Joseph R. Castro, MD
By David Larson, MD, PhD, and Theodore Phillips, MD
In 2002, ASTRO established the History Committee for the purpose of documenting and recording the history of radiation oncology in the United States. This interview with Joseph Castro, MD, took place October 22, 2004.
Question: I'll begin by asking Joe to tell us a little bit about where he was born and maybe his family life and how he eventually got his education.
Dr. Castro: I was born in Chicago. Both of my parents were immigrants. My mother came from the north of Germany from a German Danish family. My father came from Sicily from a beautiful old spa town that the Greeks and the Romans used as a resort. They met in America in Chicago where I was educated, first by the Christian Brothers at St. George High School and then by the Jesuits at Loyola University. I was there as an undergraduate and medical student, receiving a BS in 1956 and MD in 1958.
Question: What got you interested in medicine?
Dr. Castro: Well, my father was a physician. He was the first in his family to receive an advanced education, having graduated from Loyola Medical School 30 years earlier, so I had an early introduction to medicine. He and a couple of family physicians in my hometown were instrumental in making me see what a wonderful experience it would be to practice medicine. So, I could hardly remember a time when I didn't plan on going into medicine. When I graduated and went into military service, I was already commissioned in the Navy in my senior year in medical school, which enabled my wife, Barbara, and me to get married.
Question: This was your senior year in medical school?
Dr. Castro: Right, it was a program of the Navy for medical students that came with a price. After your internship you had to spend at least three years in the service. I interned at Memorial Hospital in Rockford, Ill. I wasn't expecting a great deal out of it, but it turned out to be one of the finest experiences I recall; mainly because at that time that hospital was just switching from the old-style general practitioner into more and more specialists. And these GPs were a wonder. I mean, they did everything—surgery, obstetrics, pediatrics, medicine and orthopedics, so it was a great learning experience.
Question: It was a rotating internship?
Dr. Castro: It was a rotating internship, right. There were no residents in that hospital—just eight interns and this wonderful staff, so we got a lot of experience that was very useful if you're going to eventually wind up in a specialty. After that I went on active duty in the Navy.
Question: What were you doing in the Navy service?
Dr. Castro: I spent all of my time in one of the West Coast Naval Hospitals. I did my residency training in radiology in the Naval Hospital in San Diego, then spent a year at the Naval Hospital at Camp Pendleton and a couple of years at the Naval Hospital in Oakland, Calif., where I had the great pleasure to meet Fleet Admiral Chester Nimitz, a great gentleman and patriot. In 1966, when I left the Navy, I was looking for a place to go and get some additional experience in radiotherapy. That's how MD Anderson Cancer Center came into my life. By the time I got to MD Anderson, I had already taken my boards and had passed them but that didn't mean enough radiotherapy experience to me. Gilbert Fletcher, head of radiotherapy at MD Anderson, always said, “Look, it takes five to eight years to learn your trade,”… that was the way he described it.
Question: MD Anderson has produced a lot of well-known physicians. Who was in your group at that time?
Dr. Castro: It's really hard to find adequate words to describe that experience. I think MD Anderson in that era was at its optimal size. That word didn't exist in the vocabulary of Dr. R. Lee Clark, the director. He went right from minimum through optimum to maximum and, of course, the place now is a huge institution. But at that time in the late 1960s and early 1970s, it was small enough that you still got to know all of the staff well, and Gilbert Fletcher had assembled a super roster of people—Eleanor Montague, Luis DelClos, Norah duv.Tapley, Lowell Miller, Lillian Fuller and many others on the clinical side. And, of course, there was Herman Suit and later Rod Withers in experimental radiotherapy, as well as superb physics under Robert Shalek. I should also mention Felix Rutledge, the “dean” of GYN oncology, and Bill MacComb, who virtually invented head and neck surgery.
So first of all, you had this incredible faculty, and then there was a steady stream of trainees coming through. It was just about that time that MD Anderson began a four-year training program in radiation oncology, radiotherapy as Dr. Fletcher called it. Before that, his tendency would be to accept trainees from other programs for one or two years. This list of people that Gilbert Fletcher trained in clinical research, of course, is very long and illustrious.
He had a nice arrangement, I think, in the way the department was set up. As you came onto the staff, you were eventually assigned one or two clinical areas, as well as supervision of the various treatment machines on a rotating basis. For example, Dr. Fletcher himself supervised head and neck and gyn. Breast treatment was directed by Eleanor Montague. Once you had a clinical area, you saw the patients, developed the treatment protocols, followed the patients closely and altered the treatment protocol based on the follow up data. GHF was really scrupulous about insisting that you did just that. He did not withdraw you from that specialty area, that clinical area, so long as you followed his rigorous procedures for clinical research. For that reason, he really believed in single institution studies and was not overwhelmed at all by multi-institution studies.
Question: How would you say that residency training differed from residency training now? Is it now as good? Is it worse in some ways now?
Dr. Castro: I think it's both. I think it's better in the way I see it now—people are training to be oncologists. They may decide to use radiation primarily, but they're going to know a great deal about medical and surgical oncology and so forth. Most of the trainees at MD Anderson at that time were like myself; just coming out of general radiology training, and thought of themselves as a radiologists. And I was a general radiologist who had done both diagnostic radiology and radiation therapy. That's really what Dr. Fletcher was before he decided that he would switch into therapy full time.
