Jeremie Calais, MD, PhD

 Our community is helpful. I have an 86-year-old mother-in-law who drives a gold Jaguar, and she makes sure that when we get home from our five-hour trip from UCLA [University of California, Los Angeles], we have a big pot of goulash or something that takes us through a few days. The gentleman we just had over has taken care of a lot of Joe’s things. We’ve had alarms going off in our house, just the smoke alarms and things that need to have batteries reset, and he’s been a lot of help. Our neighbors take care of our house. You need a village to help you get through all this.

 Our daughter works in a pharmacy, so she stays on us pretty good. She talks to us about cross drugs: what this drug does and what that drug does.

 And what’s for nausea. She starts talking to her dad and then she’ll research it. Then Joe will talk to Dr. Rettig or his GP [general practitioner] about the drug that they had talked about. That’s been a big help to us.

 It sounds as though you’re drawing support from the strengths of all the people in your community and family. And you’re learning new skills to get through some things that you didn’t expect you were going to face.

 It’s nice because we have 2,600 people where we live. The mail lady knows I can call her, and she’ll stop my mail. I’m not sure if it would work out the same if we were in a large city. You don’t seem to have as many personal relationships, like with the guy who checks the electricity.

 I’m glad you have those, and I appreciate you both for sharing your experiences in dealing with this and engaging with the health care community. Thank you.

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Joseph Wood and his caregiver, Deborah Wood, provide advice for patients and caregivers with prostate cancer who may be in similar situations, and comment on the support they have received from their family and community.

Support and Advice for Patients with mCRPC and Their Caregivers

Joe, how often are you going to have to go in for follow-ups and treatment while you’re on the trial?

: We do not have a hard calendar yet. I expect to receive that on Monday when I get my first injection, but it’s my understanding that the injections are every 8 weeks, with scans and blood tests in between those 8 weeks, at variable times. We’ll just have to live around that schedule when it comes.

What side effects did your doctor talk to you about as you were thinking about this trial and signing the consent?

: Dr Rettig and I discussed the dry mouth and the other side effects because I had already researched the lutetium. We had a short discussion about that, but it didn’t concern me. I was aware of them [already] and I’ve had other side effects, so it’s just a little more fatigue to push through, that’s all.

Were there any [side effects], was there anything? It sounds like you didn’t have any major concerns or other things that you were asking about. But Debbie, was there anything that you had questions or concerns about with this?

: They’ve answered most of them. I think it helps the caregiver not to have this mystery around, this mysterious thing. They’ve been working, trying to cure cancer for years. Every step has been a great step for Joe. We’ve still been able to go fishing, and do some of the things we enjoy doing. I think this video call has cleared up a lot of my questions as far as taking care of Joe. It did help me in the interim; for example, I’m going to have our hotel room longer when we come down because I don’t want to [spend] 5 hours in the car. I’m glad because the more forewarned we are, the better I can take care of both of us. Thank you for clearing all that up.

: I’d like to add something. From my perspective, as the treating physician, I appreciate and encourage caregivers to be involved. I appreciate it when they come to the clinic when it’s possible; it’s not always possible, of course. It certainly makes it easier to care for the patients with the caregiver involved in understanding what’s going on and addressing any questions they may have so that the treatments can go as smoothly as possible.

: I would like to add to that. COVID-19 really drove me nuts, because [previously] I had made every doctor’s appointment with Joe. And he comes out [of his appointments], and he’s like, “Oh, [the doctor] just said this.” That was frustrating because, “No, you were in there, the doctor had to have said more than one sentence.” So, I’m glad that I will be able to come back in because it helps me understand what’s happening when Joe’s not so forthcoming with what happens in the appointment. I’m glad to be able to go back in.

Matt, do you have any comments on that? Because as a medical oncologist, I felt like that was one of the hardest parts of the pandemic, separating people from their support, and then trying to communicate. What are your thoughts?

: I agree totally. Especially when I’m first meeting a patient, and I walk into the room, and I see the patient by himself, my heart sinks a little. I always would prefer to have a loved one near, as a provider. Hopefully, we’re getting through some of the worst of COVID-19, knock on wood, and this won’t be so much of an issue. I think that has already started to change. I share your sentiment, Alicia, about that and COVID-19.

: I have a question for Jeremie. When you give [Joe] the treatments, will we be able to come in with him? Or is it better for our health to not be able to visit him while he’s having his infusions? He has a Kindle, he can play poker, whatever, but I’m just not sure how this works.

