This is the fifth story in a series that marks the 20th anniversary of the publication of papers on the role of EGFR mutation in lung cancer. This multimedia series is guest-edited by Suresh S. Ramalingam, a lung cancer expert, executive director of Winship Cancer Institute of Emory University, and editor-in-chief of the journal Cancer. The series explores the process of discovery of EGFR mutations in lung cancer, the learning curve for using the drugs that target those mutations, and the unparalleled impact on patients with lung cancer and other diseases.

Something odd turned up in one of Lawrence Phillips’s routine health screenings in 2008.

Phillips, who was 67 at the time, had been receiving annual CT scans to monitor calcified plaque in his coronary arteries since 2005. He started this screening because he was curious about the relatively new technology, the coronary calcium scan.

Family history intensified Phillips’s curiosity. His father had died of a heart attack.

“The radiologist who was reading my coronary artery calcium score asked me what I was doing with this lung cancer that showed up on my CT,” said Phillips, an endocrinologist at Emory Clinic, a professor of medicine at Emory University School of Medicine, and medical director of the Clinical Studies Center at the Atlanta VA Medical Center.

Phillips replied that when he had learned about the mass in his left lung—a variant of non-small cell lung cancer—more than a year before, doctors had said not to worry, because it wasn’t growing.

“Well, that’s not true,” Phillips recalled the radiologist saying.

After viewing the CT scan images later that day, the two physicians agreed: the mass had clearly grown, Phillips said to Deborah Doroshow, associate professor of medicine at the Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai.

Doroshow, a historian of medicine, is a member of the editorial board of the Cancer History Project. Her conversation with Phillips is available on the Cancer History Project podcast.

The lung cancer diagnosis in the mid-2000s took Phillips by surprise. He was a lifelong distance runner, and he had never been a smoker. Although, he had often been surrounded by smoke.

“There was plenty of secondhand smoke,” said Phillips, who attended Harvard Medical School in the 1960s, where several of his classmates smoked. “In med school, you would go to a scientific meeting, and by the end of the session, there was such an amount of smoke in the air, sometimes it made the slides hazy to see.”

As soon as they would let me out of bed, I remember walking up and down the hall to be a mile, every day, before the tubes came out.

– Lawrence Phillips

Fifty years later, as Phillips learned more about his lung tumor, the radiologist said he should do something about it.

Phillips’s CT scan results came in on a Sunday in 2008. On the following Wednesday, Phillips had the mass removed via a segmentectomy.

“It seemed to be over and done with,” Phillips said. The margin came back clear of cancer, and, at the time, segmentectomy was thought to be adequate for small tumors, he said.

“But it was a bigger deal,” Phillips said.

He attended follow-up appointments for the next several years, tracking the scar left behind from surgery.

Eventually, the scar changed. And it lit up in a PET scan.

“I had to have a lobectomy,” Phillips said. “I was concerned, not so much for myself, but how am I going to tell my children about this?”

With insight from a psychiatrist, he did manage to tell his son, an electrical engineer, and his daughter, a clinical endocrinologist, like Phillips. He received a lobectomy in 2014.

Phillips went through a tough recovery from that surgery, but the athlete continued to exercise throughout this period. “As soon as they would let me out of bed, I remember walking up and down the hall to be a mile, every day, before the tubes came out,” he said.

The surgically-removed specimen turned out to have one blood vessel with a malignant cell, Phillips recalled, so he went through four cycles of chemotherapy. “I did everything I could to have chemo not interfere,” Phillips said. “They gave me IV this and that and anti-nausea drugs, and I would sit in the chemo chair with my laptop, continuing to work.”

That tumor specimen also revealed that Phillips had an EGFR mutation.

The genetic mutation’s influence made sense to him, given Phillips’s experience as a basic scientist and his wife’s work in karyotyping and oncology cytogenetics.

“The concept of a molecular signature? Standard stuff,” Phillips said. “And it was totally logical that I would be given a drug that was thought to be useful based on that particular phenotype that I exhibited.”

Phillips began by taking erlotinib (Tarceva), but it came with excruciating side effects. He then switched to a half dose of gefitnib (Iressa), which he found more tolerable.

Although Phillips had no signs of lingering disease after chemotherapy, he and his oncologist, Suresh Ramalingam, of Winship Cancer Institute at Emory University, came up with a plan to prevent recurrence.

