Neoadjuvant FLOT/MAGIC vs. CROSS in Distal Esophageal

[evilbooyaa]

The bolded is your problem my friend. Potentially resectable patients far outnumber patients who are outright unresectable. The longer a trial goes on, the more expensive it is. On top of that, unresectable patients have more issues with competing mortality. Everyone doling out the cash wants the most immediate ROI they can get. But, since the distant met rate after surgery and SOC approaches 50%, it is very feasible to do an adjuvant IO trial in resected patients. And the trial has already been done. And was positive. Checkmate577:

https://www.nejm.org/doi/full/10.1056/NEJMoa2032125

I am aware of adj Nivo after surgery... as I mentioned in my post...

Most of my esophageal cancer patients don't get surgery. That could be because of the severity of the disease or them refusing esophagectomy due to the QoL hit. There should be a trial evaluating consolidative IT in those who do not get surgery, perhaps including those hwo refuse surgery as well.

I don't know if surgery is still worth it in these patients whether the QoL is worth it for most of the 75-80 year olds I see.

---

Members don't see this ad.

 

[ramsesthenice]

Most of my esophageal cancer patients don't get surgery.

Interesting. Globally that is not typical since adenocarcinomas became the predominate histology (ie, most of your patients don't have emphysema or alcoholic cirrhosis anymore). At least not a high volume centers. From that perspective, everything you said makes good sense. I also completely agree with you that the role of esophagectomy for borderline medically inoperable or elderly patients is really questionable from a QoL perspective.

 

[heartisinradonc]

Interesting. Globally that is not typical since adenocarcinomas became the predominate histology (ie, most of your patients don't have emphysema or alcoholic cirrhosis anymore). At least not a high volume centers. From that perspective, everything you said makes good sense. I also completely agree with you that the role of esophagectomy for borderline medically inoperable or elderly patients is really questionable from a QoL perspective.

How many of these patients become non resectable after the neoadjuvant dose of RT per CROSS? Thats the problem. Should we just be treating them all to 50.4Gy so they get their best shot? CROSS is pre dominant in AUS/NZ for adenos but so many progress.

 

[ramsesthenice]

How many of these patients become non resectable after the neoadjuvant dose of RT per CROSS? Thats the problem. Should we just be treating them all to 50.4Gy so they get their best shot? CROSS is pre dominant in AUS/NZ for adenos but so many progress.

In the US, when we say CROSS, we really mean mean carbo/tax instead of cis/fu (as per Teppers CALGB trial). Multiple pattern studies show the mean dose in the US is essentially 50 Gy. I typically plan for 50/25 and have a low threshold to stop after 40 if patients are struggling since there is no efficacy difference between the 2 trials.

What do you mean about progression? I don’t think I’ve ever seen in field progression. I’ve seen distant disease pop up that makes them unresectable but fortunately even that is rare. Of course, one of those times for me was one of the few times I treated a relative (not first degree, I don’t go there).

 

[medgator]

In the US, when we say CROSS, we really mean mean carbo/tax instead of cis/fu (as per Teppers CALGB trial). Multiple pattern studies show the mean dose in the US is essentially 50 Gy. I typically plan for 50/25 and have a low threshold to stop after 40 if patients are struggling since there is no efficacy difference between the 2 trials.

What do you mean about progression? I don’t think I’ve ever seen in field progression. I’ve seen distant disease pop up that makes them unresectable but fortunately even that is rare. Of course, one of those times for me was one of the few times I treated a relative (not first degree, I don’t go there).

I'm biased to going to 50.4 as are many i bet who have seen one too many a patient back out of, or not be a candidate for surgery. Nearest gi surg onc is 60-70 miles away so there are logistical challenges for us

 

[thesauce]

What the medoncs got away with in lymphoma is now being pushed in every disease site: just publish a whole bunch of papers with inferior outcomes and put the conclusion at the end of the paper that it should still be done because of toxicity from RT, even when the toxicity of the chemo alone arm is higher.

 

[medgator]

What the medoncs got away with in lymphoma is now being pushed in every disease site: just publish a whole bunch of papers with inferior outcomes and put the conclusion at the end of the paper that it should still be done because of decreased toxicity from RT, even when the toxicity of the chemo alone arm is higher.

