WEBVTT

00:00:07.000 --> 00:00:14.000
Host: Welcome along to the third in the Ipsen Educational series, Renal Tumour Talk, Shaping The Future of Kidney Care.

00:00:14.000 --> 00:00:20.000
Host: This is a channel for sharing best practice in the management of advanced renal cell carcinoma or aRCC.

00:00:20.000 --> 00:00:23.000
Host: And in particular, it has a focus on the MDT.

00:00:24.000 --> 00:00:31.000
Host: And in this episode we are going to explore the relationship between the dermatologist and the oncologist as part of that team.

00:00:32.000 --> 00:00:49.000
Host: I'm joined in this episode by Dr. Anna Olsson-Brown, Consultant in medical oncology, skin, IO, and acute oncology at University Hospital Sussex. Also an honorary senior lecturer at the University of Liverpool and Immunotherapy toxicity Llead at Clatterbridge Cancer Care Centre.

00:00:50.000 --> 00:00:58.000
Host: I'm also joined by Dr. Elaine Hindle, consultant dermatologist and skin cancer lead at St. Helens and Knowsley Teaching Hospital NHS Trust.

00:00:59.000 --> 00:01:06.000
Host: And Elaine was the chair of specialist skin MDT for Merseyside and Cheshire until recently.

00:01:06.000 --> 00:01:18.000
Host: Now today we're going to focus mainly on the skin side effects that patients under immune checkpoint inhibitors and tyrosine kinase inhibitors, TKIs and CPIs, combination treatment might encounter.

00:01:19.000 --> 00:01:21.000
Host: So without further ado, let's get into it.

00:01:21.000 --> 00:01:33.000
Host: What are the typical dermatological skin side effects you normally see in your clinical practice with aRCC patients treated with IO and TKI treatments? Anna?

00:01:34.000 --> 00:01:44.000
Anna: With immunotherapy, you have a whole spectrum of different side effects that can affect essentially any organ or tissue and they can cause this sort of non-specific inflammation that look a bit like other conditions
but aren't exactly the same.

00:01:45.000 --> 00:01:57.000
Anna: And we know when we look at the timing of those different side effects and when they happen post-starting treatment, that skin toxicity, skin rashes are an earlier toxicity, they tend to happen before some of the other side effects that we see.

00:01:58.000 --> 00:02:05.000
Anna: I think the other thing that is really worth being aware of is with TKIs you don't tend to get a late manifestation of skin toxicity. If you're going to get a skin toxicity, you tend to get it relatively early in treatment.

00:02:10.000 --> 00:02:22.000
Anna: And generally speaking, what we say with TKIs is that the first three months of treatment is when your side effects are the most notable and then often things settle down partly because the body kind of becomes used to the blocking of a particular pathway. And so that, it doesn't mean the side effects go away, but it means they are, generally speaking, more tolerated.

00:02:28.000 --> 00:02:33.000
Host: Which skin side effects kind of overlap between TKI and immunotherapy?

00:02:34.000 --> 00:02:37.000
Anna: To understand this, you have to take a step back and think about the different mechanisms of the different drugs.

00:02:38.000 --> 00:02:51.000
Anna: Immunotherapies are drugs that essentially we put into the body that activate the person's own immune system. Quite often we'll see inflammatory type side effects, so they'll cause an inflammatory immune reaction within the skin.

00:02:52.000 --> 00:03:03.000
Anna: If we compare that to TKIs. TKIs are based on blocking certain proteins that we know certain patients' cancers upregulate to make the cancer survive and grow. But what we do know is those proteins are also not specific to the cancer. So if we block that protein in the cancer, we can also block it in other structures of which the skin is one.

00:03:13.000 --> 00:03:19.000
Anna: We're seeing lots of different subtypes of skin rashes as a result of using immunotherapies and TKIs.

00:03:20.000 --> 00:03:25.000
Anna: Blistering rashes particularly is something we don't tend to see with TKIs but we do very much see with immunotherapy. But the maculopapular rashes we can see with both.

00:03:30.000 --> 00:03:40.000
Anna: We can see things like lichenoid reactions tend to be more with immunotherapy than they are with TKI, but you can see them with both. So, there are some overlapping types of rash.

00:03:41.000 --> 00:03:51.000
Anna: So I think the overlap they do, it's like a Venn diagram, so there's TKI type rashes that we see in the distribution and then there is immunotherapy more broad conditions.

00:03:51.000 --> 00:03:58.000
Anna: And then there is an overlap where we can see rashes that look similar or have a similar onset and we have to do a bit more work to try and pull those apart.

00:03:59.800 --> 00:04:05.000
Elaine, what are the common dermatological skin side effects you normally see in your clinical practice?

00:04:06.000 --> 00:04:12.000
Elaine: The TKI rashes, it's usually a de novo thing and not really related to your previous skin history.

00:04:13.000 --> 00:04:24.000
Elaine: But for IO rashes I think very much so if you've got a history of previous eczema or psoriasis, it's quite common to have exacerbation of it because these skin rashes are immune-based and T cell-based.

00:04:25.000 --> 00:04:31.000
Elaine: And therefore if you have your immune activity increased with immunotherapy, then you can get an increase in your preexisting skin disease.

00:04:32.000 --> 00:04:43.000
Elaine: And that's helpful for us to know I think both before you start treatment, particularly if you have an undiagnosed rash or one that we might want to optimise the treatment of before immunotherapy or just to establish what's going on.

00:04:43.000 --> 00:04:48.000
Elaine: Let's be aware that you may have some more symptoms from it that we need to manage when you're on immunotherapy.

