The Oncology Podcast

S4 E1: Hot Flushes, Aspirin and AI

• The Oncology Network presents The Oncology Journal Club Podcast • Season 4 • Episode 1

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The Oncology Journal Club Podcast hosted by Professor Craig Underhill, Dr Kate Clarke and Professor Chris Jackson | Proudly Produced by The Oncology Network

Visit oncologynetwork.com.au for Show Notes, to send us Voice Notes and more information. 

We explore practical wins and bold ideas across supportive care, colorectal cancer prevention, immunotherapy timing, digital triage and equity. From halving hot flushes with an NK1/NK3 blocker to biomarker-guided aspirin in colon cancer, we weigh value, risk and what truly improves lives.

• Elinzanetant cutting severe hot flushes and improving treatment adherence
• Current non-hormonal options and gaps in symptom control
• Biomarker-selected aspirin reducing recurrences in colorectal cancer
• Limits of DFS, toxicity trade-offs and subgroup signals
• Rising early-onset colorectal cancer and system planning needs
• Possible environmental and microbiome drivers under study
• ASCO geriatric assessment guidance and G8 screening in clinics
• PD-1 with short-course radiotherapy boosting rectal pCR rates
• Large language models for safe, efficient symptom triage
• Rare cancers report on access, cost, and rural inequities
• Telehealth standards to link expertise closer to home
• Healthy workplace culture to retain a resilient oncology workforce

Join the Oncology Network, registration is free, and leave us a voice note on the OJC page at oncologynetwork.com.au. Physicians, don’t forget you can claim CME points for listening to the show!

Thanks for listening

New Series, Community Links, Housekeeping

SPEAKER_02

Hello and welcome to the Oncology Journal Club podcast, where Oncology Papers meet real-world practice. I'm your producer Rachel Babin, and joining me again are Professor Craig Underhill, Dr. Kate Clark, and Professor Christopher Jackson. Together they dive into the research shaping cancer care. The important, the intriguing, and but sometimes controversial. This podcast is proudly produced by the Oncology Network. Okay, over to you, Craig.

SPEAKER_00

G'day, g'day, g'day. Welcome to series four of the Oncology Journal Club podcast. We've got new music and some other new features in this series. Firstly, look out for the WhatsApp link at the end of the podcast notes. You'll be able to type in some questions or comments or record them with the voice file. I learned something new. Apparently, when you're on WhatsApp, if you open a chat, you can click on the little mic button in the bottom right and record. So please send us any comments or questions and we'll feature them in the subsequent episode. We often from time to time mention what we find as helpful tools or guidelines or things like the ESMO relative scale of benefit. We're going to start adding those to a page on our website so people can find them more easily. We've had some very good feedback on the episode with Professor Nathan Cherney on When Is Enough Enough. And it's really been some quite impressive, positive feedback on LinkedIn and other social media about that. So congratulations, Chris and Rachel, our lovely efficient producer. So if people haven't had a chance to listen to that, I urge our listeners to do so. So let's let the Kiwis into the room. So if anyone needs to turn on closed captions, please do so now. Professor Jackson, hello.

SPEAKER_01

Oh, well, uh, Kelda, uh, Craig, look, I've been uh staying away from social media. Do you mean that that um social media um feedback was from someone other than my mum?

SPEAKER_00

Yes, at least one person wasn't identified as your mother.

SPEAKER_01

Oh, well that's unusual, but I'll have to check that out. So OJC is active on what social media channels, Craig?

SPEAKER_00

I saw this particular feedback on LinkedIn. We also have the presence on X and Blue Sky.

SPEAKER_02

That sounds fantastic. We do have Facebook.

SPEAKER_00

Oh, we do have facing. Oh, so if you want to see some negative comments to the episode, I'm onto our Facebook page.

SPEAKER_01

So we get positive comments. No, hang on, we must get all the negative comments on uh on X monthly, um, and all the positive comments on Instagram and LinkedIn.

Alanzenotant For Hot Flushes In Breast Cancer

SPEAKER_02

Yeah, LinkedIn is a great place to find us. If you follow Oncology Network, then you'll get the OJC update.

SPEAKER_03

Um it's just the photos on Insta, uh CJ. Yeah, that's what attracts people.

SPEAKER_00

Hey Dr. Clark, how are you going?

SPEAKER_03

I'm very well, Craig. Very well indeed.

SPEAKER_00

Terrific. I think you're gonna lead us off on today's uh podcast, Kate. It's an interesting paper. Tell us all about that.