So, the training was different and it was much more oriented toward the techniques of radiotherapy and particularly time, dose and volume relationships. That's what he was about. I mean, he was a stickler for sparing normal tissue, for understanding what dose you could give to a certain volume of tissue. He did not believe in skipping treatments. I remember one time I saw a patient in his absence, a head and neck patient that I thought perhaps had a little too much acute reaction, so I gave the patient a day off. When Dr. Fletcher got back, he demanded to know why this patient hadn’t been treated. When he said 60 gray in six weeks, he meant just that.
He intuitively knew that gaps in the treatment weren't good because the tumor was growing happily during this time. His kind of training was very good. You learned a great deal about how to do radiotherapy. On the other hand, the first time the resident would see the patient was when the patient showed up to begin treatment. So I think that's a deficiency. We wouldn't do that now so much. We like to get the residents involved early on seeing the new patients in consultation with a staff member.
Question: How many years were you at MD Anderson?
Dr. Castro: I was there five years including a year of training.
Question: So during that five-year period at MD Anderson, what sorts of important things were being learned in radiation oncology to cause changes in the way it's practiced?
Dr. Castro: I think a great deal was learned, not only in the five years I was there, but in the late 1950s, 1960s and 1970s with respect to treatment of tumors of the head and neck, GYN, breast and soft-tissue sarcomas—an area that Herman Suit was developing involving surgery and radiation. There was a lot of clinical development in how you use radiotherapy including the electron beam, which was an area that Norah Tapley concentrated on, and in which she and Gilbert Fletcher did some very innovative work. I've often thought to myself that if Texas A and M had a energetic proton beam instead of the neutron beam he would've discovered the wonderful physical advantages of that beam and probably devised all sorts of elegant treatments with it. He was a master at treatment development. At surface anatomy he was legendary in designing a field to hit some deep seated anatomical structure and insisting on careful set up each day to accurately hit the target. He had that in common with other pioneers of radiotherapy such as Buschke, Lenz, Cantril et al., who were physicians dedicated to precise delivery of therapy. Also he was a careful long-term student of time-dose-volume relationships, knowledge that he put to good use in achieving excellent results.
Those five years were for me the luckiest, I think, that I've ever had. I mean, it was a little strange for somebody on the West Coast coming out of the military to somehow wind up at MD Anderson. I never actually had a conversation with Dr. Fletcher about coming there. The message was filtered through Herman Suit and Fred Durrance. So we put all of our kids and the dog and everything we could cram into our station wagon, left the Bay area and drove down. You know, from San Francisco you drive and drive and drive and you're only in El Paso! Then you still have 750 miles to go across Texas. When we got there I remember wondering if they actually had a job for me there. But the thing about Dr. Fletcher was that he was totally a person of his word. If he told you that you had a job at a certain salary, you had it. He was honest in telling me that I couldn't leave at the end of two years to go to Stanford (because Malcolm Bagshaw had offered me a job). He said, “No, you can't. You'd be useless to them. Maybe in a few more years.” So I'm the only guy who ever turned down a job at Stanford. But he was right. You needed to be there really five years to understand what was going on. After that time, he actually wanted people to leave. I mean, he understood very clearly that not everybody was going to stay at MD Anderson, and he wanted to see people with his philosophy of clinical research distributed in other institutions.
Right about that time, the AEC, I guess it was called at that time, decided they had accumulated enough californium-252 from various reactors that they would make it available to the medical community. They proposed to copy the structure of the radium needles and put californium in them, which meant that you would be in extremely close proximity to a neutron-emitting source. So they called some institutions, and a number of people were sent down there and we sort of suggested to them maybe it wasn't the best way to handle californium. They might want to think about an afterloading system and they did and we did do the first californium implants; about 20 of them were done while I was at MD Anderson. And when I came to California, we were going to continue that, but I think the shielding problems and the health hazard problems and the fact that californium did not really appear to be better than low-intensity radium pretty much ended that story, although a number of people continued in another institution.
Question: What were the enticing things about UCSF or San Francisco?
Dr. Castro: Both Barbara and I are from the Midwest and the Navy brought us out West. We lived in California for six years before we went to Texas. We made many friends there, and we still go back frequently to Houston to visit them. But we had the desire to try to get back to California, so when the opportunity came up, I would say the biggest thing was the fact that we had the chance to come to UCSF.
Question: What did you get involved with when you first came?
Dr. Castro: I did general radiotherapy until about 1975 when, for a lot of reasons, the Lawrence Berkeley Lab (LBL) clinical studies were about ready to start. Max Boone in Arizona, Mal Bagshaw in Stanford and Ted Phillips at UCSF were the ad hoc advisory committee that suggested to LBL that they now had the opportunity to test charged particle beams ranging from helium to argon. The accelerator complex at LBL could accelerate ion beams all the way up to uranium, but obviously the very heavy ions weren’t going to be clinical interest.
Question: Let me ask you this. LBL, of course, is famous for physics and yet here was something that was clinical medicine. What was motivating that at the time?
Dr. Castro: They had a long interest in Medicine at LBL because the brother of E.O. Lawrence, inventor of the cyclotron, was a physician. Dr. John Lawrence, a wonderful man, fine scientist and father of nuclear medicine, had worked with neutrons at LBL since the 1930s. Professor Cornelius Tobias, a former grad student of Ernest Lawrence, was urged by him to work in medical physics. He spent his career in medical physics and biophysics and was really the pioneer of suggesting that charged particle therapy could be used in medicine. There were many others in the radiation laboratory and Donner Laboratory at UC Berkeley who were very interested in medical applications. There is really a very rich history of biomedical studies in the past at LBL. It was now time to organize a trial that was community based, with input from many people, to treat patients at LBL and to do studies to determine whether or not these ions were really practical and improved cancer therapy.