00:04:49.000 --> 00:04:57.000
Host: So, it's interesting the skin side effects that overlap between TKI and immunotherapy. What tips have you got for differentiating the two?

00:04:58.000 --> 00:05:03.000
Elaine: TKI rashes are very typical and predictable in their pattern and they tend to happen quite early as well.

00:05:04.000 --> 00:05:13.000
Elaine: It's often maybe cycle one a little bit, cycle two a bit more of it, but in a predictable pattern to the extent that I could tell patients what's likely to happen next in the evolution of their rash.

00:05:14.000 --> 00:05:21.000
Elaine: So it would start from the head, from the scalp and go to the face, the chest, and over time spread distally and become drier and more like eczema.

00:05:22.000 --> 00:05:32.000
Elaine: So you do need a change of treatment usually as they progress, but it's very typical in appearance on the face and the scalp, sort of an acne form eruption but not actually true acne.

00:05:33.000 --> 00:05:43.000
Elaine: So we don't treat it in the same way. So you won't see things like blackheads but you will see pimples and pustules, say, scalp, face, the V of the chest, and then spreading but dissipating as it goes distally.

00:05:44.000 --> 00:05:48.000
Elaine: And it is sensitive to the light and that is probably why you have it more in that pattern.

00:05:49.000 --> 00:05:54.000
Elaine: So we can predict what's going to happen, but then it does make it easier for us to know that this is a TKI rash.

00:05:55.000 --> 00:06:01.000
Elaine: However, then over time with the immunotherapy, as you're becoming more eczematous, you might then begin to get immunotherapy side effects too.

00:06:02.000 --> 00:06:09.000
Elaine: And they are diverse because you can get almost any kind of skin rash with immunotherapy, but we tend to see particular groups of rashes.

00:06:10.000 --> 00:06:18.000
Anna: I think it's the distribution and that sort of wave-like manifestation that we see from TKIs is the bit that probably stands it apart from an immunotherapy perspective.

00:06:19.000 --> 00:06:24.000
Anna: It can appear anywhere across any amount of the person's skin distribution.

00:06:25.000 --> 00:06:29.000
Anna: With an immunotherapy rash, normally it happens in a much more visible present way.

00:06:30.000 --> 00:06:34.000
Anna: So somebody will wake up one day and they'll have a very notable rash which wasn't there yesterday.

00:06:35.000 --> 00:06:40.000
Elaine: And it's not uncommon as well with the immunotherapy rashes to have one type initially and then some months later to develop another type.

00:06:41.000 --> 00:06:47.000
Host: We've talked about rashes being quite prevalent as an adverse event. How do you manage those in your clinical practice?

00:06:48.000 --> 00:06:53.000
Elaine: A lot of the rashes are a low-grade rash that can be managed by topical treatments.

00:06:54.000 --> 00:07:00.000
Elaine: And that's really a good role for oncology CNSs and it's lot about patient education and support.

00:07:00.000 --> 00:07:14.000
Elaine: And then I think also just recognising these sort of red flags for serious drug eruption. And we tend to split them as dermatologists into inflammatory which is a sort of eczema, psoriasis, lichenoid rashes, so that's quite common.

00:07:15.000 --> 00:07:22.000
Elaine: The blistering rashes and then what we call SCARs, which sounds a bit like scary how you remember it, but it’s a severe cutaneous adverse reaction.

00:07:22.000 --> 00:07:34.000
Elaine: So I think you need to actually know whether they’re blistering, and they mean big sort of water blisters. So patients would generally be able to say yes or no to that. And that's a sign of Immunobullous disease, which is going to require dermatology input.

00:07:34.000 --> 00:07:48.000
Elaine: Erythroderma where they are red all over and be unwell. So the serious ones, I mean Stevens-Johnsons and the more severe TEN are generally quite evident because of the mucosal involvements and then the dramatic skin peeling.

00:07:49.000 --> 00:08:00.000
Elaine: So, it's not particularly sort of subtle presentation but it does move quickly. So known high risk features like targetoid lesions on the palms and mucosal involvements. And it's something that's moving quickly that we need to know about.

00:08:01.000 --> 00:08:10.000
Anna: And I think those questions are actually relatively easy to ask. So I think part of this is about supporting our oncology teams for when patients ring with rashes to ask those specific questions.

00:08:11.000 --> 00:08:24.000
Anna: There are a series of questions that you can get quite a long way to triaging and understanding how quickly you need to see them by asking the right set of questions, and those questions will be delivered by our oncology team. So, it's that joint understanding of what it is that we need to ask.

00:08:25.000 --> 00:08:34.000
Elaine: Particularly things like DRESS because the rash can look, well, morbilliform or sort of measles-like. So the rash in itself is not particularly specific, although it often looks fairly dramatic, but the patients are ill.

00:08:35.000 --> 00:08:52.000
Elaine: So, they are ill and they often have a fever and they can have liver function abnormalities, which doesn't help us because you can get that with immunotherapy anyway. But they can have abnormalities in their full blood counts with eosinophilia and the fever, the feeling unwell, the facial swelling, the lymphadenopathy. So they're all things we need to know about as well.

00:08:53.000 --> 00:8:57.000
Anna: I think a person with a skin rash who feels unwell is inherently a red flag in its own right.

00:08:57.000 --> 00:09:13.000
Anna: We also can dose reduce our TKI so we can, we know that there's a dose effect between the drug that we give and the protein that's blocked, and there is a sweet spot for each person between the dose that gives the benefit from the cancer and the dose that gives side effects.

00:09:14.000 --> 00:09:24.000
Anna: And we can dose reduce and change the dose that we're giving within the license of the treatment to try and get that balance right for the patient to get the benefit with and reduce down the toxicity as much as possible.

