Welcome to Yale Cancer Center Answers with doctors Francine Foss and Anees Chagpar. Dr. Foss is a Professor of Medical Oncology and Dermatology, specializing in the treatment of lymphomas. Dr. Chagpar is Associate Professor of Surgical Oncology and Director of the Breast Center at Smilow Cancer Hospital at Yale- New Haven. If you would like to join the conversation, you can contact the doctors directly. The address is firstname.lastname@example.org and the phone number is 1-888-234-4YCC. This week Dr. Foss and Chagpar welcome Dr. David Cheng and Dr. Ming-Kai Chen. Dr. Cheng is Associate Professor of Diagnostic Radiology, Chief of Nuclear Medicine and Co-Medical Director of the Yale University PET Center. Dr. Chen is Associate Professor of Diagnostic Radiology at Yale School of Medicine. Here is Francine Foss.
Foss Can we start off by having each one of you introduce yourself and explain a little bit about your position, and how long you have been at Yale?
Chen This is Ming-Kai Chen, and I am an Assistant Professor in Diagnostic Radiology. This is my third year on the medical staff of Yale-New Haven Hospital. I have a PhD in radiation health sciences from Johns Hopkins University and completed two years of residency training at Yale and I stayed here.
Foss And Dr. Cheng?
Cheng My name is David Cheng and I have been at Yale for 11 years. I have been the Chief of Nuclear Medicine for the last 6 years, and before that I was the acting chief for a while. I also have a PhD in Biomedical Engineering/Physics from UCLA. My claim to fame is that I was actually trained by the people who built the first PET scanner in St. Louis and I subsequently moved over to UCLA. I went to medical school in New York, and I did a combined residency in Internal Medicine and Nuclear Medicine and I did my fellowship at Sloan-Kettering before joining Yale University.
Foss Here we have somebody from Diagnostic Radiology and somebody from Nuclear Medicine. Can you tell us what the difference is between those two departments and how you guys actually work together?
Chen Nuclear medicine is under Diagnostic Radiology as one of the sections, and radiology is a broad spectrum of imaging for diagnosis and also some imaging assisted intervention. It includes x-ray, CAT scan and ultrasound, and MRI, and also nuclear medicine. Nuclear medicine is more functional imaging. The difference between nuclear medicine and other imaging modalities is that we have to inject tracers into the patient and then in a way we are imaging the photon from the patient and then in contrast to radiology which uses x-ray as an external source and then doing the transmission imaging. In nuclear medicine, we are talking about emission imaging.
Cheng I will add to that a little bit, and say that nuclear medicine to me is functional medicine in pictures because the tracer, as my colleague mentioned, gives us the ability to image and of course we
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image over time, which is quite different than a CAT scan, which will only last up to a minute or two minutes. We can image patients for up to 2 or 3 days and follow the tracer marker so that we know what is happening in the physiology of the system that we interrogate.
Chagpar One of the terms that both of you used was functional and injection of tracers, so it would seem to me that this is perhaps a branch of medicine that is a little bit on the personalized side, can you talk a little bit about different tracers that are used and how they may be different for different types of cancers? Could you inject one tracer that may light up certain organs or certain disease processes, whereas others may be lighting up other things? How does that all work and what exactly are these tracers anyways?
Chen Basically the tracer is a very small amount of molecule and it depends on what molecular you are interested in and you can radio-target with the molecule to different radioisotopes and then when you inject the molecule, depending on what kind of molecule you inject, for example for glucose you can label it with F-18 and can use the F-18 label deoxyglucose as a tracer for cancer imaging. We would use that for imaging the bone scan. So, we actually have a broad spectrum of cancers we are looking at. For example, with the FDG PET we are looking at a broad spectrum of cancer and for the bone scan imaging we are looking for primary bone metastasis from breast cancer or prostate cancer and for thyroid cancer we have a different tracer that we are going to focus on. We can give a patient iodine and circulate it in the body and you have primary pickup by the thyroid or thyroid cancer and then you can take advantage of that for imaging purposes and also for therapeutic purposes.
Foss Can you talk a little bit about these isotopes that you are using in these compounds that you are labeling? Is this all radioactivity, and is all radioactivity the same?
