ESMO 2025

[BobbyHeenan]

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Yes

I already see med onc itching to do it, but we have a fantastic CT surgeon who doesn't really endorse use for trying to convert/downstage cases so he then typically sends for chemo-XRT..but I can see what is coming.

 

[HolySmokes]

This allows for downstaging too (which prior phase III neoadj chemo-IO did not).

Yikes. Are we about to see every stage III lung case get chemo-io up front to see if then can go to surgery? Looks like a small trial but those curves aren't good for radiation.

Hard for me to grasp just how bad this could be for rad onc. If this data holds true, why WOULDN'T you give every stage III chemoIO upfront?

 

[BobbyHeenan]

Hard for me to grasp just how bad this could be for rad onc. If this data holds true, why WOULDN'T you give every stage III chemoIO upfront?

Yes.

Lots of patients can't get through any surgery, very poor lung function, etc.

. But anything even in a zip code of possibly operable is going to to go straight to chemo-IO.

 

[TheWallnerus]

Hard for me to grasp just how bad this could be for rad onc. If this data holds true, why WOULDN'T you give every stage III chemoIO upfront?

You wouldn’t for the same reason many rad oncs still give PORT for NSCLC: inertia.

“A new scientific truth does not triumph by convincing its opponents… but rather because its opponents eventually die, and a new generation grows up that is familiar with it.”
- Max Planck, talking about rad oncs evidently (jk)

 

[OTN]

Chemoimmunotherapy followed by resection, whether or not it's resectable upon presentation, is very clearly going to be the standard of care soon. The only patients we will be seeing will be those who are inoperable medically, never convert to operable after systemic treatment, or those with positive SM/gross disease left behind after an operative attempt.

However, I would bet the Stage I SBRT vs surgery data will favor SBRT, so we'll claw a little of that back.

 

[TheWallnerus]

However, I would bet the Stage I SBRT vs surgery data will favor SBRT, so we'll claw a little of that back.

 

[yesmaster]

Over half of nsclc stage 3 patients progress after radiation in less than a year? It’s definitely worse than Pacific which is not the comparator arm.

I agree that chemo/IO/surgery is becoming more popular but I will kick and scream in favor of pacific until there’s long term comparative OS data.

It may also be a nothing burger just like the pdL1 vegf bispecific for stage 4 nsclc is in limbo and hasn’t replaced Keytruda

 

[BobbyHeenan]

Chemoimmunotherapy followed by resection, whether or not it's resectable upon presentation, is very clearly going to be the standard of care soon. The only patients we will be seeing will be those who are inoperable medically, never convert to operable after systemic treatment, or those with positive SM/gross disease left behind after an operative attempt.

However, I would bet the Stage I SBRT vs surgery data will favor SBRT, so we'll claw a little of that back.

That's where I'm at now. Not sure which Kubler-Ross stage of grief that is though.

However, I do think the surgeons are going to say that lobectomy isn't standard of care anymore and will push for sublobars still in stage I patients.

 

[TheWallnerus]

Those radiotherapy results do not align with what I have seen in clinical practice. However, the data is indeed the data.

https://www.nejm.org/doi/full/10.1056/NEJMoa1709937

 

[Palex80]

Although we do have some data from phase II trials concerning IO —> CRT for stage III NSCLC, one possible explanation why this treatment combination in the Chinese trial seems to produce worse results than PACIFIC, may simply be the sequence.

Perhaps, any positive effect of a neoajuvant IO is ruined when 60 Gy land on the nodes and kill off any immune response. Perhaps this effect is not only not beneficial, but even detrimental compared to the s.o.c. CRT.

Think of the Javelin 100, with concurrent IO+CRT being worse than plain CRT in unresectable HNSCC.

If the concept of „chemo+IO followed by (C)RT“ is proven wrong, we may end up seeing the same in other proposed trials, like esophageal & cervical cancer. It may even restrict use of RT in the adjuvant setting, for some cancers.

Last, but not least, patients on the RT arm basically got sequential chemo-RT, not concurrent chemo-RT. Also, an inferior treatment.

 

[taserlaser]

Although we do have some data from phase II trials concerning IO —> CRT for stage III NSCLC, one possible explanation why this treatment combination in the Chinese trial seems to produce worse results than PACIFIC, may simply be the sequence.

Perhaps, any positive effect of a neoajuvant IO is ruined when 60 Gy land on the nodes and kill off any immune response. Perhaps this effect is not only not beneficial, but even detrimental compared to the s.o.c. CRT.

Think of the Javelin 100, with concurrent IO+CRT being worse than plain CRT in unresectable HNSCC.

If the concept of „chemo+IO followed by (C)RT“ is proven wrong, we may end up seeing the same in other proposed trials, like esophageal & cervical cancer. It may even restrict use of RT in the adjuvant setting, for some cancers.