00:09:25.000 --> 00:09:31.000
Anna: With immunotherapies, that's not the case. So, we don't dose reduce them because we don't see a predictable dose toxicity response.

00:09:32.000 --> 00:09:52.000
Anna: And whilst the majority of skin toxicity happens early in treatment, we absolutely can see toxicity that happens later on during treatment. And actually because we are essentially reformatting the immune system's own internal regulation, we know that even after you've stopped immunotherapy you can develop side effects, one of which is skin toxicity.

00:09:53.000 --> 00:10:01.000
Anna: So, whilst the toxicity with TKI is not necessarily particularly pleasant but actually very predictable, the toxicity with immunotherapy is much less predictable.

00:10:02.000 --> 00:10:09.000
Anna: And so, you can sometimes have it early, you can sometimes have it late, you can sometimes have one type of skin toxicity, you can sometimes have more than one type of skin toxicity.

00:10:10.000 --> 00:10:23.000
Anna: So it's much less predictable and you always have to have a much more open mind if you've got a patient who's receiving immunotherapy as to whether even if they were fine for the first six months of treatment, if they've developed a change, then actually it could still be related to their immunotherapy.

00:10:24.000 --> 00:10:30.000
Anna: So you tend to find the majority of people with toxicity, particularly skin toxicity, that you will be able to treat it and essentially get rid of it.

00:10:31.000 --> 00:10:44.000
Anna: You can resolve it but there is a small number of people who for whatever reason, possibly undiagnosed preexisting conditions, possibly just the degree or severity of the response that they need long-term management.

00:10:44.000 --> 00:10:48.000
Anna: And that’s why it’s really important. Oncologists we are not the right people to be doing that.

00:10:49.000 --> 00:10:53.000
Anna: We need specialist support for and that's the absolutely appropriate thing to do.

00:10:53.000 --> 00:11:01.000
Host: From your perspective as an oncologist, when do you think, "Hmm, actually, I ought to be bringing in the dermatologist at this stage," what's that trigger?

00:11:02.000 --> 00:11:18.000
Anna: So, I think this depends a little bit on the experience of the oncologist and the oncology team in terms of managing rashes. And we know that managing the TKI itself often helps with some very simple supportive management. So it's only if they're not responding to that, that we'll reach out.

00:11:19.000 --> 00:11:29.000
Anna: With an immunotherapy rash, I think actually getting dermatology teams involved as early as possible is useful even if it's in an advisory capacity because we want to make sure that we're managing things appropriately.

00:11:29.000 --> 00:11:46.000
Elaine: I would agree. I think the TKI rashes when we first started seeing them we would see a lot but they were quite easy to protocolize care for them. So I don't often see the more straightforward ones because the oncology teams are generally used to sort of managing things. But I will see the ones that are failing to respond to standard treatment and dose reduction.

00:11:46.000 --> 00:11:54.000
Elaine: I think sooner is better because if they need rapid treatment it's better sooner. And conversely, if it isn't that bad, there's still a lot of gains with just basic good skincare.

00:11:55.000 --> 00:12:04.000
Elaine: I think sometimes if they have forget the basics of good skincare. So even in patients who've had quite a long time, I think there's sometimes a sort of a drift to forget to use those things.

00:12:04.000 --> 00:12:18.000
Elaine: So every appointment we have to remind them about things like using a soap-free wash, using the moisturisers, using topical steroids, all those things we know are going to help and are probably going to reduce the amount of other immunosuppression or treatment we might need.

00:12:19.000 --> 00:12:31.000
Elaine: And I think if you explain that your skin is going to be more inflamed and sensitive, so if you use a soap substitute, some of which are prescribable, if they don't like what we give them, you can buy them over the counter.

00:12:31.000 --> 00:12:40.000
Elaine: So you just want something that is soap-free and fragrance-free. So what we say, if it bubbles it's trouble. So we need to explain that it's not going to foam up.

00:12:40.000 --> 00:12:45.000
Elaine: So patients say, "Well, I don't like it, it doesn't foam up." so we want that, we don't want any bubbles.

00:12:45.000 --> 00:12:48.000
Elaine: So we don't kind of really mind what they're using as long as with those caveats.

00:12:49.000 --> 00:12:56.000
Elaine: And then a moisturiser, so you need to put some moisturiser back in. There are a range of them, and the best one generally is the one they like using because they'll use it.

00:12:56.000 --> 00:13:07.000
Elaine: However, I think the TKI rash, you don't want anything too greasy on the facial skin. So I would go for a light cream-based emollient and as their skin becomes drier you might need a more ointment-based one.

00:13:08.000 --> 00:13:16.000
Anna: I think the other thing is about the frequency of things like moisturization. So, different people, different patients will consider a different amount of moisturization to be an actual thing.

00:13:17.000 --> 00:13:24.000
Anna: So some people sort of put some moisturiser once every week and will tell you that they're moisturising regularly and others will put it on four times a day and they probably are moisturising regularly.

00:13:25.000 --> 00:13:38.000
Anna: So understanding how they're using their preventative treatments as well as what they are using I think is actually really important because otherwise you get a slightly skewed view of what's going on so you can't necessarily know what the next step is in terms of treating the problem.

00:13:38.000 --> 00:13:50.000
Elaine: And for the immunotherapy rashes, yeah, I think it depends. I think if you have a brief grade one rash that's managed with topical treatments, that's fine. It is important to remember though to prescribe enough of your topical treatments.

00:13:51.000 --> 00:14:05.000
Elaine: It's the ones that are failing to respond to initial treatment and we need to perhaps firm down what the diagnosis is from an immunotherapy rash because the range is broad and we have other treatment options outside of corticosteroid immunosuppression.