Cheng So, it all has to be radioactive because our cameras are capturing those photons from this radioisotope and then it depends on the different kind of radioisotope, some of them have a longer half life and some of that have a shorter half life, and they have different energy of photon and then we customize this kind of different tracer using a special camera, for example for F-18 label or FDG PET scan to capture the photon and for most of other nuclear medicine tracer, we can use the general gamma camera and also SPECT imaging to image that.
Chagpar One of the things that I am sure some people in our audience must be wondering, is this whole concept of radioactivity seems really scary and people may be wondering about whether you inject this stuff and then they are going to glow-in-the-dark, talk a little bit about the safety of these radioactive tracers and what the implications of using them are?
Cheng The reason we call it tracer is because we inject a very small amount of the material because it is not supposed to interfere with your normal physiology and we will be able to label those small
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molecules with radioactivity and then for further imaging purposes or diagnosis purposes we do not require a lot of radioactivity, and also does not cause any consequences for potential radiation induced injury, and this is only for imaging purposes, although some people joke and say they are glowing in the dark, when you compare it to your normal background radiation exposure it is not much more, but for therapeutic purposes it is a different story.
Chen I can add to that just a little, the radiotracer, as my colleague mentioned, is a very small amount and not all of the radioactivity that we give to patients actually decays within the body, much of it gets excreted in the urine, and so when it is excreted and it has not had a chance to decay, the patient does not absorb any of that radiation and as the diagnostic requirement goes, the radioactivity decay has to penetrate through the patient in order to reach our detectors, therefore, the radiation that actually gets absorbed within the patient is not a great amount.
Foss Is it safe for people in the environment, say when the patient goes home, is it safe for the patient to be next to other people? Can they take the subway home? Can they hold young children? These are all the questions that we get in the clinic when we order these tests.
Cheng For the majority of diagnostic purposes, the amount of radiation emitted from the patient is read at the minimum compared to a therapeutic dose, so it should be okay for the patient to interact with the family, and if a patient is breast feeding or has young kids we usually depend on the half life of the tracer and how quickly the tracer is excreted from the patient we usually give them some oral and written guidelines such as no breast feeding for six hour or half a day, those kind of instructions, but in terms of the therapeutic agent, we have pretty strict written and oral instructions, so the patient needs to follow those instructions in order for us to send them home after the treatment.
Foss I know David, you and I have had this discussion, which has been raised by patients, and that is, how much radiation am I exposed to when I have a PET scan? Is a PET scan more dangerous than a CAT scan? How many PET scans can I have in my lifetime? How do you address those issues now that we are using these tracers, I assume that there is more radiation exposure?
Chen That is a very good question Francine, and my colleague Ming-Kai and I have done some studies looking at the actual radiation that is being absorbed from the positron itself, not from the CT as many people have concentrated their efforts on looking at radiation exposure in the patient, so the amount is much more reasonable and there is no evidence that you get secondary cancer from these diagnostic testing’s. People have looked at large series and there is no statistical significance between the two groups. So that is very reassuring. In terms of patient’s worrying about what is the threshold dose and things like that, we have tuned down our radiation doses for the nuclear medicine dosing, as well as our qualitative attenuation correction CT doses. We have done that from day 1 since we got a PET CT scanner back in 2004. So, we were ahead of the curve and recently we have also tuned down our dosing as. We have looked at dosimetry data and things
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like that so that we are definitely operating within a very safe limit. We have a very good relationship with the radiation safety office since I am a medical physicist and Ming-Kai is also medical physicist, so we converse very nicely with him and they also keep a close eye on this as well. So I think Yale offers a very high quality and minimal risk nuclear medicine service, which I think patients will definitely benefit from other institutions.
Chagpar So far we have been talking a lot of about using nuclear medicine as a diagnostic and the radiation dose and the radioactivity that you get from these diagnostic test is very low but as you mentioned and I want to go back and pick up on this that sometimes radioactivity and/or radioactive tracers may be used in a therapeutic setting. So can you talk a little bit more about that and how is it used, for what types of cancer might it be used? What is that dose like compared to the diagnostic dose? And what are the issues that people may be concerned about or fears that you may be able to alleviate with regards to therapeutic radioactivity?
Cheng In terms of using radioactivity to treat cancer, the most common cancer we treat is thyroid cancer, and using the isotope iodine I-131, it will pick up any thyroid residual tissue or thyroid cancer either macroscopic or microscopic cancer and then it will slowly emit the beta, which is an electron to destroy those tissues and we are aiming to destroy those tissues so we need to give a higher dose compared to diagnostic purpose, however, because this iodine is very selective and picked up by the thyroid, the majority of the radioiodine will get excreted out from the body in a very short period of time and it is usually within 2 days and it is more like a targeted therapy.
