:18:01.000] - Dr. Gordon

I can resonate with that.

[00:18:04.010] - Dr. Lemanne

But, yes, he did not follow a ketogenic diet or anything nearly on the ketogenic side of things and was quite the opposite, actually. You know, high starch, high carbohydrate, mostly plant based. You're right. There are a lot of cancers that preferentially metabolize glucose for fuel. There are some, however, that prefer fat. So in those cases, you would want to possibly consider a low fat diet. I actually am currently looking at diet cycling for a lot of patients. You don't want to get a tumor used to any particular diet for too long. That may give it an opportunity to kind of escape from any sensitivity to that diet. But, yes, his story goes against the idea of a ketogenic diet, but again, there are a certain proportion of cancers that are not glucose avid, and perhaps he had one of those. We don't know. He never had a Pet scan, which.

[00:18:51.150] - Dr. Gordon

Is how we can detect the cells that preferentially consume sugar.

[00:18:54.750] - Dr. Lemanne

Yes, a Pet scan is a photograph of cancer cells using sugar or other cells, too.

[00:19:01.150] - Dr. Gordon

We use it in the brain to see the cells that are actively consuming sugar and the ones that have lost the ability to incorporate sugar.

[00:19:07.730] - Dr. Lemanne

That's absolutely correct. Yeah. So, yes, his story is a little bit unusual and his illustrates just the benefit of being dogged. I think if I had to describe his story in one word, it would be dogged. So he kept looking until he found something that worked for him. At least that's how the story looks on the outside. Again, we really don't know why he made this full recovery when no one else in history, at least in written history, has ever done it before or since, may or may not have anything to do with what he did, but it's nice to think that it might.

[00:19:39.800] - Dr. Gordon

And it's a nice attitude he took and worked collaboratively with to address a health challenge, cancer or otherwise. I've got an idea. I'm going to try it. I'm going to listen to the advice of experts. I'll go their way if I have to do it that way, but I'm going to keep at this because this is my life.

[00:19:57.090] - Dr. Lemanne

And it took him 20 years, not something that he did overnight either. It was 20 years between his diagnosis and his apparent cure.

[00:20:04.190] - Dr. Gordon

That's longer than getting an advanced PhD degree.

[00:20:07.690] - Dr. Lemanne

It is quite a bit. You could get four PhDs in five.

[00:20:10.370] - Dr. Gordon

20 years of taking his own Idiosyncratic route. You've had some other cases that kind of surprised you, too, also in dramatic ways, yes.

[00:20:20.740] - Dr. Lemanne

I had a patient who came to me asking if there was anything that we could do for her advanced ovarian cancer. She'd had it for six or seven years, and the treatments weren't working anymore.

[00:20:32.110] - Dr. Gordon

And she probably already had it before she got diagnosed with it because that's a diagnosis that typically occurs in middle aged or older women, and it's often late in its detection because the ovaries don't feel much, they don't hurt, they don't take up much space as they grow. So you only feel it when it affects the digestive system, usually around.

[00:20:53.470] - Dr. Lemanne

And the ovarian cancers can grow kind of big, you know, to the size of an orange or so is rather typical. But ovarian cancers tend to spread around inside the abdomen. They don't spread as easily to other parts of the body. They can, but they spread around inside the abdomen. But the abdomen holds a lot. You can have a whole baby in that  a whole other person in there and be sort of okay. So the disease usually implants on the outside of the abdominal organs rather than invading into them. But that can disrupt peristalsis, the intestines, with all of this plaster of Paris on their outsides, which is kind of how ovarian cancer works, they are no longer able to peristalse to push the food along as well. And also it can implant on the outside of the bladder, which can decrease the action of the bladder. The bladder can't squeeze, and it hurts. So those are some of the symptoms that people come in with, digestive symptoms, bladder symptoms. But they're often for that reason, the diagnosis is often vague.

[00:21:48.780] - Dr. Gordon

So she'd had it for a while by the time she was diagnosed, and by the time you met her, she'd already been working with it for a while.

