All right. Let's go ahead and get started. Let me check one thing. All right. Again, thank you everybody for joining us today. We will get through some of this front matter since we've already covered a lot of it. But just to reiterate, we're going to keep everybody video and audio muted with the exception of our speaker. If you have any questions, please look me up. If you click on participants, you should see my name, Sterling Herring. Again, I'm a PGY3 at Vanderbilt. You should see my name up near the top. And if you double click my name, it'll pop up a little chat box and you can send me questions for our speaker. And that kind of allows us to kind of keep things as appropriate as we are able to manage them. That said, if you have any big questions regarding the series or suggestions or concerns, please feel free to reach out to me or to Candice Street at AAP. Her email is there on the screen, or you can track us down on Twitter. So without further ado, we're excited to have Dr. Power with us today from National Rehab in Washington, DC. Welcome, Dr. Power, and thank you for joining us. Oh, thank you. I'm going to be visible. Oh, hello. Thank you for having me. I look forward to chatting with you guys today. Sorry, I just ran around the hospital looking for a place that I could have visuals. So hopefully this will go better than five minutes ago when I thought I couldn't. All right. So I am a cancer rehab physician in DC. And today I am going to be talking to you about chemotherapy-induced peripheral neuropathy. So let me just see if I can share my screen soon. All right, let's see. Share. Here we go. Fabulous. All right. So I have no disclosures. I still have all my student loans. So I'm in good company, I'm sure, with all you guys. So what are the aims of today's presentation? So we want to identify the common risk factors for development of chemotherapy-induced peripheral neuropathy, be familiar with why this develops, and the different agents that are more synonymous with the condition, and then talk a bit about our current treatment options. So we're going to kind of go into these topics on my outline here. So to start with, epidemiology. So is everybody seeing my slides? Or are they seeing me? We're seeing you and we're seeing your slides, but we're seeing it in presenter mode. So we can kind of see the next slide too. Let me see if I can fix that. There we go. Okay. But are you seeing the side view? Yes. Man, I'm just not winning. Why is it so? That's right. Variation is exciting. Let's see. Resume slideshow. But how do I get out of presenter mode? All right. Now I'm just... Okay. You can keep trying there. I'll see if I can figure it out on my end. Okay. Hmm. If you click up at the top where it says slideshow, try from beginning. There we go. That does not appear to be doing anything. No. It was fun, but now it just hates me. Maybe try closing PowerPoint. We had this one other lecture where someone had to close it and reopen it. Yep. All right. I'm on board with that. Let's see if this works. Sorry for the technical difficulties. I knew there was going to be an issue. Hey, this happens. Yeah. All right. Maybe it's because I have a second screen. Let's get rid of that screen. Oh, yeah, maybe. Okay. And let's go back to Zoom and share screen. I had the tropes. There it is. Yeah? Looks great. Fabulous. All right. I lost my momentum. Anyway, so what do we know about chemotherapy-induced peripheral neuropathy? It's quite common. It has variable onset and severity and duration. So not everybody is going to present with the same kind of picture. So why is it important? So number one, it can lead to early cessation of therapy or need for dose reduction, which means that they may have an incomplete cancer treatment, which is obviously not ideal. And then from the rehab perspective, it can lead to permanent symptoms and disability up into about 40% of cancer survivors. And as many of us know, we have heaps and heaps of cancer survivors now because we're doing a lot better at treating it. So approximately in the year 2022, 40% of those 18 million would represent about 7 million patients who could continue to have permanent disability of some variation associated with this chemotherapy-induced peripheral neuropathy. So it's a huge chunk of the population, and you will definitely see it. Even if you're not a cancer physiatrist, you're going to see it. So what are some risk factors for patients that would develop it? As you may notice, I really enjoy adorable cartoons, so feel free to judge me, but you're going to see a lot more of them. So risk factors. We have increased age. So some people, even before they start treatment, may already have a history of neuropathy associated with some other condition, such as the following, like diabetes, alcoholism, HIV, sometimes medications like the ones treating HIV can also lead to neuropathy. Thyroid disorders are associated with it. Obesity has been linked to be a slightly increased risk factor for development of neuropathy. And then, of course, on the side of the treatment strategy, it's the type of chemo they used. So taxane-based and platinum-based are big offenders, as are vincoacolloids. Then we'll also see that it