Chagpar We are going to talk a lot more about therapeutic radioactivity after we take a short break for a medical minute. Please stay tuned to learn more information about diagnosis and treatment of thyroid cancer with Dr. David Cheng and Dr. Ming-Kai Chen.
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Chagpar Welcome back to Yale Cancer Center Answers. This is Dr. Anees Chagpar and I am joined today by my co-host Dr. Francine Foss. Today, we have two guests, Dr. David Cheng and Dr. Ming-Kai Chen, both of whom are working in diagnostic radiology and nuclear medicine. We were discussing a little bit about the diagnosis and treatment of thyroid cancer and the fact that radioactivity can be used not only to detect cancers but also to treat them. So can you talk a little bit more and pick up the conversation that we were having before the break about how you use radioactivity in a therapeutic way and the safety precautions that are taken as we do that?
Chen So there are fortunately for us, many-many different types of isotopes and each type of isotope will have its slightly different emission decay characteristic and some of which are very useful for diagnostics and some of which are useful for therapy. So you have to trust us to know what to use and we do and we have gone through a lot of education to do that, and so precautionary speaking, of course a diagnostic dosing are much lest injurious and so there are very little in terms of precautions for therapy on the other hand is not more damaging and is meant to be and so we have a lot more precautions for the patients to have. So we opened up an outpatient clinic about six years ago in the Yale Physician Building and we have dedicated 45-minute appointments for each patient to counsel them and to address their needs and their concerns as well as for the family and coworkers. We also involve radiation safety officers to help us counsel these patients and meanwhile we assess as medical doctors to make sure that the labs and the appropriateness of the procedure and all of that so it has worked out very-very well for us.
Chagpar It sounds like a unique resource that addresses patient concerns from a therapeutic standpoint. Tell us a little bit more about doses, I mean before the break one of the things that I was very impressed by was the fact that you had really been a trailblazer in terms of turning down doses when you needed to in terms of the diagnostic realm. Is there a balance between the dose and efficacy and how do you modulate that in the therapeutic realm?
Cheng Taking thyroid cancer as an example and how we use the radioiodine treatment, usually thyroid cancer patients, when they come to us, they have already undergone surgery so the thyroid is out. Radioiodine treatment basically is trying to ablate any residual thyroid tissue or any residual cancer the surgeon may have missed, and then before we do that we do a pre-therapy scan so we known exactly how much residual iodine uptake will occur in the patient's neck and then based on that we determine what the sufficient radioactivity we need to administer to the patient is in order to effectively ablate the thyroid related tissues and also we can see how quickly the patient can clear up the active radioiodine which no longer stays in the body.
Foss Are those calculations that you make based on the pictures? How do you actually do that dosimetry?
Cheng Basically we do the pre-therapy scan, and using a specific probe we measure the activity and then we give patients no activity, so you can calculate how much residual activity in the neck at
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24 hours and 48 hours and you can calculate the percentage of uptake in the patient, and for the dosimetry protocol it is more sophisticated. So, we have to do multiple time points of imaging and measurement and also broad sampling to see how quickly the patient excretes the radioiodine so usually we reserve those dosimetry protocol follow-ups for very sick patients with distal metastasis or for very old patients with potential renal insufficiency, you do not want to give patients too much, and you do not want to under treat those patients so we need to determine what the ideal dose is.
Foss How long does it actually take you from the time you do this dosimetry to the time you actually treat the patient with the therapeutic dose?
Cheng From our protocol, it typically takes about five days, or a week. The patient has to take a low dose of radioiodine and then come back multiple times and we withdraw blood as well as do a whole body imaging, so after 96 hours, for the study to be complete, we have to calculate, using sophisticated software, the maximum dose a patient can tolerate. When I say maximum tolerated dose, it is a dose that will not cause any bone marrow suppression or any lung fibrosis, which is the critical organ we worry about, but still deliver the sufficient effective dose to the target we are going to treat.
Chagpar How often do those complications occur? Is this something patients worry about?
