The OJC S4E6: HIPEC Hits a Wall, Beyond Curative vs Palliative + ctDNA After Metastasectomy

Negative trials matter. In this episode, the Oncology Journal Club team discuss research that challenges established practice, alongside thought-provoking papers exploring how we communicate treatment goals in the era of immunotherapy and precision oncology.

Professor Chris Jackson reviews the PERISCOPE II trial, showing that adding gastrectomy, cytoreductive surgery and HIPEC to systemic therapy does not improve survival for patients with gastric cancer and limited peritoneal metastases, while substantially increasing treatment-related morbidity.

Dr Kate Clarke examines the NeoSUMMIT-01 trial, which provides further evidence supporting perioperative PD-1 inhibition alongside chemotherapy for gastric and gastro-oesophageal cancers, with encouraging improvements in event-free and overall survival.

Professor Craig Underhill leads a discussion on a JAMA Oncology viewpoint questioning whether the traditional "curative" versus "palliative" treatment framework remains fit for purpose in modern oncology, particularly as immunotherapy and targeted therapies create new patterns of long-term survival.

The team also explores:

• Smoking cessation programmes that improve outcomes for patients with cancer 
• New ctDNA data following colorectal liver metastasectomy 
• Steroids to reduce morphine-induced nausea and vomiting 
• Highlights from the ASCO Breakthrough meeting 
• The Lancet Oncology Commission on the global cancer workforce crisis 
• Tumour-agnostic therapies and the challenges of equitable implementation 
• Five-year follow-up from TOPAZ-1 in advanced biliary tract cancer 
• A comprehensive review of recent advances in prostate cancer 

The Oncology Journal Club Podcast is hosted by Professor Craig Underhill, Dr Kate Clarke and Professor Chris Jackson, and proudly produced by The Oncology Network.

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

Transcript

SPEAKER_03 0:00

Hello

Welcome And What’s On Today

SPEAKER_03 0:01

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 the sometimes controversial. This podcast is proudly produced by the Oncology Network. Head over to OncologyNetwork.com.au for the show notes with links to all of the papers discussed today. Okay, over to you, Craig.

SPEAKER_02 0:34

G'day, g'day, g'day. Um, what episode is it again? Starting again. G'day, g'day, g'day. It's series four, episode six. Welcome everybody. It's great to be here with Dr. Kate Clark and Professor CJ Jackson. Hello, peoples. Across the ditch.

SPEAKER_04 0:55

Hello, Craig. Uh what episode was that again?

SPEAKER_02 0:59

Series four, episode six, I think.

SPEAKER_04 1:02

Six. Good. Good. Hello, Chris. Oh, pretty good, thanks, Craig.

SPEAKER_02 1:08

So I hope is everyone back to normal after Asco. We had two fantastic well, I think they're fantastic. I learned a lot by listening back. The Asco updates. So if you missed reading or going to post-ESCO meetings or just want to refresh it again, download those episodes. And today we're back to normal. Is there such a thing as normal on this podcast? I'm not really sure. Bit of a wide-ranging cook's tour of recent papers in oncology. Let's hope uh people enjoy it. Who's going to go first?

SPEAKER_00 1:43

I've

HIPEC For Gastric Cancer Tested

SPEAKER_00 1:44

got a negative paper to talk about today. This is one for the argument files at your NDT, should you ever be dragged into this conversation? Umic therapy, gastrectomy, cytoreductive surgery, and high peg versus systemic therapy alone for gastric cancer with limited peritoneal metastases, the periscope two clinical trial. Periscope two asked whether adding gastrectomy, cytoreductive surgery, and high peg to systemic therapy improves outcomes of people with gastric cancer and limited peritoneal metastases. This was an academically sponsored European phase three trial, funded by public and charitable organizations, not industry, which is important. It tested a complex, expensive, and widely used intervention that's never properly been compared to systemic therapy alone. Um patients who were enrolled had a PCI index of below seven. So those who do uh GI malignancy, PCI is it uh less than two centimetres in size, and uh which of the nine areas of the abdomen uh is it in? They get a point of zero one or two for each of those things. Uh colorectal cancer would usually say PCI of 11 or less would be considered for high pec, and this was less than seven, so that's quite a conservative, limited burden of peripheral disease and gastric cancer. Or they could be wash positive. So if you did a laparoscopy and they had a washing positive, they're um eligible uh as well. And it was a clean comparison of high pec versus surgery.

SPEAKER_02 3:07

Quick question, Chris. Just clarify that. So the seven, is that the total size of that number?