[00:21:54.950] - Dr. Lemanne

Right, right. And her doctor had recommended hospice. I took the case and wasn't sure exactly what I could do, but I reviewed what she'd already had, and we went back to one of the earliest treatments that she'd had, hoping that perhaps some of the tumor would have regained some sensitivity to the first treatment. And lo and behold, it did. We gave her a little bit of her first treatment, and she got better. She felt a little bit better, and she was no longer in hospice. She was out hiking again.

[00:22:19.760] - Dr. Gordon

That's always a great day when you say, I'm sorry, you're just going to have to be fired from hospice.

[00:22:24.150] - Dr. Lemanne

Yes. I've never had anybody complain about that.

[00:22:27.420] - Dr. Gordon

She was out hiking again.

[00:22:28.670] - Dr. Lemanne

She was out hiking again doing her thing. She was very active. She liked to be very active. And we would rotate treatments, use all sorts of different treatments with different mechanisms, but would only treat her as much as we needed to kind of keep the symptoms away. My only goal with her was to keep her up and about and out of hospice. Lo and behold, she lasted another ten years.

[00:22:47.990] - Dr. Gordon

From hospice to a decade of survival.

[00:22:51.570] - Dr. Lemanne

Yes. And she eventually did succumb to this disease, but it was a long time later and she had many, many good years where she was fully active. She spent a lot of time in the clinic too, coming in to get treatments and things like that. But we tried to keep them as gentle as we could so that we didn't lay her up again thinking our only goal is to keep her out of hospice. And that was about 15 years ago. And that was before we started thinking about the evolutionary dynamics of cancer treatment, evolution, as in Darwin. So survival of the fittest cancer cell and the fittest cancer cell is the one that can survive your chemotherapy. But there are different populations of cancer cells with any one patient's tumor situation, so some might be sensitive to drug A and others might be sensitive to drug B, but resistant to drug A and so on. By alternating treatments, we accidentally stumbled upon and giving them far apart. We stumbled upon what's now being explored very formally in the American Association of Cancer Research.

[00:23:51.130] - Dr. Gordon

It seems like such a paradoxical pairing of words like evolution, survival of the Fittest cancer. Doesn't everybody die? So evolutionary oncology?

[00:24:01.630] - Dr. Lemanne

Yes, and we try to make the cancer less fit than the patient. The problem with cancer is that the cancer cells are more fit than the patient or other cells, so they eventually win. By fit we mean that they're able to survive and propagate at the expense of the patient's normal cells.

[00:24:17.970] - Dr. Gordon

So I've never been in charge, obviously, of anyone's chemotherapy, but I've been at some proximity to it and it seems to me the goal is often, okay, we're going to treat you and then we're going to check to make sure that all the cancer is completely gone.

[00:24:32.890] - Dr. Lemanne

Yes. You've hit on something, I predict. Are you a betting woman?

[00:24:38.230] - Dr. Gordon

No, not usually because I forget about the bet, but okay, we'll think about it.

[00:24:41.800] - Dr. Lemanne

Well, if anybody asks you to bet on this here's, I think you should lay your odds. So if you treat a cancer with the patient's maximum tolerated dose, in other words, as much treatment as you can give the patient without killing the patient in an attempt to kill as many cancer cells as possible. And the idea was then it makes it easier with the second round of chemotherapies and then the patient has to recover for several weeks. As soon as they recover, you give another huge dose thinking you're going to kill even more cancer cells. Well, there's always a population of cancer cells that are resistant to that first treatment.

[00:25:10.140] - Dr. Gordon

I think that's important to know because I do think people think they've gotten an all clear.

[00:25:14.610] - Dr. Lemanne

Tell me if this is what you're thinking about is when people say my doctor told me I'm cancer free. Yes. I hate that term. Nobody's cancer free ever. We all have cancer cells and all that it means is that there was no evidence of the cancer on our tests, which are very poor tests for cancer.

[00:25:31.230] - Dr. Gordon

Very poor tests. But still they've done their best to make it a perfect test.

