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Mandelin Rain

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Stage III lung cancer is largely a systemic disease. We give immunotherapy to boost systemic immune response, and it works. Surgery is one of the greatest immunosuppressive treatments we offer.

I have concerns.
 
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xrthopeful

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I sent someone with a t1n1 hpv+ tonsil for TORS. Surgeon thought the margin was threatened so sent him back for xrt.

regretted every moment on sending him for surgery. Probably won’t do it again. Even without chemo, he did awful.

Why did he do awful? He would have done awful with 70 with chemo too? What did surgery have to do with it?

Not sure why this anecdote would prevent you for referring appropriate patients for potential single modality treatment if warranted
 

xrthopeful

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If it's still N2 after neo CRT, then that's just bad biology. Especially with the level of evidence for PORT, it would nearly certainly be useless for those cases too. If it's that bad biology, the met risk is certainly very high and they should get durva. But alas, they operated and can't do that anymore. Better solution? Don't wait to find out about biology, don't operate, and give durva.

It’s bad biology for response to chemo and immunotherapy. You don’t believe radiation can treat these cells?

I’m guessing you say No to all oligomet and all oligoprogression referrals.
 
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Mandelin Rain

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Umm because he had a defect in his oropharynx and was in pain and couldn’t swallow even before we started his therapy
 
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xrthopeful

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Umm because he had a defect in his oropharynx and was in pain and couldn’t swallow even before we started his therapy

A. Good that’s the information we needed.

B. This does not mean you shouldn’t refer patients unless you just don’t trust that ENT’s skill. It would be like one patient who crumped (I’m sure it’s happened) on chemoRT and an ENT saying see radiation sucks
 

FrostyHammer

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It’s bad biology for response to chemo and immunotherapy. You don’t believe radiation can treat these cells?

I’m guessing you say No to all oligomet and all oligoprogression referrals.
No... What I'm saying is that if cN2 disease is still pN2 after nCRT, don't "blame" that on ineffective CRT. Blame it on bad biology. CRT can somewhat compensate for bad biology, though partially at best. DM risk of those bad biology cases is through the roof... They need durva, yet can't get it because they operated.
 

xrthopeful

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No... What I'm saying is that if cN2 disease is still pN2 after nCRT, don't "blame" that on ineffective CRT. Blame it on bad biology. CRT can somewhat compensate for bad biology, though partially at best. DM risk of those bad biology cases is through the roof... They need durva, yet can't get it because they operated.

Gotcha.

I’m pretty sure this patient population will eventually get adjuvant Durva too. Just have to wait for the trial data
 

medgator

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Why did he do awful? He would have done awful with 70 with chemo too? What did surgery have to do with it?

Not sure why this anecdote would prevent you for referring appropriate patients for potential single modality treatment if warranted
The issue I have is when ENT wants to offer someone surgery with extensive oropharynx involvement or a ton of nodal disease tors upfront with the idea of thinking it will be single modality tx
 
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xrthopeful

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The issue I have is when ENT wants to offer someone surgery with extensive oropharynx involvement or a ton of nodal disease tors upfront with the idea of thinking it will be single modality tx

Oh yeah I absolutely agree.

Of all surgeons I feel like ENTs are the most oncologically sound and usually won’t do this but I’m sure there are some
 

Palex80

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Concerning PORT: a recently shown randomized Chinese trial (WCLC 2019) showed no OS-improvement with PORT.

We are still expecting data from LungArt. I‘ve heard rumprs they will report fall 2020, so perhaps WCLC or ESMO 2020.
 

FrostyHammer

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Concerning PORT: a recently shown randomized Chinese trial (WCLC 2019) showed no OS-improvement with PORT.

We are still expecting data from LungArt. I‘ve heard rumprs they will report fall 2020, so perhaps WCLC or ESMO 2020.
Not worried about lack of OS difference, that's not why PORT is done. If we really care about doing things that only improve OS, perhaps we shouldn't be operating in the first place. But don't tell that to the surgeons... Cut first, think later. BTW, fun fact, Lung ART doesn't mandate chemo for pN2.
 
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evilbooyaa

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Interesting discussion. Some folks are on the edge of 'I disagree with your variation of practice and therefore you are a dum-dum', just a pre-emptive heads up to not cross that line.

Couple points:
1) If a patient is deemed resectable (single N2 LN, <3cm, in an accessible location, will not need a pneumonectomy per Albain post-hoc) they are generally offered neoadjuvant chemo (+/- IO if there is an ongoing trial) followed by surgery. RT reserved for pN2 disease. They are also offered a non-surgical option with PACIFIC with feelings of overall similar outcomes.
We almost never do concurrent chemoRT (either neoadj doses or full-dose) anymore as Meta-analyses comparing neoadj. chemo to chemoRT have been negative:

2) Any N2 patient not meeting those criteria, especially multi-station N2, gets chemoRT to 60-66 (attending dependent) with Durva.
3) With current data, whether PACIFIC vs Neoadj Chemo (+/-RT) and surgery is better is unknown.
4) I disagree with @ROFallingDown about a hard and fast definition of 'unresectable' in PACIFIC. I imagine those definitions of resectable (which are not widespreadly adopted) were not widely available at time of PACIFIC delination.
4) The indication for PORT in patients getting chemo --> surgery desperately require a phase III trial. Residual N2 seems to be the primary indication per a few retrospective/database analyses, although there is some interest in lymph node ratio as well:
 
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FrostyHammer

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Interesting discussion. Some folks are on the edge of 'I disagree with your variation of practice and therefore you are a dum-dum', just a pre-emptive heads up to not cross that line.