00:14:05.000 --> 00:14:14.000
Elaine: So if they're not responding to that or if it's not a particularly acute thing, we need to look to see specifically what the rash is and then that often will entail a biopsy.

00:14:15.000 --> 00:14:18.000
Elaine: And how quickly that needs to happen depends on some of the features of the rash.

00:14:18.000 --> 00:14:35.000
Elaine: We talk about high-risk features which we would want our patients to know about, to know to report, but also our oncology teams, and particularly they say if you want to get your dermatologist's interest, you ring them up and tell them they've got a blistering rash or they've got mucosal involvement, that's a really important sign.

00:14:35.000 --> 00:14:42.000
Elaine: So, the lips, the mouth. You need to ask your patients about genital ulceration because they generally won't volunteer it and the eyes as well.

00:14:43.000 --> 00:14:52.000
Elaine: If they're red all over. Now that doesn't mean little red spots all over, it means red all over sort of confluently bright red, which is what we call erythroderma.

00:14:52.000 --> 00:15:01.000
Elaine: And that's significant because you lose your skin function, part of which is to keep your heat and your fluid in so you become dehydrated and have renal failure.

00:15:01.000 --> 00:15:13.000
Elaine: So, these are sort of serious things and if your skin is peeling off, obviously that's something we need to know about because they're going to indicate a higher grade serious drug rash that's going to need more active treatment.

00:15:13.000 --> 00:15:22.000
Elaine: But other than that, I think biopsy is important because we do have other treatments that are specific to us, phototherapy units that we'd have access to other classes of drugs.

00:15:23.000 --> 00:15:28.000
Host: Are there any specific treatments for IO-induced rashes or TKI-induced rashes?

00:15:29.000 --> 00:15:36.000
Elaine: Well, both the good skincare is important and for the TKI rashes, it's the sun protection is important too.

00:15:37.000 --> 00:15:45.000
Elaine: If leaving aside dose reductions and interruptions, we'd look at treating more of an anti-inflammatory basis rather than immunosuppression.

00:15:45.000 --> 00:15:52.000
Elaine: So we'd usually looking at tetracycline and antibiotic for at least six weeks and we say to the patients, it's not like taking it for a week for a chest infection.

00:15:52.000 --> 00:16:01.000
Elaine: We're not particularly treating the infection, the tetracycline group have an anti-inflammatory effect and that's what helps. However, you can get secondary infection in a TKI rash as well.

00:16:02.000 --> 00:16:13.000
Elaine: They do all look infected because they're all studded with pustules but most of the time it's a sterile inflammatory thing but it is worth taking a swab, particularly if they don't respond to your initial treatment and we might need different antibiotics at that stage.

00:16:13.000 --> 00:16:20.000
Elaine: But we're looking at immunosuppression. So, you're kind of anti-inflammatory and photoprotection with TKI and immunosuppression with immunotherapy.

00:16:21.000 --> 00:16:27.000
Anna: In terms of the types of immunosuppression, so we do use and our protocols say to use topical steroids as a first step.

00:16:28.000 --> 00:16:39.000
Anna: And one of the good things about working with our dermatology team so closely is that we don't overtreat patients with immunosuppression. We get the right balance but I think it's difficult because there isn't one type of immunotherapy rash.

00:16:40.000 --> 00:16:51.000
Anna: Whereas a TKI rash you can go, that's a TKI rash. With an immunotherapy rash, you can't really go, that's an immunotherapy rash. You can go, there's a skin condition one of many probably caused by the underlying immune activation.

00:16:52.000 --> 00:17:06.000
Anna: But the reason we use steroids and another immunosuppressants in that case is because we're trying to give the immune system an external signal that says you're being overactive in the wrong place. Please stop being like that. And the only way to do that is to give an external immunosuppressive signal.

00:17:07.000 --> 00:17:12.000
Anna: There's a lot of patients that get an immunotherapy rash that responds really very quickly to steroids and that's absolutely great.

00:17:12.000 --> 00:17:17.000
Anna: We do know that we need to wean the steroids rather than immediately stop them, otherwise they tend to get a re-flare.

00:17:17.000 --> 00:17:28.000
Anna: But there are a small group of patients, but nevertheless a notable group who don't necessarily
respond to steroids alone. And at that point, I can't overplay the importance of having a conversation with our dermatology colleagues.

00:17:29.000 --> 00:17:35.000
Anna: So that conversation and which treatment we should be using and which treatment we should
try is really important.

00:17:35.000 --> 00:17:49.000
Anna: It's not just referral to a dermatologist but it's actually the joint working between oncology and dermatology, understanding how the drugs we give have caused this and what we might use to try and push it back in line with what you were doing standard dermatology conditions.

00:17:49.000 --> 00:18:02.000
Anna: So actually the conversations, and certainly Elaine and I have managed a number of patients together, who we've worked together to work out what the best next treatment would be based on the fact that we're working together and have the understanding of each other's part of the puzzle.

00:18:02.000 --> 00:18:09.000
Host: Are there any preventative measures that can reduce the risk of skin side effects or prevent them proactively?

00:18:10.000 --> 00:18:22.000
Elaine: I think in terms of immunotherapy, I would want to know whether you had a previous history of skin disease and it generally wouldn't rule it out but we would talk about optimising your management of your existing skin condition.

00:18:23.000 --> 00:18:34.000
Elaine: So for example lupus, that we might want to institute some medical management of that to reduce the risk of flare. So I think it's important to know your prior skin history and whether we need to do anything more active.