Cheng For the dosimetry we are using a very low dose so the patients usually will not feel any of the bone marrow suppression under the regular dose of the dosimetry protocol. Only if a patient receives an extremely high dose or accumulates a high dose then you should worry about potential bone marrow suppression or lung fibrosis, but for some patients with diffuse lung metastasis sometimes you have to balance treating the cancer in the lung, with some of the risks you are going to take.
Chen I think the dosimetry program is not necessary for all patients because most patients have good renal functions and good physiology to metabolize the iodine. The retention time is not sufficiently dangerous for us to really consider dosimetry, however, those patients who are elderly and those patients that have high tumor burden, we have more concern about those and we certainly do not want to trade one disease for another.
Foss Is it common that you would have to go back and retreat a patient, if the patient develops more metastasis six months or a year later? Is it possible to go back and treat them again with a second dose?
Cheng Yes, some patients would require maybe a second dose or a third dose of treatment. It all depends on how the primary cancer responds. For example, for lungs metastasis and also bone metastasis,
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usually we are not able to ablate most of them, and most of the time the patient will require a second dose or third dose.
Chagpar One of the questions that our audience may have is we have been talking about radioactive iodine and other radioactivity tracers in the treatment of the cancer, so how does that differ from radiation therapy which many patients get for cancer, are those the same, or are they different? Tell us a little bit about that.
Cheng The difference between the nuclear medicine and therapeutic radiology is that we use the unsure source so we administer to the patient internally in contrast to therapeutic radiology where they use an external source. They emit the radiation externally to reach the target so that is the major difference between us and radiation therapy.
Chen The source that we give is internalized not just in the body, but also intracellularly. So the target is reached and when they decay, they actually work on the individual cells, where with external beam you have to traverse through the skin, soft tissue, muscle and nerves maybe even blood vessels, before you get to the target, so all of those tissues that are encountered before the target will have even a higher dose from the external beam. So we actually have a more efficacious delivery of the radiation which will minimize the amount of damage. A second point is that once we give the source, of course it decays continuously, so there is no fractionation of the dose which external beam radiation will have and the radiobiology studies will tell you that when you fractionate a dose, you need to have a bigger total dose because of the chance of recovery from these damaged, but not quite dead cells over time, and so we have both of those advantages having internal sources.
Chagpar So, then I have 2 follow-up questions. The first is why would you not always use a radioactive source to kill the cancer, why would you ever have to use external beam radiation, no offense to our radiation oncology colleagues who are listening? And then the second question is that it would seem to me that you would need to be able to very accurately target those cells so that you are killing the right kind of cells and not normal cells. How do you do that?
Cheng Actually you sort of answered the first question from your second question, so you need a more selective target which can reach your cancer cell and then using sort of a radioisotope label, we deliver additional radiation to destroy those cancer cells. We need those selective medications in order for us to target those cancer cells and radio nuclei or radioactivity is sort of doing the job of trying to destroy the cells, and the thyroid seems to pick up the radioiodine very selectively compared to the rest of your body.
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Foss So, we have been lucky with thyroid cancer because it does take up iodine, but David you are working in the lab to develop other tracers that might be taken up by other kinds of tumors. Can you talk a little bit about what is happening with that research, are we going to have other molecules like radioactive iodine for other kinds of cancers?
Chen What you are referring to is that we do have a Yale University PET Research Center and this is run by Dr. Carson and he runs it full time and they do research only. So, this is preclinical research and they are very heavily invested in neuroreceptor imaging, and as Dr. Chagpar has alluded to, the specificity of the tracer will improve the therapeutic index of our tracer, and unfortunately, we have limited targeting at this point that’s approved by the FDA, we do have radioimmunotherapy that worked out very well for lymphoma. We do have some therapies for palliative care, bone pain palliation that has been approved by FDA, but as you mentioned Francine, we got lucky with iodine. One of the downfalls, is of course it is carried everywhere in the body by the blood stream. So this is one of the areas where we cannot control the accumulation of the tracer whereas in external beam you can aim that specific area and not shift radiation to other parts of the body.
Dr. David Cheng is an Associate Professor of Diagnostic Radiology, chief of Nuclear Medicine and co-medical director of the Yale University PET Center. Dr. Ming-Kai Chen is Assistant Professor of Diagnostic Radiology at the Yale School of Medicine. If you have questions or would like to add your comments, visit yalecancercenter.org where you can also get the podcast and find written transcripts of past programs. You are listening to the WNPR Health Forum on the Connecticut Public Broadcasting Network.