depends on the dosing and the schedule, how much they get, how fast they get, all that kind of stuff. So we have listed here a chart kind of listing a few of the different types, like the taxanes and the platinums, and then you have your common name that you may see used. And then the threshold dose for when you might see these sensory symptoms. And they have protocols in which, you know, like 12 weeks of taxol every week is one of the agents that's often treating breast cancer, either neoadjuvantly or adjuvantly, so before or after surgery. And you can kind of see as you go along, as that dose increases to accumulation, that's when the symptoms of the sensation change. That's when they get the tingling and all that kind of stuff. Furthermore, they've also done studies looking at how the patients are treated. So if it's just one dose, it's associated with like a high dose, it's greater neurotoxicity. As we mentioned before, a higher cumulative dose is associated with it. If the infusion is made to be over several hours rather than an hour or two, it tends to reduce the neurotoxicity of it, which is why they don't go in and have an infusion for an hour and leave. Oftentimes they're sitting in the chair for several hours. As we go on. So what causes this? We know that chemotherapy, like diabetes, attacks the far away parts of our nervous system. So our fingers and feet are most susceptible. But why? So there's a lot of neurotoxic effects on the neurons associated with these different agents. They attack different sites as well. So some of them damage the dorsal root canglion. Several of them interfere with the microtubule dynamics. Some of them just have direct toxicity at the nerve terminals. And some of them affect the myelin formation. So some myelin cartooning for everyone because I think it's adorable. So what happens? So most commonly we see that our sensory nerves are affected. So the large diameter sensory myelinated beta fibers are at highest risks. And these nerves have less capacity for regeneration versus motor nerves, which is why oftentimes not only they are affected, but they linger. It can also affect the motor neurons, especially if the dose is at a higher, like, cumulative dose. And it can occasionally affect the autonomic nerves as well. So we have the exonal degeneration, which can be associated with the binding and linking of DNA-inhibiting protein synthesis. Can be exonal mitochondrial dysfunction, such as when the taxanes. So bortazomab, excuse me, even as a cancer physiatrist, I can't pronounce some of the agents, which makes hopefully you guys feel a little bit better when you have issues. And if you can pronounce all of them, I'm jealous. So this can be associated with swan cell degeneration. And then the platinum agents also alter the ion channel mechanics. So those that affect the dorsal root ganglion is why we also see sensory symptoms. But these, it's platinum agents that are particularly offenders in this. So tubulin, as I mentioned, microtubulin is a very common target. So several different types of chemo attack it in different ways. Some of them bind and block the polymerization. And as you see here, this lovely, beautiful, I don't know, kind of looks like a St. Patrick's Day float on its side, is broken up into these free tubulin dimers. But then this vinca and colloid will attach these, and now they can't form our lovely float here. But other agents, including arubulin and platinum agents, can interfere with it in different ways. They can block polymerization, and they can interfere with the transport. So what about the pathophysiology? Is it everybody has its own? No, mechanisms actually overlap, which accounts for why some of them may lead to more severity over time, because they can hit the nerve on more than one area, or by doing so, they can modify more than one mechanism. So additionally, there are some patients that are a little bit more at risk of developing CIPN, and there's more and more work showing the involvement of genetics. So SARM1 is a protein that promotes Eulerian degeneration, and so studies show deletion of this prevented development of neuropathy in mice treated with vincristine. There's also this GSTP1-105, which is variably associated with an increased risk. And then for those of you who may see a little bit more of the genetic or familial syndromes, there's Charcot-Marie-Tooth disease, which we know has a wide kind of phenotype. But patients that carry a gene for this may have increased severity of CIPN. Sometimes when I'm examining someone, I notice maybe they have some high arches, or maybe they have some history of certain things that might make me suspicious. Doesn't necessarily change management, but it might account for why they might have a worsening in presentation than other people. So what do these patients come in with? What do they complain of? So firstly, as they're going through the chemotherapy, they will say it starts in their toes, their feet, and then progresses upwards and affects their hands, just like we know most diabetes neuropathies are. Rarely, it can be the opposite, where it starts in the hands, then affects the feet. But it's a little less common, and it might raise your eyebrow and