Question: So once Ted Phillips, Mal Bagshaw and Max Boone helped organize this, how did you get involved and when was that?
Dr. Castro: I volunteered to go there in March of 1975 initially part time, and after 1981 full time. They did not have much knowledge of radiotherapy. While I really didn't know much about charged particles, I thought I knew what you needed to do clinical radiotherapy and clinical trials. They had an illustrious group of biophysicists that Professor Tobias had gathered around him. It was a very challenging task of starting a radiotherapy department there and trying to get Phase I - II trials going. Ultimately, we treated more than 1,000 patients over 17 years, all on research protocols. This was supported by NCI and DOE through long-term grants. The results confirmed the proton data from Harvard as to the value of precision dose deposition in critical areas and led to the development of carbon ion facilities in Japan and Germany. Had not the DOE prematurely and unfortunately shut down the accelerator, much more could have been learned. As it is, proton therapy is on the rise around the world, and carbon ion medical facilities as well, in Japan and Europe … the U.S. is a little late on that score.
Question: Can you recall the very first patient you treated with charged particles?
Dr. Castro: Absolutely. I also recall the first patient I treated with californium-252. You know, when you do the first treatment with a new radiation modality on someone, you have to ask yourself, “Is this the right thing to do? How do I inform the patient? Should I say you're the first person we've ever tried this on? Or what do you do?” So the first human patient turned out to be a young woman who'd been operated on for an anaplastic astrocytoma. She was in her mid-30s, and she was working as a facilitator of women's issues for a large corporation. She was an extremely astute person. So when I explained to her what we were doing, she was very understanding. We spent a lot of time on informed consent and, in fact, it was the policy that we would not allow anyone to consent to the treatment until they had gone home, thought it over, discussed it and had come back on another day so that there would never be any question about being rushed.
Question: Tell us about the transition to imaging-based treatments, which, I think, may have occurred with you and your operation well before it became something that was routinely used with X-ray therapy.
Dr. Castro: Before you could do clinical trials, you had to figure out a way to localize the tumor, measure the beam's range, develop the isodose plan, prepare compensators to shape the beam, hold the patient in a very precise position by finding an immobilization technique and try to figure out a way to image the port since the beam is not passing through—it's stopping in the patient, so there's nothing exiting onto a film. The solution was to back point an X-ray beam to image the anatomy and compare it to a digitally reconstructed radiograph prepared from the treatment planning CT scan. All of this was going forward in the late 1970s and early 1980s, a very exciting time. As we wanted to assure tight control over the treatments and patient safety, we elected to image every port every time a treatment was given; something I don’t think was ever done earlier. So it was a tall order, but the good thing about it was we had accelerator people who could make the machine work and computer scientists like R.P. Singh and Sam Pitluck who developed a very advanced treatment plan. Paula Petti and GTY Chen later, with help from a (then) graduate student, Mark Kessler, developed a technique that allowed you to take CT and MRI data, co- register the data sets and superimpose anatomy and dose distributions to produce an improved plan in rapid order. So that in itself was, I think, a really dramatic advance and it was the beginning of the era of that kind of treatment planning in general radiotherapy.
Question: How much do you think that the particle program was responsible for computerized planning tools we have available today?
Dr. Castro: I don't think there's any question that it certainly accelerated the process. I mean, this was going on in Boston and in Berkeley, and it had to be obvious to plenty of visitors and others that this was an improvement over the way we used to treat patients.
Question: So a lot of our technological advances started with the integration of imaging into the planning process, which really started with the particle programs.
Dr. Castro: We had to do it and necessity is the mother of invention. Now, we did it in a rather archaic fashion in the 1970s and 1980s. I recently visited the Japanese Heavy Ion Accelerator at the NIRS, Chiba, which is now in its 10th year of operation and doing very well, and I've talked often to the people from GSI and the Strahlenklinik in Heidelberg, Germany, and what they're doing now in terms of beam delivery and beam shaping is what we wanted to do at LBL. We really wanted to do a 3-D pixel-by-pixel scanning technique. That idea came up very early, and I remember a very fine group of physicists at LBL examining the potential for this technique, but guess what? The LBL machine was too old, we couldn’t do it. So we had to evolve a kind of poor man's scanning technique. We could shift the depth of penetration and vary the collimator, but that was in its infancy when the accelerator was shut down at LBL. It's an interesting story in itself because we had just been funded by DOE for another five years and about two months after that happened, the then head of the Department of Energy announced that they would close the LBL accelerator.
Question: In what year was it closed?
Dr. Castro: It closed for clinical treatment in 1992. They ran it a few more months for some physics, so the official year was 1993, but the last patient we treated was May of 1992. It's kind of ironic because we now have five proton facilities, full-range proton treatment centers in the United States. We had always said somewhere between six and 10 regional proton facilities in the U.S. would make sense. What we don't have is a proton carbon facility in the U.S., and given the success in Japan and at Heidelberg, it would be nice if we were participating in that research. Going all the way back to Professor Tobias, he always felt—and had data to show it—the best dose localization beam is carbon if you factor in the biology and correct for RBE. So there is a research question of whether carbon might prove to be better than protons for some sites.
Question: You have in your career, besides treating patients with X-rays and electrons and brachytherapy sources of various kinds, treated patients with particle beams.
Dr. Castro: Well, if you include californium neutrons, then I guess I've used neutrons, protons, helium ions, carbon, neon, silicon and argon ions.
Question: Here's the question. Has anybody treated with as many beams as you have?
