Chapter 07: A Residency and Research on Fractionation to Preserve Normal Tissue
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Description
In this chapter, Dr. Komaki talks about her residency in Radiation Oncology, an experience that gave exposed her to the noted radiation oncologists being recruited to the new program. As the sole resident, she had unusual opportunities to present cases, which offered her learning opportunities. She also began to conduct research.
Dr. Komaki begins the discussion of her research career by talking about the first research study she conducted while still in medical school. She notes that she was (and is) fascinated by basic research (and has some regrets that she focused on clinical research) and explains what led her to focus on clinical work.
Next Dr. Komaki discusses her research during her residency program: fractionation of radiation dosages to preserve normal tissues. She discusses historical shifts in approaches to dosing and explains the concept of sub-lethal damage to tissue.
Identifier
KomakiR_02_20181128_C07
Publication Date
11-28-2018
Publisher
The Making Cancer History® Voices Oral History Collection, The University of Texas MD Anderson Cancer Center
City
Houston, Texas
Interview Session
Topics Covered
The Interview Subject's Story - The Researcher; The Researcher; Definitions, Explanations, Translations; Mentoring; On Mentoring; Understanding Cancer, the History of Science, Cancer Research; The History of Health Care, Patient Care; Overview; Technology and R&D; Personal Background; Character, Values, Beliefs, Talents; Professional Values, Ethics, Purpose; Portraits; Personal Background
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.
Disciplines
History of Science, Technology, and Medicine | Oncology | Oral History
Transcript
T.A. Rosolowski, PhD:
So you started, in your residency program in 1974.
R. Komaki, MD:
Right.
T.A. Rosolowski, PhD:
So, had your husband, first husband, gone back to Japan?
R. Komaki, MD:
Right.
T.A. Rosolowski, PhD:
Had you divorced at that point?
R. Komaki, MD:
Yes.
T.A. Rosolowski, PhD:
Okay. So you were continuing. Tell me about that residency program and how you’re thinking about all this.
R. Komaki, MD:
I was the first resident under Jim Cox [at the Medical College of Wisconsin]. I was so busy. I had to deal with all the cancer of the cervix. At three o’clock in the morning, I had to wake up and remove the implants. I was so busy, but I had the most wonderful residency program, because I was surrounded [and taught] by renowned --very famous-- radiation oncologists. As I mentioned, I think, six months after Jim Cox arrived, Dr. Gueninger died, so he had to ask his colleagues … They did the residency program at Penrose Cancer Center with Juan Del Regato, MD. So he asked them,”Can you come to the Medical College of Wisconsin,” and they all came. I was surrounded by six famous radiation oncologists, and at the beginning, I was the only one [resident]. Then, every year, we had two or three residents coming, and so eventually, we had six residents total. But I was the chief resident at the beginning --[since I was] the only [resident at the beginning and the only]-- and one fellow who came from Georgetown. Then every year, we had one or two residents. Every morning, we had a conference, new patients conference. Depending on the day [of the week]: Monday at the VA Hospital, Tuesday at the Milwaukee Children’s Hospital, Wednesday at the VA Hospital, and Thursday, we had to go to West Allis, Friday at Deaconess Hospital. So we went to all different hospitals. Attendings in the hospital, as a radiation oncologist --attendings presented the cases, and I was asked all the questions. I was just scared to death at the beginning, since I was the only resident. But oh my gosh, [I am so grateful] how much they taught me.
T.A. Rosolowski, PhD:
What did they ask you?