SPEAKER_00 3:13

So PCI is a score. Uh you get 01 on two points for every one of the nine areas of the abdomen. Uh 0 is nothing. One is a deposit less than two centimetres, and two is a deposit greater than two centimetres. And so you add up nine of those, so the most possible score would be what? Uh 18, and less than 11 is um, you know, not much, and uh less than seven is quite low. So it's truly limited peritoneal disease and gastric cancer.

SPEAKER_02 3:38

These were low volumes, in other words.

SPEAKER_00 3:40

Yeah, low volume peritoneal disease, absolutely. And in Western patients, not in Asian patients, because Asian patients have a different disease biology, usually a different primary location in the stomach, often different risk factors, and have often had different uh primary surgery as well. So patterns of reapse are different. So these are more representative of the types of patients we would see in our MDM. Um already I'm gonna say how much I love this study because it had a primary endpoint of overall survival, the uh the best possible uh endpoint in all advanced cancer trials, which is exactly the right choice. A major intervention intended to prolong life. So if response rate or PFS wouldn't have been enough. And the result was clearly negative. Uh median overall survival was 16.6 months with systemic therapy and 15.7 months with surgery and high hazard ratio 1.1, no suggestion of benefit. The curves were completely overlapping, and PFS was also not improved in the intentions of treat. And the harms were substantial. Grade three or worse adverse events were worse in the uh high pet group with 42% compared to 20% in the control group. Serious adverse events occurred in 44% uh with high PET compared to 6%. Uh, and under those who went surgery and astomotic leak occurred in 27%, I less in 35%, and three patients died from treatment-related complications. So just don't do it. There are some um issues with it. I mean, 16 months with uh systemic therapy is quite good. Uh standard um overall survival in gastric cancer studies these days about 11 months. If you add in second-line therapy, you might get up to 13 months or 16. Some people might say that was quite good. Um, but this study uh enrolled people after they had not progressed on three cycles of chemotherapy. So they were already the good uh responders. So I think that probably accounts for the better performance of the control arm. Um and we don't actually have enough information from the uh appendices or the um or the trial report itself uh on what the amount of first and second line therapy was and what the types of therapies were, and how many people got um PD1 therapies and how many got subsequent studies, that type of thing. There's a little bit a little bit of uh insufficient information. The um bottom line is straightforward. It's selected patients with gastric cancer, unlimited perineural metastases, adding gastrectomy, pseudoreductive surgery, and hype does not improve survival, markedly increases morbidity, and causes treatment-related deaths. This is a highly valuable academic negative trial with the right primary endpoint answering an important clinical question in an appropriate population which is comparable to ours and should reduce the use of a hazardous intervention outside of clinical trials in our population.

Where The Negative Result Fits

SPEAKER_02 6:09

Great. So I guess the other reason people on the control arm did better than expected is because the pattern of relapse was peritoneal rather than fever or elsewhere. Chris, the other question I had was in the constellation of other literature, where does this fit? Like have there been positive studies for peritonectomy and this refutes that, or is the first sort of robust phase three?

SPEAKER_00 6:34

Well, there was the German gastry PEC study with no overall survival benefit observed for people with gastric cancer and peripheral testes treated with pseudoreductive surgery and high pec compared to those treated with cytorred surgery alone. So that was a high-pech study. Um, and then you've got the Renaissance uh trial, which was another German randomized controlled trial showing no survival benefit for people with gastric cancer and oligometastatic disease who underwent uh extensive surgical intervention compared to those who continue systemic therapy. So, what that shows is is in the suite of studies of do you resect oligometastatic disease and gastric cancer? No. Do you resect limited peritoneal disease and gastric cancer? No. Uh, does high pick add much to peritoneal uh surgery alone? No. So what's the right treatment? Metastatic gastric cancer? Drug treatment.

SPEAKER_04 7:20

Can I just ask a question? In the trial, they included the washing positives only. Did they show any signal of anything?

SPEAKER_00 7:28

Uh no subgroup analysis that I could see on that particular Kate. So uh no forest plots reported to you in that study. Good question, though, because the wash positive.

SPEAKER_04 7:39

We shake our heads a lot when if it's only a few cells floating and washing, and you feel like you're writing people off on the basis of a few cells floating and washings. So I would love some data in that space. So if the investigators are listening, if they could share with us the wash positive only data, we would be fascinated. Of course, we're using reading the paper to see if we can find it.

SPEAKER_02 7:59

We'll try and uh link up in social media then about that on LinkedIn or X Blue Sky. All right, Kate, what was your paper today?