SPEAKER_03

So I want to talk about a topic that's increasingly close to my heart, Alan Xanotent, used for vasomotor symptoms, aka hot flushes, in those women who are taking endocrine therapy for breast cancer, written by lead author is Dr. Fatima Cordoso, who breast cancer treaters will all know from the ABC Global Alliance, so Advanced Breast Cancer Global Alliance. And just so you understand how severe the the this is for women, and a little bit of personal story, I probably have one to two hot flushes on a bad day to get into this trial. You had to have moderate to severe symptoms, which was 11.4 on average, moderate to severe hot flushes a day. So that means no sleep, it means embarrassment, it means changing your clothes. Uh so this is a significant issue and is a reason a lot of women are not compliant with their endocrine therapy. So alinzenatent is an NK1, NK3 antagonist and has already been used in women going through natural menopause, whereas we're at about halves the rate and severity of hot flushes and sleep disturbance. And those trials, if you're interested, are called Oasis 1 and Oasis 2. And so this trial, Oasis 4, looked at a dose of a tablet a day for these women. And I quite liked the randomization. So what they did was they randomized two to one. Um, two out of every three women were started on a lanzanotent and were to take it for the whole 52 weeks. One out of every three were on a placebo for one to 12 weeks and then switched to a lanzanotent. Um, and this strategy is really common in a symptoms trial because the wait list effect is where symptoms that are distressing get better with time anyway. And you want to see what happens both during that wait period, but also when you switch people to an active agent. Uh so at four weeks, those on the tablets had gone from 11 events a day to five events a day. Those on the wait list had only lost two or three. Uh and at 12 weeks, that was down to three events a day versus a sustain of that initial drop in the placebo group. Later, when the when both groups of women were on active agent, uh, the women who had been on placebo caught up and got that benefit. And so everybody ended up at the same point. There was no difference in the PK of either a lanzenotant, comparing it with Oasis 1 and 2 women, because these women were on adjuvant hormones, and no different in the PK of the adjuvant hormones. So the toxicity was fascinating. Women on a lanzenotant have fewer headaches than women on placebo, slightly more fatigue, slightly more sombrance. But when they offered all women at the end of a year another two years Alan Xenotant for free, 91% of women said, yes, please. So I think that is uh potentially the best safety data that we have available. So I'm very excited by this. It is hundreds of dollars a month at the moment. So it's relatively affordable for an anti-cancer therapy. Uh, and if you attach that, they didn't do compliance with hormones. But if I think if you attach that to the compliance with hormones, compare that with something like ribo or or you know, adjuvant ribocyclib, it's significantly more affordable. So yeah, I was really impressed.

unknown

Yep.

SPEAKER_00

Yeah. So that's great, Kate. Tell us what do we have available now as a sort of standard of care therapy to support women who are getting severe vasomotor symptoms with associated vanduccin therapy.

SPEAKER_03

So currently we have uh some very good non-pharmaceutical uh methods, so uh yoga, uh other mindfulness, cutting out uh caffeine and alcohol, which I think is immoral. And then the pharmaceutical methods, gabapentin, uh, venlofaxine, and oxybutanin all help about a third of women. But as I tell my patients, it's not a third, a third, a third. It's they seem to help this, you know, women who do well, do well. And there are some women for whom they don't get benefit at all. And this does mean that the significant number of women beg me for permission to stop.

SPEAKER_00

And and do you think that this uh drug might have a role outside of women with breast cancer having endogene therapy took good or work for more broadly?

SPEAKER_03

Yeah, so I did read only a couple of sentences on a Google search that it is being trialed in men with prostate cancer as well, because obviously uh men on GNRH agonists suffer, or or the old-fashioned um orchidectomy, suffer significantly also, uh, hot flashes and um mood changes and anxiety that are common in menopause. So I uh yeah, I I think this may well have a role in in all those who are being hormone-starved.

SPEAKER_00

Yeah, okay, so interesting stuff. We might have uh invented a new clinical trial endpoint proportion of subjects who take up uh taking the investigational drug beyond the lifetime of the trial, 91% positivity that there. That's a really interesting result.

SPEAKER_01

I think that's a really important um patient outcomes that matter thing there, isn't it? You know, you what you really want to know is when people use throwaway lines such as the toxicity is manageable, blah, blah, you know, that line drives me nuts because who gets to define what toxicity is manageable?

SPEAKER_00

Yes, we know we know that, Chris. You do mention that from time to time.

Current Options And Broader Hormone-Therapy Uses

SPEAKER_01

Once or twice. Well, I'm glad that um people are starting to recognise my hatred of that particular line. But in terms of the, you know, and the word compliance, I struggle with a wee bit too. I think adherence is one more preferred one, but showing that people actually wanted to stay on the treatment at the end is a really good endpoint. When we ran our study of oral peclatexil versus IV, we gave patients the option of staying on the oral or switching to the IV, and that was a really important endpoint for us too, because people preferred the oral. And that, you know, came through so much more strongly than all the other toxicity stuff that you did, the basic preferences question. Yeah.

SPEAKER_03

Yeah. Just while we're on phrases that people hate, I can't stand no new safety signals. Because you're like, yeah, so eight people died of pneumonitis, but we've seen that before. Yeah?