Couple points:
1) If a patient is deemed resectable (single N2 LN, <3cm, in an accessible location, will not need a pneumonectomy per Albain post-hoc) they are generally offered neoadjuvant chemo (+/- IO if there is an ongoing trial) followed by surgery. RT reserved for pN2 disease. They are also offered a non-surgical option with PACIFIC with feelings of overall similar outcomes.
We almost never do concurrent chemoRT (either neoadj doses or full-dose) anymore as Meta-analyses comparing neoadj. chemo to chemoRT have been negative:

2) Any N2 patient not meeting those criteria, especially multi-station N2, gets chemoRT to 60-66 (attending dependent) with Durva.
3) With current data, whether PACIFIC vs Neoadj Chemo (+/-RT) and surgery is better is unknown.
4) I disagree with @ROFallingDown about a hard and fast definition of 'unresectable' in PACIFIC. I imagine those definitions of resectable (which are not widespreadly adopted) were not widely available at time of PACIFIC delination.
4) The indication for PORT in patients getting chemo --> surgery desperately require a phase III trial. Residual N2 seems to be the primary indication per a few retrospective/database analyses, although there is some interest in lymph node ratio as well:
Great points, but three things need clarification:

1) Being "deemed resectable" is often done in practice. However, in reality, the first step after diagnostic workup should NOT be to "deem resectability". It assumes that surgery deserves to be the initial gatekeeper. And again, in practice, they are. But they most certainly do not deserve it. Surgery has done and earned nothing to deserve that. I understand you referred to that in the sense of what mostly occurs in practice, but I vehemently disagree that it should.

2) "They are also offered a non-surgical option with PACIFIC with feelings of overall similar outcomes." - I really hope this does not happen. As written later on in the post, these have never been compared. However, it's not that much of a stretch to reason that if you compare surgical based approaches vs definitive CRT minus durva, they're all equivalent. Tons of prospective data on that. And if definitive CRT + durva massively improved PFS and OS over that without durva, it's a HIGH likelihood that durva is the only reason why it would be superior to surgical based approaches. However, if you did surgical based approaches with durva, does that change things? Potentially. That's what we really can't comment on. But the point is that durva is a POWERFUL drug. If you really want to operate for some unproven theoretical benefit, withhold durva at your own risk.

3) I would highly recommend not sleeping on neoadj CRT (when comparing to chemo alone). We should NOT interpret those meta analyses like surgeons by stating that "OS not improved, it's thus useless". Not correct. RT's value in the neoadj setting is NOT to change OS (hell, if that's the motivation, then why are we operating in the first place?). But it has many practical advantages to chemo alone. Firstly, chemo isn't a local therapy and depending on the series you read, up to (but not always) 20% of patients can progress on chemotherapy alone (compared to less than 5% when adding radiation). That's what a suboptimal neoadj therapy will get you. And once the patient progresses, you've basically eliminated surgery as an option and now you have to give definitive CRT having given only induction chemo. But alas, now you're stuck giving induction chemo followed by CRT, which we know from randomized data that it does nothing for outcomes and increases toxicities. And BTW, since they progressed, they're not a durva candidate either, and thus you leave them with literally no options. Thus, adding RT preserves all management options. Second, take to any surgeon and they'll tell you about the importance of mediastinal downstaging. Chemo alone can never match CRT for this. Thus, you give chemo alone for cN2, mediastinum has a very high chance to stay pN2, then you gotta give Port anyway. What have you really accomplished in that case? All you get is blame from surgeons who quote old Port meta analysis data and say that Port is unsafe. You try to assuage them about Port, but it's very hard to defend Port given its quality of evidence especially as compared to neoadj CRT (see argument above despite no OS difference). Third, draw an analogy to esophageal and rectal cancers, for which adding neoadj radiation similarly does not statistically add outcome benefits, but does have several similar practical advantages for which surgeons don't whine about adding RT.
 
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xrthopeful

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i would rather give pre-op RT over PORT all day.

