Converting Neoadjuvant to Definitive Esophageal?

[Haybrant]

Treated a guy for GEJ adeno per CROSS (but went to 5040); he refused a J-tube up front. Developed quite a bit of esophagitis, was hospitalized for dehydration/thromobocytopenia/anemia half way through treatment then improved after hospitalization. Sent him for J-tube but he was doing better at that point and refused tube again. Completed treatment with significant esophagitis and had last cycle chemo held for persistent thrombocytopenia. Now he has been hospitalized with persistent nausea (does have a tube now) now 2 wks since RT and an ECHO that shows a drop in his EF. If he ends up not being a surgical candidate, what do you do now? Does not appear to be in good shape for more RT right now. 2 wk post tx PET shows persistent uptake in the lesion SUV only slightly reduced . CROSS shows 23% CR for adenos, not so sure he will be the 1 in 5.

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[Gfunk6]

If you went to 50.4 Gy and surgery is a no go, then you are done. Only thing you can do is systemic chemo.

 

[seper]

Done, nothing else to do. This situation is very common. For my surgeons, everyone with heartbeat is for neoadjuvant.

 

[seper]

Also, PET 2 weeks after radiation is pretty useless, to state the obvious.

 

[medgator]

Your window has passed. Technically, guidelines don't bless dose escalation in esophagus or GE-J above 50.4 Gy, but people still do it, generally all upfront though, not after a break

 

[Haybrant]

That sounds fair, thanks guys! I have another case I am about to treat that is a large field, im thinking of going to 4500 or even 4140 if I cant meet certain contraints. Its a mid/distal esophageal tumor. Do you have to cover all the way down celiac in all guys with distal esophageal? Its just such a big field. Thanks

 

[ramsesthenice]

I agree, nothing more here. I frequently go a little bit higher, 54, if they are not going to get surgery. But not after a break and not if he is that sick. Its really for durable palliation if we are being honest, and it sounds like more RT would be anything but palliative for this man.

 

[hot sauce]

That sounds fair, thanks guys! I have another case I am about to treat that is a large field, im thinking of going to 4500 or even 4140 if I cant meet certain contraints. Its a mid/distal esophageal tumor. Do you have to cover all the way down celiac in all guys with distal esophageal? Its just such a big field. Thanks

If you are treating neoadjuvant 414o cGy is a reasonable dose based on CROSS. I generally will boost at least gross disease (with a margin) to 5040 cGy as you never know when someone will get surgery or not. Also, I would cover the celiac nodes in distal esophagus. There was an interesting presentation at ASTRO about only covering involved nodal stations but the patient population in that study was significantly different than my patient population.

 

[seper]

I often do conedown after 45 Gy

 

[Phantom1]

I like planning the whole thing to 45, then with a boost to 5040. 41Gy is what was done in Cross, but there may be some concerns with data and consistency of Path review...

 

[Haybrant]

Did everyone get surgery in Cross after neoadj; what did they do with the patients that didn't? Also, what is the local vs distant failure pattern in Cross, I feel like that was a in service question that I wasn't sure about

 

[seper]

study results were published twice; those paper have your answers

 

[Damn_Daniel]

What a field. The brightest and best get in. They read and write so many papers. They work at fancy places. And then they make the proclamations.

So, we have a disease where most everybody dies. PCR is 30-40%. Median survival is terrible. And then we get a dose escalation trial which fails. Which fails miserably. The 64.8 Gy arm was no better than the 50.4 Gy arm. 11 people died in the high dose arm. 7 of them died before 50.4 Gy. So ... Does anyone want to analyze this again? Maybe run another trial? Why did so many people die in that arm before the RX dose?

And... The conclusion is that 50.4 is enough?

No one seems a little astounded that our friends at the RTOG aren't running another trial with modern techniques and dose constraints? Minsky Himself goes to 59.4 Gy, definitively. He was an author of the trial! And, yet many in our community give their own patients much less log kill than that, based on a lousy trial, with a weird outcome.

Evidence based medicine means more than picking "a" trial to make decisions. It means evaluating the evidence and coming to a conclusion that hopefully benefits your patients.