Perioperative PD-1 In Gastric Cancer

SPEAKER_04 8:10

So my long-ish paper is the Neo Summit 01 trial. This isn't earth-shattering. This is, I think, confirmatory. Um, and unlike Chris's paper, this is an 100% Chinese population, mostly Guangzhou, which is a lovely south region. Uh it was looking again at gastric and gastroesophage or cancer. This is chemo, a plus or minus an anti-PD1 perioperatively. The chemo, this being a Chinese population, is K-pox or SOX being S1 and not celloplatin. And the anti-PD1 is terripillomad, which interestingly is 200 bucks a dose in in China and 8,000 bucks a dose in the US. So wow, which is cheap by anti PD1 status, but uh great. So only 108 patients, but they got three cycles pre-operatively, five cycles planned post-operatively, and then a further six months of terripilomad uh in those in that arm. The three year event-free survival, 75 versus 50 something percent, the overall survival at three years, 81 versus 72%, which is bang in line with what you'd expect from Matterhorn, uh, but one year further over fewer patients. So I think it's confirmatory that an antiped1 does assist curative intent therapy for people with gastric and gastrocosophageal cancers. A shout out to this investigator was although they included DMMR patients, three in each arm, they then excluded them from their analysis once they figured out that they should do well. So this is a purely PMMR group that we're talking about in the analysis. So yeah, nice paper. The other curious thing, and maybe gives us some hope after our very negative discussion from Professor Jackson, is that the addition of anti PD1 in this small trial decreased the peritoneal relapse rate from 40% to 15%, which is interesting. It's like most of the distant metastases that they avoided was peritoneal. There's only 108 patients, whether that's just a fluke or whether there's a signal in that.

SPEAKER_00 10:06

So that I was curious about it. That was interesting, isn't it? Yeah. Well, I'd like to name it after my Conservative Party friends, Tori Palamab.

SPEAKER_04 10:14

That makes it easy to say, doesn't it? Yeah. Yeah.

SPEAKER_02 10:17

Well done, Chris. Very that's very useful today's okay.

SPEAKER_04 10:22

The brand name is even harder to say. It is L-O-Q-T-O-R-Z I LOC torzy, I suppose. But yeah, there you go.

SPEAKER_00 10:29

Yeah. Okay, with the um with the molecule, is it IgG1, IgG2, IgG4? Anything particularly special about it that is different from the other PD1 inhibitors?

SPEAKER_04 10:38

No, not that I can see immediately. So I don't think you know it's flashly humanized or run through a mouse first or whatever, as they're all trying to claim I think it's just a standard antiped one. It has had FDA approval for a very long time because it was first tested in nasopharyngeal cancer, which is obviously something the Chinese are much better at than the rest of us.

SPEAKER_01 10:55

Okay, was there a tail on the curve?

SPEAKER_02 10:57

In terms of long-term survivors, yeah. Because it's going to segue into the paper I'm going to do in a sec.

SPEAKER_04 11:03

Not as yet, because we're only at, so although they're reporting three-year median um duration of follow-up is only 40 months, so only a few months longer than their reported EFS.

SPEAKER_02 11:12

So I I picked a bit of a curveball paper, I guess, not uh one of a practice-changing new treatment.

Rethinking Curative Versus Palliative

SPEAKER_02 11:20

Uh this paper's called Rethinking Treatment Intent Beyond the Curative Palliative Binary in Modern Oncology. It's in JAMA. Oncology, sorry, just out it's a viewpoint. I was doing some research about this topic about endpoints recently. Some people use m other endpoints like there might be just to delay symptoms or other headings, other other categories of treatment intent, but a lot of people use this binary curative or palliative. So this paper sort of points out that in the modern oncology area, maybe this doesn't fit very well as a binary construct because of the longer survival we're seeing, seeing tales of curves and um long-term survivors, perhaps cures in people who had metastatic cancer previously thought to be incurable and melanoma and lung cancer springs to mind. But even they actually quoted uh the example of in metastatic gastric and esophageal adenocarcinoma studies with immunotherapy. We're seeing some, in some studies, tails on the curve with some very long-term survivors. So this is something that's sort of risen in the era of targeted therapy and immunotherapy. So they postulated that maybe with these advances in treatment that's blurring the lines, we should move to some other type of construct because it's no longer fit for purpose. And they're saying the problem is when you present it as this sort of binary choice, even though, for example, you might be intending, let's say, someone with resectable, again, they used the gastric cancer example, someone with resectable gastric cancer receiving perioperative chemoimmunotherapy might be told the treatment's curative. But despite that, 25% of people die within two years of embarking on the treatment. And so similarly, uh despite improvements in resceptable pancreas cancer with um fulfurinox added to surgery, a third of people still die within two years, and many more will die in the two years after that. So people may then delay making choices or about treatment because of that overly optimistic uh spin on things. And and equally, even though you're starting a treatment with someone with metastatic disease and they may well die of the disease, there's some people, it's a palliative intent, but some will be long-term survivors. So, how do we get around that? And so they were saying that maybe we should invent some new terms, new categories. And I'm not sure that they've quite got these right, but this is what they suggested. One was a treatment aimed to increase the chance of completely removing the cancer and thus cure you from the cancer. So that would be in the neo-eduvent space, it's a bit of a mouthful, isn't it? A treatment aimed to prolong life and prevent symptoms by preventing tumour growth for as long as possible, but with less than 5% chance of completely removing the cancer, or a treatment that does not try to slow down the cancer yet does attempt to reduce the symptoms. So they've come up with these different categories. So what they just they're I think one of their useful suggestions was uh structuring the discussion around outcome ranges or possible scenarios rather than a binary uh picture. And they thought there needed to be further work in this space. And we need to maybe use more written materials, including within uh informed consent forms, to lay out these scenarios or ranges rather than having this rigid dichotomy. So they were saying the conclusion was they were calling for a transition to a flexible and precise lexicon of treatment intent that uses precise goal-aligned language and communicates prognosis with outcome ranges or outcome scenarios. Yeah, I'd love to know, Kate or Chris, your thoughts on it.