say, hey, maybe we need to do a little bit more workup for this patient, not just assume. So how do they describe it? So I've heard a lot of different descriptions over the years. But yeah, so you have the traditional sharp stabbing, needle-like, shooting, burning. Then you could say, like, walks on blocks of ice, or my feet feel like I'm walking with concrete blocks attached to them, or I'm walking on clouds. That kind of feeling of the proprioception loss affecting their ability to kind of sense the ground and understand what they're walking on is a big component. But sometimes they'll just have some tingling. Other times they'll just say it's completely numb. Other times people will feel like their feet are swollen, and they'll say it feels tight. But when you look at them, they don't actually have a lot of swelling. It's just that kind of sensation of which. So what does it lead to? So it can lead to proprioception issues, just like we were discussing, with time that can result in gait and balance issues, which we know is super important for us rehab doctors. It also leads to fine motor impairments, difficulty with ADLs. So there is a phenomenon, like I was discussing. Normally it starts in the feet, kind of goes to the hands. It starts during, you know, the end of their chemotherapy cycles. But what happens is sometimes the symptoms actually worsen when they complete their cycle of chemotherapy. So say they finish their 12 of 12 treatments. They're like, yay, good, I'm happy. Now hopefully this will start getting better. But over the course of a month or two, the symptoms actually get a bit worse. And that's what's called this coasting phenomenon. After that slight worsening, it will tend to trend down again. It doesn't just progressively get worse. But it's commonly seen in platinum agents, like cisplatin. And a lot of the times people will have started another treatment after that. So they'll assume it's, say, the new treatment. And I have to say, no, no, this is most likely still associated with that cisplatin that you got. Even though it's getting a little worse now, I would expect that, you know, in about a month or so it's going to start getting better regardless of what we do. Which is reassuring because some people don't want to take the next agent on their regimen because they're associating this new worsening with this new thing rather than what they've already been exposed to. So what's your differential diagnosis? You should ideally have one and not just assume always that it's chemotherapy driven. So as we've mentioned before, diabetes, hypothyroidism, HIV, Hep C and B can be associated with it. Alcoholism, vitamin deficiency, especially B12, exposure to heavy metals. I haven't seen that in practice, but I'm sure it happens around the world, including the U.S. Then there's the hereditary causes, which we alluded to in the genetics area. And then there's the hereditary neuropathy with liability to pressure palsies, which fairly rarely I see. And then there's also the possibility it could be some sort of peroneoplastic syndrome. There is this subacute sensory neuropathy in non-small cell lung cancer. A little bit different presentation, but it should be kind of on your radar if they have lung cancer. So what makes you really want to think about these other diagnoses? So what if they're saying, oh, you know, my right hand is tingling and numb. You know, my doctor said it's my chemotherapy induced peripheral neuropathy. Well, it's not in your typical stocking glove distribution. So you'd really be thinking, hey, maybe there's just some carpal tunnel going on or maybe some ulnar neuropathy. So you want to be as aware of your regular bread and butter rehab nerve type diagnoses to make sure that that's not what's going on or that it's superimposed on that, because sometimes you do have some carpal tunnel in addition to the chemotherapy induced peripheral neuropathy, and that can help to guide your treatments. So there's also effects of these agents that are not leading to just peripheral neuropathy, but also other neuromuscular effects to be kind of aware of, because they present often concurrently, and it can be difficult to say, oh, this is just this or it's just this. It might make you a little bit like, well, what is going on? So oxaloplatin, for example, has this syndrome where it has this acute neuropathic pain. So typically in their hands and face, people will be exceedingly sensitive to colds, and they'll feel these dysesthesias. And it often will begin pretty early in treatments by the second or third, and it lasts for two to four days or so. So I mean, if you imagine, especially if it's like wintertime and you're in a colder state or area, it can be pretty dramatic because it's just exaggerating what's going on around them. Oxaloplatin is also associated with muscle cramping and spasm-like contractions, so that's something to be aware of. So you might say, oh, that's not your neuropathy, and it's not, but it could be something related to the oxaloplatin. So cisplatin can preferentially decide it wants to pick on one of the cranial nerves, and that can lead to some hearing loss or taste changes. Paclitaxel can lead to kind of just this aching