Dr. Castro: Well, no, because they couldn't have used silicon and argon. No, I guess I have the record.
Question: You should be in the Guinness Book of Records.
Dr. Castro: Professor Tobias was an extremely bright individual, very hard-working, very intelligent and also very curious and so he kept finding reasons for using different ion beams. Actually, the idea he had wasn't a bad one, which was that you sort of have a dial on the machine and for some sites you would pick silicon and for others you'd pick carbon or oxygen or nitrogen. There's got to be someone who dreams ahead and has the vision, but it's never proved to be practical to do that as yet.
Question: Let me ask you about a story—maybe you can confirm this. I was told at one time that when the first astronauts were sent out into space, they described blue flashes that they had seen. At some point a deuterium beam was created and Ed McMillan, the lab director, stuck his head in the beam and saw the blue flashes that confirmed that it was Cerenkov radiation. Is that a true story?
Dr. Castro: Yes, it is. Tom Budinger, who has been in LBL for many years in research medicine, set it up
and then had Professor McMillan, the head of the laboratory, put his head in the beam. We had a few patients describe this also.
Question: Your group published an enormous number of papers over the years. Do you have any idea how many publications came out with the various aspects of clinical and scientific research?
Dr. Castro: Probably a couple of hundred because there was an extremely productive group of biologists and biophysicists as well as clinical . . . I never counted them up.
Question: Do you continue to be active internationally among the proton groups and facilities?
Dr. Castro: I haven't been as active with the proton groups, but I have tried to keep up with the carbon ion groups in Japan, Germany, France and Italy because I think that's one that I'd like to see an American facility studying. My view of the LBL experience is that it strongly helped to indicate that there were important clinical advantages for protons in a number of anatomical sites in tumors. We didn't use protons because our proton beam was too energetic, so we used helium instead. But the results are virtually identical with MGH proton results in other institutions. So the good news out of LBL in my judgment is that it solidified the clinical advantages of protons for some sites. Not all, but for some. What we didn't accomplish was to get a definitive answer about heavier ions.
People were focused in the 1970s on improving results by using the biology more than the dose distribution. Neon came out a little better on that score than carbon—not so much on physical dose distribution. I think with carbon ions you get a better dose distribution. I've heard when Henry Kaplan was talking about pions so many years ago, he indicated that he thought that dose distribution might be more important than the biology localization. With carbon ions you get that plus you also get a little high-LET, and that might give you an edge in some situations. People say, “Well, the cost is way too much,” but if you're going to build a synchrotron, to build that ring a little bit larger so you can accelerate carbon ions in the overall cost analysis, that does not add very much.
Question: Having been a pioneer, and that's what you are, do you think our training is deficient in imaging for what we have to do each day? You were trained as an imager, and perhaps that gave you an advantage.
Dr. Castro: Yes, and without that I don't know what I would have done at LBL. While we did have radiologists who would come over and help us, I realized afterward I was very lucky to have a background in diagnostic radiology. That's the one thing that bothers me a little bit about describing the modern radiation oncologist as an oncologist, and how conversant they are with medical oncology and so forth, but somewhere in the back of my mind, I think they ought to have some period of training time in diagnostic radiology.
Question: We now know how important axial imaging is to radiotherapy. The LBL program pioneered that and even had their own special CT scanner. Why don't you tell us about the origin of the dedicated CT scanner and what that meant to treatment at LBL?
Dr. Castro: Well, in the case of our particle beam, which was a fixed horizontal beam, we really wanted the patient in some kind of secure upright position, either seated or standing. We were worried about organ shift and had some studies to suggest kidney shift when you went from a horizontal position in an ordinary standard CT scanner to a vertical treatment position. So together with the MGH-Harvard group we had a pilot group of physicists and physicians talking to manufacturers about making a scanner that would rotate from horizontal to vertical. If my memory doesn't fail me, they approached GE, which was so busy making scanners that they basically said, “Forget it. We're not interested.” The company that was interested was EMI and so they agreed to make those units. I think they only made two. One went to MGH and the other to LBL. They were really excellent scanners and with care, they worked very well. We ran that machine I think from about 1981 or 1982 until 1992 and then it went to Boston because their machine was no longer functioning well. The nice thing about it was that we were able to scan patients in the treatment position and that helped a great deal in giving confidence that you could measure the range accurately and compensate reasonably well for tissue inhomogeneities. It wasn't perfect, obviously, because you still had some bowel motion, for example, or some respiratory motion.
Question: Did it work by the patient going up and down vertically or the machine going up and down?
Dr. Castro: The machine went up and down. The ring could be elevated to slide the patient and then brought down and it was a large enough ring to get a patient and some immobilization devices in it. I forget the exact diameter.
Question: Now that you're not working full time, what do you do?
Dr. Castro: Well, [ laugh ] I'm doing more and more things like sailing, genealogy … when you retire you get to do all the things you've always wanted to do but didn't have time for when you were working. One of the things I’m grateful for was the opportunity to meet so many of the pioneers of radiation, people like Gilbert Fletcher, Franz Buschke, Henry Kaplan, Simon Kramer, Fernando Bloedorn, Mort Kligerman, Juan del Regato and many others. I realize that to people coming into the field now these are just names out there in the past. It was a small specialty when we started, and it was possible to know or work with virtually all of them.
Question: Well, part of the reason of this interview is to get your thoughts and recollections, so that a lot of this information is retained.
Dr. Castro: I have nothing but admiration for the modern trainees and the young radiation oncologists, who I now consider as oncologists who happen to specialize in radiation. I think that's better for the long run. It's very different from the last 40 years, I think, and for the better.