R. Komaki, MD:
Okay. At the beginning, when I was a first year resident, they never asked about radiation oncology, such as how much radiation dose do you give. And fractionation --do you give radiation treatment every day or every other day? They never asked those questions, because I just started. The way they asked the question was human anatomy. [If the] larynx is up here, what kind of structure do you expect [to be irradiated by treatment for laryngeal cancer] and what kind of normal tissue do you have to avoid from the radiation treatment. When you treat the esophagus, what kind of structure? You have to avoid the heart here and the lungs here. So anatomy was one of the most important things, so I can separate out when I give radiation treatment, the place where the cancer is, I can avoid surrounding normal structure, that’s one. The other [important] thing [I was asked] is how the cancer spread. [The histology of the] prostate [is dominantly] adenocarcinoma, but it doesn’t metastasize to the brain. Why? It metastasizes to the bone but adenocarcinoma of the lung metastasizes to the brain. So what’s the difference? I started to think about all those [patterns of spread depending on histology and the organs of primary cancer] and the behavior: how certain types of cancer spread to the [certain] lymph nodes, this lymph node, that lymph node. That’s why we have to give, we call it elective radiation treatment. If this type of cancer metastasizes 95 percent to this lymph node, you have to cover. Around that time, we did not have PET scan or anything to detect [early metastasis]. So we had to have all the knowledge: the percentages from the surgical experience, when they did the radical operation which lymph nodes were attacked, invaded by the cancer. SoI had to memorize all the percentages and if the chance was less than 5 percent, I don’t need to cover that lymph nodes, but if that’s like a 65 or 75 percent or 90 percent, I had better cover the lymph nodes. So that’s the knowledge, lymph node mapping. I had to memorize the whole thing before they started to ask those questions.
T.A. Rosolowski, PhD:
Now, this is around the time when you really began your research career as well.
R. Komaki, MD:
Yes.
T.A. Rosolowski, PhD:
Tell me about that process. You had had a publication in 1969, when you were actually in medical school, but this is really the full on beginning of your publication career.
R. Komaki, MD:
Basically, when I was a medical student, I really wanted to be a basic researcher, I was doing calcium pumping. The contraction of the oyster heart, it depends on calcium channel, so I started to do the research with Professor Irisawa, I-r-i-s-a-w-a, Irisawa.
T.A. Rosolowski, PhD:
Irisawa, okay great.
R. Komaki, MD:
He taught me the contraction of the heart is based on calcium channel. Everybody knows now this beta blocker: it stops the contraction and slows down heartbeat, beta blocker. But around that time, nobody knew. That was a new thing. In Hiroshima, there are many oysters. They have an incredible production of oysters, so we used the oyster. I studied to do removing calcium from the sea. [water that immersed the oyster heart]. I had to remove the heart from the oyster, and looked at the contraction [of the heart] by controlling calcium concentration. [ ] That was my project during the summertime. [One of my classmates was my collaborator for this project and he became the Professor of Physiology at the Kyoto University.] I did that as well as going to the RERF. I was fascinated with the basic research, but my parents told me I should not be basic researcher, because they wanted me to have enough money to support myself. They didn’t think I will be a genius, to get a Nobel Prize or anything. Well, there was a guy, he asked me to get married, he was a basic researcher, and he was that associate professor. Don’t put his name out. But I asked my parents and they said no, you are still a medical student and you cannot get married and you should not be engaged, you have to study, you have to graduate from medical school. They were also against it: that I would be a basic researcher. They said, “You are very kind and you will be very popular among the patients and I want you to treat the patients, rather than basic researcher.” [Sometimes] I regret [not being a basic researcher]. [ ] I’ve always been fascinated with basic research, and I have done so much translational research. I’ve got those fellows coming from Japan, and so I [collaborated with experimental radiation oncologists at MD Anderson]. [ ] I’ve always been curious about basic research, that’s the [key to] advancement [in cancer treatment]. Just treating patients [without knowledge of cancer research], you cannot really advance [treatment]. After I got married with Jim, I asked him, “Can I take a couple years [off from my clinic] to do basic research?” He said no. He said, “You are so good [at treating] the patients and I don’t want you to waste time doing basic research.” I still regret, because we can do translational research. Well, I supervised and I worked with basic researchers, but to do some really basic research, which I did when I was a medical student and I was very good at it, to do some basic research things, but when you treat the patient, you do need some kind of knowledge about basic research. Of course, I always wanted to get some grant and to get a grant from NCI. You have to have some kind of knowledge about the just pure clinical research. It doesn’t go too far, so I always encourage the residents to get some basic research knowledge. More and more our residents, they have PhDs in flow cytometry or molecular cancer research. They have a lot of PhD background in addition to an MD, and I think that’s our future. That makes radiation oncology residency program very strong [in the future].
T.A. Rosolowski, PhD:
So what research did you begin doing during your residency program?