Last, but not least, patients on the RT arm basically got sequential chemo-RT, not concurrent chemo-RT. Also, an inferior treatment.

Your last point is an important one. And you’re right, it is interesting how hidden rt immune effects are purported to influence all these IO trials. I suspect you’re right on RT in the adjuvant setting for many cancers. NSABP-51 and the TNBC cohort also give the side eyes here 👀

 

[medgator]

Chemoimmunotherapy followed by resection, whether or not it's resectable upon presentation, is very clearly going to be the standard of care soon.

I think it will be like esophagus. If you don't have access to a good multiD surgical team nearby these pts will continue to get chemo rads.

Amazing to consider when you consider there was no survival benefit to surgery in stage 3 nsclc in the intergroup RCT

 

[madchemist89]

After ESOPEC, no more esophagus here. I went from commonly treating esophageal cancer to nothing overnight. There are no surgeons who do esophagectomy here. Med onc is treating everyone with FLOT.

 

[medgator]

After ESOPEC, no more esophagus here. I went from commonly treating esophageal cancer to nothing overnight. There are no surgeons who do esophagectomy here. Med onc is treating everyone with FLOT.

Not everyone can tolerate it and not really sure it addresses local sx as well.

 

[madchemist89]

I’m not arguing the efficacy of the treatment. I’m stating that any trials showing that systemic therapy can potentially eliminate RT we can expect most med oncs are going to run with it, sometimes inappropriately.

 

[BobbyHeenan]

I’m not arguing the efficacy of the treatment. I’m stating that any trials showing that systemic therapy can potentially eliminate RT we can expect most med oncs are going to run with it, sometimes inappropriately.

yes. Esophagus will continue now that FLOT+immunotherapy trial was showing benefit.

I think for places that don't have regular CT surgery they will just start chemo-IO and work on getting an out-of-town CT surgeon to eval them "at some point" down the road. It actually makes the med onc decision making easier in many ways.

 

[Palex80]

NSABP-51 and the TNBC cohort also give the side eyes here 👀

Imagine, someone evaluated patients with TNBC receiving neoadjuvant IO+chemo and then looking at outcomes depending on the receipt of adjuvant RT, matching for stage.

Could it be that the cT1-cT2 cN0 that went on to mastectomy without PMRT have better outcomes than the ones with BCS+RT?
Simply because post-BCS RT of the breast compromised the IO effect?

Anyone aware of any data?

 

[medgator]

I’m not arguing the efficacy of the treatment. I’m stating that any trials showing that systemic therapy can potentially eliminate RT we can expect most med oncs are going to run with it, sometimes inappropriately.

I guess it depends on who you work with. Just treated a pt with low volume m1 disease who got FOLFOX

 

[OTN]

I guess it depends on who you work with. Just treated a pt with low volume disease who got FOLFOX

I agree- my medoncs routinely still send for chemoRT in patients who cannot get surgery, or for chemoRT in patients who cannot tolerate FLOT. If your medoncs are saying each and every esophageal patient can tolerate FLOT then I'm afraid they're not being thoughtful physicians.

Edit: I should probably say that the relationships I have with all the medoncs in my practice are ones that I have very, very carefully curated over the years, and I would strongly recommend to new radonc attendings to do the same. I think it has helped move the needle, but it's a process that takes years to bear fruit. You have to make sure they know when you are not recommending RT, so when you do recommend RT they know it's a sincere recommendation. I'm also not saying the above poster hasn't done the same- sometimes no matter what you do they're practice patterns are going to be stable.

 

[taserlaser]

Imagine, someone evaluated patients with TNBC receiving neoadjuvant IO+chemo and then looking at outcomes depending on the receipt of adjuvant RT, matching for stage.

Could it be that the cT1-cT2 cN0 that went on to mastectomy without PMRT have better outcomes than the ones with BCS+RT?
Simply because post-BCS RT of the breast compromised the IO effect?

Anyone aware of any data?

That would indeed be an interesting question. Haven’t seen anything yet. Pre IO era for sure that data exists for breast cancer in general, not sure if by molecular subtype and of course favors BCS+RT

 

[yesmaster]

Yeah I would just be cautious about reading too much into a 40 patient phase 2 abstract with non-SOC radiation arm and assuming nsclc will go the way of esophageal adeno. Perhaps the data will eventually favor surgery, perhaps not

 

[yesmaster]

Breast is a totally different story, it’s hard to justify mastectomy and subsequent healing as being less immunosuppressive that bcs/RT

The role of surgical tissue injury and intraoperative sympathetic activation in postoperative immunosuppression after breast-conserving surgery versus mastectomy: a prospective observational study - PubMed

This pilot study revealed substantial early postoperative immune suppression after BCS and mastectomy that appears to recover in the following days. Differences between BCS and mastectomy in release of DAMPs and intraoperative sympathetic activation could affect postoperative immune homeostasis...

pubmed.ncbi.nlm.nih.gov