musculoskeletal pain. People might say, oh, my bone pain. Vincristine also tastes impairment and occasional cranial nerve mononeuropathies. So how do we assess these? Unfortunately, we don't have a gold standard. Ideally, these task force recommendations for these cancer societies say you want to have a baseline neurological assessment prior to starting chemo because you want to know what was there before and how functional they were. But it should ideally include both objective evidence and the patient's subjective symptoms because they don't always correlate at all. And that would be ideally followed by routine assessments during the chemotherapy, which would include assessment of motor function, sensation, pain, and function. And they recommend, they refer to a specialist like a rehab doctor if patient especially has atypical symptoms, severe preexisting condition, or significant functional deficits. Obviously, I'm biased, so I would want them even before that so I could kind of educate them on what they can do and what to look for. But I can't force their hands. So what clinical questions should be addressed? So as we alluded to earlier when we were talking about the differential, is this neuropathy? If so, is it because of the cancer treatment or something unrelated or something related to the actual tumor itself? Are the symptoms severe enough to require intervention? If so, what are we going to do? Are they severe enough that they have to modify their cancer treatment? Weighing pros and cons here is especially important because obviously you want people to have good function and quality of life, but you don't want them to miss out on something that could make a difference in actually getting rid of their cancer. So diagnosis. So most of this, as you may have picked up, is probably clinical. So we know based on taking a history, may start after the first cycle and improve before the next and then slowly progress to where they don't improve between cycles. Usually starts distally and progresses proximally. It usually will present more with the paresthesias and then over time progress to numbness. On exam, you're going to see the sensory deficits in that stocking glove distribution. If they've received quite a bit or maybe they had a history of prior chemotherapy exposure and then this is maybe a second round, you can see a progression to where they have some weakness in their dorsiflexion, plantarflexion or their hand grip. Achilles, deep tendon reflexes can be lost. So as we see in our physical exam, you want to test strength, sensation, reflexes, balance and gait, especially important, and obviously function. So the six-minute walk test has actually been shown to be pretty promising as a mobility assessment. As you may have guessed, when you have worse symptoms, it's associated with the less distance total walked in six minutes. And this is correlated to patient reported disability. Furthermore, asymptomatic cancer survivors were shown to have decreased distance on the six-minute walk test compared to controls. So even though they're not saying, hey, I have neuropathy, it's bothering me, it's affecting how I get around, just the exposure to things, including chemotherapy and the cancer treatment, can lead to this decrease in function compared to people their own age that haven't been. If you're not able to do a six-minute walk test in the office, which most people probably can't because they don't have all the time in the world. Quick is timed up and go test. If you're sending them to physical therapy, they might do the Berg Balance Scale. It's a little bit more involved to do in an office. So for fine motor, you can do the DASH questionnaire, which is 30 items asking how difficult it is for patients to do certain things like button their shirts or get ready for work. You can actually just ask a patient to demonstrate what they find is the most difficult. So if their concern is, like, I'm having trouble buttoning my kids' shirts before they go to school in the morning or my handwriting has gotten really bad, you can have them demonstrate it for you so you can kind of get an idea about it. OT, sometimes we use this standardized Purdue pegboard test, which you see above. Physical therapists sometimes use a dynamometer. So when would you do a diagnostic workup? Would you do a diagnostic workup? So often, I don't because everything is so consistent with it from the way they describe it to the timing. So there's really not that much value. If you're worried about an alternative reason for their symptoms or, you know, if you're worried about an alternative reason for their symptoms or, you know, they are reading studies online and they think that maybe, you know, like, if they alter their own nutrition, it will be better. You could consider doing things to kind of help to confirm that they have good vitamin levels or whatever the scenario is. So what are some laboratory studies? So obviously, if you're worried, even they might be pre-diabetic because more studies recently have shown that even the presence of pre-diabetes can lead to some elements of neuropathy. So you can do an A1C or whatnot. Thyroid, obviously, B12 folate. You can look for metabolic causes