SPEAKER_00

When we deal. Yeah. All right. Professor Jackson is in currently in India. It's a very we're a global, global crew this week. We had Rachel in Spain. I am in um Bordeaux. Uh, and Professor Jackson is somewhere on the subcontinent.

Patient-Centred Endpoints And Tolerability

SPEAKER_01

Yeah, so I I'm in uh in central India in um uh the province of uh Chattisgarh in a place called RIPOR, uh helping out uh with some teaching at a friend of mine's who uh runs a uh a hospital here on Ocean. I want to shout out to uh my colleague Bhavna Sarohi, uh, who is an absolute global superstar and who's the medical director of her hospital. And the um and the program she's running over here is fantastic, improving education. And also one of the goals of her hospital is to uh make treatment available for the people of her local community where head and neck cancers and cervical cancers are absolutely rife. And the amount of work um that her hospital does to meet the needs of those who have otherwise no uh access to healthcare at all is nothing short of staggering. So I'm never going to complain about my workboat again after having um coming over here and seeing how hard Bavna and the team work. Uh so big shout out to those guys. The big study I wanted to talk about um this week is one that people may have come across um, and that's the Alaska study, which is the randomised double-blind placebo-controlled trial of um aspirin. Now, we have seen a number of studies uh with aspirin and colorectal cancer before. Uh, in context, we had the physician's health study, which is a prime primary prevention study of 22,000 people, um, where people took uh a full-strength aspirin every other day or placebo and they had reduced colorectal cancer risk after 10 years. The woman's health study of 39,000 people of aspirin 100 megs every other day, and found there was a reduction in colorectal cancer after 10 to 15 years. And of course, the AGITG zone ascolt study of aspirin for stage 2 and 3 colon cancer. That was unfortunately negative for DFS at three years. But let's hold on for a bit more data for a few more years, given that it's often a late signal. Uh, and then um we know that uh aspirin has benefits in COX-2 uh expressing tumours, which led to the Salacoxid prevention studies, which showed a reduction in adenomas, but unfortunately kill people with an increase in cardiovascular events. But Kate, no new safety signals. Uh, we knew that already about the COPS2 inhibitors. Uh, and this is important because a PIC3 kinase pathway is upregulated in COX2 expressing colon cancer, which is a subgroup of colorectal cancers. So the Alaska study was my favorite study design of all: randomized, double-blind, placebo-controlled, with overall survival as the end point. It could not be better. What a beautiful study. Uh, patients who were eligible had stages 1, 2, or 3 rectal or stage 2 and 3 colon, and had 160 MGs of uh aspirin a day or placebo, and they were uh checked for somatic mutations in PIC3 pathway genes. Now there were two categories of PIC3 um kinase genes. So group A was exon 9 and 20, which are the ones that most of us are familiar with with our extended panels, and then those were uh then group B, which had other moderate or high somatic variants in PIC3 kinase, PIK3R1 and P10. Um so there were 3,000 people who were screened prior to surgical consent, and alterations were detected in 1,100, so almost a third. Uh and then uh those who uh met all the inclusion criteria ended up being about 600, 310 in each R. And to cut a very long story short, the three-year recurrence rates were 7.7% in the aspirin group and 14.1% uh in the placebo group. So almost 7% is a 6.5% reduction in events in the uh aspirin group. There were three deaths with aspirin compared to one with placebo, and there were more GI side effects and an overall 9% increase in toxicity with aspirin. Uh those two uh additional deaths with aspirin are balanced off against the cancer survival. Uh, there also appears to be a gender interaction, which is absolutely fascinating and wasn't something that I've read before about PIC3 kinase or uh aspirin studies. Uh and the question was: was that a dosing thing? Because obviously men have generally got higher weight, uh, and so would that make a difference in the gender? Uh, but apparently they did explore for that and found no relationship between weight uh and a benefit there so they did control for that variable. Uh, and uh so that remains exploratory. So overall, I think this is uh really exciting. This is a study which uh uses a low-cost drug. The high cost thing here is the screening uh for these variants, uh, and there's well at least five of them. So that's going to mean probably a panel uh on your stage two or three colon cancers run, just running a bunch of IHCs. So that will add to that molecular cost. Uh but you know, six and a half to seven percent in terms of prevention, that's almost as much as exercise. Uh, and it ranks as another really good uh intervention there for our stage two and three colons for our stage one through three rectals.

SPEAKER_00

So wow, that's really interesting stuff, uh Chris. But this fellow said there was a couple of excess deaths on the aspirant. How many lives were saved across the group of participants?

SPEAKER_01

So okay, I I did actually get my intro wrong when I said it would had overall survival as its primary important. It didn't, it was disease-free survival initially, so we'd have to wait a little bit longer for overall survival. Um so we don't have the overall survival uh data uh, I don't think, as yet, Craig, but the uh the DFS data is what, six and a half to seven percent. So Number needs to treat around, you know, 12 to 15, and which is again a pretty good streak, and it's again similar strength to oxaloplatin for a drug that's a whole lot less toxic.