In 2002, ASTRO established the History Committee for the purpose of documenting and recording the history of radiation oncology in the United States. This interview with Joseph Castro, MD, took place October 22, 2004.
Question: I'll begin by asking Joe to tell us a little bit about where he was born and maybe his family life and how he eventually got his education.
Dr. Castro: I was born in Chicago. Both of my parents were immigrants. My mother came from the north of Germany from a German Danish family. My father came from Sicily from a beautiful old spa town that the Greeks and the Romans used as a resort. They met in America in Chicago where I was educated, first by the Christian Brothers at St. George High School and then by the Jesuits at Loyola University. I was there as an undergraduate and medical student, receiving a BS in 1956 and MD in 1958.
Question: What got you interested in medicine?
Dr. Castro: Well, my father was a physician. He was the first in his family to receive an advanced education, having graduated from Loyola Medical School 30 years earlier, so I had an early introduction to medicine. He and a couple of family physicians in my hometown were instrumental in making me see what a wonderful experience it would be to practice medicine. So, I could hardly remember a time when I didn't plan on going into medicine. When I graduated and went into military service, I was already commissioned in the Navy in my senior year in medical school, which enabled my wife, Barbara, and me to get married.
Question: This was your senior year in medical school?
Dr. Castro: Right, it was a program of the Navy for medical students that came with a price. After your internship you had to spend at least three years in the service. I interned at Memorial Hospital in Rockford, Ill. I wasn't expecting a great deal out of it, but it turned out to be one of the finest experiences I recall; mainly because at that time that hospital was just switching from the old-style general practitioner into more and more specialists. And these GPs were a wonder. I mean, they did everything—surgery, obstetrics, pediatrics, medicine and orthopedics, so it was a great learning experience.
Question: It was a rotating internship?
Dr. Castro: It was a rotating internship, right. There were no residents in that hospital—just eight interns and this wonderful staff, so we got a lot of experience that was very useful if you're going to eventually wind up in a specialty. After that I went on active duty in the Navy.
Question: What were you doing in the Navy service?
Dr. Castro: I spent all of my time in one of the West Coast Naval Hospitals. I did my residency training in radiology in the Naval Hospital in San Diego, then spent a year at the Naval Hospital at Camp Pendleton and a couple of years at the Naval Hospital in Oakland, Calif., where I had the great pleasure to meet Fleet Admiral Chester Nimitz, a great gentleman and patriot. In 1966, when I left the Navy, I was looking for a place to go and get some additional experience in radiotherapy. That's how MD Anderson Cancer Center came into my life. By the time I got to MD Anderson, I had already taken my boards and had passed them but that didn't mean enough radiotherapy experience to me. Gilbert Fletcher, head of radiotherapy at MD Anderson, always said, “Look, it takes five to eight years to learn your trade,”… that was the way he described it.
Question: MD Anderson has produced a lot of well-known physicians. Who was in your group at that time?
Dr. Castro: It's really hard to find adequate words to describe that experience. I think MD Anderson in that era was at its optimal size. That word didn't exist in the vocabulary of Dr. R. Lee Clark, the director. He went right from minimum through optimum to maximum and, of course, the place now is a huge institution. But at that time in the late 1960s and early 1970s, it was small enough that you still got to know all of the staff well, and Gilbert Fletcher had assembled a super roster of people—Eleanor Montague, Luis DelClos, Norah duv.Tapley, Lowell Miller, Lillian Fuller and many others on the clinical side. And, of course, there was Herman Suit and later Rod Withers in experimental radiotherapy, as well as superb physics under Robert Shalek. I should also mention Felix Rutledge, the “dean” of GYN oncology, and Bill MacComb, who virtually invented head and neck surgery.
So first of all, you had this incredible faculty, and then there was a steady stream of trainees coming through. It was just about that time that MD Anderson began a four-year training program in radiation oncology, radiotherapy as Dr. Fletcher called it. Before that, his tendency would be to accept trainees from other programs for one or two years. This list of people that Gilbert Fletcher trained in clinical research, of course, is very long and illustrious.
He had a nice arrangement, I think, in the way the department was set up. As you came onto the staff, you were eventually assigned one or two clinical areas, as well as supervision of the various treatment machines on a rotating basis. For example, Dr. Fletcher himself supervised head and neck and gyn. Breast treatment was directed by Eleanor Montague. Once you had a clinical area, you saw the patients, developed the treatment protocols, followed the patients closely and altered the treatment protocol based on the follow up data. GHF was really scrupulous about insisting that you did just that. He did not withdraw you from that specialty area, that clinical area, so long as you followed his rigorous procedures for clinical research. For that reason, he really believed in single institution studies and was not overwhelmed at all by multi-institution studies.
Question: How would you say that residency training differed from residency training now? Is it now as good? Is it worse in some ways now?
Dr. Castro: I think it's both. I think it's better in the way I see it now—people are training to be oncologists. They may decide to use radiation primarily, but they're going to know a great deal about medical and surgical oncology and so forth. Most of the trainees at MD Anderson at that time were like myself; just coming out of general radiology training, and thought of themselves as a radiologists. And I was a general radiologist who had done both diagnostic radiology and radiation therapy. That's really what Dr. Fletcher was before he decided that he would switch into therapy full time.