[00:25:35.930] - Dr. Lemanne

The test may look good, but you can't see a single cancer cell on a CT scan. You can only see a billion cancer cells on a CT scan.

[00:25:43.130] - Dr. Gordon

A billion?

[00:25:44.010] - Dr. Lemanne

Yes. When you have something on a CT scan, things are kind of far advanced. So I think it's a little bit misleading and I don't use the term “cancer free” with my patients. I say things are looking good on the scans right now and we'll continue to watch you with scans and with all sorts of other modalities, blood tests, circulating tumor DNA, which is the new liquid biopsy technology.

[00:26:09.270] - Dr. Gordon

So the patient we were then talking about went back and hiked. She was an early experiential case of evolutionary.

[00:26:18.650] - Dr. Lemanne

We stumbled upon it. Accidentally stumbled upon it, yes. I was not able to think that way in those days. Didn't have the vocabulary, didn't have the mental models and constructs to think about cancer in a deeply Darwinian way. And now when I look back at that case, that was kind of a good example of some of the things that we can accomplish with that particular approach.

[00:26:36.230] - Dr. Gordon

It was an instructive case, really. The truth revealed itself without you having any concept of it ahead of time.

[00:26:42.980] - Dr. Lemanne

Now, a lot of ovarian cancer patients are treated this way. It turns out that that's just an intuitive way to treat an ovarian cancer patient. The art of oncology has led many oncologists down the same type of path and we do see in ovarian cancer many patients who live 6, 8, 10, 14 years. You know, we can start measuring their survival in decades and I think partly because they are often treated this way. Back when this patient presented, there was no program for patients who had failed previous treatments and were ready for hospice. So you could kind of just do what seemed to make sense. A lot of oncologists automatically, accidentally or intuitively again treated ovarian cancer patients with this kind of success. So it's not just me.

[00:27:27.550] - Dr. Gordon

No. But it was interesting that you stumbled upon it.

[00:27:30.020] - Dr. Lemanne

I did.

[00:27:30.500] - Dr. Gordon

And others have too. So the cancer is being instructive, in other words.

[00:27:34.000] - Dr. Lemanne

Yeah, it's a good way of putting it.

[00:27:35.410] - Dr. Gordon

Yeah. Yeah, like that. And it's a not uncommon cancer in women. And you and I were talking a little bit ahead of time and I brought up melanoma. So you also have, I think, a melanoma case.

[00:27:45.570] - Dr. Lemanne

Melanoma is a common cause of cancer death. It's not one of the most common cancers, but we see it regularly in our oncology clinic. Ten years ago, before the advent of certain immunotherapies metastatic, melanoma was universal death sentence. So if the tumor had spread outside of the original site to a distant organ, the original site is usually the skin. The patient was going to die of melanoma.

[00:28:08.770] - Dr. Gordon

Is that also true if it spreads to a different part of the skin? Or is that just still more evidence of the same primary not being metastatic? I got it on my ankle and now I've got on my elbow.

[00:28:20.610] - Dr. Lemanne

The answer to that would be it depends on whether this new skin lesion is a second primary, completely new tumor that arose in the elbow and has nothing to do with the tumor that arose in the ankle. If it looks the same under the microscope and has the same genetics and things as the tumor in the ankle, that would be a very bad sign. It would suggest it was a metastasis.

[00:28:38.960] - Dr. Gordon

You can't tell with a patient in your office. It's only the pathologist who can tell if it's the same exact tumor or not.

[00:28:45.670] - Dr. Lemanne

This is an aside that I think is really important and I want patients to understand this. The doctor who diagnoses your cancer is a doctor you will never meet. It's not your surgeon, it's not your oncologist, not your family doctor. Someone will biopsy this tumor and send it to a doctor called a pathologist. These are MDs. They work in a laboratory. They rarely see patients at all. They do biopsy and other specimen analysis. They do autopsies, those kinds of things. They don't work with live patients mostly, but that's the doctor that will make the diagnosis of cancer.