What a field***

*** I still go to 50.4. When I'm feeling daring, I go to 54 Gy. I'm a huge weenie.

 

[medgator]

I go higher than 54 in upper and mid esophagus when I know surgery is off the table and I can get away with it dosimetrically. I'm sure others do too.

There are randomized French and German esophageal scc trials where they dose escalate in lieu of surgery

 

[Gfunk6]

RTOG 0617 was a well designed modern trial that demonstrated that more is not always better.

Good dosimetry does not equal good clinical outcomes. That's why they run the trials.

The above two facts should be kept in mind before one decides that two randomized trials shouldn't apply to their practice.


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[Palex80]

Persistant FDG-uptake post RCTx is very bad prognostic factor. I am afraid you are not going to "rescue" the patient with an extra 10-15 Gy, if 50.4 Gy didn't manage to do so.

Interim PET seems to be promising as a tool to guide further treatment. It has become standard in Hodgkin's lymphoma (especially advanced disease) and may be a good tool for other tumors as well.
We need a trial, where patients with good PET-response after 4 weeks of RCT are randomized to surgery or definite RCT.

And we should do that both in NSCLC stage III and esophageal cancer stage II-III.

Patients with a cCR on PET at 4 weeks may benefit the least from surgery, cause surgery will almost always kill something like 3-10% of all patients, diminishing any survival benefit it may offer through enhanced control.

If a trial like this shows equivalence of surgery and RCT, it's over for surgery.

 

[medgator]

Persistant FDG-uptake post RCTx is very bad prognostic factor. I am afraid you are not going to "rescue" the patient with an extra 10-15 Gy, if 50.4 Gy didn't manage to do so.

Interim PET seems to be promising as a tool to guide further treatment. It has become standard in Hodgkin's lymphoma (especially advanced disease) and may be a good tool for other tumors as well.
We need a trial, where patients with good PET-response after 4 weeks of RCT are randomized to surgery or definite RCT.

And we should do that both in NSCLC stage III and esophageal cancer stage II-III.

Patients with a cCR on PET at 4 weeks may benefit the least from surgery, cause surgery will almost always kill something like 3-10% of all patients, diminishing any survival benefit it may offer through enhanced control.

If a trial like this shows equivalence of surgery and RCT, it's over for surgery.

Why would you do that in stage III nsclc? Definitive chemoradiation is pretty much soc for most pts esp with any significant N2 disease

 

[seper]

RTOG 1106 is very similar in concept. Agree, PET at 4 weeks into XRT is prognostic.

 

[Palex80]

Why would you do that in stage III nsclc? Definitive chemoradiation is pretty much soc for most pts esp with any significant N2 disease

Well, that's the approach in the US and some parts Europe too. But in big academic centers in many parts of Europe stage IIIA3 is treated with induction chemo followed by surgery.
There is clearly little evidence for this approach being superior to definitive radiochemo, but it happens unfortunately.

We even have Stage IIIB patients getting neoadjuvant chemo or radiochemo followed by surgery nowadays. It all comes down to how aggressive your thoracic surgeons.

 

[medgator]

Well, that's the approach in the US and some parts Europe too. But in big academic centers in many parts of Europe stage IIIA3 is treated with induction chemo followed by surgery.
There is clearly little evidence for this approach being superior to definitive radiochemo, but it happens unfortunately.

We even have Stage IIIB patients getting neoadjuvant chemo or radiochemo followed by surgery nowadays. It all comes down to how aggressive your thoracic surgeons.

That's unfortunate for the IIIB patients. Are they just leaving disease behind post op? Those patients are particularly screwed as the neoadjuvant treatment has been delivered up front, right?

 

[evilbooyaa]

Why would you do that in stage III nsclc? Definitive chemoradiation is pretty much soc for most pts esp with any significant N2 disease

I remember reading a while back about some experimental trimodality therapy for Stage III NSCLC, with essentially full dose chemorads followed by surgery. Have there been any updates to that within the past year or so?

 

[Damn_Daniel]

Do you mean dose escalation before surgery? CALGB 9781 went to 50.4 Gy preop. I think that's "full dose'. People are giving the same dose for preop and definitive... Anecdotally, the 41.4 Gy/CROSS is way easier to tolerate, amirite?