“I think that’s part of the genius of Dr. Ramalingam,” Phillips said. “He discussed it with me, signs of a scientist to a scientist: there’s evidence for this, it’s probably useful for that, in patients who no longer have evident disease. But it seemed logical to him and logical to me.”

Today, at 82, Phillips continues to take gefitinib and get CT scans every three months.

Besides a growth spotted in his left lung in 2019, which was taken care of with radiation therapy, Phillips has remained free of evidence of disease. He still exercises daily—using an elliptical and weights these days, rather than running—and he continues to work.

“My patients ask me, ‘Are you going to retire?’ and I say, ‘Look at what I get to do. I get to see patients, teach, and do research—and they even pay me!’”

Transcript

Deborah Doroshow: Hi there. Glad to be with you, Dr. Phillips. Why don’t you tell us a little bit about yourself.

Lawrence Phillips: I’m a physician and a person beyond that. And I’ll tell you a little bit about how I happen to be where I am.

So, I grew up in Washington, DC. DC in the 1940s and 50s was largely people that came to Washington, DC, to advance their lives in some way, shape, or form and advance the nation. And no physicians in my family. My father worked in the civil service, he apparently aced the civil service entrance exam when he graduated from college in 1934, and then came to DC to work with Roosevelt help the country.

My mother grew up in a small town in western Pennsylvania, and went to college and did things like shorthand, stenography, whatever it was called, and was educated in teaching that, but then came to Washington.

My parents married in 1938. I was their first kid. And they said I hadn’t been from home for the hospital that long before Pearl Harbor. My father tried to enlist, but his eyesight was inadequate.

And so, I grew up in a typical middle-class home in Washington, DC, from people that were not professional DC people and had come to the to Washington to grow and to help the country.

I went to public schools, and I was not a particularly good student in high school. But good enough, I guess. And I ran track and cross country, I was a distance runner. I played the clarinet in the school band; I wasn’t very good. And I was I was an Eagle Scout.

That’s not easy.

LP: Well, it was something that I think people did when I was growing up.

Somehow the Boy Scout troop had acquired some land outside of DC in Maryland, and there were monthly camping trips. So that, and they had a small structure that stored some of the cooking utensils and such, Dutch ovens and trays.

But we hiked in, carried half of a pup tent on each of our backs, and they were buttoned up together. And then tents were pitch. And we stayed overnight Saturday night, and then came back on Sunday. And it was a regular monthly thing.

It was terrific. And I also grew up at a time when students were tracked, whatever that meant, in public schools. So, you were given a multiple-choice test. And based on that test, you were kind of put in different homerooms.

And you pretty much stayed with your group throughout junior high school and high school. If someone had particular talents—language, mathematics, whatever—they could take classes with a different group.

But by and large, that group stayed the same. And I was with kind of the same kind of people through junior high school and high school that I got to know in college and in medical school. That can be good, bad, or indifferent, but those were my colleagues.

We all went to college, and we went to some colleges that were difficult to get into. Music was an element in who and what I was. Athletics, distance running, exercise were part of who and what I was. And I liked science. I was a… I should say math and science.

And someone who was a friend of my folks had worked at NIH, and he was a PhD biochemist. And he said to me, “You like math and science. You like biology. You should do…” And I had worked at National Institutes of Health to near where I grew up, as a summer student. And he said, “You should do biomedical research. And you would like that.” And he said, “Moreover, you should do it as a physician rather than a PhD.” Because it would open doors for me.

So, when I went to college—and I went to a small liberal arts college, Swarthmore, near Philly—I was pre-med, but mainly I majored in science.

I was a chem major and minor in math and physics, and discovered that I wasn’t very good in physics. But the school had at a program called the honors program where junior and senior year, all you took was two seminars a semester; they were supposed to be related to each other. And I whined enough that they relented and allowed me to take a seminar in symbolic logic and philosophy of science my senior year in place of a second semester of physics.

That was an absolutely wonderful seminar for me to take. And we read and thought hard about how we know things, what the process of science involves. And the seminar was taught by someone who was called a logician, and he would say things like, “That’s demonstrably false.” And, you know, it was sobering. But it was just wonderful.

In college, I sang in the college chorus. I was a distance runner, cross country—wasn’t fast enough to be good at track. And I liked math and science. And when it came time to apply to medical school, I still intended to go to medical school to find out what the problems were and learn how to approach those. But my essay started with—and I was kidded about it by my friends—I said, “Basically, I like people.”