with the CMP studies if you're worried about infectious causes or mucus. And then obviously, heavy metal tests, which I've never actually ordered, but if indicated. So what do we do? We do EMGs. Would you do an EMG? When would you do an EMG? So just like the lab studies, you only would really favor doing it if you want to rule out something else that's going on maybe in addition. So if my patient is saying that they have their neuropathy, it started in their feet, went to their hands, but their right hand is particularly bad, depending on how they describe it, I might think, oh, maybe there's some carpal tunnel going on. I might just treat it as if it's carpal tunnel with use of a nighttime splint or whatnot and see how it goes. And if it's not getting any better, then consider EMG. It's perfectly normal to go to EMG since it's not the typical pattern at that point as well. It really depends on the severity of symptoms and will it change your management. But it can help to monitor nerve recovery, guide decision making, and assess severity of the nerve damage. Of course, as we know, it's not going to be able to assess small fiber neuropathy. Symptom severity, as described by the patient, is not always correlated to electrodiagnostic severity, as we well know. Sometimes people with perceived bad carpal tunnel, everything fits carpal tunnel, they have a completely normal study because it's mild on their test. So it's not always the best test for that. It also could be painful and uncomfortable for a patient. So, as we know, the amplitude would affect paraxonal functioning, velocity, the integrity of the myelin. And as we see here, So what would we expect? So the especially if you're looking at the upper extremities and comparing them, the radial might be more normal because it's a little bit more proximal. Whereas if you're looking at the lower extremities, you would first expect to see that the serral would have a low amplitude. So you hear nice amplitude, lower. And same with the motor neuropathy. You see here, you know, if you're looking at the legs and the legs are affected and the hands aren't, you have happy median, not so much on the peroneal. So additional findings can be shown like abnormalities in F waves, absence of distal sensory motor action potential if it's really severe. EMG testing can evaluate for acute or chronic denervation. I really, most of the time if it's straightforward and they're sent for an EMG, I might not even do EMG, but it can be done. And the presence of spontaneous activity would suggest that active denervation, so sharp waves, fib potentials, as we well know. Usually show this to people that have never seen an EMG so that they kind of understand what the sounds we're hearing and all that kind of stuff. But hopefully all of you have seen plenty of EMGs, unless you're coronavirused out of your rotation, unfortunately. So we have some grading scales. Again, there's no consensus as to which one is best. And much like other scales, there's not a lot of variation between them. So it's like the value can be limited. So here we have like the World Health Organization. So you have zero to five. So zero is no symptoms and four is paralysis. And grade two is severe paresthesias and or light muscle weakness. So I mean, for me, the value of this is not very strong. And it doesn't really take into account everything the patient is expressing. Same with the ECOG. I mean, basically it's like zero, they're doing awesome. And four, I believe they're dead, which I don't understand why that's a grading mechanism, but regardless. And so, I mean, yeah, one seems pretty fine. But once you get to two, we'd want to have a talk and then three, you're done. You've already kind of crossed the point of we need to really reassess what we're doing. And then we have ones looking at just motor and just sensory. And like I said, there's nothing more than like this one to five and it doesn't really seem as helpful. However, there, or in addition, rather, there's only a moderate level of inter-observer agreement with these. The CT CAE. So if the reliability isn't even that great, it's not as valuable. If they're all very well trained in it, it's more reliable, but as with everything else. So anecdotally, a lot of oncologists will say for grades zero to one, they're not going to adjust the dose. Two to three, they might decrease the dose a bit. And if it's three to four, discontinue treatment. So then there's this total neuropathy score, which is a composite score. It's a much larger range, which is helpful. It does show more precision and it combines both objective scoring of sensory loss and neurophysiological parameters because it has like an EMG component. But even without the EMG component, it's still a pretty good score. And then there's this total neuropathy component. But even without the EMG component, it's still more sensitive to change than the other ones. And it addresses that lack of distinction between moderate to severe. That was my kind of gripe with the other ones. So this, it includes like vibration sensibility, strength, dependent reflexes, and then it talks about like the amplitude and things. So even without seral and peroneal amplitude, this is still