: There is no strict rule. Treatment will last around two to three hours, so in the meantime, you can take a walk or be in the waiting room. But if you felt strongly you wanted to be by your husband’s side, you can definitely come into the room. Many patients are doing that. There is lead shielding protection from the source of the radiopharmaceutical therapy during the 30 minutes while the infusion pump is taking the drug. Again, it is the gamma radiation that we fear for the surrounding people, because most of the radiation we’re using is just emitting in an area of a couple of millimeters. This is the 1 that treats the cancer in Mr Wood’s body. The types of radiation we fear for the surrounding people are the X-ray-like ones, and with these, if you’re 2 or 3 meters away from the source, you’re already pretty safe. Many patients have their caregiver come in the room as well, sitting on a chair maybe 4 or 5 meters away, doing something on their computer or just staying by their side. It’s up to you.

: Yes, a lot of times, it’s up to Joe. Sometimes he prefers to just listen to his iPod. It depends on him if I go, normally, because I’d be in everything. I’m kind of that kind of person.

: You’ll see, you can try both ways. You will have multiple cycles to try different scenarios.

: You have a big lounge chair for me, right?

 Yes, and it is California, so the weather is supposed to be nice.

 Dr Calais gives massages to all caregivers.

 It’s a good thing because I have a bone disease and it isn’t my friend. Dancing now, that’s OK. I can’t walk the next day, but I enjoy it.

This is certainly prime multidisciplinary care. Between the resources, the facilities, and the massages by Dr Calais, certainly, the care is better at UCLA [University of California, Los Angeles] than elsewhere, and we can all aspire to that.

Joseph Wood and his wife and caregiver, Deborah, share their concerns and questions about radioligand therapy and how the COVID-19 pandemic has impacted their treatment experience. 

Follow-up and Side Effects in Patients Treated with Lutetium 177-PSMA 167

Jeremie, I’d love to hear you give a little more information to the caregivers and patients. What should everyone be aware of before, during and after treatment with lutetium-PSMA-617?

: First, it’s a drug that is injected. It’s a radioactive drug, but the way we administer it is via an IV [intravenous] line. Usually, patients will sit in a chair. It’s a bit like an infusion chair and similar to a chemotherapy setting. Patients will stay in the ward for 2to 3 hours where the treatment is administered at intervals of 30 minutes. Patients are prepared with an IV line, hydration, and some antiemetic treatments. We observe them, make sure everything is fine, and then the patient uses the restroom to void the first urine, which is the most radioactive. We measure the radioactivity to make sure that the patient is under the threshold that would require a hospital stay. As soon as we have that [radioactivity level], [the] patient can go home and be released from the hospital. It’s pretty straightforward in the hospital. It’s a 2 or 3-hour appointment. It’s done through an IV line and you sit in a chair.

The second thing is the time interval. Usually, you can get 4 to 6 cycles of therapy, depending on the setting. And you get an interval between each cycle of 6 to 8 weeks, also depending on the setting. So 1 cycle every 6 to 8 weeks, and this you do 4 to 6 times. It takes about 6 months, something like that, during which there will be some back and forth to the nuclear medicine clinic for these injections.

Then in terms of radiation safety, and for the people around the patients, this is most important during the first days following the administration of the treatment, that’s when the patient is the most radioactive. The drug will go into the patient, circulate through the body, and most of it will go to the target lesions and stay there, that’s what we want. It will be locked and trapped there and continuously deliver radiation just around where it has been emitted. Then there is the rest that is not used or eliminated by the kidneys. This will be eliminated during the first two or three days. That’s when the patient is a bit radioactive for the surrounding people because there is a tiny part that is emitting different types of radiation that goes out of the body. It’s a low dose of radiation, more or less similar to an X-ray. If you stay very close to a patient for consecutive hours, you could get a little bit of low-dose radiation.

I usually take the example of sleeping in the same bed the night just after the administration of the treatment. If you sleep for 8 consecutive hours side by side, very close, you may get an amount of radiation similar to a CT [computed tomography] scan or an X-ray. It will not create real damage, but you don’t want to do a CT scan or an X-ray if there is no medical reason. It’s just a common sense rule, as a measure of precaution. 

Radiation, how does it work? The closer you are, the more you’ll get. And the longer you stay, the more you’ll get. The basic protection rule is to keep 2 or 3 feet of distance, and already there will be almost no radiation from that standpoint. If you have to hug, or if you have to stay close, stay 5, 10, 30 minutes, that’s OK. You just don’t want to stay 12 hours consecutively, side by side. The more important thing is the person. Younger children and fetuses are more sensitive to radiation, so you stay away from kids, pregnant women and babies during the first 2 to 3 days following the administration. Again, it will probably not harm them, but you just don’t want to expose them for no reason. It’s an easy precaution to keep some distance for 2 to 3 days. That’s pretty much it.