So, the training was different and it was much more oriented toward the techniques of radiotherapy and particularly time, dose and volume relationships. That's what he was about. I mean, he was a stickler for sparing normal tissue, for understanding what dose you could give to a certain volume of tissue. He did not believe in skipping treatments. I remember one time I saw a patient in his absence, a head and neck patient that I thought perhaps had a little too much acute reaction, so I gave the patient a day off. When Dr. Fletcher got back, he demanded to know why this patient hadn’t been treated. When he said 60 gray in six weeks, he meant just that.
He intuitively knew that gaps in the treatment weren't good because the tumor was growing happily during this time. His kind of training was very good. You learned a great deal about how to do radiotherapy. On the other hand, the first time the resident would see the patient was when the patient showed up to begin treatment. So I think that's a deficiency. We wouldn't do that now so much. We like to get the residents involved early on seeing the new patients in consultation with a staff member.
Question: How many years were you at MD Anderson?
Dr. Castro: I was there five years including a year of training.
Question: So during that five-year period at MD Anderson, what sorts of important things were being learned in radiation oncology to cause changes in the way it's practiced?
Dr. Castro: I think a great deal was learned, not only in the five years I was there, but in the late 1950s, 1960s and 1970s with respect to treatment of tumors of the head and neck, GYN, breast and soft-tissue sarcomas—an area that Herman Suit was developing involving surgery and radiation. There was a lot of clinical development in how you use radiotherapy including the electron beam, which was an area that Norah Tapley concentrated on, and in which she and Gilbert Fletcher did some very innovative work. I've often thought to myself that if Texas A and M had a energetic proton beam instead of the neutron beam he would've discovered the wonderful physical advantages of that beam and probably devised all sorts of elegant treatments with it. He was a master at treatment development. At surface anatomy he was legendary in designing a field to hit some deep seated anatomical structure and insisting on careful set up each day to accurately hit the target. He had that in common with other pioneers of radiotherapy such as Buschke, Lenz, Cantril et al., who were physicians dedicated to precise delivery of therapy. Also he was a careful long-term student of time-dose-volume relationships, knowledge that he put to good use in achieving excellent results.
Those five years were for me the luckiest, I think, that I've ever had. I mean, it was a little strange for somebody on the West Coast coming out of the military to somehow wind up at MD Anderson. I never actually had a conversation with Dr. Fletcher about coming there. The message was filtered through Herman Suit and Fred Durrance. So we put all of our kids and the dog and everything we could cram into our station wagon, left the Bay area and drove down. You know, from San Francisco you drive and drive and drive and you're only in El Paso! Then you still have 750 miles to go across Texas. When we got there I remember wondering if they actually had a job for me there. But the thing about Dr. Fletcher was that he was totally a person of his word. If he told you that you had a job at a certain salary, you had it. He was honest in telling me that I couldn't leave at the end of two years to go to Stanford (because Malcolm Bagshaw had offered me a job). He said, “No, you can't. You'd be useless to them. Maybe in a few more years.” So I'm the only guy who ever turned down a job at Stanford. But he was right. You needed to be there really five years to understand what was going on. After that time, he actually wanted people to leave. I mean, he understood very clearly that not everybody was going to stay at MD Anderson, and he wanted to see people with his philosophy of clinical research distributed in other institutions.
Right about that time, the AEC, I guess it was called at that time, decided they had accumulated enough californium-252 from various reactors that they would make it available to the medical community. They proposed to copy the structure of the radium needles and put californium in them, which meant that you would be in extremely close proximity to a neutron-emitting source. So they called some institutions, and a number of people were sent down there and we sort of suggested to them maybe it wasn't the best way to handle californium. They might want to think about an afterloading system and they did and we did do the first californium implants; about 20 of them were done while I was at MD Anderson. And when I came to California, we were going to continue that, but I think the shielding problems and the health hazard problems and the fact that californium did not really appear to be better than low-intensity radium pretty much ended that story, although a number of people continued in another institution.
Question: What were the enticing things about UCSF or San Francisco?
Dr. Castro: Both Barbara and I are from the Midwest and the Navy brought us out West. We lived in California for six years before we went to Texas. We made many friends there, and we still go back frequently to Houston to visit them. But we had the desire to try to get back to California, so when the opportunity came up, I would say the biggest thing was the fact that we had the chance to come to UCSF.
Question: What did you get involved with when you first came?
Dr. Castro: I did general radiotherapy until about 1975 when, for a lot of reasons, the Lawrence Berkeley Lab (LBL) clinical studies were about ready to start. Max Boone in Arizona, Mal Bagshaw in Stanford and Ted Phillips at UCSF were the ad hoc advisory committee that suggested to LBL that they now had the opportunity to test charged particle beams ranging from helium to argon. The accelerator complex at LBL could accelerate ion beams all the way up to uranium, but obviously the very heavy ions weren’t going to be clinical interest.
Question: Let me ask you this. LBL, of course, is famous for physics and yet here was something that was clinical medicine. What was motivating that at the time?
Dr. Castro: They had a long interest in Medicine at LBL because the brother of E.O. Lawrence, inventor of the cyclotron, was a physician. Dr. John Lawrence, a wonderful man, fine scientist and father of nuclear medicine, had worked with neutrons at LBL since the 1930s. Professor Cornelius Tobias, a former grad student of Ernest Lawrence, was urged by him to work in medical physics. He spent his career in medical physics and biophysics and was really the pioneer of suggesting that charged particle therapy could be used in medicine. There were many others in the radiation laboratory and Donner Laboratory at UC Berkeley who were very interested in medical applications. There is really a very rich history of biomedical studies in the past at LBL. It was now time to organize a trial that was community based, with input from many people, to treat patients at LBL and to do studies to determine whether or not these ions were really practical and improved cancer therapy.