more sensitive than others. But least we forget, we should certainly be talking to our patients and finding out what they feel because that is a huge component that unfortunately can be overlooked at times. So we have these like promise outcome kind of things. And it does, and the studies already have shown that patients report significantly greater neuropathy than what is reported by clinicians. So it's really important to kind of really listen to your patients basically. And you see none of these nerves are social distancing because I started this lecture prior to Corona. But I think it's cute. So treatment principles. So we want to minimize our risk factors. Obviously, those other components that could lead to an increased risk of the neuropathy being worse or ongoing. So we want to keep glucose under control, avoid excessive alcohol, eat a good diet, try not to be vegan. I don't know. Not the thing against vegans. And then you want to manage symptoms. So if they're complaining of falls or balance issues, you definitely want them in PT and assessing the need for an assistive device. And if they're not, you know, or if they're having enough discomfort that it's affecting their quality of life, you want to talk about medications that you can use to kind of dampen that. So medications unfortunately only treat the positive symptoms. So this is a very common conversation I have with my patients because a lot of the times they'll say, oh, I'm feeling numb. And unfortunately, if that's truly what they're feeling, there's no medication on earth that's magically going to give them their regular sensation again. It's all based on kind of decreasing these positive symptoms like tingling, burning, numbness, or pain. And that can be a hard conversation to talk to about people or with people. Unfortunately, there's not that many quality studies for the treatment of chemotherapy-induced peripheral neuropathy. So most of the time, the principles that we use to guide treatment are based on how medications and agents work for patients with diabetic neuropathy. So in our practice, we use duloxetine first line. And I'll kind of go into the study that kind of gives us credence for that. But as you may imagine, other neuropathic pain medications are used. I know I certainly use pregabalin, gabapentin, the tryptolines. Unfortunately, compound cream I find difficulties getting approved by insurances. So I have backed off, not because they aren't helpful. So there was a randomized double-blinded multi-center trial for duloxetine. And it showed that the regimen of 30 milligrams once a day for a week followed by an increase to 60 milligrams ongoing for four weeks had an improvement in the amount of pain they had. And the difference was clinically significant. Of note, of course, there were higher percentage of patients that dropped due to adverse effects with the duloxetine versus the placebo group. And you also note, placebo did improve because it's time since exposure to chemo. So there is an element of just kind of waiting it out. So sometimes, you know, my patients that really are not excited about medication usage will just monitor and say, hey, if it's not interfering with your quality of life too bad, it's totally fine to just keep an eye on this and see how you do. And then the other argument is, well, you don't have to be on this forever if it's going to improve your quality of life for the short time in, you know, a couple months. We can say, hey, maybe you don't need this anymore. Maybe it's been enough time since chemotherapy exposure that it's gotten better on its own and we can kind of come down off of it. You don't need it. Sometimes it works. Sometimes they still need it. So there's nonpharmacological treatments, of course, as well. So we have TENS unit and we also have this scrambler therapy that has been shown some positive effects. So the TENS, I believe most of the trials were not based specifically on chemotherapy-induced neuropathy patients rather than using like diabetic. And unfortunately, the randomized control trial in 2017 showed no significant difference. As you also know, there's not that many studies that have big numbers, unfortunately. So it can lead to some question marks. So scrambler therapy is another cutaneous neurostim treatment. Recently, I think late or early last year, they had a study specifically looking at chemotherapy-induced peripheral neuropathy patients. And it compared TENS to scrambler. And the effect and toxicity was measured by patient-reported outcomes. And it showed that scrambler had greater success overall in the tingling that they endorsed as well as numbness. So we wouldn't be talking in a rehab talk if we didn't talk about exercise. We know based on several research studies that regular physical exercise and activity has shown to lessen the severity of symptoms of neuropathy. And this is both during the chemotherapy exposure and after. So the hypothesis is that physical inactivity leads to visceral fat accumulation and development of this inflammatory state, which then leads to neurodegeneration. And since exercise has anti-inflammatory effects, it can kind of combat this. It also causes neural organization and can lead to