00:18:34.000 --> 00:18:44.000
Elaine: But from an oncology team point of view, I think particularly with TKIs it's very common that you are going to get some skin irritation and that's when we'll be talking about, good skincare and your soap substitutes and your moisturisers.

00:18:45.000 --> 00:18:50.000
Elaine: But yeah, I'd just be starting with good skincare, photo-protection's probably reasonable for TKI rashes, so that's a simple thing to do.

00:18:51.000 --> 00:19:03.000
Host: And does lifestyle play a part in this? Because you're talking about your IO-TKI treatment and we're looking at the impact on skin, but what impact does lifestyle have?

00:19:04.000 --> 00:19:13.000
Elaine: So stress is important, we know in so many conditions. And of course with your skin, it's quite immediately apparent if you're stressed because you can see your skin reacting quite quickly.

00:19:13.000 --> 00:19:22.000
Elaine: We know your cortisol goes up, your inflammatory cytokines are up, everything is more active. So, stress management, in as far as it's possible will help.

00:19:23.000 --> 00:19:36.000
Elaine: Mindfulness, walking, some exercise, eating well is important. So, having a good diet is going to
support your skin health in general, antioxidants, so fruits and vegetables, healthy fats in nuts and fish.

00:19:37.000 --> 00:19:48.000
Elaine: But also your microbiome is really important for your response to immunotherapy, we know that. And your tumour response too. So as well as all those healthy eating principles I've mentioned, you want to have diversity in your diets.

00:19:49.000 --> 00:19:59.000
Elaine: But also not smoking. So, we know it doesn't help with your immunotherapy response but it doesn't help with your skin health either. And we found recently that pollution actually increases the effect of UV on your skin.

00:19:59.000 --> 00:20:08.000
Elaine: So you can't avoid some of the pollution like diesel fumes, for example. But smoking is its own form of localised pollution, so that's another reason why it's important not to smoke.

00:20:09.000 --> 00:20:18.000
Anna: All patients will get a health needs assessment done within the beginning of their treatment and quite often patients will then have a subsequent healthcare needs assessment either during or at the end of their treatment.

00:20:19.000 --> 00:20:33.000
Anna: So that absolutely really is helpful and it's normally done by our clinical specialists or support teams. But our patients are often trying really hard to improve things. So it's just getting that balance of conversation and communication right for them because normally it's trying to be a move in the right direction.

00:20:34.000 --> 00:20:51.000
Anna: In terms of the things that patients can do, one of the things that we need to do more commonly in oncology is to essentially have that laid out and some centres have got that sort of things that you can do to help sort of help promote how well you are during treatment with all of those things on it.

00:20:51.000 --> 00:21:02.000
Anna: So there's quite a lot of work going on about the benefits of exercise around the commencement of cancer therapy as well as surgery. There's a lot of conversation about diet and exercise and wellbeing.

00:21:03.000 --> 00:21:13.000
Anna: And I think alongside that, the recommendations of keeping your skin as healthy as possible. So, I think it's just about giving patients the information. They need some digestion time because there's an awful lot going on at the beginning of this journey.

00:21:14.000 --> 00:21:25.000
Anna: So I think it's about breaking it down but one of the things about recommendations about what you can do to just sort of prevent and promote, it gives a degree of control back because it's something people are actively doing to try and keep themselves healthy through treatments.

00:21:26.000 --> 00:21:31.000
Host: What role does stress management play in minimising skin adverse events?

00:21:32.000 --> 00:21:45.000
Anna: Encouraging people to be able to talk about the elements of their stress and acknowledging that it's normal to be stressed at this point. This is a very stressful period of time but there is multiple ways and multiple support mechanisms and people who feel supported don't generally feel stressed.

00:21:46.000 --> 00:21:53.000
Anna: So it's about us putting that scaffolding around them. But I do think a big part of it is acknowledging that this is a very stressful time.

00:21:54.000 --> 00:22:02.000
Anna: The other thing is once you're on treatment, your stress levels, generally speaking, tend to improve and there is that big fear of the unknown at the beginning of treatment.

00:22:03.000 --> 00:22:09.000
Anna: You're worried about what's going to happen with your cancer, you're worried about what's going to happen with your treatment and it all feels very overwhelming.

00:22:09.000 --> 00:22:23.000
Anna: So that acknowledgement and that is very normal reaction that it will start feeling better when you get into the rhythm of things where you need to go for your treatment, what you need to have done before you have your treatment, why you are having the blood test, what they might show. All of those things are quite important.

00:22:23.000 --> 00:22:34.000
Anna: And we tend to bring into that the unpredictability of the immunotherapy side of things in terms of side effects because if people don't know that they are unpredictable they will often feel like they've done something wrong.

00:22:35.000 --> 00:22:42.000
Anna: So people will often say to me, "I was doing really well, I was managing treatment brilliantly
and then suddenly out of nowhere this significant thing happened and I don't know what I did wrong."

00:22:42.000 --> 00:22:52.000
Anna: So, understanding early that it's not something that they're going to do wrong, that actually it is very unpredictable and can happen at any time, helps diffuse that stress and make it more manageable when it happens.

00:22:53.000 --> 00:23:04.000
Anna: So, you can't avoid stress in this situation. It's incredibly challenging. But actually, understanding
the ebb and flow of it and how we might support people to get through it I think lowers it as much as possible.

00:23:04.000 --> 00:23:11.000
Host: How important is patient communication in terms of adverse events? What do you recommend is best practise?

00:23:12.000 --> 00:23:29.000
Anna: When we start somebody on treatment with both drugs, we spend an awful lot of time educating and discussing both the potential benefits of treatment, but also the potential side effects so that they understand the fact that these are driven by different things that we need to know about them.