SPEAKER_04 15:18

There are three audiences, and there's probably more, but I think there's the patient infano, there is the MDT decision-making group, and then there are other clinicians who have involvement with this patient for other illnesses. And I think we don't communicate well with we can probably communicate well within the MDT, and at least in some of the diseases that I treat, we now have uh radical. We don't use the word curative, actually, we use the word radicals. We have radical, um, as I'm trying to eliminate the cancer. We have disease control, and then we have palliation, and that's and we understand within the MDT what those three things mean within the disease. But I think it's really hard when a patient has a heart attack and ends up in ICU who's on palliative hormone theory for metastatic ER positive breast cancer. Because they're actually got a life expectancy of years ahead of them. Uh so that that is really interesting. And then in terms of the patient, I like the Australian organ uh research group that talk about best case scenario, worst case scenario, unusual scenario. I really like that structure. And it doesn't have a thousand words in each title. So I try and do that, and then I tell the patient about things like conditional survival, disasters, unexpected events, and sometimes we're wrong. Because I've got one dude who progressed through first-line chemotherapy. We gave him a little bit of IO and all of a sudden his esophageal cancer has disappeared. Um that happened, I think, two years into his journey. And we've all got stories like that. So I think we we have to be open to uncertainty as well.

SPEAKER_00 16:46

I really agree, Kate. I think the um good case, bad case, terrible case is a really good construction. And I think your example of the ER-positive metastatic breast cancer with bone-ary disease with a life expectancy of more than a decade is an excellent one where palliation, well, yeah, strictly according to our definitions, it is. The one that I really struggle with in my practice every day is the melanoma brain metastases, where at Benevo, they've got a 50% chance of a decranial response if they're asymptomatic, but also a high chance of death in the next few months if it doesn't work. So it's either going to be a total train wreck and a complete disaster, or they're gonna be cured. And those two quite dichotomous situations, those two realities that patients have to live with, are very difficult. And then you have the person undergoing a whipple, and we know that most people undergo a whipple, we're gonna recur and die in a very short space of time as well, which actually milanum brain matases are good better outcome than um than buffles do in many ways, just the time frames are a wee bit different. So I think reevaluating the prognosis and updating it frequently is a really important thing to do as well, understanding that prognosis is not a one-off conversation. It's one that you have to revisit. And I personally revisit that at every change in line of therapy. It's important to do that. And we started um on each of our clinic letters, we have a uh diagnosed molecular phenotype, treatment that they're on, and then a treatment intent. And so we use languages like of the brain metastases, for example, likely palliation with a small chance of cure or higher chance of long-term disease control. So phrases like that, which we use to try and communicate and lay language for those patients that get admitted to ICU or for those patients who are seen in primary care, where they can have some language to use as well, which isn't quite that classical uh palliative curative, which, as you say, is uh not all that helpful uh and doesn't reflect the full spectrum uh of uh possible outcomes.

SPEAKER_02 18:30

Yeah. So shout out to Belinda Keighley and her colleagues uh in Sydney who's uh led on some of this work. They published a paper in 2022. I will link that in um to the show notes. But it was interesting that this uh international group was putting it out there that, you know, we also needed to think about changing. This came up in a couple of contexts recently. One was uh defining a minimum data set for MDT software in Victoria, and um at the moment there's a it's that binary choice, and everyone's expected to fill in either curative intent or palliative, which doesn't quite fit it in the modern era, does it? But it's not so simple to create some more drop boxes for the MDT report, I think.