SPEAKER_00

Yeah, that's right. It's fascinating, isn't it, how we as we understand the biology or the biomarkers of these common tumors, we're getting these smaller subsets and may be able to stratify treatments accordingly. So, you know, as always, it's an exciting, exciting field for us to be working in, really.

SPEAKER_01

Yeah, it really is. And I think uh Kate, we're gonna segue into you in a wee bit about um one of your papers too, about the different genomic stratifications of uh colorectal cancer too. So the colon guys are feeling left out by the lung and breast team, so we're trying to catch up.

Global Check-In And Access To Care

SPEAKER_00

No, she says looking I'm looking flummoxed. I like some words to that silence. It was a bit of confusion.

SPEAKER_03

When you're doing what do you want to see colorectal cancer, Kate? Yeah, but only from an epidemiological point of view.

SPEAKER_01

Oh, okay. That's not the genomic ones in Lancer. No.

SPEAKER_03

No, you couldn't remember. I'm I'm not academic, so I get uh I only get access to everything that's like open source these days. Yeah.

SPEAKER_00

But you mean you're you're referring now to the restrictions on the journals by the LCS.

SPEAKER_03

Yeah, that I am. Yeah, yes.

unknown

Yeah.

SPEAKER_00

Well fate, would you like to then would that be a segue for you to tell us about that paper that you had selected?

ALASCCA: Aspirin In PIK3 Pathway CRC

SPEAKER_03

Oh, lovely. So look, I think this is something we all know, and but I think it's useful to have it documented. And for if there are any health planners listening, please listen to this one, right? Okay. So this was a paper by Professor Sung, who worked for American Cancer Society, published in Lartson Oncology this week or last week, um, looking at colorectal cancer incidence trends in those who are who are called early onset under 50, uh, or usual onset over 50. Um, and the relevance to our um New Zealand and Australian listeners is that the Australians' rate number one in uh incidents of early onset colon cancer, New Zealand, it's fine, we're on the podium, we're number three, compared with our respective uh rates of those over 50 of 8 and 10. But more concerning is that although the rates of older people getting colon cancers are falling by about 2.5% a year, the rates of young people getting colon cancer is increasing in New Zealand by 4% a year, in Australia by 3% a year. Uh, the epidemiologists feel this is a birth cohort effect. So this is not a blip. These people will just keep getting more colorectal cancer as they go through their age cohorts. So we will lose that all of the advances we have in the falling incidence in older colon cancers as these people age, is their best guess of what's happening in the epidemicology of it. Uh, and then the rest of the paper presents all of the stuff we're working on, the suppositions as to why. You know, it has to be an environmental or lifestyle exposure. To what that is, I think there's a lot of questions still hanging over everybody's head. But I think the most worrying thing for planners is that the rates of young people's colon cancer is rising. But as those young people move through the older cohorts, their incidence is not expected to drop off. It is expected to keep at that higher rate. Uh and so we will need more colonoscopies, more surgeons, more oncologists, more scanners to look after the colorectal cancer uh uh epidemic that is on out on its way.

SPEAKER_00

So it's been so great. And of course, get activity now, current screening guidelines, adjusting down the age, making primary care physicians and patients aware of suspicious symptoms so that they do present earlier or would be picked up in screening, um, which is so effective in colon cancer.

SPEAKER_03

Yes, definitely. And the move into nurse practitioners, being able to do scopes, all of that is uh is something we're going to have to to take in our stride and to fund appropriately because it's so much better than to to screen than it is to treat somebody as a stage three, how expensive that is and how mervid that is for the patient.

SPEAKER_01

Yeah, so there's also uh an article in August's Lancer Oncology, which is looking at the genomic differences in early onset colorectal cancer versus late onset, and they're clearly uh different molecular. Now, lots of the historical literature is that you said, look, young people's manifestations and natural history of uh colorectal cancer are actually pretty similar. It's just they present later, but stage for stage it's pretty similar. That that had been shown uh a bunch, but this is a different disease which is coming through in these younger people. Uh, three to four percent a year is in of itself not that much because only 10% is under 50 anyway, and 3 or 4% of 10% is not very much. But I think more concerningly, like you said, Kate, is that if it's a birth cohort effect, it'll get bigger as they get older, which is perhaps where it's going to be uh important. And I think we have to understand, as you've already highlighted, what the causes of it are, because that's actually where um we can get to trying to prevent it. Uh, and undoubtedly it's going to be microbiome related, but what are the key features in that microbiome and how has it been manipulated, which are causing that? I've heard people talk about microplastics, I've heard people talk about uh antibiotic usage, uh, obviously processed um food, nitrates and water, etc. So there's a lot of theories there, but a hard area to study.