I'm not seeing this push away from RT in goose, maybe it's just my neck of the woods.... Definitely more so in gastric though

 

[heartisinradonc]

What the medoncs got away with in lymphoma is now being pushed in every disease site: just publish a whole bunch of papers with inferior outcomes and put the conclusion at the end of the paper that it should still be done because of decreased toxicity from RT, even when the toxicity of the chemo alone arm is higher.

What they have done with lymphoma is absolutely shameless. There is going to be an entire generation of people in their 40s with cardiac functions of 100 year olds. Yeah, sure, you guys have improved your systemic therapies, thats nice and all, but RT delivery/technique has been completely revolutionised. These people still think we do inverted Ys and have no understanding of DIBH, but apparently their new strategy of replacing one toxic systemic therapy with another is a 'game changer'.

 

[ramsesthenice]

I'm not seeing this push away from RT in goose, maybe it's just my neck of the woods.... Definitely more so in gastric though

Me neither. Gastric is pretty much gone. Only Gastrics I treat anymore are the ones that have no pathologic response to neoadjuvant FLOT (which is more than I would expect). In my neck of the woods, it’s honestly more surgeon driven than med Onc. Very old school guy does most of the gastrectomies and he hard core thinks there is no role for focal therapy for a “systemic disease” after D2 resection. Even when patients still have 10+ positive nodes post FLOT, the whole group has to explain why we are not going to just do more chemo. It’s crazy.

 

[metallica81788]

Where are you people finding these goose patients that actually get surgery?

 

[heartisinradonc]

I have some creative med oncs who also believe in radiation (amazing what being in a multi specialty group with machine ownership will do).

5040+chemo followed by short interval EGD with persistent disease? Easy immuno approval

Rad oncs shouldn't need to convince med oncs in RT. It is proven that RT as sole treatment or in multimodality management provides best chance of cure in nearly every solid tumour..med oncs are the one should need to show evidence for any efficacy from their treatment modality, especially including breast cancer where their regimens are becoming increasingly aggressive. 5 year survival in any locally advanced oesophageal adeno is absymal; aim should be to provide as much physiological function as possible in the invariable failure.

 

[ramsesthenice]

Nearest gi surg onc is 60-70 miles away so there are logistical challenges for us

This right here is why I (and others at high volume centers) see so many patients who do get surgery. A lot of people who can afford it just want to do everything at the same place because the surgeon told them it helps with logistics. There is some truth to it for the people who have bumps along the way but honestly in our area this is an example of one bad apple poisoning the pool for everyone in the community. There is one practice in our region that single handedly drives surgeon fear of community rad oncs. I’m doing “salvage” T&O right now. What’s that you ask? That’s when you start the T&O for a FIGO 2b cervical tumor 12 weeks post EBRT because the original doc realized at the 12 week post treatment PET scan they forgot to refer back for the Brachy boost. Oops 😅

Everyone else is great. I have the email and cell for most of the community folks in our state and we work great together. If there are any issues they let me know right away, I loop in the surgeons, and everything is fine. My nurse is outstanding about following up to get treatment schedules once folks I refer out are simulated so we can help coordinate surgical planning. It’s extremely doable for folks who communicate well and are good with logistics.

 

[evilbooyaa]

How many of these patients become non resectable after the neoadjuvant dose of RT per CROSS? Thats the problem. Should we just be treating them all to 50.4Gy so they get their best shot? CROSS is pre dominant in AUS/NZ for adenos but so many progress.

Have not, to this day, treated a patient with 41.4 as an attending. I am not seeing easily resectable T3N0 healthy 50 year olds with esophageal adenos. Most of them are in their 70s, and/or have significant other co-morbidities that make resection not a slam dunk. One guy had a mid thoracic esophageal with a lymph node abutting cervical esophagus. I'm glad I took him to 50 because surgeon saw him post-RT, asked the patient (and me) why he was treated to 50Gy, and then didn't operate on him because he wasn't surgically resectable. He called me with a mea culpa after I had taken him to ask for 50Gy in a bulky N2 esophageal adeno pt.