I wanted to do research on things that were important to people. And I wanted to go to medical school to find out what the problems were.

When I went to med school, I found it really intellectually stultifying compared to the opportunities we had to delve into problems in college, particularly with the seminar program, and I attended all the lectures. But in addition, periodically, I would get interested in something, and they had a small science library where I could read and look into things, and I found that that helped a lot in the first couple of years.

By the time I entered my third year, when we went on the wards, I was lost. It was difficult.

You were expected essentially to remember everything. And I’m a terrible audio learner. So, you can tell me anything, and I’ll forget.

So, I remember things better if they’re written down. And if I had a patient with one or another problem, then I was pretty good at kind of tying things together with it. But they would tell me things, and then I’d fall asleep in conferences. So, I got a C in medicine, and did my residency. But I digress.

As a fourth-year student, we had electives, and we were on the wards. And it turned out that my understanding was starting to gel. The patients seemed to appreciate my seeing them. Although I had not intended, originally, to go into residency, it seemed like it would be silly not to do that, in a vague kind of way. But the reinforcement I got as a fourth-year student helped me do that.

I had two years of residency at Rush in Chicago, Presbyterian St. Luke’s Hospital, which was not as intensively academic as the Harvard hospitals had been. And I really liked it. I liked the practice of medicine. And I particularly liked the outpatient clinic that I had.

My patients ask me, ‘Are you going to retire?’ and I say, ‘Look at what I get to do. I get to see patients, teach, and do research—and they even pay me!’

– Lawrence Phillips

I regarded those patients as if they were private patients; I made a house call or two. And I thought that was just great.

I sang in some choruses during residency. I think one of the large department stores had a Christmas concert in which people sang the Messiah. And I found it possible to do that. I continued to run through the streets on my days off. And I just thought, clinical medicine was great.

I graduated from med school during the Vietnam War era, and all male graduates had to give the country two years. There was a lottery, and if your score was high, you were allowed to finish your residency before going in—called the Berry Plan. I didn’t win the lottery.

So, it was planned—and I’d already had a pre-induction physical—that I was going to go into the Navy. And I had the papers to sign on my desk in August, second month of internship, when I got a phone call on the wards, saying that the CDC, to which I had applied, had an opportunity for me to join their lab program for a couple of years in Atlanta instead of going into the Navy.

But I thought Navy was okay, I figured they’d send me to Vietnam in some way. I was single, I figured I’d see the world, and probably not get shot. But you couldn’t tell, you take risks in life. But I was very happy with the idea of going to Atlanta and doing research. I had done summer research at NIH. So, I that seemed to fit pretty well.

And it was wonderful. I did infectious disease-related work at the CDC. And I also went to the epidemiology course that was overseen by Alexander Langmuir at the at the CDC, one of the great men of America and epidemiology at the time. And I took the course at along with the epidemiology intelligence service, the EIS service, at CDC.

I thought that was just wonderful. We’d had some epidemiology in med school. But I was kind of a numbers guy, and liked math and science. The epidemiologic approach made a lot of sense to me. I didn’t use it much as a house officer, but I used it a lot, subsequently.

So, I was in the CDC trying to improve generation of antibodies for typing streptococcal disease. And I ran trips for the Atlanta ski club. And I did distance running just through the neighborhoods. And I sang in several different small groups. And through singing, I met my wife.

I had seen her a couple of times before, but nothing particularly clicked. She was seeing another gentleman. And I auditioned for the Atlanta Symphony Chorus, and sang Beethoven’s Ninth under Robert Shaw.

And it just happened that Carol had been to the concert, and we’d kind of waved at each other. She was also working for CDC, and we saw each other in the lunch line at the cafeteria. And she said, “I really enjoyed that concert you were in.” And I said, “Well, why don’t you sit down, let’s talk about that.” One thing led to another.

And they paid you a lot when you worked for the Public Health Service. That was a salary that was way better than being a house officer. So, that was terrific. But I thought about what would come afterwards. I hadn’t particularly planned on applying for fellowship training, I just hadn’t gotten to that point. I’d received offers to be an infectious disease fellow here and there. But I decided to go into endocrinology. I had enjoyed the endocrine rotation when I was a resident.

But this was now January of my second year at CDC, and I was running out of time. But I applied to University of Washington, University of Michigan, and Washington University of St. Louis way late. I said I wasn’t sure if I was going to be an internist with a scholarly interest in endocrinology, or to go into academic medicine. But I’d like to give it a try.