SPEAKER_00 19:17

Anyway, we'll discuss this a lot with our data collection exercises too, Craig. And then people start to get into quite quite reductive, or does it have to be a 5% chance of cure, a 2% chance of cure? What degree of life is this? Yeah, yeah, yeah. Uh and then at some point you have to draw lines and appreciate the rules we use for these terms for data collection purposes are imperfect.

SPEAKER_03 19:35

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.

SPEAKER_01 20:06

Chris,

Send Papers And Claim CME

SPEAKER_01 20:07

I think you got a couple other quickies to tell us about.

SPEAKER_00 20:10

Yeah, I've

System-Level Smoking Cessation That Helps

SPEAKER_00 20:11

got a couple of quickies. There's a paper in the JCO uh just out this month, uh, which is called No Smoker Left Behind. Now, we know that even people with metastatic lung cancer who quit smoking live longer and have fewer complications than people who continue to smoke. So quitting smoking, even when you're diagnosed with advanced cancer, is a good thing to do. Uh, and people often say, Oh, what's the point? I've already got cancer, what's the worst can happen? I'm gonna get more cancer. You go, well, actually, you're gonna live longer if you quit, so it's never too late to quit. But also getting people to quit smoking um remains a challenge, and it's something I think probably we don't do all that well in the clinic, actually, probably, um, because it's a bit confronting, uh, and perhaps we feel it's a bit victim-blamy to talk to people who've already got cancer about their smoking cessation habits. So it's not something which has done well, in my opinion. Um, this particular intervention was uh undertaken at the University of Chicago Comprehensive Cancer Centre, uh, and patients were systematically contacted via interactive voice response, phone calls, texts and emails for up to six months. So it was a whole system approach where the organization took on the responsibility for uh catching up with people rather than just leaving it up to the individual clinician. Um and with this uh systematic response uh and intervention effective, they they helped people quit smoking. About 10% more people quit smoking uh with the intervention than than didn't. Only about uh a quarter to a third of people who were eligible and indeed enrolled, uh, and the cost per patient referred to treatment was about 400 US dollars and the cost per quit was about 6,000 US dollars. So it does cost a bit in terms of the intervention. The uh engagement rates aren't huge, um, but it does actually help some people quit smoking. And if you're looking at things that improve overall survival, uh then this is one of them. So it's important, I think, for institutions and organizations to think about how they engage um with these quit programs. Um, and my third and um final quick bite um was another page.

ctDNA After Liver Metastasectomy

SPEAKER_00 22:00

In the CT DNA suite. This is another paper in circulating tumor DNA. It's a Japanese study which looked at the prognostic and productive value of circulating tumor DNA in people who'd undergone metastasectomy and metastatic colon cancer. Randomised trials of chemotherapy after lived metastasectomy have generally shown improved DFS without convincingly improving overall survival. J. COLGO603 was particularly sobering where post-doptimate modified full FOXIX improved DFS but not OS, and numerically survival went the wrong way. Meanwhile, CT DNA guided treatments not automatically beat better. The Australasian dynamic stage two study, CT DNA guidance, reduced chemotherapy overall, but exposed a higher proportion of treated patients to auxiliplaten without evidence of overall survival benefits. So we've got prognosis a lot, we don't have predictive. Part of the theory in stage two and stage three is maybe we just don't have very good escalation strategies or treatment intensification, whereas we do have that now with bladder cancer. But in live metastasectomy or post-metastasectomy and colon cancer, is that a group where you could escalate therapy if they're CT DNA positive? Well, it's a possibility. This is a prospective registry analysis from Circulate Japan. It was observational, not randomized, 300 patients following curative intent resection of colorectal live metastases using CT DNA personalised tumour-informed SA two to 10 weeks after surgery. And unsurprisingly, post-op CT DNA was an exceptionally strong prognostic marker where those with CT DNA positivity had a fourfold greater risk of recurrence and a ninefold greater risk of death. So again, another study which shows CT DNA is strongly prognostic. Is that enough to mainstream it? No. The provocative finding was among CT DNA positive patients who'd undergone upfront surgery, adjuvant chemo was associated with a markedly better DFS and OS with an adjusted hazard ratio of 0.27. So the advent chemotherapy seemed to work in people who had uh positive CT DNA. So that was that. That was not reproduced in patients who'd already received neoadvent chemotherapy, and this cohort post-op chemo was not associated with better outcomes, irrespective of circulating tumour DNA status. So a little bit more nuanced the situation there as well. CT DNA clearly prognostic, whether it's genuine or predictive, uh, is much less certain. And I think we may need a randomised trial in this exact context where the role of advent chemotherapy in post-op liver resection remains somewhat controversial now.

