Understanding and Managing Chemotherapy-Induced Peripheral Neuropathy

Welcome to the ninth episode of Supportive Care Matters, a podcast Hosted by Medical Oncologist Professor Bogda Koczwara AM from Adelaide, Australia.

Navigating the silent struggle that many cancer survivors face, this episode promises insights into the lesser-known yet impactful world of chemotherapy-induced peripheral neuropathy (CIPN).

With the expertise of Professor David Goldstein and Associate Professor Susanna Park, this episode sheds light on how CIPN disrupts daily life in ways that go unnoticed by the medical community.

From the nuanced challenges of assessing the severity of this condition to the cognitive toll it takes on patients, Bogda leads a discussion on the critical need for sensitive and precise management strategies that can truly make a difference.

The conversation takes a deep look into the tools and techniques that are transforming how we understand and measure CIPN. Our guests articulate the importance of patient-reported experiences in guiding interventions and the potential benefits of exercise in mitigating neuropathic symptoms. Through this dialogue, we recognise the dedication and collaborative efforts that are pushing the envelope in neuropathy research and care, offering a glimmer of hope for those battling with the long-lasting effects of their cancer treatments.

This episode stands as a testament to the resilience of the human spirit and the ongoing efforts to provide supportive care that truly matters. Subscribe and like to join our mission of bringing these crucial conversations to the forefront and make supportive care matter.

This conversation is produced by The Oncology Network.

TO VIEW SHOW NOTES AND MORE INFORMATION ABOUT SUPPORTIVE CARE MATTERS, HEAD TO WWW.ONCOLOGYNEWS.COM.AU

Transcript

Bogda Koczwara: 0:03

Many years ago, a patient of mine whom I treated for breast cancer had a car accident. She had no particular problems with chemotherapy but, on questioning, admitted that she simply could not feel the pedals. It was exactly at that moment that I understood the real importance of chemotherapy-induced peripheral neuropathy. I'm Bogda Koczwara, and this is Supportive Care Matters. My guests today are a pair of researchers from Sydney, Australia. Dr David Goldstein is a medical oncologist and a professor at the University of New South Wales. Dr Susanna Park is a scientist and associate professor at the Health Brain and Mind Centre at the University of Sydney. Together, they lead a major multidisciplinary effort to improve management of chemotherapy-induced peripheral neuropathy, or CIPN. David and Susanna, thanks for joining me this morning. Thank you for having us.

Bogda Koczwara: 1:01

Pleasure to be with you, thank you for having us Pleasure to be with you. So CIPN is something that perhaps is not very well known to the audience, so let's start with something basic. Can we have a bit of a definition of what chemotherapy-induced peripheral neuropathy is?

Susanna Park: 1:17

Absolutely CIPN is nerve damage to the peripheral nerve which is caused by chemotherapy treatment for cancer. So, like other adverse events for cancer treatment, some therapies cause CIPN and others do not. But some very commonly used chemotherapies for common cancers, such as breast cancer, gynecological cancer, colorectal cancer and blood cancers, are affected by this form of peripheral nerve damage.

Bogda Koczwara: 1:44

So is it common? One tends to think about nerve damage as something that would be important for a concert pianist. But does it matter for a regular person? And is it severe? Not severe? How does that impact on patients?

David Goldstein: 1:57

So it really does matter. Clearly, we think even more so, and I do have a number of musicians that I have treated with CIPN-related drugs because that was the right thing to do. But we had very extensive conversations. One is a concert-level touring person, and so we had very extensive conversations about the pros and cons and really every person I work with ultimately wants the best treatment and they are willing to take the risks involved. But it affects everyday activities. It is not just about watchmakers and concert pianists, saxophonists and, in one other case, cellists. It's actually about people dropping cups because they can't feel them properly. It's about buttoning buttons, it's about using a keyboard and a smartphone. So it really is about daily activity and is important for everybody.