It just so happened, that there was an unexpected vacancy at WashU in St. Louis. So, I went there. And it was just marvelous. I kind of stumbled around in research and wasn’t very successful in what they’d asked me to do, initially. But while my boss was out of town, I had an idea to do something else, and the results were kind of interesting. So, we pursued that, and I stayed on for a third year of fellowship.

Then, I joined the faculty at Northwestern. And I had also thought about going to LSU in New Orleans and going to Denver—I like to ski. But I thought that the academic opportunities were better at Northwestern, so I went there.

My research had to do—not with diabetes then, until it developed. But when I went to fellowship and people interviewed and people asked me, “Oh, were you interested in?” I said, “I think diabetes; there are a lot of interesting things about it.” And my boss said, “You will study the regulation of growth by peptide hormones,” because he had done some growth hormone work.

I had gotten interested in clinical phenomena, where growth wasn’t regulated by growth hormone the way it is in growth hormone deficiency. And I had noticed that there were reports of poor growth in people, children with malnutrition or poorly controlled diabetes. And their growth hormone levels were high. So, no growth despite growth hormone.

On the flip side, there were children that had had a hypothalamic surgery for one problem or another. And they had insatiable hunger, appetite subsequently. Even though their growth hormone levels were extremely low, they grew well.

So, I thought that there were probably parallels in control of growth by nutrition and insulin. And we showed this by measurements in children with diabetes and so forth. And there were animal models, rats, and I was very interested in these clinical models, if you will, experiments of nature, if you will, and studied that beginning in St. Louis, and more extensively in Chicago at Northwestern, and was reasonably successful with it.

I began after about seven, eight, nine years, I had succeeded, gotten funded, was promoted to associate professor with tenure. But I was starting to look at division directorships. And a fellow who was working in my lab had applied, was originally from South Asia, and was particularly interested in fellowship programs that were in warmer parts of the United States.

She had applied to Emory, looking for an assistant professor position. And the response letter, said something like, “We’re not hiring any assistant professors until we complete our search for a division director.”

So, I responded to that, and eventually moved here to Atlanta in 1983. And I’ve really been enormously privileged to do a combination of seeing patients, teaching, and doing research since then.

I closed my lab in 1999. I had gotten to the point where I could talk the talk. I could write the grants and get them funded. But we needed to be able to clone transcription factors, and we did not succeed. So, I closed my lab in 1999. And I did clinical research after that. I wrote some grants that I thought they might find that were more clinical, but they weren’t immediately successful.

But I hit upon the idea of screening for diabetes with an approach that was analogous to screening for diabetes in pregnancy. In most centers now, pregnant women are given a 50-gram glucose challenge test at any time of day, and without a prior fast. Glucose is measured an hour later, and if it’s above a certain level, then they have a formal fasting overnight oral glucose tolerance test to see if they have diabetes.

It had been shown that this approach improved outcomes of pregnancy for both mother and baby.

So, it occurred to me that I could use—and I had some interactions during fellowship with the high-risk OB clinic at WashU with issues of gestational diabetes. And Northwestern had an interest in diabetes in pregnancy as well. That was one of the things I was aware of, and in Atlanta at Emory, I was able to do studies of screening for diabetes in nonpregnant individuals with a similar approach.

We had success in demonstrating that that was a pretty efficient and cost-effective way to find diabetes.

So, I did that at Emory. And I was also able to pursue additional aspects of type 2 diabetes at Emory. It’s not just one hospital. But Emory includes clinical services at Grady Hospital in downtown Atlanta, our safety net hospital, and at Emory Hospital, our tertiary referral center, and the VA.

I became interested since I was responsible for endocrinology at Grady, I was responsible for the function of the Grady diabetes clinic. And we were patting ourselves on the back, because people would come in with an average A1C of nine, and we would bring the A1C down, at the end of the year, by 1% or more. But that meant we were only lowering A1C by 1%. They were far from ideally controlled.

We had established a database, and were capturing data systematically in the Grady diabetes clinic. And we looked at what was done when patients came in for a visit.

Their glucose was measured at that visit, hemoglobin A1C was measured, and I discovered that when people had a glucose that morning that was over 200 and an A1C from the previous visit that was 9% or higher, for control, we did something. We increased the dosage or added a medicine only 50% of the time. So, I was appalled.

