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Dr. Daniel Spratt: On Becoming A Doctor

Dr. Daniel Spratt is a radiation oncologist and the Chair of the Genitourinary Division of Clinical Research at the University of Michigan Health System.

Dr. Spratt talks to Prostatepedia about why he became a doctor.

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Why did you become a doctor?

Dr. Daniel Spratt: There are no physicians or healthcare workers in my family. I took an unconventional path to becoming a doctor. I started working as a personal trainer when I turned 18. I was always involved in fitness and exercise. I took some time off from going to college and worked one-on-one with clients.

At that time, I noticed that I liked being able to help change people’s lives and have that unique interaction. But there are limitations to what a personal trainer can do for a person. That inspired me to go back to college, focus on the research, and go to medical school to become a radiation oncologist.

How did you make your way to radiation oncology versus urology?

Dr. Spratt: In medical school, we rotate through a bunch of different specialties. All along, I thought I was going to be a neurosurgeon; that was my focus and my research. But I started to realize that I love to connect, to have the time and flexibility to discuss how patients are doing. I care more than just about the technical treatment. I enjoy emotionally connecting with patients.

The radiation oncology industry is a unique specialty in that a machine delivers our treatments, and then we get to see the patient. I almost do two things at once. If a surgeon is operating all day, they can’t see anyone other than the one patient in front of them. I get to see and treat dozens of patients a day.

Are you still involved in the exercise world?

Dr. Spratt: Definitely. It is not as strong, but if you spoke to any of my patients, they’d tell you that I prescribe exercise to all of them. The side effect profile for my patients who are inactive versus the ones who are active is like night and day. It’s amazing how patients undergoing prostate cancer treatment, including radiation and especially hormone therapy, are improved by exercise. It doesn’t need to be joining a gym—just being active in some way.

The guys who are active have much fewer side effects during treatment. I jokingly prescribe exercise while

I prescribe radiation to them.

Maybe you shouldn’t joke and really do it!

Dr. Spratt: Exactly. I don’t think a pharmacy can fill that.

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Shop Around For A Radiation Therapist

Dr. William Hall of the Medical College of Wisconsin offers advise to patients looking for a radiation therapist.

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Dr. Hall says: Radiation therapy is an extremely technical specialty that is rapidly evolving. Many patients think that radiation therapy is the same, regardless of where they receive it.

That is not so.

Expertise, delivery methods, and the unique methods of radiation therapy administration can vary tremendously from hospital to hospital. That’s extremely valuable for patients to understand.

You should seek a radiation oncologist who specializes in your type of cancer, someone who focuses their research and clinical efforts on a few types of cancer. In larger academic centers, radiation oncologists tend to do that.

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Why Combine RT + Immunotherapy?

Dr. Charles G. Drake, of New York-Presbyterian/Columbia University Medical Center, discusses the thinking behind combining radiation therapy with immunotherapy.

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Dr. Drake says: “The basic idea is that radiation, and perhaps other local modalities like cryotherapy, leads to destruction of tumor cells. If they’re destroyed in a way that’s immunogenic or pro-immunogenic, then the dying cells are taken up by resident antigen-presenting cells. These antigen-presenting cells get activated; they traffic to the draining lymph node, if you’re lucky. If they traffic to the draining lymph nodes, and then activate a systemic immune response (T cells), then maybe you can turn a local therapy into a systemic therapy. When that happens, it’s called the abscopal effect. We can demonstrate this in mice fairly readily, but it’s quite hard to demonstrate in humans.

In the literature, it’s not that common. There’s a review paper that reports around 60 total cases in the world that are clearly documented. But if you talk to people who take care of patients, everybody has one or two that they can talk about.”

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Dr. Robert Bristow On Genomics, Radiation Therapy + Prostate Cancer

Dr. Robert B. Bristow talks with Prostatepedia about the intersection of genomics and radiation therapy for prostate cancer.

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Let’s talk about genomics. Do we have a way of predicting who will respond to radiation? And who will have severe side effects?

Dr. Robert B. Bristow: The short answer is no. My work with my colleagues in Canada involved a huge effort to sequence the entire genome, or the entire DNA network within prostate cancer in patients in the localized setting. What we know in localized disease is that there are a number of patients that under the microscope look like they have the same Gleason score. When we do whole genome sequencing, we see that about a quarter of these actually have a number of genetic rearrangements and mutations within their tumor.

It’s quite clear that the patients who have more aggressive mutations and increased number of mutations actually do worse. The way that they do worse is that they actually fail radiotherapy quite quickly after treatment. We therefore think that genetic instability, or the increased burden of mutation, is associated with hidden metastases as opposed to information about responding to surgery versus radiotherapy.

We’ve looked very hard in the Canadian study for a predictor of who would respond to radiotherapy versus who would respond to surgery. Although some early leads suggested one gene or another, I’m not confident right now that we actually have a marker so that when a patient comes into the clinic, we could do a quick test to say whether his disease was more or less sensitive to radiotherapy. We hope that will change, of course, with further data. But we don’t have it yet.