 That’s extremely practical advice, thank you. I wonder how you follow patients for response to treatment? And if you could comment, you and Dr Rettig work together very closely, do you both follow the patient for response? How do you manage that, one of you, the other? Who does that?

: That’s a good question. I think the way you can assess the efficacy and the toxicity of treatment is by talking with the patient. Ask how he’s feeling, his level of activity, and if he’s feeling better. If he had pain, has that pain improved? Then you have the PSA [prostate-specific antigen], of course, and then you have the imaging. For imaging, you can use conventional radiography with a CT bone scan, and also now more and more a PSMA PET [positron emission tomography]-CT. You will use all these parameters, again, to put that in your computer brain. as Dr Rettig says, and finally, decide if a patient is benefiting.

I have some stories where the PSA doesn’t go down, there is a clear progression on the images, but the patient is feeling much better. In that case, even if you have signs of progression by some kind of test but the patient is reporting feeling better, then there is maybe a no better therapeutic option for them at the moment, so we continue to treat these patients. And they have been grateful for that and reported some bone pain improvements, for example. That’s the way we monitor response to treatment. I think after 2or 3 cycles, you can get a good idea if the patient is benefiting. Quite frequently, after 2 or 3 cycles, we stop because the patient doesn’t necessarily need the full 6 cycles to get the benefit. Let’s say the first 2cycles are the most important, and if we will see patient is benefiting, sometimes we have this nice PSA decrease over time.

Who is performing the treatment? I think this will depend on the local setting. Here at UCLA [University of California, Los Angeles], we have strong nuclear medicine clinical research programs, so we were here using these agents since the beginning. There is nice communication; it’s a nice network. For me, it’s very enjoyable to have this multidisciplinary approach. I communicate a lot with Matt, of course, and it’s always a pleasure with our radiation oncologist colleagues as well. We, as nuclear medicine physicians, as well as the nuclear medicine physician team, would report the main findings to the medical oncology team, Dr Rettig, and ask, “What do you want to do? What do you advise us to do?” In the end, Dr Rettig will probably make the final call. We filter the first set of information about how the patient is feeling, and if there are some test results we need to report, and then in collaboration, in coordination with the medical oncology team, we will report that and make a decision on what to do.

I think that’s great. It really speaks to the multidisciplinary approach. I imagine not every center will be set up quite like that, but it’s wonderful that you have that collaboration. Do you have any comments on that, Matt?

: I totally agree. I think patients are fortunate to be able to go to a place where so many different specialties are working together and bringing their expertise to the table for the patient. During radionuclide therapy, during the lutetium PSMA, I do co-follow the patients. I typically see them perhaps not as often as Jeremie while they are receiving radionuclide therapy, and I also will be communicating with Jeremie, as he indicated. I want to emphasize what Jeremie said about how we follow patients. There are really just 3 things that we can follow. It’s pretty simple: how you’re feeling, so you’re symptoms; your PSA; and your scans.

One thing that’s important that Jeremie already alluded to is that sometimes these 3 factors that we use to follow patients don’t go in the same direction at the same time. A lot of the time, the PSA does not track well with the scans. So sometimes a PSA can be going up, and the scans are looking a lot better. I think that’s really important for patients to keep in mind. Because, of course, from the outset, patients and their doctors are so PSA focused. But as the disease advances, what we see are these discrepancies between how they’re feeling, the PSA, and the scans. It’s important to work with your doctor to decide what is the best next step. Is the treatment working, or do we have to make a change?

I would agree with that. I certainly have patients where the PSA is going up, initially at least. But then I started to see other things, like alkaline phosphatase coming down, and patients feeling really well, and scans suggest that there’s a benefit. There’s some literature on this, some case series that I looked to when I saw this. And I said, I just want to reassure myself that this is what I think it is, it’s just a disconnect, but the patient’s really benefiting. So you are not alone. And if you have a big series, you could put it out there in the literature because we would all benefit from that. That’s a really important message, I think, as people are using these agents.

Dr Jeremie Calais shares some clinical pearls for lutetium-177 PSMA 617 and how this therapy has changed the treatment landscape for patients with metastatic castration resistant prostate cancer (mCRPC).