SPEAKER_02 24:28

And are those trials underway, Chris?

SPEAKER_00 24:30

Do you know? Or I don't know, probably, but I don't know actually. What the current set is the CT DNA trials in stage four colon cancer are correct. Do you have any inside running on that?

SPEAKER_02 24:38

No. I don't know if it's a mad, Kate.

SPEAKER_04 24:41

Well, in your uh group, what are the proportions of CTGNA positive patients? This is a quick bite. This is a quick bite, Kate. Oh, I'm just curious, because if we we're looking at 40% long-term survival, are they just the guys that are negative? Yeah, we put 100% of people with isolated liver mets through quite an intensive proportion, and we expect about 40% of them to do well long time two. So are 40% CTGNA negative? Is it that is it that straightforward or is it is it yeah? So that would be what I would be curious about.

SPEAKER_00 25:08

I need to dig out the paper. I'll tell you what, why don't we uh look that up and put that in the show notes later? Yeah, perfect.

SPEAKER_02 25:13

This is probably silly Christian. Any access to circulating tumor DNA tests in New Zealand?

SPEAKER_00 25:19

There's a whole bunch of people who are doing it investigationally uh in the research context. Uh but again they're personalised uh ones rather than the the bigger panels, Craig.

SPEAKER_02 25:27

Yep, great. Chris has got some kind of boutique beer and cake's got and looks like a savvy blanc. I have to be in the day here, I've got nothing but water.

SPEAKER_00 25:36

I have got Tiny by Garage Project, which is Tiny But Mighty, which I could say is like my ego, tiny but mighty, is non-alcoholic, uh less than 0.5% beer, uh made by Burish Rock New Zealand. Very tasty. It's the tastiest non-alcoholic beer I've ever had. But now just to show that I'm I'm a modern man, I'm moving on to my kombucha. Oh my god.

SPEAKER_04 25:56

So tiny is made in Wellington. I'm not drinking so many of Blanc once, I'm drinking sake, which is made in Queenstown, uh, which is just down the road from Chris. Well, four-hour drive in the in the dark, but yeah, yeah, just down the road from Chris.

SPEAKER_00 26:09

Just across the hill.

SPEAKER_04 26:10

Yeah. But I want

Practical Quick Bites From Breakthrough

SPEAKER_04 26:12

to talk about smoking too, talk about vices. Uh I went to Asco Breakthrough for a variety of reasons, but one of them to hang out with Martin Stopfer, which is always fun. Kira Martin, if you're listening. And Chinese University Hong Kong, uh, they did a very similar study to the one Chris presented, but probably significantly cheaper. So people got one research nurse visit of five to eight minutes. Then they got six months of instant messaging on a text message and four educational videos that they could look up themselves versus people just being told to stop smoking. And the self-reported quit rates six months went from 17% to 26%. So delta very similar to Chris's intervention. And the thing that I find hilarious is they also tested for saliva cotinine, which apparently is a nicotine uh byproduct, and expired air carbon monoxide levels, and then your real quit levels go down to about 2%. But to be fair, smoking is ubiquitous in Hong Kong, so I suspect there's a whole lot of passive smoking going on there. So that that was uh interesting. So if you give people a little bit more support, you can get some more people over the line. My other quick bite came out of also Ask a Breakthrough. There's a supportive care session where the presenters were all people who wouldn't not come from uh backgrounds of a lot of experience being principal investigators. Many of them, this is the first trial that they had designed or run themselves. Many of the people were very young looking. Um this one comes out as this one comes out. I am getting old, I'm 15 October. This is coming out of India. And I think this is really interesting. So this was looking at 150 adult cancer patients. They were one to one, they're people who were about to start oral morphine, they were one to one randomized to oral dexamethasone, given a few hours before their first morphine dose, and the vomiting rate is halved. And that's a very simple intervention. They did point out it's a small group. The six-hour lead time means that you have to leave people without morphine for six hours after you think they might need it. So maybe the lead time needs to be figured with, and they didn't have a placebo. But I think there's something in that. And uh by day five, most people have settled down whether they had the steroids or not, but it decreased nausea and vomiting on day one and day three. There was an interesting conversation thereafter in the room about why are people still using morphine when things like fentanyl and stuff are better. And a lovely lady from India pointed out morphine's dead cheap and still very effective, which I thought was very brave of her in that in that environment. And shout out to Asco Breakthrough, which is finding who it is, and it's becoming an increasingly useful meeting.