We drafted a paper, and I was concerned that the hospital, Grady Hospital, might not be willing to allow me to submit that paper because it didn’t look so good. But fortunately, the Grady Hospital people said, “We want to make things better, and if this is the what it takes, then we do it.”

So, I published that, and we named it clinical inertia. The term has certainly, since then, been used. And we became interested in provider behavior. What went on when we didn’t do enough?

So, in the diabetes clinic, when we recognize this, we said, “If somebody’s glucose is high, you have to do something about it.” And we showed that that improved care in the diabetes clinic, the specialty clinic, and we got funded to do a randomized trial in the Grady medical clinic, where the medical residents… that was Grady’s largest clinic.

We randomized the residents to receive clinical reminders. Piece of paper that showed trends and made specific reminders placed on the top of the chart—couldn’t miss it—or feedback on behavior with five minutes of face-to-face feedback from a faculty endocrinologist showing the residents what they had, what their care consisted of and whether they did things, and we developed a set of questions and graphs, charts that could be shown.

Because the residents would say, “Well, certainly I would absolutely intensify therapy.” But we would show them, here’s your note, here’s what you did. And that feedback on behavior improved.

I think that the combination of research, teaching, and patient care absolutely can’t be beat. If you like to serve people, and you like math and science, and you like to grow to do different things, there is no better job in the world.

– Lawrence Phillips

So, I had this background, and I had been program director of the GCRC [General Clinical Research Center] at Emory. And I didn’t have my R01s anymore after I closed my lab in 1999.

And it was an opportune time to take a position at the VA. They happened to have an opening to be medical director of the clinical studies, which is like an outpatient-only general clinical research center.

So, I had some support from the VA. We repeated our studies of screening for diabetes in the VA. And I had a succession of opportunities to do research of different kinds as a clinician, and to teach, and to continue to see patients one very long half day a week at Emory.

I think that the combination of research, teaching, and patient care absolutely can’t be beat. If you like to serve people, and you like math and science, and you like to grow to do different things, there is no better job in the world.

So, my patients ask me, “Are you going to retire?” and I said, “Look at what I get to do. I get to see patients, teach, and do research—and they even pay me.” So, I have the best job in the world.

And I had—just because I’d heard that it was available—had some CT studies for looking at coronary artery calcium.

I had a fleck of calcium in one of my coronary arteries, and they read these year after year. And I got a page on a Sunday morning in 2008, where the radiologist who was reading my coronary artery calcium score, asked me what I was doing with this lung cancer that showed up on the CT. And I said, “Well, they I’ve asked that, and they’ve told me that that it isn’t growing, it’s stable, it’s nothing to worry about.” And he said, “Well, that’s not true.”

So, I walked over and sat with the radiologist on Sunday. It was quite clear that the mass had grown. And that was on a Sunday.

And how long had the mass been there for?

LP: Well, I think it had been six months or a year or two growing slowly. And I had, what was relatively novel at the time, a VATS approach, video-assisted thoracic whatever. It was like endoscopy, except on the lung. And I had a segmentectomy.

This was thought to be a slowly growing tumor. I think it was called basal cell, I don’t remember, a variant of non-small cell lung cancer. And there were reports from Japan, that segmentectomy for small tumors was thought to be adequate.

The margins were all negative. There may have been one node they obtained, but everything was negative. So, that was 2008. Over and done with. And I had follow-up CTs done.

Were you surprised to have lung cancer?

LP: Oh, absolutely. I had never been a smoker. There was plenty of secondhand smoke in med school. You would go to a scientific meeting, and by the end of the session, there was such an amount of smoke in the air sometimes it made the slides hazy to see.

So, lots of secondhand smoke, and people, other members of my class smoked.

So, this was around, but I’d never been a smoker. And I was surprised. But it seemed to be over and done with.

But I’d had follow up studies, and the surgery had left a scar, and questions had been raised as to whether the scar was changing. And I was reassured, scar’s not changing.

The scar changed.

I had to have a lobectomy. And that was a much bigger deal. And I was concerned, not so much for myself. But how am I going to tell my children about this.

I saw a psychiatrist a few times. It was very helpful. And I’ve managed to tell my children. My daughter is a clinical endocrinologist. My son is an electrical engineer. And I managed, but it was pretty scary to me.

Had they known about the original one that had been resected?

LP: Yeah, but that was handled so quickly. Again, evidence on Sunday, had your surgery on Wednesday. And everything was clear, margins clear, a slowly growing tumor. But it was a bigger deal.