Clinical Considerations Related to Lutetium 177– PSMA-617 Treatment in mCRPC 

I’d love to hear too, other than “my PSA [prostate-specific antigen] is going up,” patients will have other concerns about getting radioligand therapy. From your perspective, Matt, are there any myths that you want to get out there? Is there anything you’d like to put out on the table and speak to and hope to dispel?

: Yes, I think that’s really important because radiation can carry with it this myth of being this horrible thing, and you’re going to grow an extra arm, or you’re going to get cancers because of the radiation. And really what we’re talking about is therapeutic doses. Long-term complications of this are not really a concern, especially in the near term when we’re treating advanced prostate cancer. Very rarely, and over many years, sometimes there is a small increase in the risk of some cancers. But really, it’s negligible, especially when compared to the importance of gaining a therapeutic effect from radiation. Whether it’s the very low doses with scanning, some diagnostics, or the slightly higher doses, we’re still talking about therapeutic [dosing]. I do want to dispel the myth that getting radiation is going to cause some terrible things for you or your family members or friends; that’s important to understand.

It’s an important take-home message, and it [the radiation] is well tolerated. I think we’ve talked about that. It’s an important message, that these treatments are effective and well tolerated. Treatment does not have to be associated with a lot of side effects to be effective. I hear patients asking me, “Do I really want to take an aggressive treatment?” Meaning, that it’s going to cause side effects in order to get a treatment effect and response, and that’s just not the case. In fact, I think some of the most effective treatments are the ones that are more selective, and more specific, where we have a specific molecular target. As Jeremie talked about, PSMA [prostate-specific membrane antigen] is a molecular target. When we have such specific therapies, the side effect profile tends to be very favorable, because the target is specific to the cancer. So, I think that’s also an important concept to recognize in PSMA therapy and diagnostics.

That’s a great message. The better you are at targeting the cancer, the more on-target wanted effects you have against the cancer, and the fewer off-target side effects you’ll have. That’s a great point and so important for people to hear. Now, we have heard through the course of this discussion about how wonderfully you and Jeremie work together. I want to ask you first, and then I’ll ask Jeremie, what are some of the ways that you make it work? Nuts and bolts, day to day, how do you make it work because you’re both extremely busy? You’re both doing many jobs as academicians, some of those are clinical, but then you have other responsibilities. Jeremie’s reading scans, you’re seeing patients maybe with other cancers, how do you get together to actually make multidisciplinary care for radioligand therapy work?

: I think, first of all, it’s premised on having a friendly relationship. We like each other and we communicate. And ultimately, although we wear a lot of different hats, the most important thing is the patient. The patient comes first. When there’s an issue, whether it’s research or administration, or a clinical issue, the patient comes first. Communication comes in a lot of different forms. We have formal venues for discussing cases, like multidisciplinary tumor boards, where we bring up difficult or interesting cases. We communicate all the time, whether it’s by phone, or by email, we’re constantly in touch. We’re in touch about clinical trials, and we’re in touch about specific patients, so there’s an ongoing dialogue. We’re never caught off guard, and we know what the other is doing. It makes for a very productive and efficient way of treating patients. So it’s not that complicated, it’s communication, and doing it together and taking care of the patient as a team.

That’s a wonderful message. Jeremie, how do you make it work?

: It’s always hard to come after Matt; he said everything. I want to highlight that it is the patient first. You have all your emails and your calls, and sometimes it can be related to research or administration, but what matters is when you have a colleague who says, “OK, I have this patient, I need to do this, tell me what you think.” That’s when you have to stop everything and make the patient your priority. For radionuclide therapy, when there is a side effect you’re not sure how to handle, you send a text message or email, and try to communicate with your colleagues. When my colleagues are telling me, “I have the patient in front of me, can you look at the scan quickly and tell me what you think,” I always try to make that my first priority. That’s a key priority. I think we’re lucky to have that. But we get along very well here at UCLA [University of California, Los Angeles] with all our colleagues, and with Matt in particular, so for us, it’s very pleasant.

Drs Matthew Rettig and Jeremie Calais explain what it means to be a part of a collaborative team and how communication plays a big role in patients receiving optimal treatment. 

Jeremie Calais, MD, PhD

Support and Advice for Patients with mCRPC and Their Caregivers

Follow-up and Side Effects in Patients Treated with Lutetium 177-PSMA 167

Clinical Considerations Related to Lutetium 177– PSMA-617 Treatment in mCRPC

A Multi-Disciplinary Approach to Treatment for Patients with mCRPC

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