Susanna Park: 3:02

I think, if we go into the key symptoms of CIPN, so it causes sensory predominant nerve damage, so this is things like tingling, numbness, pain in the hands and feet, but it's really, I guess, the functional consequences of these symptoms that are really a problem for patients. So people affected by CIPN report difficulty with their fine motor skills as David said, doing up buttons, typing, texting using the hands but it also leads to prominent problems with the feet, problems with balance, gait, walking and exercise. We know that these downstream effects affect sleep quality, ability to exercise, and we know that chronic CIPN reduces quality of life. I think one of the other key issues is that for some patients it becomes chronic and persistent, and so you have a proportion of people and the exact percentage will vary by the agent. But for something like oxaloplatin for colorectal cancer, you can have 30% of patients that are left with this moderate to severe chronic neuropathy symptoms which can persist permanently, or at least four studies have shown out to 15, 20 years post-chemotherapy treatment.

David Goldstein: 4:12

And that's the key, Bogda, that our work suggests, although we haven't quantitatively definitively proven it is people adapt, they go back to life, they reintegrate into society. But when you really question them, their adaptation includes limiting function. There's certain things. I have a particular colleague who was a very avid tennis player and basically stopped and that was one of his major social activities. So if you just talk to them briefly as unfortunately oncologists like myself tend to do because there's a pressure of number of patients and if you talk to them briefly oh everything's fine and I'm doing really well and that's it right, but if you either get them to fill out a questionnaire before you see them or you have the time and you have a bit of a chat, it suddenly becomes clear that it's adaptation, but it's somewhat maladaptive.

Bogda Koczwara: 5:15

So really that means that we need to be very good at assessing neuropathy, because you can't just sort of say that well, do you have any tingling in your fingers? Neuropathy, because you can't just sort of say that well, do you have any tingling in your fingers, and that's enough, because you may not get those nuances of adaptation or maladaptation or potentially symptoms that may not be categorized as neuropathy. Can you give me some examples of how you would go about asking questions in a 15 minutes, 10 minutes that we might have on this particular task?

Susanna Park: 5:46

Absolutely so. As you've outlined, one of the key challenges we have is that there's a lack of a gold standard assessment tool, and we know that for many toxicities, but especially for CIPN, that if you ask clinicians to rate the level of neuropathy severity and then you ask the patients to rate the severity of their symptoms, you get very different outcomes. So patients are reporting higher severity symptoms than are reported by the clinicians, and some of this gap is, I guess, a lack of standardization in the questions that are available. So there are a lot of patient reported outcome measures that can collect more of this information, but they're not currently routinely used in clinical practice and I guess this is something that applies not just to CIPN but across a whole range of cancer care. Our research has shown that even just a simple two-item questionnaire about the severity and impact of CIPN can dramatically improve the further conversation. So highlight to clinicians when they need to ask more questions or where there might be a problem. There are also longer, more in-depth questionnaires that look at more the functional impacts and that can help identify the patients who might need other services.

Susanna Park: 6:57

So I think, like anything, there's a range of severity, and really critical is what we're now understanding is we need to find the patients that need the support. So who needs intervention with balance and gait, who needs intervention with pain management, who is having early and severe symptoms, so that those things can be mitigated. I guess, in the absence of something that's neuroprotective obviously that's one of the holy grails is to find something that people could take or some preventative strategy. But I think, even in the absence of that, before we've developed that there's so much we can do today to improve identification of this toxicity, to improve management and triage of these patients, just using routinely available tools. So I guess, increasingly, over the years of our collaboration, a lot of our research has now become focused on this implementation gap of how we can improve the situation for patients today, make it easy for clinicians to be able to improve the way we assess and manage toxicities. It's not an easy thing by any means, I guess, but yeah, it's a really important focus.

David Goldstein: 8:02

Susanna is an expert in neurophysiology and she has an enormous number of tools that she can work with and she's literally done hundreds of patients' worth of objective nerve testing and I'll let her expand on this. But it turns out that patient-reported outcomes almost better than I hesitate to say this because Xeneral Kilmig is. This is what her life's work is all the in-depth testing but almost as good in helping identify and triage as the in-depth testing, which is more, I think, has evolved to be an understanding of mechanism and an ability to start to think about what interventions would make sense therapeutically right and perhaps afterwards. But I'll get her to expand now.