SPEAKER_00 28:42

Where would you recommend goes to Esco Breakthrough these days? What sort of people would it be?

SPEAKER_04 28:46

I actually think that youth, young investigators should consider presenting at Asco Breakthrough. It is a small meeting, it's a very friendly meeting because it is in Singapore now. Uh, and actually, to be fair, when it was in Japan too, it is a meeting where you eat at least every hour as part of the meeting. And the poster sessions and stuff, you will have the most amazing researchers walking past and discussing your research with you. It's access to worldwide research in a much more intimate environment, and yet you also have access to incredible speakers. Uh, one of the speakers from uh the Chinese University of Hong Kong has done absolutely remarkable work on the tiny little bits of DNA, the size of the bits that float past. And I've forgotten the word. Anyway, he is just incredible and has just been gifted simultaneously honorary doctorates from universities all over the place as a result of his work. But it's that's just a really interesting meeting. So you're young people, I think, particularly from Asia Pacific, who want to meet like-minded researchers and fine collaborators, it's a really good place to start. And Singapore, so it's easy to access.

SPEAKER_02 29:55

Thank you, Kay. This is a bit like San Antonio used to be the San Antonio Breast Cancer Conference used to be, I don't think it maybe still is with uh cocktails and snacks at the end of the sessions uh at the end of the day. All right. I've got

The Global Cancer Workforce Crunch

SPEAKER_02 30:10

a few things to mention. First one is uh entitled Cancer Workforce a Global Crisis, a Lancet Oncology Commission. So this there was a bit of mainstream media about this, but uh this group did uh some projections uh modelling on the global landscape for 17 common cancers and eighteen workforce personnel types and looked at how many uh cancer workforce people we might be short. And of course, this problem's gonna be the biggest projections of shortages are gonna be in Africa and Asia with a rapidly um uh aging population in those continents. But the projection is something like a shortage of 100 million people in 2050, the largest shortages being 65 million nurses, 16 million radiologists and pathologists, um, and of course that's exacerbated in Africa and Asia. But if we're able to scale up the workforce to avoid those shortages, it's projected to avert 170 million cancer deaths and yield net economic benefits of a US $120 trillion between 2030 and 2050. So that was uh particularly interesting, and they called for um sort of global action with establishing workforce and cancer registries, cross-sector international partnerships to improve access to education and research training programs, implementation of task shifting digital health and artificial intelligence solutions to improve workforce productivity. So it was interesting and quite sobering.

SPEAKER_00 31:45

Craig, I'm gonna get my little wee uh trumpet out. I got invited to do a guest editorial to accompany that Lance Oncology Global Workforce. So that's showing yeah, it's in the same um issue with the Lance Oncology. Yeah. Yeah. Look, a couple of things. I I found the paper or the whole commission absolutely fascinating. It's written by some really big names internationally. It's very well written, very comprehensive work, and the most comprehensive look at the workforce uh issue. One of my part-time jobs is uh helping the National Cancer Services do their planning stuff, and one of the things that was quite salient out of that was that the workforce crisis was only about 10% doctors, you know, like the rest of it was associated with nurses, with pathologists, with path techs, not the pathologists aren't doctors, but uh the non-patient-facing uh workforce as well. So like the numbers of people who we were looking at was mostly non-medical and radiation oncologists, so quite a lot of other specialties there. And we often think in oncology workforce crisis only uh medonc, radonc, surgeon, but it's much, much bigger than that, of course. Yeah. Um and the other thing I think that we need to wrestle with is that um the oncology workforce is actually a global development um issue. Uh, because as the West gets um, you know, more and more well, more and more desperate for workforce, because of course the workforce crisis hits the West as well, is that we start to import people from other countries. And New Zealand and Australia are pretty bad at pinching uh docks and nurses from the Pacific and from low and middle-income countries like Philippines, for example, Indonesia, next door neighbours, pinching their workforce for um healthcare, workforce, healthcare assistance, etc., uh as well. So that becomes quite a big development issue when those countries train up their workers and they then shift to our country as well. So we have to be careful about that, which is difficult because there's a balance between uh human rights of the rights of people to migrate and to move, uh, and yet at the same time it being a development issue that how can they possibly sustain their own uh healthcare systems if we keep pitching their staff all the time? Uh in New Zealand, the healthcare workforce is 40% overseas trained doctors, 40%, four out of the ten doctors are overseas trained. Yeah. So I think it's a country's obligation to actually pony up and develop their own workforces to meet their own needs and not pinch other countries' uh workers off them.