00:23:30.000 --> 00:23:43.000
Anna: Because the other thing is that patients are often a little worried about reporting their side effects, particularly if it's something like a skin rash. Because they don't view it as particularly worrying in the first instance. It can become that after a period of time but they worry about us stopping their treatment forever.

00:23:44.000 --> 00:23:54.000
Anna: A lot of the conversation we have with them is about the fact that the earlier we know about a side effect, the quicker we can treat it, the easier it is to treat, and the more likely it is that we're going to be able to continue their treatment in some form or other.

00:23:55.000 --> 00:24:04.000
Anna: So we do that bit and then we also do the education about the types of side effects that we're seeing and also the potential that we might see them at any time point.

00:24:04.000 --> 00:24:20.000
Anna: From a patient perspective it's about the education about a change. So you're not asking them to identify what kind of skin problem they've got, what kind of skin rash or condition they've developed. It's more about the fact that they've had a change from where they were and
is that change persistent and is it getting worse?

00:24:21.000 --> 00:24:31.000
Anna: But actually because they tend to have a really good relationship and often regular touchpoints with their oncology team, it's just about them saying, "I've now got this and I didn't have it," or, "I've had this and it's been getting worse."

00:24:32.000 --> 00:24:43.000
Anna: Then the key is that the oncology teams then pick up and go, "That's possibly an issue and are you doing all of those preventative things?" And the education is about sort of registering that change and trying to do as much preventative things as possible.

00:24:44.000 --> 00:24:55.000
Anna: Some centres and we're trying to make this a more national thing, have got things like post-treatment alert cards. So the patient, once they finish their treatment, are given an alert card that says, "I've had immunotherapy and I could still get a side effect."

00:24:55.000 --> 00:25:01.000
Anna: So that they've got something a bit beneficial, a bit formal so that that conversation is easier to have.

00:25:02.000 --> 00:25:13.000
Anna: And a lot of places in the country will send letters to their primary care teams to say they've had a immunotherapy, they've had a TKI these are the side effects that we would expect and they may occur either later on in treatment or after treatment's finished.

00:25:14.000 --> 00:25:19.000
Anna: So that we are trying to expand that education at the point the patient started on treatment so that they know this is a possibility of what their journey might look like.

00:25:20.000 --> 00:25:33.000
Elaine: I think a copy written down of what is going where, and how often, and how much they should need. And then making sure that the GP has that too and to ask for that to go on the repeat prescription because they are going to run out before I see them again if they're using the right amounts.

00:25:34.000 --> 00:25:50.000
Elaine: But I think, yeah, copy of information and a contact number so they know if anything is wrong, this is my secretary's name, this is the number, and she manages the clinic directly. And they will bring up and they'll email pictures in and whether they go via us or the oncology just kind of team
just depends where they're at with their treatment journey.

00:25:51.000 --> 00:25:58.000
Anna: I think informing the patients that they will be looked after by their normal oncology team but they may also be supported by a toxicity team at some point in their journey is useful.

00:25:59.000 --> 00:26:07.000
Anna: If I see a patient in clinic and I have to prescribe five or six things, we will often write to them, but letters can take a long time. So my immunotherapy team will email them with a list of instructions for their medication.

00:26:08.000 --> 00:26:23.000
Anna: So I think it's about making sure that we've got the relevant information to give them at certain points and also reassuring them that if they have any questions, even if they've had to start a treatment, if they've then had the headspace to sit down with a cup of tea and read the information they were given three weeks ago before they started, it's never too late to ask questions.

00:26:24.000 --> 00:26:36.000
Anna: And actually if something comes up they didn't take on board the first time then actually to ring up. And if they need clarification over their medications again, certainly our teams expect to be asked those questions 'cause we know that it's really complicated.

00:26:37.000 --> 00:26:47.000
Anna: Sometimes patients really worry about contacting us and putting pressure on the service but actually I always say to them, "I've given lots of people treatment but I've never given you treatment before and I don't know how it's going to, I don't know how you're going to react to it. So if there's a problem or any questions we want to know."

00:26:48.000 --> 00:26:56.000
Elaine: They perhaps underestimate the effect on a patient's quality of life having a skin condition, particularly the itch and you can get itch alone.

00:26:57.000 --> 00:27:08.000
Elaine: Although I think often when you look, there is often some active skin disease there too and it is important to treat that and not just focus on the itch without treating any obvious skin condition. So, I think patients need to know to report it.

00:27:08.000 --> 00:27:12.000
Host: How do these skin side effects affect patient quality of life?

00:27:12.000 --> 00:27:23.000
Elaine: It's very distressing, particularly itch. It's a big symptom and you can't see it. So you can sometimes underestimate as a healthcare professional how much it's affecting your patients but you will itch more at night.

00:27:24.000 --> 00:27:31.000
Elaine: So that disruption to your sleep and perhaps the sleep of your partner and this is going on for days, weeks, months it is significant.

00:27:32.000 --> 00:27:40.000
Elaine: Also the visible side of having a skin eruption, particularly with TKI because it is all on the face and neck initially.

00:27:40.000 --> 00:27:50.000
Anna: So, when we talk about the side effects of treatment, we often break them down into symptomatic things and biochemical things and we know that we can cause both with our drug therapies.

00:27:50.000 --> 00:28:05.000
Anna: But the symptomatic things are the things that really interrupt quality of life and skin rash and itch are two of the two really big impactors in terms of quality of life. But actually in terms of the impact on the patient's life, I'd say it's one of the biggest impacts and as Elaine was saying, it can last for quite a long time.