SPEAKER_03

I think the other concerning thing for me is if this is true, a both birth cohort effect as a result of an environmental exposure, I can't believe it's isolated to colon cancer. Yeah. So yeah, so you know, we we maybe we are seeing the beginning of it in biliary cancers in young people. Right. And my personal practice pancreatic cancer in young people, but you know, and one of my delightful, I fall in love with all of my patients, but one of my delightful people in his early 30s with medicine at pancreatic cancer, presented, said to me, said, What have we done? And I said, Oh sweetheart, if only we knew, you know, we'd we we could stop doing it. But yeah, we've done something. That's a very sobering thought. Should we cheer up?

SPEAKER_01

It's important also to know that we um have video of each other on this podcast where we can see it, and Craig just got up to um open his curtains while he's in um Bordeaux. I was quite concerned for a moment that Craig was doing the old Zoom thing of not wearing any pants.

SPEAKER_00

No, I've got my red, red French shorts on. I'm definitely wearing pants.

SPEAKER_03

I'm not sure the red shorts are much better, Craig. Are we on it?

SPEAKER_01

Ladies and gentlemen, we have knees. I'm gonna screenshot that for my favourite style or maybe make up my new screensaver. Right. Okay.

SPEAKER_02

Before we get back to the papers, if there's a study you think we should be covering on the Oncology Journal Club podcast, feel free to send it our way. You can join the Oncology Network. Remember, registration is free, and leave us a voice note on the OJC page. That's at Oncolynetwork.com.au. Or come and chat with us on our socials. And physicians, please don't forget that you can claim CME points for listening to the show. All right, back to the journal club.

Interpreting DFS, Toxicity, And Subgroups

SPEAKER_00

So just changing tack a little, I want to talk about an ESCO guideline, Girachi Assessment ESCO Global Guideline. This was published in the JCO. One of the co-authors is our very own Bogda Kozwara, who is lead on the Supportive Care Matters podcast. Many of you probably subscribe to that. And if you don't, you may want to. So Bogda runs a great series focusing on how we can improve supportive care for our patients. So she was an author on this guideline, which was a multidisciplinary multinational expert panel who reviewed existing ESCO guidelines and conducted a modified adapt and a formal consensus process. So this is a podcast. I'll just mention briefly that this adapt methodology is an alternative to de novo guideline development. The objective of the adapt ADAETE process is to take advantage of existing guidelines to enhance sufficient production, to reduce duplication, and to promote the local uptake of quality guideline recommendations. So this guideline focused on an important issue. Chris is in India at the moment, Kate's in New Zealand, and I work in regional Australia. And the relevance of that is the panel wanted to look at what are the optimal recommendations for managing older people with cancer over the age of 65 in a system of basic resources, a system which had more enhanced resources, and then a system that has fully enhanced resourcing, so able to offer a wide range of supportive therapies to patients. So there's a table with three columns, basic, limited and enhanced, with suggested ways to manage various deficits identified in older people, whether it be physical or functional, nutritional weight loss, and absence of social supports, depression, anxiety, and comorbidities, cognitive issues. So for each one of those domains, there's suggestions, practical suggestions in this guideline of how to assist and put in place some management steps to better support the patients. Overarching all this is a recommendation that all people over 65 who are proposed to receive cancer treatment should undergo a screening assessment. And that could be a simple G8 score. I don't know, Kay or Chris, if you've had experience using that in your practice, but in Aubru Donga for a number of years, that's routinely done by the treating oncologist at the time of the first appointment and subsequently through patient's journey. It takes a couple of minutes to do and it quickly identifies people who may have a deficit and then need a more comprehensive geriatric assessment, either with uh a specialty nurse or referral onto a geriatrician uh if they're available. So uh very interesting and practical guideline, and as I said, sort of divided up in mind with comprehensive centres, not so comprehensive centres, and then basic uh centres or services with their recommendations. So congratulations to Ucta and the co-authors for leading on that.

SPEAKER_03

And what of a genuinely practical, including a practical geriatric assessment that has a link to that you can then use for those under-resourced centres who do not have availability otherwise. So I thought that was really helpful.

SPEAKER_00

Yeah, that's right.

SPEAKER_03

Do you use the G8 score routinely, Kate? No, no, I don't. Uh but actually looking at it, I think I do a very sort of similar thing. Like I took a very sweet young man today for a walk and uh we made a cup of tea together. So, you know, that that is a way of sorting out the sweep from the chaff of your old people. If you can keep up with me, you can probably deal with chemotherapy. But no, I don't have a formal, I don't use a formal GS.

SPEAKER_01

Well, Craig, as you're getting closer to 65. What do you think about the cutoff of 65 as defining old adults? I mean, to me it's 80 is the thing.

SPEAKER_00

I'm I'm at least two years away from 65 credits.

Early-Onset Colorectal Cancer Trends

SPEAKER_03

I and I thought it was 65 if you had significant morbidities, and we've seen his knees now, so you know, he's probably got a weird. All of that football. Yeah.