kind of changes in that sensory pathway. So this study looking at about 350 patients treated with these chemotherapy-induced peripheral neuropathy-causing chemo agents were randomized to just chemo or chemo with exercise in this X-CAP protocol. So low to moderate aerobic exercise as well as resistance exercise daily. And they demonstrated that the exercise group had decreased hot-cold sensations in their hot feet as well as the numbness and tingling compared to the control group. Older patients, interestingly enough, showed more significant improvement in these than younger patients. So all the more reason why we should get our older patients up and moving. As an aside, I always like to just bring in a very bread-and-butter exercise prescription for cancer patients because a lot of people in years past were a little bit more hesitant and worried about, you know, like, oh, they're too frail, they're too fragile, they're at risk of things. And so they didn't encourage our cancer patients to exercise as well as the general population. But now we know that's not the case, and I'm sure you guys are well aware of that. We had the ACSM Roundtable Guidelines published again last year with updates, and it definitely supports that emphasis on, you know, a minimum of 120, 150 minutes of aerobic exercise in addition to resistance exercise training. I usually tell people it's important to start slow and progress gradually, and while that is an important guideline for anybody starting exercise, it's even exaggerated more in these patients, especially if they're having ongoing treatment or they've just recently finished treatment and they're just a little bit more frail than they were. I tend to get very specific, so I'll tell them, you know, like, step one, and I don't give them, like, week one, week two, because I think it's more tangible to say, hey, step one. It's okay if it takes you a while to get to step two. And I'll say, hey, ten minutes, twice weekly power walking. If you can't do ten minutes all at once, do five minutes, take a break, do five minutes. Give them something very tangible, and they're a little bit more apt to do it. I definitely educate them on what moderate intensity is, and unless they are, like, I'm not sure, like, a marathon runner to begin with, to kind of stick with that. Resistance exercises, I usually tell people body weight's fine or resistance bands, especially in the arms. So functional deficits, as we kind of call this, okay. So as we alluded to earlier, several studies have shown worsening balance. So those patients are particularly showing benefit if they can get into physical therapy to work on this. They can do some lower extremity training or strengthening and balance training, can see if they need these devices, and determine if there's any modifications to the home environment that might be helpful. This can also be the effect for autonomic neuropathy. So you can slow the positional transitions from supine to sitting to standing, make sure they're adequately hydrated. This goes for all cancer patients pretty much throughout the continuum, regardless if they're autonomic or not. You can consider abdominal binders and stockings and, if needed, medications. Also goes for, just like spinal cord, neurogenic bladder and bowel, eliminate other factors. You can do catheter, and you can do a bowel program if needed. This rarely comes up because autonomic neuropathy is less common, but it's good to know. So prevention, is there anything we can do? So they've looked at a lot of different options, and a lot of them have been very unsuccessful. So I'll just talk about two or three, and then we'll wrap up. So vitamin E levels were shown to be reduced in cisplatin patients, or patients treated with cisplatin that developed neuropathy. And so they theorized, since it works as an antioxidant, it can minimize neuronal damage, that maybe if we supplement it, it can show decreased CIPN. They did this study, and unfortunately it didn't really show any difference. And then there was some concern, initially from the oncology perspective, that if it's an antioxidant, it might suppress the chemo efficacy. So they were a little hesitant. So then they did a rat model that shows that there shouldn't be any difference in the effect of the chemo, to kind of caution that. But unfortunately, with no difference, there was not a lot to argue. So calcium, magnesium. So in oxaloplatin-associated chemotherapy-induced peripheral neuropathy, there was the interaction with the ion channels. So they were looking at supplements of calcium and magnesium. Unfortunately, the first study was terminated, because there was some suspicion that the treated group was showing a lower response rate to the treatment. This was disproved later, but definitely made people cautious. And the second showed no significant difference. So that was next. Alpha-lipoic acid has shown some help in other types of neuropathy, not chemotherapy-induced. So there was a trial in 2014. Unfortunately, many of them didn't complete the trial, but they were metastatic cancer. So there was an element, unfortunately, of people passing. Unfortunately, there was no statistical significance in pain scores nor functional