Question: So once Ted Phillips, Mal Bagshaw and Max Boone helped organize this, how did you get involved and when was that?
Dr. Castro: I volunteered to go there in March of 1975 initially part time, and after 1981 full time. They did not have much knowledge of radiotherapy. While I really didn't know much about charged particles, I thought I knew what you needed to do clinical radiotherapy and clinical trials. They had an illustrious group of biophysicists that Professor Tobias had gathered around him. It was a very challenging task of starting a radiotherapy department there and trying to get Phase I - II trials going. Ultimately, we treated more than 1,000 patients over 17 years, all on research protocols. This was supported by NCI and DOE through long-term grants. The results confirmed the proton data from Harvard as to the value of precision dose deposition in critical areas and led to the development of carbon ion facilities in Japan and Germany. Had not the DOE prematurely and unfortunately shut down the accelerator, much more could have been learned. As it is, proton therapy is on the rise around the world, and carbon ion medical facilities as well, in Japan and Europe … the U.S. is a little late on that score.
Question: Can you recall the very first patient you treated with charged particles?
Dr. Castro: Absolutely. I also recall the first patient I treated with californium-252. You know, when you do the first treatment with a new radiation modality on someone, you have to ask yourself, “Is this the right thing to do? How do I inform the patient? Should I say you're the first person we've ever tried this on? Or what do you do?” So the first human patient turned out to be a young woman who'd been operated on for an anaplastic astrocytoma. She was in her mid-30s, and she was working as a facilitator of women's issues for a large corporation. She was an extremely astute person. So when I explained to her what we were doing, she was very understanding. We spent a lot of time on informed consent and, in fact, it was the policy that we would not allow anyone to consent to the treatment until they had gone home, thought it over, discussed it and had come back on another day so that there would never be any question about being rushed.
Question: Tell us about the transition to imaging-based treatments, which, I think, may have occurred with you and your operation well before it became something that was routinely used with X-ray therapy.
Dr. Castro: Before you could do clinical trials, you had to figure out a way to localize the tumor, measure the beam's range, develop the isodose plan, prepare compensators to shape the beam, hold the patient in a very precise position by finding an immobilization technique and try to figure out a way to image the port since the beam is not passing through—it's stopping in the patient, so there's nothing exiting onto a film. The solution was to back point an X-ray beam to image the anatomy and compare it to a digitally reconstructed radiograph prepared from the treatment planning CT scan. All of this was going forward in the late 1970s and early 1980s, a very exciting time. As we wanted to assure tight control over the treatments and patient safety, we elected to image every port every time a treatment was given; something I don’t think was ever done earlier. So it was a tall order, but the good thing about it was we had accelerator people who could make the machine work and computer scientists like R.P. Singh and Sam Pitluck who developed a very advanced treatment plan. Paula Petti and GTY Chen later, with help from a (then) graduate student, Mark Kessler, developed a technique that allowed you to take CT and MRI data, co- register the data sets and superimpose anatomy and dose distributions to produce an improved plan in rapid order. So that in itself was, I think, a really dramatic advance and it was the beginning of the era of that kind of treatment planning in general radiotherapy.
Question: How much do you think that the particle program was responsible for computerized planning tools we have available today?
Dr. Castro: I don't think there's any question that it certainly accelerated the process. I mean, this was going on in Boston and in Berkeley, and it had to be obvious to plenty of visitors and others that this was an improvement over the way we used to treat patients.
Question: So a lot of our technological advances started with the integration of imaging into the planning process, which really started with the particle programs.
Dr. Castro: We had to do it and necessity is the mother of invention. Now, we did it in a rather archaic fashion in the 1970s and 1980s. I recently visited the Japanese Heavy Ion Accelerator at the NIRS, Chiba, which is now in its 10th year of operation and doing very well, and I've talked often to the people from GSI and the Strahlenklinik in Heidelberg, Germany, and what they're doing now in terms of beam delivery and beam shaping is what we wanted to do at LBL. We really wanted to do a 3-D pixel-by-pixel scanning technique. That idea came up very early, and I remember a very fine group of physicists at LBL examining the potential for this technique, but guess what? The LBL machine was too old, we couldn’t do it. So we had to evolve a kind of poor man's scanning technique. We could shift the depth of penetration and vary the collimator, but that was in its infancy when the accelerator was shut down at LBL. It's an interesting story in itself because we had just been funded by DOE for another five years and about two months after that happened, the then head of the Department of Energy announced that they would close the LBL accelerator.
Question: In what year was it closed?
Dr. Castro: It closed for clinical treatment in 1992. They ran it a few more months for some physics, so the official year was 1993, but the last patient we treated was May of 1992. It's kind of ironic because we now have five proton facilities, full-range proton treatment centers in the United States. We had always said somewhere between six and 10 regional proton facilities in the U.S. would make sense. What we don't have is a proton carbon facility in the U.S., and given the success in Japan and at Heidelberg, it would be nice if we were participating in that research. Going all the way back to Professor Tobias, he always felt—and had data to show it—the best dose localization beam is carbon if you factor in the biology and correct for RBE. So there is a research question of whether carbon might prove to be better than protons for some sites.
Question: You have in your career, besides treating patients with X-rays and electrons and brachytherapy sources of various kinds, treated patients with particle beams.
Dr. Castro: Well, if you include californium neutrons, then I guess I've used neutrons, protons, helium ions, carbon, neon, silicon and argon ions.
Question: Here's the question. Has anybody treated with as many beams as you have?
Dr. Castro: Well, no, because they couldn't have used silicon and argon. No, I guess I have the record.