Susanna Park: 8:55

Thank you, David, you make me laugh.

Susanna Park: 8:57

It's true, my background is as a clinical neurophysiologist and I think initially, when we started our research program, I probably was guilty of thinking we can resolve this very quickly.

Susanna Park: 9:07

We will do some nerve tests, we will prove that these objective nerve tests give us all the information we need, and then we will implement it and move on.

Susanna Park: 9:15

But I guess, as with anything, the real picture is so much more complicated and interesting perhaps, but our work has demonstrated, I would would say definitively, that something like a patient-reported outcome, where you ask people about the impact of their symptoms and the severity, is more sensitive than an objective nerve test that we can do. And I guess one of the reasons for this is that when you ask someone these questionnaires, they're reflecting on what's important to them and they're reflecting on their function globally and the symptom impact. And when we're doing a nerve test or even we do other tests which are quantifying sensory loss, looking at fine motor function, looking at balance and gait function, these are all really important research tools, but they're all looking at a component of this issue, so we're measuring nerve function at a few discrete sites. So I guess it makes sense that that is not going to be as sensitive as something when you're asking people about the impact and significance of this entire global issue for them, which affects many areas of their life.

Bogda Koczwara: 10:19

So if I were to use an analogy here, for example, a person might have problems with neuropathy that affects their feet, but how well they walk will be affected by how well lit the corridor is and how good their vision is and how good their muscle strength is and whether they have a limp because of a sore hip or something like that. So in a way the neuropathy is taken in context of the overall function and they can be affected significantly even with moderate neuropathy, if those other factors occur. Is that what you're talking about, or am I just making it up.

Susanna Park: 10:58

Absolutely, absolutely, Bogda, you're spot on. In fact, we've done some collaborative studies with scientists who measure gait and balance, and one of the interesting things that we found is that in normal challenge kind of environments, the gait is pretty normal when you start to add a cognitive load, which is a fancy way of saying normal life, because you're very rarely walking without doing something else, so you know you're crossing a road you're thinking about when you're going to cross it. Is the floor bumpy, what other things are happening? What are you going to have for lunch, what's for dinner? All of those things. When you have CIPN, it requires more of your attention and energy to maintain your balance, to visually guide where you're walking, and so our research found that if we add a cognitive load to a walking task, that's when we start to see these impairments that come out, sort of showing, I guess, the impact. How, other factors in combination with the CIPN, what produces this functional disability?

David Goldstein: 12:00

So actually, this perhaps anticipates your question later, but it's definitely higher order issues, like in chronic fatigue syndrome. It's the same thing that cognitive ability seems to be normal until it's challenged in a more discrete way and then you uncover higher order functions that wouldn't be uncovered in your standard straightforward test, and the same applies here. So pain as a manifestation or sleep disturbance, these other extra dimensions another example of what you were saying that would influence the individual perception of their problem with the nerve disturbance.

Bogda Koczwara: 12:45

So can I pick up on some of those symptoms because I think they're really relevant from the clinical perspective? I recall that in a very common way, the questions that oncologists would ask of patients looking for neuropathy is do you have any tingling in fingers or toes and can you do up your buttons? But the symptoms that you have mentioned were pain and sleep disturbance. What are some of the sort of, let's say, less conventional symptoms that would alert you to the presence of neuropathy?

David Goldstein: 13:16

So, from my perspective, the other things that I try and remember to do is ask about near misses. So not just falls, but nearly falling over, for example, would be another one. Yeah, it's always remember pain is actually pain's a difficult one, because pain as we normally think about it, like our patients with hepatic metastases and liver capsular pain, is not what this is about. True severe pain that requires narcotic analgesics is incredibly rare. Even pain that requires intervention with non-steroidals, for example, is uncommon one in five but that discomfort of pins and needles is extremely common. It's a problem that makes people disturbed and not functional, especially at night. They hate it at night bedclothes covering these hypersensitive toes, but Susanna's going to make it more scientific, as usual.