And the scar, and I was PET scan positive there, nowhere else. But having a lobectomy was a bigger deal.

I had continued my exercise program when I had the surgery. And as soon as they would let me out of bed, I remember walking up and down the hall to be a mile every day before the tubes came out.

And they said that the surgical specimen had showed one blood vessel with a malignant cell in it. So, I should have four cycles of chemo that included cisplatin, and I don’t remember the other stuff, and that I should start on a medicine to try to prevent regrowth. And I had CTs every three months, and because of my EGF receptor mutations patterns, I was given erlotinib.

Larry, can I go back for one second and ask you what it was like to get chemotherapy? Because that’s not an easy chemo regimen.

LP: As I said, I’m a strong believer in putting one foot in front of the other. And I’m a strong believer in exercise. I did everything I could to have chemo not interfere. They gave me IV this and that and anti-nausea drugs. And I would sit in the chemo chair with my laptop continuing to work.

They wanted me to eat because you were nauseated. So, I ate the kind of junk food I wouldn’t normally eat. Oh, it was wonderful. The chemo itself was nauseating. They gave me anti-nausea drugs. At one point, I got overloaded with fluid and had to be given some furosemide.

But I did every single thing that I could. I kept on working, I kept on running, and I didn’t think about it. I didn’t tolerate the erlotinib very well.

Let me ask you, when do you find out that you had this EGFR mutation?

LP: With the second specimen. So, first, a diagnosis and the segmentectomy in 2008. And then second surgery in 2014.

And were you familiar with this concept?

LP: Well, I was an endocrinologist that was doing clinical research. But I’d been a basic scientist at WashU, and at Northwestern and when I came to Emory. So, I was kind of used to the idea of thinking about whatever science did.

And it made the idea of having a molecular signature that told you something about diagnosis and prognosis and therapy A) was something that was logical to me, just given a background in science, B) my lab was doing molecular work, and C) my wife, when we were in Chicago at Northwestern, had been in a very small lab at Evanston hospital that was doing karyotyping.

So, she was used to the idea of, and educated me, about DNA being important for, at that time, mainly prenatal diagnosis. But when we moved to Atlanta, she became the associate director of a lab that was focused on molecular diagnosis of cancer.

So, she did oncology cytogenetics. And this had started at the University of Chicago, and she was aware of that work, but it wasn’t widely applied.

However, it has burgeoned, and is probably the best example of precision medicine applied to clinical problems that there is.

So, her lab—and I, in discussion over the dinner table—she would present papers to her clinical lab group just to help them be aware of the literature. And they had some interesting cases that were made into posters that she presented at meetings.

So, the idea of the concept of a molecular signature? Standard stuff. And it was totally logical that I would be given a drug that was thought to be useful based on that particular phenotype that I exhibited, and I took the drug.

It messed up my bowel function and gave me skin rashes. And they tried halving the dose, and it was still misery. So, I took gefitinib. Although I didn’t tolerate the full dose of it, I tolerated half of it. And I still have skin problems, itching, and had to take medicines to make my GI function. It’s something I can live with.

Now when you were taking the erlotinib and then gefitinib, those were being primarily used for people who had advanced lung cancer that had spread elsewhere. Was there some point at which they had discovered it elsewhere? Or did they decide to sort of use it in an earlier-stage setting for you?

LP: Well, I think that’s part of the genius of Dr. Ramalingam. And he discussed it with me, signs of a scientist to a scientist. There’s evidence for this, it’s probably useful for that, in patients who no longer have evident disease. But it seemed logical to him and logical to me.

As an endocrinologist, we take care of people with thyroid cancer, and we’re accustomed to the idea that there may be microscopic persistence of nest small groups of cancer cells that don’t show up with X-rays or CTs, but can be biologically important.

I think it was really a scientific connection you made with Dr. Ramalingam, an ability to speak with him at that level about exactly what was going on.

LP: It seemed logical to me, based on the science I had done, and and was doing. My VA work had involved the VA’s Million Veteran Program where they have DNA samples now from over a million veterans that can be correlated with their clinical status. And I was fortunate enough to get funded and then refunded as a PI on MVP grants.

So, it seemed totally logical to me, and it made total sense that I should do something that was somewhat uncomfortable, but could be lived with. And I continue to see patients and teach and do research.

I had CTS every three months, and then those were all stable. So, we switched to every six months, but that showed a recurrence. And it was decided that I should have radiation therapy, which I did, and I was interested in the science of how they aimed the radiation at the “bad guy” part of your thorax.