SPEAKER_01

But I think though, to me these days, my 65 is a is a typical age patient in our clinic these days. Mid 65, you know, is is normal in an oncology clinic, really. I mean, it's the 75 to 85, uh well, 80 plus, I would say, who are the um the ones who present with real frailty and stuff in the 75 uh group if you've got more bitter teeth, but there's very, very, very many, many, many, very fit 75-year-olds out there.

SPEAKER_00

Yeah, that's right. But that's why you do the G8 score, Chris, because uh it's age, isn't it? It's not the age on the clock, it's how the engine's running. And that's coming from a 62-year-old who was just part of the Albi Ronga over 35 soccer championship winning team uh this year. But so there's 65-year-olds and 65 year olds, as you say, and that's why that's just an arbitrary cutoff of suggestion that rather than a fairly subjective follow me up to the tea room test, it's a series of questions. It really literally takes a few minutes to do. And people can present as looking like a pretty fit 75-year-old or a 70-year-old, and then you apply these questions and it reveals that in fact there may well be a deficit and requires further, more comprehensive testing. So it's just a screening tool, and I think very quick to do, very practical.

SPEAKER_03

So outside of our personal experience, because obviously Professor Jackson and myself in the coming months can have our early onset coloreal cancer. You're not 50 yet, are you? No, very close, very close. It's available on MT Calp G8, if anybody uh uses that free app.

SPEAKER_00

It's widely available free online, various websites. It's a tick score. If you're doing the ECOG or staging, it's about takes about as long as that to do. So all right. Uh Chris, what else do you have for us?

SPEAKER_01

The next trial I wanted to talk about was the Spring 01 study, which is just out in Lancer Oncology. Uh, this is a phase two randomized study in locally advanced rectal cancer. Uh, patients all receive short course radiotherapy uh of the rapido style, followed by capox chemotherapy, and half were given the PD1 inhibitor Cinetilimab or Cintilimab. Uh, the primary input was pathologic complete response, which I don't think is a great um input, but I'm going to talk about that in a moment. And PESCR, of course, is the complete absence of tumour in the viable tumor and surgical spectrum. And the result, just to again cut to the chase, is the syntillomab um achieved a PCR response of about 59% compared with 33% in the chemo-only group, which is a big, big step up. And that's the first randomized signal that adding a PD1 inhibitor to TNT, title management therapy, might really enhance um tumor clearance. On toxicity, this was interesting. Grade 3, 4 adverse events were uh were similar, uh, around a third of patients in each arm, but there were more adverse events and particularly postoperative complications with scintillomab, which we're not seeing with other PD1 uh inhibitors uh at this time. So it's going to need a bit more follow-up there. Now, why is this one interesting and why have I uh highlighted a PATCR study? Well, because elsewhere, adding PD1 to chemoradiotherapy has not been a slam dunk. Uh, in head and neck cancer, both Javelin head and neck 100 and keynote 412 were negative. Uh, and in rectal cancer, the NRG platform study with Pembrolizmab showed no clear benefit. And even smaller near studies like Volta J showed activity, but not of this magnitude. So spring 01 really does stand out as a positive randomized study in those with micro-satellite stable, so not DMMR rectal cancer. And so that is tantalizing. We do have to temporarily excitement because PASCR is not a perfect endpoint and doesn't always translate into survival, and it can be misleading in isolation. Uh what it does show uh is that PD1 inhibitor in uh operable rectal cancer uh may be a target we're going to see more of uh in that um TNT setting.

SPEAKER_03

The scintillomab was run with the K Pops, not with a short course of that. Yeah. So do you do you think it was the timing of the um of the IO? Do you think giving IO and then an awful lot of radiotherapy is and then a suppressant? What do you or do you think this is just a red hero?

SPEAKER_01

Yeah, look, I think that's hard to know. Um uh Kate, but I think they're all really good pointy because all those other studies that I'd highlighted were longer course uh radiation studies, weren't they? Um so you know, over multiple weeks rather than just one. So the hypothesis that maybe it's related to short course versus long, that's a really provocative thought. Uh I'd been focusing more on the disease site, uh, I suppose, the rectum and the overall uh regime rather than thinking too much about the length of the course, but that's a good hypothesis.

SPEAKER_00

So where to you next with this drug? Do you think Chris will be there for the studies or uh there'll have to be really Craig?

SPEAKER_01

I think that uh scintillomab is clearly a uh a fast follower in terms of the world of PD1. So it's an IgG4 monoclonal antibody different to IgG1 and IVGG2, which is your Pembrose and your Nevos. Whether or not that's relevant or not, I I I doubt it, probably. But when you're getting a signal like this, you can bet your bottom dollar that the company's going to double down on the indication uh and expand that quite rapidly. Clearly not a um, you know, anything which is ready for prime time and nothing that I'll be talking to my patients about in the near future, uh, but certainly something that uh I think it's a space to watch and something that if that trial did come along and be offered to my centre as part of a collaboration, I'd certainly want to pick up on uh and look this is participate in further studies of it.