 

[deleted1111261]

If I don’t know surgeon or their practice pattern, I tend to ask what dose they expect pre-op. It’s harrowing going to 41.4 Gy. It’s seemingly homeopathic. Not that there is anything wrong with. 45 Gy seems to make surgeon happy, but still feels low. This cancer - where preop and definitive dose are the same. Odd.

 

[Palex80]

This cancer - where preop and definitive dose are the same. Odd.

Astro °II would like to have a word with you.
(although that would be adjuvant and definite)

 

[heartisinradonc]

Have not, to this day, treated a patient with 41.4 as an attending. I am not seeing easily resectable T3N0 healthy 50 year olds with esophageal adenos. Most of them are in their 70s, and/or have significant other co-morbidities that make resection not a slam dunk. One guy had a mid thoracic esophageal with a lymph node abutting cervical esophagus. I'm glad I took him to 50 because surgeon saw him post-RT, asked the patient (and me) why he was treated to 50Gy, and then didn't operate on him because he wasn't surgically resectable. He called me with a mea culpa after I had taken him to ask for 50Gy in a bulky N2 esophageal adeno pt.

How many T1-T3N0M0s have you seen without locoregional progression 5 years out post definitive surgery? I have seen none, and I thought historical numbers were 20-40% at 5 years, basically the same as a definitive RT approach. To me talking about resectability of distal esophageal is like talking about whipple's as "potentially curative" for pancreas. I think CROSS protocol has caused so many problems.

 

[seper]

There is a fair chance of cure after tri-modality therapy.
Most people stick to 50 Gy/25 for now

 

[RSAOaky]

I treat them all to 50.4 and honestly don't see a lot of issue in terms of toxicity. If someone is really struggling to get through then I'm OK with stopping at 41.4 and if someone has a really large tumor then I may conedown to gross disease at 41.4 but I concur with everyone's experience that a not insignificant number of these patients don't make it to surgery and so I'm happier knowing they got a truly definitive dose.

 

[deleted1111261]

I treat them all to 50.4 and honestly don't see a lot of issue in terms of toxicity. If someone is really struggling to get through then I'm OK with stopping at 41.4 and if someone has a really large tumor then I may conedown to gross disease at 41.4 but I concur with everyone's experience that a not insignificant number of these patients don't make it to surgery and so I'm happier knowing they got a truly definitive dose.

Are we all waiting for yet another de-escalation study of pre-op 41.4 vs 50.4? It will be non-inferiority. Then, can test 30/10, non-inferiority of course. Then 20/5. Then back to 0 - no RT at all.

What a joke of a field. 😂

 

[deleted941485]

Are we all waiting for yet another de-escalation study of pre-op 41.4 vs 50.4? It will be non-inferiority. Then, can test 30/10, non-inferiority of course. Then 20/5. Then back to 0 - no RT at all.

What a joke of a field. 😂

That’s how we lose rectal. Breast is up next.

 

[RickyScott]

Are we all waiting for yet another de-escalation study of pre-op 41.4 vs 50.4? It will be non-inferiority. Then, can test 30/10, non-inferiority of course. Then 20/5. Then back to 0 - no RT at all.

What a joke of a field. 😂

Btw The 4140 comes from treating appa on these trials 20 years ago so spine stays within tolera
Nce

 

[deleted1111261]

Btw The 4140 comes from treating appa on these trials 20 years ago so spine stays within tolera
Nce

Wait til evicore starts making us do complex isodose on these

 

[evilbooyaa]

How many T1-T3N0M0s have you seen without locoregional progression 5 years out post definitive surgery? I have seen none, and I thought historical numbers were 20-40% at 5 years, basically the same as a definitive RT approach. To me talking about resectability of distal esophageal is like talking about whipple's as "potentially curative" for pancreas. I think CROSS protocol has caused so many problems.

Well I haven't been an attending for 5 years yet, so.... 0. Only like 2 of my patients have gotten surgery out of the 8-10 I've treated thus far?

I don't disagree that re-assessing value of surgery is warranted. See my posts previously. But SOC for these patients, if resectable and willing to proceed w/ the toxicity hit of it (worse than a Whipple, IMO), is to get the surgery, especially for esophageal adenoCa.