[00:29:17.910] - Dr. Gordon

And you'll never meet them. And I have a good friend who's a pathologist. She says I'm really not that good and don't like dealing with patients that much. Sure, people gravitate towards that field who love the science and maybe they love the microscope science more than the physiology or social science of it. But their job is important and sometimes not completely clear what they read.

[00:29:43.100] - Dr. Lemanne

Right, exactly. Sometimes it's really important to get a second pathology opinion, especially if there's any difficulties with the first pathology pass. I look very carefully at the pathology notes. So I ask my patients to send me their path reports if they're distance patients and I get them myself if they're local and I read them really looking for subtext and if there is any hemming and hawing like, well, this kind of looks like this type of tumor, but it could be that, I send it for a second opinion because every now and then we will get a completely different diagnosis. I had a patient come in to see me, and he said, I had melanoma a few years ago, and then I developed a lung metastasis, and it was removed. And then I developed another one, and that was removed, and now I've got a third one, and they want to remove another piece of my lung. And he said, I don't think this is a good idea to keep going down this path, do you, Dr. Lemanne? They're going to keep removing my lungs, and I think I need them.

[00:30:41.530] - Dr. Gordon

Where did he get that idea?

[00:30:44.090] - Dr. Lemanne

He said, is there anything else we can do? And I had just read about a study that was completed at [redacted] in [redacted], [ redacted], that had reported a few patients with durable, complete responses to some new immunotherapy drugs, a combination of [ ], and [ ]. You have to practice saying those. It looked like it had worked for some of these patients with metastatic melanoma, and this is a big deal, but there's an FDA process that has to occur before these things can be released for public use in other institutions, and that process takes at least a year. So at this patient's hospital in another state, they were telling him, well, we can't give you that treatment because it's not FDA approved and won't be for at least another year. So I decided I was going to call up the doctor that had performed the study in [redacted], and I talked to him, and he said, well, yeah, the study is over and it's not FDA approved, but I have a course of both of those drugs left over. One patient didn't show up. They're sitting in my cupboard, and I was about to send them back to the drug company.

[00:31:51.940] - Dr. Lemanne

If you send your patient down here, we'll give it to him.

[00:31:54.900] - Dr. Gordon

Oh, my goodness. How fortuitous. How likely is that going to happen?

[00:31:58.890] - Dr. Lemanne

Yeah, off trial, the patient got the treatment, and he just got in touch with me a couple of weeks ago. He's doing great. He was cured. There's no sign of melanoma anywhere, his lung metastases are gone, and he feels great. And the point of that story is, it doesn't take any big brains at all. Well, it did on the part of the researcher who did this study in [  ], but on my part, it just took a phone call and asking around, and I didn't know what I was going to find when I asked. It just illustrates that you want to be at the right place at the right time, and the only way to do that is to be in a lot of places all the time. So I try to stick my nose in a lot of business and see what's going on.

[00:32:34.710] - Dr. Gordon

So you have to have sort of the ears to the ground kind of in a diffuse cancer network.

[00:32:40.990] - Dr. Lemanne

Yes, I know a lot of oncologists do that and do a better job than I do with that. But illustrates to patients, I think I want patients to understand, ask and see what's out there and don't take no for an answer. See what can be dug up and get your oncologist to help you.

[00:32:54.790] - Dr. Gordon

And how often do you think cancer patients end up having to actually travel to get the most optimal treatment?

[00:33:01.620] - Dr. Lemanne

I think a lot. I think that's another thing that sometimes patients don't realize that smaller communities, by that I mean anything out of the three biggest cities in the United States don't have the cancer treatment resources that are available in large cancer centers. So it's really important to make sure that if you have a difficult situation that you at least get an opinion at one or two of these big cancer centers so that you are availing yourself of something that you may not have access to in your community. And travel is often necessary. Unfortunately.

[00:33:30.620] - Dr. Gordon

It’s one of the realities of I think, medical treatment in general is not every patient has the resources. And I mean, that complexly financial personal support. If he was a completely lone person without much money and was going to have to travel to [  ], was it a treatment that was hard on him?

[00:33:51.020] - Dr. Lemanne

Yes, it was tough.