SPEAKER_00

Fantastic. Okay, I think you're going to tell us something about uh Chat GPT that you found um potential tool.

Causes, Microbiome, And System Burden

SPEAKER_03

Well, I think this is this is a long way from prime time, but I thought this was interesting. So uh this was a group from Yale. Uh Dr. Lisa Chan led them. Now I know less about computers than my mother, so here we go. So they used large language models, ChatGPT and ChatGTP1Pro. So physicians acted as patients. So that's first bias, and they um asked the the um large language models to triage uh when these pretend patients, who were all oncology physicians, rang in with common problems that women who are having treatment for breast cancer in the early, late, and survivorship setting uh might have. Interestingly, of those 66 scenarios, which they tested multiple times, 97% were given medically appropriate advice. 89% of the replies had the correct diagnosis as number one, 98% had the correct diagnosis in their differential diagnosis, 92% had highly appropriate triage decisions. So this group wants to take this into a group of real patients. They wonder whether doctors ask questions differently than patients, and I think that's probably fair because we use different language. But even if this would be used as a screening tool to, I don't know how your centers work, but we have a triage nurse who's on the phone the whole nine hours, and that's a very expensive use of somebody's time. I thought this was intriguing. And so I I I looked for more work from uh Lisa Chan and her group, and it was also in a journal called a Journal of Clinical Oncology, Oncology Advances, which was actually quite an interesting read.

SPEAKER_01

That really surprised me, Kate, because a lot of the uh corporates are using uh chatbots, for example, to help you sort stuff out, and chatbots can't even help me amend my flights. And so how they're gonna be able to sort out unperped breast cancer symptoms is is a bit of an advance.

SPEAKER_03

Interesting. So they did have an example. So the person asked, Hello, this is Dr. Smith. I understand you've developed some new symptoms. How can I help you? I am having bad aches all over, said the patient. I'm sorry to hear that. Can you tell me where the um aches are in muscles, joints, or bones? And the patient says, in my joints and bones. Thank you. Have you been receiving any supportive medications recently? Um, yes, I did receive new laster after my last treatment, which is a granularised colonised stimulating factor. Thank you. It sounds like this bone pan may be related to the new laster. Blah, blah, blah. And then the patient says, I got my last shot four days ago and it began about a day after I got the shot. Based on what you've described, the timing of your bone aches and the pattern of pain, the most likely cause is peg fill gastrum-induced bone pain, and then they assessed them. So I think there was a very narrow group of things with the patient. So the patient had very exact language. I agree with you. I can't stand the one on the supermarket apps and the airline ones are worse useless. But you know, maybe they haven't been investing enough money and time in training them.

SPEAKER_01

Oh, look, 100%, you know, AI is here, and our challenge is really how do we integrate it and how do we best maximise its use uh in the clinics to bend the curve of the work um work demand, right? The workflow demand. We've been using ambient listening in our um practice, uh one of our practices, and that's been going really, really well. Uh my GP's using it uh in his practice as well. It's going really, really well for him. Uh, and so I think that that'll be something that we're all gonna do in the very near future, I would anticipate. And it's an exciting time, uh, and it really feels like the next big uh change or the biggest change since you all got cell phones and emails.

Listener CTA, CME, And Network

ASCO Geriatric Assessment Guidance

SPEAKER_00

Exactly. But I think we're gonna have increasingly numbers of these kind of papers on uh on the program as Chat GPT and other AI tools uh brought in to help support our interactions with patients, uh, and something that we're probably all going to need to try and understand uh a bit better. So I'm just gonna change track a little bit now. I just wanted to highlight briefly a major report that's come out from uh Rare Cancers Australia. It's entitled Now It's Personal, Access and Equity for All. So it's a review about the issues and evidence in this space about the issue of inequity of access to treatment and support for people with rare cancers. There's about 80 references uh used in this report. But they highlight a couple of interesting uh facts that about delays in diagnosis, waiting time to get treatment. There's a higher uh so there's some blowout in times for people with uh rare cancers, especially in those under 34, um, often delayed testing, um, believing their symptoms weren't serious, a lack of access to mental health and other supportive care. And so it's created a number of issues as well in our system that is common cancer focused. Um there's a lot of out-of-pocket costs for diagnostic tests. Um, people often had to drain savings to access testing, patients in rural and regional areas facing extra barriers to access subspecialty care, and they were three times more likely to decline a recommended treatment due to the distance compared to those living in metropolitan areas, and often a lot of lack of readily available information. So this came off the back of a Australian government sent an inquiry into this issue, and over the next few months um there's going to be a series of national workshops with various uh cancer control experts to try and look at ways to uh better care for people with rare cancers. There's a number of recommendations uh in this report outlining ways in which we might be able to improve equity, speed up diagnosis, and in short comprehensive support for all cancer patients, including the rare cancer patients. So I'm sure that's a an issue in New Zealand as well, Kate and Chris. You know, our paradigms are sort of based around common tumours, not necessarily about rare diseases.