Susanna Park: 14:25

I think what David's pointing out. So certainly there are significant numbers of people with CIPN affected by pain. However, it's not the majority and it can vary by agent. So in our studies it's usually around 25% to 40% of people with CIPN will also report neuropathic pain. So neuropathic pain is a particular type of pain usually characterized by sort of burning, sharp sensations, as compared to other types of pain which are more conventionally managed inflammatory pain, things like non-steroidals. So neuropathic pain there's a whole.

Susanna Park: 15:02

I guess there are pharmacological therapies that are used, including things like duloxetine and other strategies. There are some trials for duloxetine demonstrating benefit for people with pain, so that 25% of people and CIPN. However, I think there's still a lot more work to do to identify, if there are, which pharmacological strategies are better for people. But certainly things like numbness and non-painful tingling or paresthesia. There's no pharmacological agent that has been demonstrated to improve those symptoms.

Susanna Park: 15:37

So I think to me pain in CIPN is really important. So we have a recently published study which demonstrates that the people who report pain so that 25% they typically have worse CIPN and they are more than two times as likely to report sleep disturbance. They are more than two times as likely to report exercise intolerance and they are more than three times as likely to report that they've tried to seek some treatment for their symptoms. So really, while it's not to the majority, that's a really important group to pay attention to, perhaps to refer them on to other pain management services or to try to implement different interventions to improve their quality of life, while recognizing that there are other people who have a lot of severe symptoms that maybe are not painful. I guess a lot of what we can do today to improve management for CIPN is based on grouping patients into these smaller groups so it's not a one-size-fits-all solution and trying to figure out what do we have that can support these patients today, such as physiotherapy or pain management approaches.

David Goldstein: 16:44

And that segues quite nicely, Bogda, into our current big project that you're a part of, which is a health implementation project to do exactly that to refine and triage and improved identification and therefore getting the right treatment for the right patient and therefore getting the right treatment for the right patient, right Precision medicine. So appropriate analgesics for that, 25% exercise physiology perhaps for a different group, sleep disorder for yet another group but really refining it for practice to help people like us, triage appropriately and get people help early, rather than now, where often it's really a long time, if ever, before they get some assistance. That's appropriate.

Bogda Koczwara: 17:36

So let's unpack that implementation challenge, and I would imagine it starts with the assessment no-transcript with any of these issues.

Susanna Park: 18:07

It's complex. I think it's unfair to say that it's because people don't want to assess CIPN. I think it's really having the right tools and being able to seamlessly integrate it into the clinical workflow, and this is probably something that is going to be different for different centers and even for different doctors, so it's got to really be something that is fit for purpose. We've recently completed a pilot implementation study at two centers and the way that the, which was just to implement a short CIPN screening questionnaire, the way it was implemented, even between two different hospitals in the same city, was completely different, and I think that's really informed our upcoming project, which is to work with implementation scientists, to really unpick this, because I think, perhaps foolishly we sort of thought this is a short questionnaire, we can just whack it into clinical practice. How hard can it be? Exactly?

Susanna Park: 19:05

I see you've been there too, bogda, but I guess what you need to think about is CIPN doesn't happen in isolation. These are people having ongoing cancer care. They've got a lot of consideration. There's other toxicities, there's other issues for them. It's very unreasonable to expect that CIPN should have a lengthy consultation time. It's not practical. So what we want is something that really integrates seamlessly, ideally also getting patients on board so that they can understand what symptoms would be of concern and can help guide those conversations with their oncologist and other clinical personnel, so that there's less confusion over what you should report and when and what the outcome might be.

David Goldstein: 19:48

So I just want to say it sounds good, Susanna talks the talk beautifully, but the problem is the implementation and that's why we're really pleased to have a very experienced implementation group who understands the physical and emotional barriers and time barriers within the system and that are really going to help us from their previous experience in other areas, including in general practice. Actually, with asthma for example, what are the effective ways and how do you engage health professionals in that and patients so that they facilitate it happening seamlessly?