[00:33:52.150] - Dr. Gordon

I've heard those immune treatments for melanoma can be difficult.

[00:33:55.340] - Dr. Lemanne

Yes. He was laid up for several months.

[00:33:57.210] - Dr. Gordon

So if he didn't have any resources. You have to be lucky in the right place at the right time, have an oncologist who's called around and then be able to comply with the demands of obtaining the treatment.

[00:34:09.290] - Dr. Lemanne

You're absolutely correct. And unfortunately, at this point, our medical system isn't set up to be fair in that regard. And I still think it's important for people to know about it, to make their own decision as to how much of their resources they can afford to use in that direction if it's called for.

[00:34:26.210] - Dr. Gordon

I think I'd like to wrap things up by talking about a cancer that I have a particular bee in my bonnet about and a lot more questions than be in my bonnet about it, which is the cancer I think of as the most common cancer affecting men, which is prostate cancer. And in fact, again, another apocryphal myth that this primary care doc carries around in her head is that if any man lives long enough, he will eventually get prostate cancer.

[00:34:50.690] - Dr. Lemanne

That's absolutely not a myth. I think autopsy studies have shown that by the age of 85, I think almost everybody has prostate cancer.

[00:34:57.650] - Dr. Gordon

Every man?

[00:34:58.110] - Dr. Lemanne

Every man. Thank you.

[00:35:00.350] - Dr. Gordon

I'm pretty sure I'm not going to get it.

[00:35:02.080] - Dr. Lemanne

Okay.

[00:35:03.390] - Dr. Gordon

And for many men and this is one of the reasons that the advice about testing for prostate cancer stops at a certain age which is still relatively young. I think it's currently 60. I'm not sure what it is, because if you get diagnosed with prostate cancer at 70, most prostate cancers at 70 are not going to take you out before whatever else is going to take you out. So I think of it as, oh, it's kind of a fairly benign cancer, and it's one of those cancers that I think does like sugar. But prostate cancer can be surprising too, can’t it.

[00:35:35.360] - Dr. Lemanne

Protstate cancer is poorly understood, and yes, every man will develop prostate cancer if he lives long enough. What prostate cancers will be clinically relevant, in other words, which ones will make a person sick and which one won't, is an area of intense study. And we have some clues. So there's something called a Gleason grade. And if the Gleason grade is six or less, and that's determined on a biopsy of the prostate, those patients can often just be watched. Some doctors consider that not actually prostate cancer, just a precancerous condition.

[00:36:11.250] - Dr. Gordon

And some, like ductal carcinoma in situ of the breast.

[00:36:14.690] - Dr. Lemanne

Exactly. So a certain proportion may progress to invasive cancer and a certain proportion may not. We can't perfectly determine which patients will have a disease that progresses or not, but the Gleason total six score is one way to do that, and that seems to be helpful. Certainly, the younger a man is when he develops prostate cancer, the more likely it is to be an aggressive, life threatening one. So that's important to consider that when looking at younger men under 60, for very old men 70 and older, you might diagnose a prostate cancer that will never bother that patient and never requires specific treatment. As far as prostate and nutrition. So in the earliest stages, there's some interesting work out of Moffat Cancer Center by Dr. Robert Gatenby looking at rats. They're called TRAMP rats. The males always develop prostate cancer and die of it. I think by a year. They develop invasive prostate cancer and they die soon after. He put baking soda in their water, he alkalinized their water. And that prevented these mice, if it was given from birth on, from getting invasive prostate cancer, giving that alkaline water after maturity didn't prevent the prostate cancer.

[00:37:25.880] - Dr. Lemanne

So just starting to drink alkaline water once you're in middle age or something like that is not going to prevent prostate cancer in humans. And we don't know if that translates to humans anyway. This is kind of an artificial model of prostate cancer in these animals. Another thing about prostate cancer is there's some evidence that in the early stages it is more sensitive and will grow faster with a high fat diet. It looks like, as it becomes metastatic, that the metastatic deposits, however, go into that glycolytic high glucose utilizing form that you mentioned before in terms of cancer. So it depends on where the patient is in their cancer course as to what their ideal diet might be. We still don't understand that. One thing that we do know is that the more obese a man is that diagnosis of prostate cancer, the more likely he is to have an aggressive course. And also exercise seems to play a role. Once that cancer has been diagnosed in prolonging life of these patients with an aggressive prostate.