00:28:06.000 --> 00:28:18.000
Anna: Also, patients with rashes and skin toxicities also tend to have quite a lot of fatigue. They tend to go together possibly because they don't sleep. And so, they get really quite tired and that has a massive impact on their quality of life.

00:28:19.000 --> 00:28:25.000
Anna: So, when we're assessing severity, we normally assess ability to do activities of daily living and how effective the skin is.

00:28:27.000 --> 00:28:40.000
Anna: But actually their quality of life scores I think are as important because that is the bit that they remember and that is the bit that impacts on whether they're able to gain the benefit of the efficacy of their treatment if they're having a really significant impact on their quality of life
from the side effects.

00:28:41.000 --> 00:28:49.000
Elaine: We do routinely measure it in dermatology and it's actually criteria for some of our access to some of our drugs, even outside of the oncology population but just in general.

00:28:49.000 --> 00:28:57.000
Elaine: So for psoriasis and eczema and urticaria, you have a physical score and we have a DLQI, so it's a dermatology-specific quality of life index.

00:28:58.000 --> 00:29:09.000
Elaine: And the two things are taken together because we know of the massive impact of the symptoms on patient's quality of life and we do take into account for decision making. And so, a lot of our drug access is controlled on those two parameters.

00:29:10.000 --> 00:29:20.000
Elaine: So we can sometimes have difficulty with things like itch and other drugs because the DLQI, the
quality of life index can be really high but there isn't much to see on the skin. So, that can affect some of our access to therapies.

00:29:21.000 --> 00:29:32.000
Anna: And I think oncologists are behind the time in that. So we know that we need to do quality of life assessments and we know using PROMs is really important but we're sort of saturated and not, it's really unclear as to what tool is best to use for our patient group.

00:29:33.000 --> 00:29:48.000
Anna: So, there are certain teams in the country that are doing regular quality of life assessment and our supportive oncology colleagues will do that, but we should be doing it more routinely. And I think again that's why working together is really useful because if we've got somebody with a skin toxicity using a dermatology score would be the right thing to do.

00:29:50.000 --> 00:30:00.000
Anna: If we have somebody with a joint problem, using a rheumatological score will probably be the right thing to do. But certainly we do assess it but not formally as commonly as we should I think.
And it's something we can certainly learn from our dermatology colleagues.

00:30:01.000 --> 00:30:11.000
Elaine: Well, you get quite focused on the second-line treatments and yeah, the other things, don't you?
And it's also the same thing with the topical treatments, isn't it, to remember still every appointment, "Are you using your topical treatments?"

00:30:12.000 --> 00:30:29.000
Elaine: And in terms of the IO patients, yeah, I have a small number of complex patients that are requiring second-line therapies. And by then I know them quite well because they will generally stay with me for the duration of their immunotherapy. And as we said, often the 12 to 18 months afterwards. So yeah, it's not high numbers but they are high complexity.

00:30:29.000 --> 00:30:37.000
Host: So, as we've got you both in the room, Elaine, what questions would you have for Anna as an oncologist?

00:30:37.000 --> 00:30:54.000
Elaine: My dermatology colleagues who don't manage a lot of these conditions in patients who are on immunotherapy often come up with some concern about the notion of immunosuppressing a patient who's having cancer treatment. So, how do you manage that and how do you sort of get people around the idea that this is what it means, this is what's required?

00:30:55.000 --> 00:31:09.000
Anna: It's interesting because historically, we know that people who have been on immunosuppression for a long time are at risk of developing new cancers because essentially we're taking away one of their internal defence mechanisms before they create a cancer.

00:31:09.000 --> 00:31:28.000
Anna: I think it's about understanding that this is a very different situation. So, we've essentially hyper activated their immune system. So we're immunosuppressing to try and restore that order as opposed to taking it from a normal sense of order and suppressing it further. So the risk of making a cancer advance in the short term it is negligible.

00:31:29.000 --> 00:31:37.000
Anna: I think the other thing is about understanding the duration of immunosuppression. So that historical experience comes from patients that have been on immunosuppression for a long time.

00:31:38.000 --> 00:31:49.000
Anna: Particularly with immunotherapy toxicity, we're looking at suppressing a very abnormal response. We're generally speaking using them for a short period of time. But you're right, it's
a case of reassuring.

00:31:50.000 --> 00:32:05.000
Anna: In a similar way that I often get asked for patients who have been on immunosuppression for an autoimmune disease that then come to me with a new cancer they will almost certainly flare with their autoimmune disease if I take them off what's controlling it before I give them something to make their immune system increase in its activity.

00:32:06.000 --> 00:32:09.000
Anna: So it's about the harmony, I think, between what we're trying to achieve with the immunosuppression.

00:32:10.000 --> 00:32:12.000
Elaine: Is there a decision or protocol about PCP?

00:32:13.000 --> 00:32:21.000
Anna: So, we know that if we immunosuppress people for a long period of time, that they are at more risk of PCP and other opportunistic infections.

00:32:22.000 --> 00:32:29.000
Anna: There is a challenge with PCP prophylaxis because we often use a drug that can cause quite a lot of drug-induced hypersensitivity, particularly skin rashes.

00:32:30.000 --> 00:32:43.000
Anna: We've done quite a lot of work now looking at whether you get hypersensitivity reactions to other medications that a patient is on and we know there is an increasing list of drugs that patients will have a increased reaction, often a skin reaction to when they're on a checkpoint inhibitor as well.

00:32:45.000 --> 00:32:56.000
Elaine: There often does seem to be another trigger for a reason for an acute drug rash when they've been on immunotherapy for a while. And sometimes it's just the nature of immunotherapy rashes but sometimes there does seem to be another precipitating agent.