Bogda Koczwara: 20:32

I think one of the challenges in assessing patients' needs is that the tools often are developed for one particular symptom and the tool in itself, in isolation, is not particularly complex or challenging. But when you think about it, where you have two minutes for CIPN, two minutes for cardiotoxicity, two minutes for fatigue, two minutes for anxiety and depression and two minutes for sexual needs and maybe something else financial toxicity, et cetera, et cetera before you know it the poor patient is faced with a battery of 20 minutes of tests, which might be a challenge. So I think that there is a need for us to figure out how we integrate that assessment, and perhaps this is where patient-reported outcomes come into it, because patients can prioritize what's most important to them.

Susanna Park: 21:26

Absolutely. I think that's really the way forward because patients, they know what affects them, they know what their top issues are. Certainly there are some problems developed which are trying to be more broad and pick out those kind of issues, but I guess one of the great things about working in this area has been the people you meet over the years working on other areas and seeing these commonalities, how we can work together, because these things don't happen in isolation.

Bogda Koczwara: 21:55

David, there is a view, and I don't know whether that reflects a reality or a myth in clinical practice. So I want to ask you as an oncologist that for some toxicities and CIPN could be one of them there might be a reluctance on the part of clinician to ask because they don't know how to fix CIPN if they discover it, and there might be a reluctance on a part of a patient to admit it because there's a fear that if CIPN is discovered, then the solution is to stop the drug that potentially could be beneficial in terms of treating the cancer. Is that something that is kind of imaginary or is that a real problem and if so, how would you manage it?

David Goldstein: 22:44

No, it's extremely real. When we did some work on sexual function about 10 or 15 years ago with a PhD student who's now a medical oncologist with an interest in survivorship, it became very clear that it was something that was almost never mentioned, and also that when it was actually asked, or when patients were asked independently, it was a problem that they also had reluctance to engage with practitioners about. So you are absolutely right. And, by the way, despite that research, I still don't do it as well as I should, and I've actually been involved with it, and so it's a problem. And it's about it's the question of implementation, it's about how to do it in a non-confronting, comfortable way, and that's true of chronic fatigue syndrome as much as it is sexual function, as much as it is neuropathy, and how to do it in a comfortable way is a challenge I certainly have not worked out yet, but I hope with CIPN we might start to think about that and, from that learn for perhaps more challenging topics, how to move in that direction as well.

Susanna Park: 23:56

I think from my perspective as a non-clinician, I guess people that are not clinicians might be surprised that even currently there's quite a high rate of dose reduction and premature stopping of chemotherapy due to neuropathy. So you know, in our breast cancer, early breast cancer apaclitaxel cohorts, you know, 30% have some modification to the apaclitaxel simply because of neuropathy. So this is already something which is impacting on intended cancer treatment. I guess, from my perspective as a scientist, what I would like is to be able to offer better information to the clinicians so that it can inform that decision making. Obviously it's not a black and white decision, but I think currently the information that clinicians have available to help them make these decisions, particularly in terms of how is this going to affect the patient, potentially longer term into that post-treatment phase, that's where we can really provide better information to inform those decisions I guess that are already happening on a daily basis.

David Goldstein: 25:02

And it sets the research agenda as well, led by patients as well as clinicians, because it says there's a chronic problem that's significant and in fact in our surveys it was the second most common problem survivors talked about in a 1,000-patient survey that we did, after fatigue. So it sets a research agenda and it also helps you start to think about well, what are the interventions. So you know the nirvana would be therapeutic prevention. No such luck for 20 years of trying, including several randomized trials. We did that we were certain was going to be the answer. And then for established CIP and what might work? Neuropathic drugs, enhanced nerve functioning, neuropathic drugs, enhanced nerve functioning or other interventions like exercise, and what sort and what dose of exercise. So thousands of questions come up for which clinical research is possible to answer them.

Bogda Koczwara: 26:06

Is there a particular need to design research in a particular way? You already mentioned input from patients. It seems to me that long-term outcome monitoring would be important because you would want to know how long it takes before CIPN resolves or not. What are the challenges of designing research or funding research in that area, of designing research or funding?