I mean... whipple and esophagectomies are both gonna be done until there is evidence to say we don't have to.

 

[jondunn]

There will never be evidence not to do a whipple unless systemic therapy improves 100 fold

 

[heartisinradonc]

There will never be evidence not to do a whipple unless systemic therapy improves 100 fold

I'll take a whipple's 100 times out of 100 over any systemic therapy

 

[ramsesthenice]

How many T1-T3N0M0s have you seen without locoregional progression 5 years out post definitive surgery? I have seen none, and I thought historical numbers were 20-40% at 5 years, basically the same as a definitive RT approach. To me talking about resectability of distal esophageal is like talking about whipple's as "potentially curative" for pancreas. I think CROSS protocol has caused so many problems.

I have treated around 3-4 esophageal cases per month at a high volume center for the last six years. Surgery improves locoregional control after preop chemo rads for distal adenos. Hands down. I’d have to pull the numbers but it’s way over 50%. With primary chemoradiation alone, long term local control in clinical complete responders (not even including all comers) is not even 50%. I’ll grant you, we are talking about all comers and I suspect if we did a better job of defining complete responders there will be a cohort that probably doesn’t benefit from surgery. I would be very supportive of trials to figure that out. But at this time, in unselected patients, preop+ surgery wins.

 

[heartisinradonc]

I have treated around 3-4 esophageal cases per month at a high volume center for the last six years. Surgery improves locoregional control after preop chemo rads for distal adenos. Hands down. I’d have to pull the numbers but it’s way over 50%. With primary chemoradiation alone, long term local control in clinical complete responders (not even including all comers) is not even 50%. I’ll grant you, we are talking about all comers and I suspect if we did a better job of defining complete responders there will be a cohort that probably doesn’t benefit from surgery. I would be very supportive of trials to figure that out. But at this time, in unselected patients, preop+ surgery wins.

I completely agree, primary RT to 50.4 Gray with chemo and no surgery is not going to be upwards of 50% long term but neither is a primary surgical approach omitting RT. How have your parents fared in terms of long term toxicity post trimodal therapy?

 

[ramsesthenice]

I completely agree, primary RT to 50.4 Gray with chemo and no surgery is not going to be upwards of 50% long term but neither is a primary surgical approach omitting RT. How have your parents fared in terms of long term toxicity post trimodal therapy?

I’m sorry, I thought you were referring to trimodality, not surgery alone. Our guys so rarely even attempt it because you are right, local control with surgery alone for anything other than T1N0 (which since we don’t screen are essentially non existent) is piss poor.

Long term toxicity depends on a lot of different things of course but it’s what you would expect. Swallowing function isn’t totally normal and people have to adjust their eating habits (similar to post-Whipple without all the exocrine deficiencies). Anastomotic structures are fairly common but typically addressable with dilation. The biggest problem isn’t treatment toxicity. It’s that half of them still end up meting out eventually even after chemorads and surgery. It’s the best of what we got and I would absolutely take it if I needed to but admittedly I’d feel a lot better about going through all of that if my chances were better.

 

[jondunn]

who is doing surgery alone? no one.

 

[ramsesthenice]

who is doing surgery alone? no one.

Pretty much the only cases of esophagectomy alone should be completion esophagectomies post EMR with high risk features.

 

[medgator]

Pretty much the only cases of esophagectomy alone should be completion esophagectomies post EMR with high risk features.

I've seen several of those pts getting chemo/RT.... Wouldn't they have gotten esophagectomy instead of EMR in the first place if they were surgical candidates?

 

[ramsesthenice]

I've seen several of those pts getting chemo/RT.... Wouldn't they have gotten esophagectomy instead of EMR in the first place if they were surgical candidates?

Not necessarily. If by EUS they are T1N0 it’s reasonable to attempt EMR instead of an esophagectomy regardless of respectability. A good boards question is what are the criteria to determine if completion surgery is needed.

And your right, I have done preop for a lot of these depending on which features are high risk. If it’s superficial but over 2 cm it’s reasonable to go right to surgery. High grade with LVSI…nope. You know there will be positive nodes on path.