1) lower dose
2) patients aren't deconditioned like post-op when we have to then get them through RT
3) shorter overall package time for patient

lots of patients get their 'PORT' skipped at the back-end when they are 'too sick' from surgery


pre-op chemo alone --> surgery --> PORT is a much less favorable approach IMO

this will soon be a moot point of course with pre-op chemo/IO soon being SOC
 

medgator

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what are you doubting?

don't talk about things you don't understand or know about.
I've been treating lung cancer longer than you've been eating avocado toast, son. Outside of specific scenarios like a large tumor etc, very little proven role for surgery at all in these patients
 
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xrthopeful

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Okay, you are right. For patients undergoing surgery, induction IO/Chemo data is terrible and not promising at all in multiple trials now. no future there, nope!

you should stick to stuff you're suited for.
 

PhotonBomb

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i would rather give pre-op RT over PORT all day.

1) lower dose
2) patients aren't deconditioned like post-op when we have to then get them through RT
3) shorter overall package time for patient

lots of patients get their 'PORT' skipped at the back-end when they are 'too sick' from surgery


pre-op chemo alone --> surgery --> PORT is a much less favorable approach IMO

this will soon be a moot point of course with pre-op chemo/IO soon being SOC


agreed.

would also add that there is better data supporting RT in neoadjuvant setting than the PORT setting, where basically we are hanging out hat on the PORT meta-analysis and a subset of the ANITA trial...

of course this is institutional. Ive been at both, and if you get stuck at an institution where the med onc likes pre-op chemo, then you're stuck waiting until the back end, hoping they send your way if N2.

The pre-op chemo/immunotherapy trials all allow PORT at least, but with the excellent response rates, good amount of clearance of N2 disease, removing the nee for PORT. GREAT for patients, but bad for the role of RT in operable stage III...
 

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One issue that has not really been addressed with the addition of Durva to Stage III (nor do I think there is sufficient appetite to do so) is the age old question of adjuvant vs. salvage. Is there is a benefit of adjuvant immunotherapy (PACIFIC) vs. salvage chemoimmunotherapy (KEYNOTE-189) vs. salvage dual checkpoint blockade (CheckMate 227)?
 

xrthopeful

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One issue that has not really been addressed with the addition of Durva to Stage III (nor do I think there is sufficient appetite to do so) is the age old question of adjuvant vs. salvage. Is there is a benefit of adjuvant immunotherapy (PACIFIC) vs. salvage chemoimmunotherapy (KEYNOTE-189) vs. salvage dual checkpoint blockade (CheckMate 227)?


right, this is a GREAT question. hope we get some good data on this soon.

even in the metastatic setting the keynote vs checkmate, would love to see a head to head but will never happen.
 

evilbooyaa

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@medgator attack the argument not the individual making the argument.

NCCN already defines induction chemo as A standard of care. Not the cat 1 rec for IIIA/N2 but is an acceptable one. If we get the systemic benefits of IO in upfront will surgery have better outcomes than RT in well-selected patients? Potentially.

@FrostyHammer I don't disagree with you on the value of RT in terms of mediastinal downstaging, just defining my institutional practice and the fact that it doesn't worsen oncologic outcomes. Surgeons wanna surgerize and they (here at least) prefer to do it without RT in the neoadjuvant setting.
 
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xrthopeful

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@medgator attack the argument not the individual making the argument.

NCCN already defines induction chemo as A standard of care. Not the cat 1 rec for IIIA/N2 but is an acceptable one. If we get the systemic benefits of IO in upfront will surgery have better outcomes than RT in well-selected patients? Potentially.


This may potentially be true, but I wasn't even going this far. I was just saying that the preferred SOC induction strategy for patients going to surgery won't be chemo or chemoRT, it will be IO/Chemo.
 

FrostyHammer

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This may potentially be true, but I wasn't even going this far. I was just saying that the preferred SOC induction strategy for patients going to surgery won't be chemo or chemoRT, it will be IO/Chemo.
Right. And medgator was stating correctly that even though that may eventually come true, it still doesn't address the poor evidence for doing surgery in the first place. Sadly, those neanderthal surgeons will use it as evidence to cut, and say that if chemo/IO is given then it's OK to cut. Typical misinterpretation like their neverending misinterpretation of the Albain data.
 
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FrostyHammer

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@medgator attack the argument not the individual making the argument.

NCCN already defines induction chemo as A standard of care. Not the cat 1 rec for IIIA/N2 but is an acceptable one. If we get the systemic benefits of IO in upfront will surgery have better outcomes than RT in well-selected patients? Potentially.

@FrostyHammer I don't disagree with you on the value of RT in terms of mediastinal downstaging, just defining my institutional practice and the fact that it doesn't worsen oncologic outcomes. Surgeons wanna surgerize and they (here at least) prefer to do it without RT in the neoadjuvant setting.
Totally understand. I hope when you get out into practice that you advocate for definitive even though you may not be used to it in training. Literally the only reason neoadj radiation is often withheld is because of surgeon whining. So I think we have a right to whine about operating in the first place!
 
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xrthopeful

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I did. And responded to the snide comment addressed to me.

Surgery isn't cat 1 in the nccn for a reason....


again, this is besides the point.

the discussion was about the optimal induction strategy for patients going to surgery. the the questioning of the role of surgery was not even germane.
 
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