The other aspect that you pointed out is whether or not radiation side effects are associated with germline or blood DNA. Some data suggests there are specific gene mutations associated with cell growth, the way the cells contact each other, or DNA repair that might put patients at risk for erectile dysfunction or rectal bleeding. A lot of validation studies still need to be completed. It is also not ready for prime time.

Something that has come up in the last two to three years is that patients can have defects in genes associated with DNA repair. Your readers will have heard about the BRCA1 and BRCA2 genes normally associated with ovarian and breast cancer. We now know if you are a male BRCA2 carrier you have an increased risk for prostate cancer and an increased risk of aggressive prostate cancer.

One Canadian study suggested that some of these localized cancers in BRCA carriers already had acquired resistance patterns to hormone therapy and other types of therapy even though they had never seen the therapy. They are almost primed for resistance.

We also know that maybe up to 15% of patients with metastatic castrate-resistance prostate cancer have DNA repair defects. This is important because it speaks to mechanisms of resistance and aggressiveness based on genes in your bloodline. The other important thing we’ve learned in the last five years is that prostate cancer patients with BRCA1 and BRCA2 DNA repair defects respond to PARP inhibitors.

This is a very exciting area of precision oncology using genomics to predict those patients that might respond to a molecular-targeted therapy in this case.

One can only assume that there might be other stories like the DNA repair defect story that would give us more information about different types of tumors.

Dr. Bristow: This comes back to what we were talking about before: carefully designing clinical trials to compare one treatment versus another in large numbers of patients in which there is high content information about the immune landscape, genetics of the tumor, genetics of their bloodline, and functional imaging of the tumors. This will allow us to start to put this information together to come up with a more precise way of treating our patients.

Cancer is complex. The complexities of cancer are for us to discover, but also for us to develop a number of tests that give us a sense of that complexity so that we can use the right treatment for the right patient at the right time.

The promise of genomics in the last decade is now leading to novel treatment for patients. There are still situations for which we don’t know the best treatments. In those cases, patients need to demand from their healthcare givers information about which clinical trials are available to them so that we can solve these questions together. The reality is that we do require clinical trials to answer them.

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Dr. Robert Bristow On Precision Radiation Therapy

Robert Bristow portraitDr. Robert G. Bristow is the Director of the Manchester Cancer Research Centre (MCRC) at the University of Manchester in the United Kingdom.

Prostatepedia spoke with him about precision radiation therapy.

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What is meant by precision radiotherapy?

Dr. Robert Bristow: There are at least two aspects to precision radiotherapy. The first is the “physical precision” of radiotherapy; the actual targeting of the radiation beams or radioactive compounds to the specific tumor tissues that you want to treat, with maximum protection to the normal tissues that surround that particular tumor. For example, external precision radiotherapy uses intensity modulated radiotherapy or proton therapy where you then deliver the radiation in very precise defined volumes.

The other type of physical precision in radiotherapy uses brachytherapy, actually placing seeds or catheters with radioactivity directly in the prostate and being able to conform the dose tightly to the prostate gland, with that dose falling off rapidly around the surrounding normal tissues that could acquire side effects (e.g. the bladder or rectum). The concept of physical precision has allowed us to increase the total dose to the prostate cancer and yet maximally spare the normal tissues from side effects.

Another aspect of precision radiotherapy is “biological precision” whereby we think about the entire treatment using radiotherapy based on the innate characteristics of a particular patient’s tumor.

This includes information about the genetics and microenvironment of the tumor cells within the cancer that make it uniquely suited to be cured by radiotherapy alone, or in combination with drugs that modify biology or the immune system.

This can have the effect of increasing the chance that the cancer is cured locally and also attack cancer throughout the entire body to kill what we call occult, or hidden, metastases.

Precision radiation therapy therefore now means both an understanding of the biology of the tumor in a specific patient as well as physics to optimally deliver that radiotherapy.

What role does functional imaging play?

Dr. Bristow: Imaging is a cornerstone for staging cancer and understanding its biology. It is absolutely required for staging patients to understand the anatomy of their cancer—not only where the local tumor is, but also the spread to the pelvic lymph nodes and beyond that to the bone, for example.

Anatomic imaging therefore gives us the geography of where those tumors are in the body. Functional imaging adds further components to start to understand the biology of those tumors. For example, by using functional imaging with MRI, we can look at differences in tumor blood flow, oxygen levels, or metabolically active versus metabolically inactive tumors.

For PET scanning, we can use specific radioactive tracers that will tell us about the glucose in the tumor, the amount of the tumor that has low oxygen status (called hypoxia), and the relative growth rate of tumors.

So imaging can now give us both anatomy and biology.

Totally different world, right?