SPEAKER_03

I think also our paradigms are based around uh big centres with everything there. And I I don't know what it's like in Australia, but people don't want to move to another island to have their therapy. They need to be with their with their loved people or with their own environment, you know, own environment. And there's that pull, isn't it, between expert and local? Pull, pull, pull all the time.

SPEAKER_00

Yep. Because how do we better manage that? How do we better link and network the experts to ensure that treatment can be delivered as close as home as possible, where it's safe to do so. So it's a thought-provoking report. And so again, we have a broad listenership, and I'd urge people to have a look at that. We'll provide a link. And then I wanted to talk about a couple of other guidelines as well. Uh so just a sort of segues into we're just talking about access to care, Kate. There was a report from ASCO publishing supportive care for cancer and standards and practice recommendations for telehealth and oncology. Mask endorsed practice recommendations developed by the American Society of Clinical Oncology. The Multinational Association of Supportive Care and Cancer on Mask, through its digital health study group, used a framework called the Agree To Instrument, uh, which is a formal process to assess the quality of guidelines and found them to be methodological sound, clearly presented, and highly applicable to practice. They basically endorsed them rather than uh writing their their own. And they do feel that they could be now updated because they're a few years old and uh they were then planning to do that jointly together. So Mask and ESCO are under the process of uh updating those guidelines. But I think that's you know still of relevance, relevance for clinical trials, but it's also relevant for day-to-day care. And as we talked about, Kate, how can we um better network centres to ensure patients are in the center and we can minimize uh travel where where we can? There's a really good table in that paper too with some practical suggestions, and so again, I'd urge uh people to have a look at that. And the last thing I wanted to mention is a statement that's come out, a joint statement from ASCO, COSA and ECHO, Principles for Advancing Healthy Workplace Cultures. Sabe Saberson, who has led a lot of the work in Australia and internationally on telehealth in oncology. Sabe has just become president of COSA, and one of his um goals is to try and highlight this issue about healthy workplace cultures. The paper points out that the WHO projects a global health workforce shortfall of 11 million professionals by 2030, and a contributing factor is rising levels of workforce burnout, which leads to clinicians working fewer hours, in some cases leaving clinical practice altogether. We have an unbalanced distribution of workforce between metro and rural areas and between high-income and low-income middle-income countries. So to put in place some principles for advancing healthy workplace culture so we can attract and retain more healthcare professionals in what, let's face it, a very exciting and rewarding specialty to work in, but a very tough specialty as well.

SPEAKER_01

Well, I'm I think that's fantastic leadership uh really by Sabe. You know, the people who you work with and the way in which you work with everyone every day is what keeps you going as well on college. Obviously, we get into it for the patients, but you know, your colleagues are uh are what keeps you in it. Um and um in a in a good department is just absolutely utterly um there's no better substitute for a good department, you know, when you have a bad day having colleagues there, lifting you up when you're feeling low, uh and simply being able to be there for others at a time in which you know they need it as well, is something which is I think one of the most beautiful, wonderful things about being an oncology, really. Uh in New Zealand, we have relatively smaller departments and other places, and so we also have a quite a nice net national network um of friends and colleagues too, uh, which I think is important for fortifying each other too. So getting that culture right, getting those relationships and helping each other and supporting us through what what, as you say, is a uh challenging but beautiful specialty.

Screening Tools, G8, And Practical Triage

SPEAKER_00

Fantastic. All right, well done everybody. What quite a wide-ranging number of topics is as usual. Hopefully, people will find that interest. Please feed us back some uh feedback or pay papers that you've come across that you think we should cover and highlight to others. Um keep those coming in as well. And thank you, Rachel.

SPEAKER_02

Always a pleasure, thank you.

SPEAKER_00

Thank you, Chris.

SPEAKER_01

I'm gonna see if I can say uh goodbye in uh today or Mari.

SPEAKER_00

So thank you, and goodbye.

SPEAKER_03

Uh Matherwa, goodbye. I'll see you soon.

SPEAKER_00

And as I'm in Bordeaux, I'm going to say uh au revoir or a la prochaine foi. See you next time. And uh bonjournée, a tous.

SPEAKER_01

Um Craig, can't you say I'll have a bottle of your best red in your best French accents, isn't it? We're about to say at lunch.

SPEAKER_00

Oh parfait, gates. Okay. Till next time, see you all soon. Bye.

SPEAKER_02

That's it for this episode of the Oncology Journal Club podcast, where Oncology Papers meet real world practice. If you'd like to explore the papers we discussed today, head to oncology network.com.au and visit the Oncology Journal Club tab where you'll find show notes, links to the research, and a growing collection of OJC resources. Don't forget to join the Oncology Network, it's free. You can send us voice notes and chat with us on social media. And physicians, you can also claim CME points for listening to this show. This podcast was proudly produced by the Oncology Network. Until next time, thanks for listening.