Question: You should be in the Guinness Book of Records.
Dr. Castro: Professor Tobias was an extremely bright individual, very hard-working, very intelligent and also very curious and so he kept finding reasons for using different ion beams. Actually, the idea he had wasn't a bad one, which was that you sort of have a dial on the machine and for some sites you would pick silicon and for others you'd pick carbon or oxygen or nitrogen. There's got to be someone who dreams ahead and has the vision, but it's never proved to be practical to do that as yet.
Question: Let me ask you about a story—maybe you can confirm this. I was told at one time that when the first astronauts were sent out into space, they described blue flashes that they had seen. At some point a deuterium beam was created and Ed McMillan, the lab director, stuck his head in the beam and saw the blue flashes that confirmed that it was Cerenkov radiation. Is that a true story?
Dr. Castro: Yes, it is. Tom Budinger, who has been in LBL for many years in research medicine, set it up
and then had Professor McMillan, the head of the laboratory, put his head in the beam. We had a few patients describe this also.
Question: Your group published an enormous number of papers over the years. Do you have any idea how many publications came out with the various aspects of clinical and scientific research?
Dr. Castro: Probably a couple of hundred because there was an extremely productive group of biologists and biophysicists as well as clinical . . . I never counted them up.
Question: Do you continue to be active internationally among the proton groups and facilities?
Dr. Castro: I haven't been as active with the proton groups, but I have tried to keep up with the carbon ion groups in Japan, Germany, France and Italy because I think that's one that I'd like to see an American facility studying. My view of the LBL experience is that it strongly helped to indicate that there were important clinical advantages for protons in a number of anatomical sites in tumors. We didn't use protons because our proton beam was too energetic, so we used helium instead. But the results are virtually identical with MGH proton results in other institutions. So the good news out of LBL in my judgment is that it solidified the clinical advantages of protons for some sites. Not all, but for some. What we didn't accomplish was to get a definitive answer about heavier ions.
People were focused in the 1970s on improving results by using the biology more than the dose distribution. Neon came out a little better on that score than carbon—not so much on physical dose distribution. I think with carbon ions you get a better dose distribution. I've heard when Henry Kaplan was talking about pions so many years ago, he indicated that he thought that dose distribution might be more important than the biology localization. With carbon ions you get that plus you also get a little high-LET, and that might give you an edge in some situations. People say, “Well, the cost is way too much,” but if you're going to build a synchrotron, to build that ring a little bit larger so you can accelerate carbon ions in the overall cost analysis, that does not add very much.
Question: Having been a pioneer, and that's what you are, do you think our training is deficient in imaging for what we have to do each day? You were trained as an imager, and perhaps that gave you an advantage.
Dr. Castro: Yes, and without that I don't know what I would have done at LBL. While we did have radiologists who would come over and help us, I realized afterward I was very lucky to have a background in diagnostic radiology. That's the one thing that bothers me a little bit about describing the modern radiation oncologist as an oncologist, and how conversant they are with medical oncology and so forth, but somewhere in the back of my mind, I think they ought to have some period of training time in diagnostic radiology.
Question: We now know how important axial imaging is to radiotherapy. The LBL program pioneered that and even had their own special CT scanner. Why don't you tell us about the origin of the dedicated CT scanner and what that meant to treatment at LBL?
Dr. Castro: Well, in the case of our particle beam, which was a fixed horizontal beam, we really wanted the patient in some kind of secure upright position, either seated or standing. We were worried about organ shift and had some studies to suggest kidney shift when you went from a horizontal position in an ordinary standard CT scanner to a vertical treatment position. So together with the MGH-Harvard group we had a pilot group of physicists and physicians talking to manufacturers about making a scanner that would rotate from horizontal to vertical. If my memory doesn't fail me, they approached GE, which was so busy making scanners that they basically said, “Forget it. We're not interested.” The company that was interested was EMI and so they agreed to make those units. I think they only made two. One went to MGH and the other to LBL. They were really excellent scanners and with care, they worked very well. We ran that machine I think from about 1981 or 1982 until 1992 and then it went to Boston because their machine was no longer functioning well. The nice thing about it was that we were able to scan patients in the treatment position and that helped a great deal in giving confidence that you could measure the range accurately and compensate reasonably well for tissue inhomogeneities. It wasn't perfect, obviously, because you still had some bowel motion, for example, or some respiratory motion.
Question: Did it work by the patient going up and down vertically or the machine going up and down?
Dr. Castro: The machine went up and down. The ring could be elevated to slide the patient and then brought down and it was a large enough ring to get a patient and some immobilization devices in it. I forget the exact diameter.
Question: Now that you're not working full time, what do you do?
Dr. Castro: Well, [ laugh ] I'm doing more and more things like sailing, genealogy … when you retire you get to do all the things you've always wanted to do but didn't have time for when you were working. One of the things I’m grateful for was the opportunity to meet so many of the pioneers of radiation, people like Gilbert Fletcher, Franz Buschke, Henry Kaplan, Simon Kramer, Fernando Bloedorn, Mort Kligerman, Juan del Regato and many others. I realize that to people coming into the field now these are just names out there in the past. It was a small specialty when we started, and it was possible to know or work with virtually all of them.
Question: Well, part of the reason of this interview is to get your thoughts and recollections, so that a lot of this information is retained.
Dr. Castro: I have nothing but admiration for the modern trainees and the young radiation oncologists, who I now consider as oncologists who happen to specialize in radiation. I think that's better for the long run. It's very different from the last 40 years, I think, and for the better.