MDACC is treating patients on protocol to 64.8 with a SIB/IMRT plan. Other groups have published favorable outcomes going to 63 Gy, and 56-60 Gy. I don't mean to be too provocative, but that was a really odd outcome in 0123, and the post trial clinical decision making didn't seem scientific in the least. The field sizes were yuuuuge, much bigger than we currently utilize. They did not do 3D planning, and there was no way to see if the technique led to high lung/heart toxicity. There can be type I and II errors, especially in small trials When 7 people die before 50.4 Gy, something is fishy. I'm certain Belushi wouldn't have believed the results.

 

[seper]

For large, N+ esophageal cancers escalating local therapy does not make huge sense, anyway. Distant relapse rates are very high.

 

[Palex80]

That's unfortunate for the IIIB patients. Are they just leaving disease behind post op? Those patients are particularly screwed as the neoadjuvant treatment has been delivered up front, right?

Not really.
I am talking about selected cases with contralateral mediastinal involvement or T4 N2 disease, where a surgeon can actually resect everything, if the nodes are accessible.
You can have a look at the ESPATÜ data if you want to:
http://jco.ascopubs.org/content/early/2015/10/26/JCO.2015.62.6812.abstract

It shows again that definitive radiochemo is as good as induction followed by surgery, but the second approach is also doable even for stage IIIB patients (selected ones at least).

 

[radiation]

Many people forget about the toxicity of the high dose cisplatin/bolus 5-FU used in the Minksy trial (based on Herskovic regimen) contributing to the premature deaths. In RTOG 85-01, 10% of patients in the combined modality arm had grade 4 toxicity or higher vs. 2% in RT alone arm. In contrast, many of the radiosensitizing regimens used today are much easier to get pts through (ie carbo/taxol), making dose escalation potentially more reasonable (in addition to improvements in RT delivery).

 

[seper]

I don't agree with this at all. Pac/carbo is associated with worse hematologic toxicity than cis/5Fu. Severe esophagitis rates are just as bad, at least. It is very hard to get an esophageal patient to 50 Gy without a break.

Many people forget about the toxicity of the high dose cisplatin/bolus 5-FU used in the Minksy trial (based on Herskovic regimen) contributing to the premature deaths. In RTOG 85-01, 10% of patients in the combined modality arm had grade 4 toxicity or higher vs. 2% in RT alone arm. In contrast, many of the radiosensitizing regimens used today are much easier to get pts through (ie carbo/taxol), making dose escalation potentially more reasonable (in addition to improvements in RT delivery).

 

[radiation]

I don't agree with this at all. Pac/carbo is associated with worse hematologic toxicity than cis/5Fu. Severe esophagitis rates are just as bad, at least. It is very hard to get an esophageal patient to 50 Gy without a break.

http://www.ncbi.nlm.nih.gov/pubmed/24492674

Retrospective data, but best comparison of this issue I have come across

 

[medgator]

I don't agree with this at all. Pac/carbo is associated with worse hematologic toxicity than cis/5Fu. Severe esophagitis rates are just as bad, at least. It is very hard to get an esophageal patient to 50 Gy without a break.

Anecdotally, I've had better luck with carbo/taxol over the cis regimens in terms of getting patients through 50.4 Gy. Most med oncs in our area pretty much do weekly carbo/taxol at this point, although one time I saw folfox which made me pause until I looked it up in the nccn

 

[seper]

http://www.ncbi.nlm.nih.gov/pubmed/24492674

Retrospective data, but best comparison of this issue I have come across

Nice study, thanks.

 

[Treat]

If you went to 50.4 Gy and surgery is a no go, then you are done. Only thing you can do is systemic chemo.

How about a patient who's had 4140, but completed that about a month ago? Surgeon is now having cold feet and asking me to convert to definitive!

I don't think there's much value to giving 9Gy more and hence am reluctant, wondering if anyone would... And perhaps go higher?

 

[Gfunk6]

Tough situation. If tolerable, would consider sending to specialist surgeon in academic center. If not, then options are available but evidence is poor.

 

[McConaughey]

It's why a lot of folks just stay with 50.4 regardless...


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