Susanna Park: 26:30

research in that area. Yeah, I mean, obviously long-term studies don't fit the funding model that we have, which is sort of discrete and shorter-term funding available for studies. But I think obviously it's critical to know what happens long-term, and that's something that's of great interest to patients and clinicians as well. I think, in terms of designing the studies, a really critical factor has been outcome measure selection. So there's already been lots and lots of trials of potentially neuroprotective strategies and we've often been let down by the outcome measures, which is not to say that these strategies would be successful, but we really need to set ourselves up in the best possible way to be able to demonstrate if something's effective or not. If you can't measure change in neuropathy accurately and sensitively, you obviously can't measure if an intervention is going to be successful. So in recent years there's been a lot more international collaborative work, sort of outlining what the key outcome measures are, what should be included, and it's typically thought to be a combination of different types of assessment tools. So obviously, increasingly patient-reported outcome measures are very important for some types of studies. Particularly if you're trying to demonstrate neuroprotection, then it's also optimal to include something more objective so you can see at what level is this intervention working? Is it preventing nerve damage? And there's a lot of new and emerging types of techniques that can help us measure, non-invasively, the development of axonal damage. I think another important element yet is including patients in this and ensuring that their perspective is included on what they think is important as outcome measures, because even if we use a patient-reported outcome measure, if we pick up a certain symptom as being the most important for them and we don't consult them, we may be off the mark in terms of reducing the impact.

Susanna Park: 28:26

I think also, David briefly mentioned exercise, and we and other groups have done a bit of work in this area, as you know. Obviously, the role of exercise in oncology care has taken off in in many, many different directions, but I think there is promising initial evidence that this has a great effect and even if this is not a specific effect to neuropathy, we have evidence that it's improving patients' function. It's improving patients' quality of life and I think this is also something, particularly if we're able to give people more specific guidelines on what they can do. That's really empowering for patients. We have a lot of patients come in from our studies that sort of feel that this is a problem that's not dealt with, that it's put in the too hard basket and then there's nothing that they or anyone can do to help them. They tend to get referred to the research because that's the only option available to them. So at least having something that they can practically manage I think has a really big impact on people's lives.

David Goldstein: 29:26

And Bogda. In partial response to your question about funding and type of funding, I think Susanna and I have to give credit to the Cancer Institute New South Wales because they do have these five-year programmatic. Here's a problem, here's a request for applications to look at this problem holistically and we were fortunate enough to get involved in such funding for five years. And we were fortunate enough to get involved in such funding for five years and that's why we have some of the questions that we now have, because we're able to do that, including long-term, five-year. Through those five years we were able to set up a cohort and follow them and get some idea of timing.

David Goldstein: 30:06

It's a bit sad that we couldn't maintain that cohort after our funding had gone, but in a way we sort of have a bit. But my important point is that it was multidisciplinary, it was epidemiology, it was mechanism, it was preclinical models and it was therapeutic interventions. We're able to cover all of that because of holistic, five-year sort of funding. The US has these things called SPOR grants, which are similar and longer term, and I think there's room for that to become more national. I think the Cancer Institute has really demonstrated in several different areas that this is a good idea that has its role.

Bogda Koczwara: 30:53

Because what you're describing now is a very rich program of research that has generated evidence in a lot of areas, but it's also identified some key priorities for future research. And I remember very well before that time, CIPN was one of those topics that nobody wanted to study because you didn't even know where to start and you had no obvious solutions to offer to patients. So it wasn't exactly a sort of a hip area to get into. And now it's so much more advanced and you've listed some key elements that are required to get to that point. I think there is lesson in it for other aspects of supportive care or cancer survivorship or both.

Susanna Park: 31:39

Absolutely, absolutely, and I think one of the key lessons, as David highlighted, is getting people from different professional backgrounds involved. That's been one of the really great joys of our program coming from different perspectives and then collecting large numbers of different types of people across whole fields of research and getting their perspective. How can we look at the health economic aspects of this problem? How can we look at the genetic aspects of this problem? There's lots of different areas that this can help us uncover how we can assist patients.