[00:38:26.620] - Dr. Gordon

Cancer, that exercise is beneficial.

[00:38:29.030] - Dr. Lemanne

Yes. And a lot of exercise. It's not a walk 30 minutes a few times a week. We're talking about more intense and longer duration and also resistance training.

[00:38:38.760] - Dr. Gordon

So do you have a prostate cancer case? In this case.

[00:38:45.270] - Dr. Lemanne

A gentleman came to see me, actually. His wife dragged him in and threw him in the chair and said, do something, doctor. She pointed at him, I remember this. And I said, well, what's the problem? She said, he wants to go in hospice. He was in a lot of pain and he had signed up for hospice from a bony metastasis, from bony metastases from prostate cancer. Thank you. Yes. So this gentleman had prostate cancer. He was around 70 years old and he had been very active, athlete, liked to do trail runs and compete and those kinds of things. Now he couldn't do any of that. He was in a wheelchair. He was most in time when he was out and about, he could walk, but it was painful. By that time, I had heard of the evolutionary approach to prostate cancer coming out of Moffit Cancer Center and the Arizona State University, those kinds of places, and Cleveland Clinic. We're looking at these things and doing pilot studies. So I put him on a program that recapitulated one of the pilot studies where we did very intermittent androgen deprivation therapy, which is an injection that lowers the testosterone level.

[00:39:41.930] - Dr. Lemanne

But I didn't give him very much, just a little bit. And we lowered the testosterone level for about a month or so and he got better and then we stopped. Let him just do his thing.

[00:39:51.870] - Dr. Gordon

Let him have his testosterone back.

[00:39:53.540] - Dr. Lemanne

Yes, let him have his testosterone back. He went back to the gym. He started getting stronger. He started resuming his athletic activities. He actually competed in trail runs, long ones, and then his PSA would go up and his back would start to hurt again a little bit. I gave him another shot many months later, not every month, which is the usual, I think it was eight months later or something like that. We did that a few times. And he eventually did die of prostate cancer, but he got a couple of really good years where he was out and about traveling. He went all over.

[00:40:24.240] - Dr. Gordon

Not for cancer treatment, but for his life.

[00:40:25.750] - Dr. Lemanne

Yeah, visit people and do these runs and yeah, had a good life for a couple more years. He was out of hospice.

[00:40:32.730] - Dr. Gordon

I have encountered people who had a prostate cancer and had androgen deprivation and kind of felt like they had to be off of it for the rest.

[00:40:42.660] - Dr. Lemanne

Of their life on it.

[00:40:44.400] - Dr. Gordon

Right. They needed to be off of testosterone.

[00:40:46.730] - Dr. Lemanne

They had to be on android deprivation therapy their whole life.

[00:40:49.340] - Dr. Gordon

Right. I've consulted with you and you suggested that one way to get a little bit of the benefit of androgen is to do some heavy lifting and eat more meat.

[00:40:57.950] - Dr. Lemanne

So that's correct. The patients who are on androgen deprivation therapy typically have advanced disease with bone metastases. So their metastases are involved in this glycolytic Warburg or Warburg effect metabolism using lots of glucose and sugar. So you try to counter that with diet, and exercise is important for maintaining muscle mass. Dramatic drops off when you stop the testosterone signaling with these androgen deprivation, testosterone being beneficial.

[00:41:23.300] - Dr. Gordon

In both men and women for maintenance of muscle mass. I'm thinking that this patient who I don't remember having bone metastasis, but perhaps he did, is it fairly common.

[00:41:34.210] - Dr. Lemanne

What gave him pain in his back and that was the reason that's your.