SPEAKER_02 33:53

Great. Thanks, Chris. So I'm gonna find that editorial and A, read it, and B, we'll include that also in the links on the show. I'm worried now that um I picked that one if you'd done that editorial for it. But it's a bit of a landmark paper, isn't it?

SPEAKER_01 34:09

It's gonna be thousands of times.

SPEAKER_02 34:13

The other

Tumour Agnostic Access And Equity

SPEAKER_02 34:14

one just quickly tumour agnostic therapies translating scientific breakthroughs into global implementation. First author, Jenny Liu from Sydney. I was an international group who wrote this position paper pointing out again with the advent of some tumour agnostic listings, how do we bring those benefits to the cancer patients more broadly globally? So they discussed the current position and then talked about a four-pillar framework for equitable implementation, including comprehensive biomarker testing capability, innovative clinical trial designs with support decision support systems, harmonised regulatory approval and reimbursement mechanisms, and investment in genomically competent workforce development. Um, see our recent uh discussion about the global workforce. So good on them for putting out this um framework and again discussing what will be um an important issue going forward. In a tumour-based paper. The Volumab

Topaz-1 Follow-Up In Biliary Cancer

SPEAKER_02 35:18

plus chemotherapy for advanced spillary tract cancer. This is a post-hoc analysis, the TOPO one, Topaz one randomised clinical trial with some follow-up, longer follow-up, up to five years, and median overall survival was 13 months for patients with the Volumab plus Gem CIS and 11 months um for placebo plus Gem Cis. So hazard ratio uh there was statistically significant, but confidence intervals 0.64 to 0.88. So small uh benefit um for these patients. I'm not sure if you have access to a to Villymab in New Zealand or whether you would use it if you do.

SPEAKER_04 36:02

It's obsessionally expensive. So it is something I discuss with patients, but it's a small benefit. Um I think also, and correct me if I'm wrong, gentlemen, um this trial presented PD1 status, but didn't present MMR status with an abiliary trial population, I'm pretty sure. Um and I remember having some concerns about that when it was first published, but I may be wrong. I'm curiously googling.

SPEAKER_02 36:24

Um, yeah, I'm just looking through the tables. It's it's a short report. I don't think they've analyzed it by TMMR cake. They clearly the curves separate, but and there's a tail in the curve with you know, more long-term survivors reference our previous discussion in this episode, but it is a small yeah.

SPEAKER_00 36:42

What increases long-term survivals by 10%, doesn't it? So, I mean I'd frame it as it doesn't help nine out of ten people, and it actually helps one out of ten people quite a lot. And that's an awful lot of money to spend for a one in ten chance of improving your chance of being alive at two years. So it's definitely a statistical benefit, as it clinically meaningful, certainly not a home run, and uh it's a minor incremental, really, and uh the the financial toxicity is quite significant.

SPEAKER_02 37:06

Right. And the last thing I want to mention was just a review again in the Lancet on prostate cancer, it's out in the current print issue. It's

A Fast Update On Prostate Cancer

SPEAKER_02 37:15

basically an up-to-date review of all the recent advances in prostate cancer. There's been a substantial number in the last five years. They talk about the new androgen deprivation therapies, uh, advances in chemotherapy, new targeted therapies, and as well as lutetium, PSMA, radioligame therapy, and PARP inhibitors. Um it is all there. And we mentioned in the last non-ASCO podcast as well the new prostate cancer working group classification system as well. That's not mentioned in this paper, but otherwise it's if anyone wants to uh any trainees, pharma, people, nurses who would like to read a bit more about prostate cancers, they've seen a patient that didn't understand what was happening, it's all there in that paper. That's it.

unknown 38:06

Cool.

SPEAKER_04 38:06

Sorry, just just to hark back, uh 50% of patients we didn't know what their MMR status was in the uh Topaz trial.

SPEAKER_02 38:14

Well done, okay. So that's they weren't being routinely tested at the time that the study was set up, probably.

SPEAKER_04 38:21

Yeah. And no analysis was made on the basis of MMR status.

SPEAKER_02 38:25

Fantastic. All right. Great.

Wrap Up And Where To Find Links

SPEAKER_02 38:28

Lovely to see you all. We'll see you all again in a few weeks. Well, I'll see you all and we'll all listen to us all in a few weeks.

SPEAKER_04 38:37

And Rachel will try and not be too smug on Monday if her team wins the football.

SPEAKER_02 38:46

Good luck with that. All right.

SPEAKER_03 38:51

Thank you.

unknown 38:52

Ta.

SPEAKER_03 38:53

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 oncologynetwork.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.