David Goldstein: 32:14

And having all those people in the same room, including affected patients as well, generates all sorts of new ideas. Pre-clinical scientists who say I didn't really understand what this meant for patients. Maybe we could design a different neurophysiology model in mice that would answer that question better. As Susanna said, it's a joy to every. What did we do? Three times a year we were all in one room together for a day and said where are we up to? Everybody would present their data and then discuss it in a group from all 360 degree perspective. It's really a wonderful thing.

Susanna Park: 33:02

And I think, despite all this great progress, there's a lot more to do and a lot we still don't know, and, in fact, chemotherapy-induced neurotoxicity was selected this year as one of the grand cancer challenges by the National Cancer Institute and Cancer Research UK. As saying, this is a tough challenge that requires multidisciplinary impact, many people to come together to still resolve this issue, and particularly in terms of designing something that could protect the axons from this damage.

Bogda Koczwara: 33:33

So what are the next steps for your research in CIPN?

Susanna Park: 33:37

I think there's, as I said, a lot more to do. Part of our work is now focuses on implementation. So how can we improve clinical practice? Now, as David mentioned, we've developed a clinical pathway designed for Australia so how we can improve screening and management of CIPN. We did a Delphi study with 70 multidisciplinary colleagues to get consensus on this pathway, and so part of our project is now working with implementation scientists for how we can implement that.

Susanna Park: 34:04

I think we're also trying to improve how we can identify patients at risk of this toxicity. So, despite all this research, the specificity of clinical risk factors is still quite low. So we know that broadly, people who are older, people who have higher BMI, people who have comorbidities are more at risk, but at an individual patient level, this information is really not sufficient for us to explain why one person gets a severe CIPA and another doesn't, and so we know that there are multiple contributors to this and we've done, as part of our program, some studies into a potential genetic risk and also looking at potential biomarkers of risk, so things like metabolism that might be able to explain the variation in outcomes between people. So an important area of our work is trying to get additional cohorts to validate some of these markers that we've found.

David Goldstein: 35:00

And we still continue in a small way to look for therapeutic interventions. We're in the middle of evaluating, possibly beginning at a phase one level, an entirely novel approach. So we try to maintain that kind of principle that we were funded to do for five years of looking at all of the aspects of this problem and seeing in a small way what contribution we can make and then through Susanna, who's very plugged in internationally, to make sure that we understand what other colleagues are doing and look for ways to collaborate.

Susanna Park: 35:44

I think the other element is looking at rehabilitation interventions, and so, while we also look for neuroprotective strategies so we've recently completed our exercise study, which we're currently analyzing, and one of our colleagues has got a recent grant to implement a new home-based exercise strategy, and that trial is also starting this year but I think the next step, I guess, of implementing this story about how exercise can benefit patients, is how can we put this information into the hands of all patients now. Obviously, research takes a long time for the outcomes to be generated, but I think for things like, you know, improving screening and for things like improving exercise rehabilitation, we need to be able to synthesize this evidence and provide it to patients today so that patients can feel empowered. There's things they can do that possibly might help them today. And this is really speaking to all the patients that have been enrolled in our exercise studies. This is the kind of thing that they say that they want to make this information available to people so people know what sort of strategies they could use.

Bogda Koczwara: 36:53

So this is such a nice example of the richness of the field within which you operate, from understanding the mechanisms and epidemiology to developing interventions, to implementing evidence, to engaging with patients, delivering multidisciplinary care, being timely in delivering that care. These are really important building blocks for CIPN as a problem, but also could be potentially transferable to other conditions. How can we sort of package that knowledge? How can we take it to other conditions? David, you already referred to fatigue, but I would see analogies to frailty or cognitive dysfunction or other symptoms that patients can experience. How can we take this knowledge and adapt it to other conditions? Any advice from you?

David Goldstein: 37:45

So serendipity plays a huge role. Serendipity plays a huge role. So finding colleagues in other areas who want to work with you is the first step and the most important one. And then something I'm fortunate to have two superb collaborators that challenge me and channel me to be productive, because they're so much smarter than I am. So Susanna is one and you've heard today why but Phoebe Phillips, in pancreas cancer biology, is the other. So the first step I had to learn in both cases in neurology and in basic cell biology was a new language, and learning each other's language and learning how to work with one another is the first step. And then you need to multiply it by all the other disciplines you want to do that with is a very important part of successfully moving forward. Susanna and I like to joke that we don't need to actually speak anymore because we already know what the other person's response is going to be and what our next planned pathway going forward should be. But that takes many years.