Well, it speaks to your earlier work in physics.

LP: Well, yeah. And epidemiology as well, and trying to focus on the bad guys and leave the good guys alone. And I think it hit the bad guys.

But I had horrible radiation pneumonitis, and even an endocrinologist could see it on the CT. And it made me short of breath. But they assured me that it would go away, which it did, and left some scars.

I continue to have CTs on every three months, but my left diaphragm is elevated because of the left lower lobectomy. And compensation when you have that procedure in your 70s is probably not as good as when you’re younger.

I first noted problems when I was running on the track. As a distance runner, you may get tired, but you never get out of breath. You can get out of breath if you’re a sprinter or something, but you never get out of breath. But I got up to a certain speed on the track. And it was like running into a wall. I couldn’t get enough breath.

So, I went in and had a drink of water, went back to the track, gradually increased my pace, and I met the same wall.

Then, I said, “Well, I don’t know what’s causing this.” I had this fleck of calcium in my coronary arteries, and I had no angina. But we had to make sure that this was not coronary artery disease.

So, I had a catheterization, which showed elevation in left ventricular and diastolic pressure. As the heart was filling, the catheter—this was an arterial cath—the pressure in the left ventricle was higher than it should have been. So, that’s one way of identifying heart failure.

But my ejection fraction was fine. So, I had diastolic dysfunction. My heart was not filling with blood the way it should. And I said, “Well, I’ve been an athlete all my life. Why would this happen?”

Well, when I was in my 40s, despite the distance running and stuff, I started to have some elevation in my blood pressure, and my LDL cholesterol went up above 100. And we treated both of those. But I was less assiduous, particularly in managing the blood pressure, than I am now.

And there were times when my blood pressure got to 140 or 150, and I was taking care of myself, and I changed up the medicines. But that’s the only cause I can think of.

So, I have what’s called HFpEF, heart failure with preserved ejection fraction. And that, combined with the loss of lung volume, means that we when I try to run or go up the flight of stairs rapidly, or on a hike if I have to go up something, I get short of breath. Never happened before.

It’s required, some fiddling with my medications to try to minimize that. It turns out that heart failure with preserved ejection fraction is something that medicine’s really not very good at dealing with right now.

So, I take all the things that are known to help this and some that are not getting adequate attention, but I also take those. And I deal with it.

Do you continue to run?

LP: I don’t run. But when we remodeled our house, we had a flat roof that always leaked. And we didn’t have a big enough master bedroom.

So, we remodeled our house, we extended the house out over our garage, and put on a pitched roof, which doesn’t leak. And there was room right off the bedroom to have a 10-by-10 small room that has an elliptical, bench, and some weights.

So, I get to work out every day in my pajamas. I continue to do that.

I can’t do things as rapidly as I’d like. But I exercise every single day.

And how is your cancer being monitored these days?

LP: Well, I take the gefitinib, and I have CTs every three months. There is no longer a discussion of whether I should go to every six months. Although after I have the CT, I go straight to radiology and look at it with one of the faculty radiologists there.

And one of them said, “Well, maybe you ought to go to every six months.” So, I’m not quite ready to do that. And Dr. Ramalingam isn’t quite ready to do that. But that’s kind of encouraging.

And how do you talk to your family about it these days? And has that changed over time?

LP: I don’t discuss the cancer much.

I like to ski, or I did ski, and we would go out to Utah, and ski Alta, and we liked the powder. Every year, just wonderful.

But the base is 8,000 feet high, and the top is about 11,000 feet. And I had the experience of trying to ski some bumps and being totally out of breath. I could not walk; all I could do was bend over hands on my knees and try to get my breath again.

So, I think there are some things that I can’t do. And I desaturate now if I go on a plane flight. Planes are pressurized to 8,000 feet. And sitting in my seat, no problem. But if I jog slowly up and down the aisle, I desaturate.

I don’t feel short of breath. But it’s a combination of the loss of lung volume, and the diastolic, HFpEF. And I do what I can. And I continue to exercise every day, which I think is terribly important.

And I still work full time. I get to see patients and teach and to do research. And it’s not possible to have a better job—and they even pay me.

Miraculous. Well, I want to thank you so much for taking the time today to chat with us about all of your adventures and experiences. It’s been an absolute joy, and I know others will really benefit from hearing about them as well.

LP: It’s a privilege to be able to help.