R. Komaki, MD:
What I did was, I started to do a low dose of radiation, [multiple] fractionation, that’s what we call it. [Multiple] fractionation [with low doses per fraction is supposed to] spare normal tissue. Like cancer of the pancreas. It’s surrounded by a duodenum, small bowel, and we cannot give very high dose of radiation to the cancer of the pancreas because of the surrounding normal tissue gets damaged. So by giving low dose of radiation, we can spare like small bowel, but we can give adequate dose to kill cancer cells in the pancreas. I have done that [with the help of Dr. Frank Wilson who leaned this technique in the Institute Gustave Roussy where my husband Dr. James D Cox spent his fellowship in 1969].
T.A. Rosolowski, PhD:
Was that your first project, the pancreatic cancer?
R. Komaki, MD:
No, that was not the first.
T.A. Rosolowski, PhD:
I mean I’m just trying to figure like how did it evolve, you know like what were the questions that...
R. Komaki, MD:
Right, yes, okay. So fractionation that was my real interest in [association with] volume and [whether] the low dose of radiation is good for immune system or not [when people have total body radiation]. Sparing normal tissue that’s good, but when you give very high dose to the tumor, we can kill cancer cells with very focused radiation, but the normal tissue, surrounding normal tissue, suffers. The reason why I became very interested in this fractionation project [was that I saw patients treated by different fractionation] [ ] at the [Radiation Oncology Clinic of the] Medical College of Wisconsin. Before Jim Cox came [to MCW], there was very famous professor --he was a section chief of Radiation Oncology. He was under Department of Radiology and his name was Dr. Frank Ellis, E-l-l-i-s, who came from Oxford. He retired there, and he came as a section chief of Radiation Oncology. He was using NSD dose. That’s a calculation of the dose fractionation, and he had [his own calculation scale, which he invented]. If you give radiation like on a Monday, Wednesday and Friday --high dose, like head and neck area-- it’s better than giving low dose of radiation every day [of the week], because you can kill cancer cells. When we kill cancer cells, we have to kill those double strands of DNA –double strands, [not single strands]. We have to cut [the double strand] by radiation. But if you do not break through two strands and just only one strand was cut off, that’s what we call sublethal damage. The cells will survive and will mutate. When they start to grow back, it’s impossible, to kill those cancer cells. [This is called proliferation of clonogens.] So, according to that high dose, just cut it off, the double strands, and the completely killed cancer cells. It’s better than giving low dose of radiation and causing sublethal damage. So that was their fear, but they never considered normal tissue [damage by high dose per fractionation]. When they gave the radiation once a week or twice a week, or sometimes three times a week, those patients, I saw the late effect that was osteonecrosis and/or skin necrosis. The late effect was incredible.
T.A. Rosolowski, PhD:
Wow.
R. Komaki, MD:
Yeah, and I saw those patients when they came back for follow-up. Some of the patients, they were very elderly. They were treated and they went to nursing homes and they [were never seen by radiation oncologists at their follow-up clinic]. But I [observed] the late effect --we call the type of fractionation less than 4 fractionations per week. ‘hypo-fractionation’. So, when Jim Cox came, he was just totally against hypo-fractionation [due to the late normal tissue toxicities]. He started to give daily dose, lower dose each time, but an adequate dose to kill cancer cells and sparing surrounding normal tissue. That’s when I really started to do clinical research. Also I have done some of the translational research. Some of the experimental patients, they were treated very low dose, like from a cobalt unit. We gave a very low dose of radiation. [Patients with pancreatic cancer] had to be treated for ten hours a day because of the low dose --sparing small bowel, but giving adequate dose to the cancer cells. Yeah. I thought that was very, very fascinating. These days, we find a tiny, tiny cancer, and we can zap it. Like in a lung. It has a lot of capacity. Even if we treat the one spot, the [other part of the] lung will compensate. So it doesn’t matter if we zap it, very high dose, one or two or up to like three or four treatments a week [to the small volume of the lung]. We finish treatment, and the patient can tolerate that as long as we don’t radiate ribs or skin or right next to the esophagus or the heart. We avoid those, but a really tiny spot, we can zap it. That’s the technology we have learned. We call it stereotactic body radiation treatment. But when I did my residency program, the only one way we can do that was like implants or maybe surgery. We couldn’t use --there was no image guided radiation treatment around that time and we could not check the tumor motion.
Recommended Citation
Komaki, Ritsuko MD and Rosolowski, Tacey A. PhD, "Chapter 07: A Residency and Research on Fractionation to Preserve Normal Tissue" (2018). Interview Chapters. 1288.
https://openworks.mdanderson.org/mchv_interviewchapters/1288
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