outcomes. Glutathione, so it's a naturally-occurring antioxidant. So hey, that might be helpful. They did some small human studies, no adverse effect on tumor response, and some decreased neuropathy symptoms. But when they looked at a bigger study, specifically on carboplatin-paclitexel, there was no significant difference. So unfortunately, that was also next. This one looked to be neuroprotective, but unfortunately, it actually showed to adversely affect CIPN scores. So we don't use that for good reason. So that was a lot of me talking. And when I usually give lectures, I like to ask questions and throw candy at people so that they're awake. Unfortunately, I was not able to do that for you guys, so I apologize in my heart. I threw candy at several of you, whether it was to keep you awake or just to support the fact that you actually paid attention. But in summary, so we know that the symptoms are primarily symmetric sensory stocking glove. We want, as good physiatrists, to assess risk factors, to look for motor and autonomic symptoms, assess for functional deficits, and assess well and assess early to prevent things from going down the wrong path. Unfortunately, there's not that many good studies on medications to treat CIPN. You can certainly use duloxetine and other ones can be tried as well. Unfortunately, we can't even use duloxetine on some patients because, you know, maybe they're taking something that interacts with it. Many of my breast cancer patients take tamoxifen. It, in theory, interacts with that in potentially causing less effectiveness of tamoxifen, so we don't use it for them. So it definitely isn't applicable to everyone, but it is something that we could try. And there's no current agent recommended for prevention, but I certainly support patients trying to get up and exercise and prevent things from getting worse themselves, and many of my patients are very motivated. I actually had a patient call when she had read herself on some of these exercise trials, and she wanted to be on a treadmill on her infusion days, which is not very practical, but definitely shows that there are a lot of educated patients out there that are looking for what they can do to minimize these side effects, and it can be very helpful for us to treat them. Thank you. Thank you. We appreciate that. I do have a quick question. This is kind of an off-the-top-of-your-head question, so I apologize in advance for that, but do you happen to know the citation for the duloxetine at CIPN? Yes. I might have it on the bottom of the slide there. Here we go. Here we go. All right. I appreciate that. Somebody was asking. Excellent. If you do feel the need to give out candy, I can give you my address. You can mail it to me. I don't want this social distancing or physical distancing to induce social distancing and make you feel worse. I appreciate that gesture. Someone else says they've been eating candy the whole time. Even better. They're ahead of the curve. Yeah. Looks like there aren't any ongoing questions right now, but a lot of feedback. This is very helpful. Thank you very much. Hold on. One more. Peds populations. How common is this? Is this a typical thing? Is this something that you can see for two to three more years? That's actually a great question. I, myself, don't treat too many pediatric patients, so trying to kind of look through the research in my head, I can tell you that there's not that many specific pediatric studies looking at this. They tend to bounce back a little quicker when it comes to neuropathy, but they can still have it. I mean, I have some people that are like late effects, like in their 30s, and they were treated as, you know, teenagers or adolescents, but I don't have really good, like, research in my brain that I can give you a good informed answer. All right. No, no, no. That's fine. I appreciate it. Thank you so much. I think, like I said, I think this is something that many of us are going to see, I mean, all the time, let's be honest. And 7 million people. Right. Exactly. And the longer we practice, the longer this is, you know, survivor bias is going to lead to, hopefully, reduced incidence, but, you know, yes. Yes. But again, thank you so much. Sure. I appreciate it. If anybody has any questions, let's see if we have it up here. I believe we do. Oh, there it is. There it is. All right. So that's up there. So if anybody has any questions, they can reach out to you directly. Is that okay? Yes, absolutely. Feel free to email me. Excellent. Thank you so much. And for anybody who didn't get to watch this whole lecture or has colleagues that would like to watch it, again, they're at physiatry.org slash webinars. You can find the recordings of all of these lectures. And again, these will be hosted at least through the end of the calendar year. If you have any questions, please feel free to reach out to Dr. Power or me or people at AAP. Those are our Twitter handles and her email address. Again, thank you very much, Dr. Power, for joining us. Of course. Thank you very much. Have a great day, guys. Stay safe.

chemotherapy-induced peripheral neuropathy

CIPN

tingling

numbness

burning

pain

diagnosing CIPN

treatment options

prevention strategies