[00:41:36.900] - Dr. Gordon

Patient no, I'm thinking of my patient prolonged prohibition against allowing his testosterone to replenish itself.

[00:41:46.930] - Dr. Lemanne

So there's a treatment sometimes it's combined for a couple of years with radiation therapy. The radiation is just a few weeks, and then the androgen deprivation therapy, though, is carried on for 18 or 24 months, and that's in a curative attempt, and then it'll be stopped after that course is done.

[00:42:01.400] - Dr. Gordon

And so your patient who you gave an injection that blocked his androgen production for a while.

[00:42:07.680] - Dr. Lemanne

I gave him a short term one. So many of those injections that are three months long or even longer, they're called depot injections. And you push the drug into a fat area and then it leeches out with a needle, and then it leeches out over the next few months.

[00:42:22.940] - Dr. Gordon

And was he then making his own testosterone as that shot wore off?

[00:42:29.070] - Dr. Lemanne

As the shot wears off so that affects the brain. The pituitary is signaling that turns on the gonads and tells them to make testosterone. That's where the shot actually works, in the Pituitary signaling system. When that wears off, then the pituitary starts to send the signal again to the testes to make testosterone.

[00:42:44.590] - Dr. Gordon

Did the testes ever get removed in prostate surgery?

[00:42:47.210] - Dr. Lemanne

Not anymore. Now that we have drugs, we don't need to do that. But that was a treatment for prostate cancer in the old days. It's called castration, and unfortunately, that word is still around. It needs to go away. Once the drugs stop working we call the disease castrate resistant prostate cancer.

[00:43:03.040] - Dr. Gordon

When they weren't really castrated. So unlike women whose ovaries lose their ability to generate hormones through life, men's testes can maintain that and it can recover it after this injection?

[00:43:17.000] - Dr. Lemanne

Not perfectly. A lot of times men don't recover complete testicular function after the drug wears off. So that's a concern.

[00:43:23.720] - Dr. Gordon

But this gentleman had a sunny interlude between his readiness for hospice.

[00:43:30.060] - Dr. Lemanne

He had a couple of years, yes.

[00:43:31.520] - Dr. Gordon

Couple of years of good life. Those are great stories and in all cases there's an agility and switching gears that's not only part of this evolutionary oncology approach, which is innovative, but both the patient and the doctor have to be in that frame of mind as well.

[00:43:48.680] - Dr. Lemanne

Yes, and you just hit the nail on the head. One of the things that the evolutionary approach to metastatic prostate cancer shows that if the disease is incurable, we know we're not going to get rid of all of it, one of the worst things we can do is to push the PSA, which is the prostate specific antigen, a blood test that tells us how much prostate cancer there is in the body. One of the worst things we can do is to push that PSA down as low as possible. The lower we push it, the quicker we induce resistance and the sooner the patient will die. So it's really important not to overtreat these patients. At least that's what the trials are showing us at this point. There's been some intuition about that in oncology over the past 20 years or so, and there's been some attempts to do what's called intermittent androgen deprivation where the androgen deprivation is removed for a while, but that's been based on the calendar, not on the patient's tumor dynamics.

[00:44:40.930] - Dr. Gordon

What you mean is if you have to stay in contact with the patient and see what their state is on.

[00:44:45.070] - Dr. Lemanne

A right, it's better to actually look at the PSA and treat based on the PSA and the patient's symptoms. I'm going to rephrase that. It's more important to treat based on the patient's symptoms if they're having pain or other symptoms.

[00:44:55.910] - Dr. Gordon

Right. Because if he's not feeling pain, you.

[00:44:58.050] - Dr. Lemanne

Don't want to treat.

[00:44:59.730] - Dr. Gordon

That's great. Well, I love all these people who got a little lease on life that they were not expecting. It's not a purchase of more life, but it's a lease. They get an extended occupancy agreement. That's great. Thank you. You have been listening to the Lemanne Gordon podcast where Docs talk shop.

[00:45:22.820] - Dr. Lemanne

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[00:45:59.510] - Dr. Gordon

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[00:46:14.530] - Dr. Lemanne

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