00:32:57.000 --> 00:33:12.000
Elaine: So, given that really you need sometimes dermatology advice quite quickly, and I know our routine waiting time is nine to 12 months. It's helpful to have a relationship with a dermatologist who can give you timely advice. So, have you got any tips for how you might find one?

00:33:13.000 --> 00:33:23.000
Anna: So, I think there's a couple of ways. An interesting case is always a good place to start. So what I tend to find with my medical colleagues across different specialties is if you've had a joint case it sort of seems to stimulate the interest.

00:33:24.000 --> 00:33:39.000
Anna: Because underneath it all as doctors, I think we are inherently quite fascinated, quite interested in individuals. But obviously the pressure of service and capacity often overlays that. So if you've had a joint case, I think that's really helpful and often can trigger conversations. Quite a lot of the relations I have with my colleagues have built on that.

00:33:40.000 --> 00:33:57.000
Anna: Then actually having a conversation with your skin oncology colleagues and saying, "Who is your dermatologist and MDT? Who might we be able to start with?" And that might not necessarily be the person you end up forming the relationship with, but just knowing where to start on a name and a conversation is really helpful. And then they can either signpost to somebody who might have time and interest.

00:33:57.000 --> 00:34:10.000
Elaine: I think it is important to, train our colleagues and just the idea I think of supporting cancer patients through their journey. I think from a dermatology group, they can feel a little bit cautious about it, they don't want to make things worse.

00:34:11.000 --> 00:34:21.000
Elaine: And I think the patient can almost get lost a bit in the middle of that because they're worried about doing anything. But if you sort of understand the landscape and how best to manage it,
I think it really supports patient's quality of life to do that.

00:34:21.000 --> 00:34:26.000
Host: And Anna, what kind of questions would you have as an oncologist for the dermatology team?

00:34:26.000 --> 00:34:39.000
Anna: So if I was an oncologist who hadn't necessarily had a formed relationship yet with a dermatologist, what are the things that are the right questions to ask or the right conversations to be having to try and just start building that relationship, do you think?

00:34:40.000 --> 00:34:54.000
Elaine: I think asking about what the best way for rapid access opinion is. And it doesn't need to be
face-to-face necessarily, but I think, yeah, you need a contact number and an email and somebody who's willing to have a look at the literature.

00:34:55.000 --> 00:35:13.000
Elaine: And when we started there wasn't a lot in the guideline space beyond corticosteroids. We've had to sort of find our way with that. But now we have various international guidance and we have UK guidance coming out. So it's much easier I think to step into this field knowing that you've got supports for knowing the various stages of treatments.

00:35:13.000 --> 00:35:19.000
Anna: I think the UK guidance that's coming out will be really helpful 'cause it's co-written by oncology and dermatology.

00:35:19.000 --> 00:35:20.000
Elaine: It is, it is.

00:35:20.000 --> 00:35:37.000
Anna: I would really encourage any team to reach out to the oncology team on call and the organ-specific team on call because it's just getting that information early. They might not know the answer at the beginning because they might not have heard of it, but it starts those conversations off as early as possible and then working out where the patient's best looked after as well.

00:35:38.000 --> 00:35:49.000
Anna: Because I think that depends very much on the depth of their symptoms and what's going on. So, there are so many different variables that having those conversations nice and early I think is really, really helpful and really important.

00:35:50.000 --> 00:36:00.000
Anna: Part of my job then becomes coordinating the conversations with the different specialties to make sure that we can burden the patient in the most limited way but make sure that we're getting the best management for them.

00:36:00.000 --> 00:36:09.000
Host: Thank you both very much. That's been absolutely fascinating. For those watching, if you had to summarise perhaps your top three tips, what would they be?

00:36:10.000 --> 00:36:26.000
Elaine: I think mine would be, first of all, the importance of the good basic skincare that we talked about.
The soap substitutes, finding a moisturiser that you like, using your topical steroid if that's what you've been given, and knowing when to contact us.

00:36:27.000 --> 00:36:51.000
Elaine: And then for the oncology viewers, I would say remember the red flag signs. So mucosal involvement, blistering red all over, skin's falling off for patients unwell. They are things to know about. And my third one would be finding out who your urgent contact is in dermatology in your area and foster a relationship with them. And then work together in supporting your patients may be my top three.

00:36:51.000 --> 00:36:53.000
Host: Fantastic. Anna?

00:36:53.000 --> 00:37:08.000
Anna: So I think mine are about giving in enough information upfront to patients to prepare them for what might happen, but also allowing it to be in a digestible form so they don't have to do it all in the same consultation that they can take a bit of time. Making sure that people know who to contact if they have problems.

00:37:09.000 --> 00:37:20.000
Anna: And alongside that, making sure that the people receiving the call don't diminish a new skin rash in thinking it's a mild and non-concerning thing. And making sure that they assess the patient properly and ask the right questions.

00:37:21.000 --> 00:37:30.000
Anna: And I think just echoing the working together as an MDT approach is actually a real pleasure. It actually feels like we're working together to get the best for our patient group.

00:37:30.000 --> 00:37:46.000
Anna: And I definitely would find managing the toxicities associated with our drugs much, much harder if I didn't have the group of amazing medical colleagues including Elaine that I work with. And so, it makes it so much better for patients, but also for us as professionals.

00:37:47.000 --> 00:37:46.000
Host: Dr. Elaine Hindle and Dr. Anna Olsson-Brown, thank you very much for your input. I think absolutely fascinating conversation. I hope it's been really interesting for all the viewers as well. So, thank you.

00:37:59.000 --> 00:38:07.000
Elaine: Thank you very much. / Anna: Thank you.