David Goldstein: 39:10

But it doesn't take that many years to forge the initial collaboration. You both have to be excited, or all of you have to be excited, about the problem. There has to be something in it for everyone. There has to be a gain, and I don't just mean financial, I mean intellectually, in the collaboration, because you all get on together. There are a million reasons for patience. It's about somebody finally wanting to get a solution to what matters to me, for example. And then you have to be creative and you have to be willing to put your shoulder to the wheel, sometimes with no money, and you have to be willing to accept that it won't always work. You have to be willing to accept that it won't always work. You will get knocked back and the grants will be hard to get, and sometimes you have to take a step back to take two steps forward. They're kind of motherhood statements, but they really are true and they reflect, in the two areas that I've particularly been collaborating with, to find collaborators, how you get to a reasonable place.

Susanna Park: 40:13

Yeah, I think I would also reiterate the joy of collaboration. I think you know I've been so lucky to have so many wonderful clinical collaborators as well. Obviously, everyone is really busy. There's a lot of load that you have on your plate but so many people you know that have given their time and knowledge to this topic to, I guess, get it to the point we have today.

Susanna Park: 40:34

I still remember the first time I ever met David Goldstein and I was introduced as a potential prospective PhD student looking at CIPN, and David lent in and said, great, when can you start? And we sort of took off from that point. So I think it's really that enthusiasm from clinicians like David for wanting to change something for their patients and wanting to build collaborations and to really bring people together that has enabled this research in Australia. I think there's a lot more we can do, combining across different areas of supportive care, research and initiatives that you've created, Bogda, I've really strengthened this across the whole country and internationally. So, yeah, it's very exciting, I guess, to be part of a dynamic research community like this.

Bogda Koczwara: 41:23

It's lovely to see that, at the end of the day, however your neurons travel, it's all very, very human, pursued both for the people that are affected by CIPN and by the people who are your colleagues, that you work with, and it is the human quality of curiosity and collaboration and sort of goodwill what really builds both research and practice. So the final question for me, for both of you, just bringing CIPN into the broader field of supportive care, for you as a researcher and clinician, why does supportive care matter?

Susanna Park: 42:01

I'm happy to start this one. I really think that the distinction between supportive care and other forms of cancer care is false. Supportive care is care, it's an integral part of cancer care and it shouldn't really be separated into a separate basket. I think maybe it needs a rebrand. I guess the philosophy of person-centric care. This is something that applies to all forms of care. It's important to people, it's important to people's lives. Yeah, that's my two cents.

David Goldstein: 42:33

It's an integral part of curative treatment, and palliative treatment is support, and support covers everything. It covers the drugs, it covers the emotional reaction to the initial diagnosis, it covers understanding the problems that arise during and the problems that arise afterwards, and it's a holistic overview of how to make the patient the center of the activity. But also remember that that means it's a whole person. It's not just the blood vessel in which you're injecting the drug or delivering the radiation, it's actually the whole person. If you think of it like that, then, as Susanna said, supportive care is not supportive care, it's just part of care.

Bogda Koczwara: 43:26

Couldn't have finished on the better note. Thank you very much, Susanna and David. You've given me so much insights into not just what we can do about CIPN, but what truly is the appropriate research and care that really, really makes a difference. So thank you for taking the time to join me today.

David Goldstein: 43:45

A pleasure.

Susanna Park: 43:46

Thank you so much, Bogda. It's been a real pleasure.

Bogda Koczwara: 43:49

That is all for Supportive Care Matters, a podcast created by me, Bogda Koczwara, for researchers, clinicians, policymakers and patients passionate about improving the lives of people affected by cancer, thanks to Mark Tie, who composed the original music, and the Oncology Network, our producers. For show notes, go to www. oncologynews. com. au. Subscribe to this podcast at your favourite podcast provider and rate us. It will help others find us.