Dr. Bristow: It is. If you understand the biology from the imaging and where things are, you can certainly target specifically those areas with precision radiotherapy using novel biological agents, which we call molecular targeted agents.

Join us to read the rest of Dr. Robert Bristow’s comments on radiation therapy for prostate cancer.


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Dr. Robert Bristow: On Becoming A Physician-Scientist

RobertBristowDr. Robert G. Bristow is the Director of the Manchester Cancer Research Centre (MCRC) at the University of Manchester in the United Kingdom.

Prostatepedia spoke with him about how and why he became a physician-scientist.

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Why did you become a doctor?

Dr. Bristow: I was very interested in doing a PhD to understand how cancer cells actually divided. As part of my graduate studies, one of my mentors, a clinician-scientist, invited me to the clinic so that I would understand the implications of my research with respect to real patients undergoing real therapy. This was when I was in Toronto training at the University of Toronto.

From that experience, I realized three things. One is that the models that I’m using to try to understand how patient tumors respond to radiation and chemotherapy can be quite limited. Finding new ways to study cancer directly in patients would be profound.

The second is the reality that every patient is different and has a different story to tell; therefore, the impact of the cancer, as well as the impact of the cancer treatment on the patient can be very different, even if the biology might be exactly the same. That was a really important lesson to learn.

As I attended more and more of the clinics with my mentor, I saw that there really was a satisfaction in a career as a clinician-scientist; having the benefits of both worlds for basic and clinical research. You can ask clinical questions in collaboration with patients, but at the same time you can interrogate tumor resistance or side effects back in the lab and bring the information into the clinic. That is the real truth. I started off as a scientist, and I became a physician after meeting patients in real clinics with real clinical problems.

You’re saying that your role as a physician and your role as a scientist have a push-and-pull: each informs the other?

Dr. Bristow: That’s exactly right. Most days are terrific as they both feed off each other. But sometimes the laboratory studies do not go as well as planned as your experimental hypotheses are proven incorrect or the funding for studies is not optimal. Even with those setbacks, the reality is that when you go into the clinical realm, it’s just so rewarding and challenging.

The second part, of course, is that your favorite patients may, despite all of the best treatments that you try, not do well. In fact, some will even die of their disease. That really is an upsetting moment. The first time you’re a physician and that happens even though you think you’ve done everything right for that patient, just as you did the same for others, suggests that we don’t have all of the precise answers for an individual patient.

You’ve got to go back into the lab and work harder. It absolutely is a push/pull, but also it’s so rewarding to go back and forth. There’s a real challenge in terms of getting it right: to feed each area with the best ideas that will maximally impact on patients.

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Frontiers In Radiation Therapy

When you’re diagnosed with prostate cancer, you’re usually offered three options: monitor the cancer to see if it progresses, elect to have your prostate surgically removed, or elect to have the cancer treated with radiation therapy. Radiation is also used after surgery or in the event that the cancer comes back after that initial treatment.

Most of you are familiar with radiation therapy for prostate cancer—how it works, potential side effects, and special considerations. Even if you have not had radiation, chances are you’ve got a friend of relative who has.

This month, however, we’re delving into less often discussed aspects of radiation therapy: the role genomics will play in radiation therapy, why we might consider combining radiation with immunotherapy, the impact imaging has on radiation therapy, and the role radiopharmaceuticals play.

Dr. Robert Bristow of the University of Manchester gives us a sweeping overview of precision radiation therapy—from functional imaging to genomics—as well as a run-down of molecularly-targeted agents.

Dr. Charles Drake of the New York- Presbyterian/Columbia University Medical Center discusses radiation therapy and the elusive but intriguing abscopal effect.

Dr. William Hall of the Medical College of Wisconsin talks to us about the precision radiotherapy movement and how it will revolutionize patient care.

Dr. Daniel Spratt of the University of Michigan Health System talks abouta clinical trial he’s working on with Dr. Felix Feng from the University of California, San Francisco (UCSF) that uses genomics to determine which patients will receive a combination of radiation therapy and Erleada (apalutamide) and which will get a placebo.

From Dr. Ralph Weischelbaum of the University of Chicago we hear about the thinking behind combining radiation therapy with immunotherapeutic agents—with a cautionary note.

Dr. Johannes Czernin from the University of California, Los Angeles (UCLA) talks about a clinical trial he’s running on a radiopharmaceuticalagent—a PSMA targeted lutetium-177. He is looking for patients to join, so if you think you might be a fit, please reach out to him at the email address included at the end of his conversation.

Ms. Merel Nissenberg offers the National Alliance of State Prostate Cancer Coalition’s stance on hypofractionated radiation therapy.

Finally, Ron B. tells us about his experiences with stereotactic body radiation therapy. He has some advice for those of you in a similar situation to the one in which he found himself.

We suggest you read through this month’s conversations and then send the issue to your health care team so that you can discuss the contents with them.

Subscribe to read our July conversations about radiation therapy.