BobbyHeenan

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Hello. Looking for any input on this challenging case.

58 yo male, obese. neoadj chemo (carbo/taxol)-XRT (50.4 Gy total dose as 41.4 then boost gross disease) for cT3N0 GE junction adeno completed 7/2018. Ivor Lewis Esophagectomy 10/2018 with 4mm residual disease ypT1bN2 (4 nodes + out of 18 submitted).

1 year later (11/2019) on imaging he has a high level 4R mediastinal node look slightly larger. It is above his anastomosis (at carina) and above his prior radiation. It's hot on PET (no other sites of disease); EUS biopsy + for adeno, Her2 (-). He completes capecitabine/oxiliplatinum and new PET (3/2020) shows no new disease but not much if any response in the node.

Right now CT surgery says no mediastinal dissection (he had a VERY tough time with the esophagectomy, nearly died due to anastomotic leak, prolonged ICU stay/hospitalization).

Image below. Node touches esophagus but does not invade it.

Treat upper mediastinaum/SCLV then boost the node with xeloda? Consider radiosurgery (or a more ablative dose like 70 in 15 or something?)

2020-03-31 08_37_12-Greenshot.png
 
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RickyScott

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Have given 60 gy in 15 in similar situation with xeloda.
 
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RickyScott

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Yes, with 0 expansion into esophagus/ pull-up. I had 2 mm margin between ptv and esophagus ie treated ptv
was 2mm away from esophagus. Not sure the role of immuno in esophageal but if it did not respond to 1st line chemo in recurrent setting-would see if you could give immuno with radiation.
 
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BobbyHeenan

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I'm thinking 60 in 15. Not only esophagus there, but tracheoesophogeal fistula possibility as it's kind of tucked in between the two. no plans for bevacizumab, obviously, as this is a major risk factor for this.

No current plans for IO.
 
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Palex80

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This thing touches the esophagus. What are you planning to use as a constraint for the esophagus when giving 60/15?
 

RickyScott

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Would expand the esophagus by 2mm and make sure your ptv doesn’t overlap with that expansion. Esophagus can get a high point dose- just don’t know how high. Point doses 74 gy with carbo taxol in lung would happen in past. Also hdr boost for esophageal cancer following chemorads were delivered at one point. It’s tolerance is higher than bowel. There were some fistulas in hdr when catheter did not have a spacer and source was right against wall.
 
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BobbyHeenan

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This thing touches the esophagus. What are you planning to use as a constraint for the esophagus when giving 60/15?

I’m thinking max dose < 102% of Rx of 60/15
Avoid circumferential 50 Gy dose
Nccn for 50/5 says < 105%.
Pretty good Cleveland clinic data for safety at 50/5 as long as no bevacizumab.

Im open to any and all suggestions though.
 
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I'd be wary of 60/15 TBH. Circumferential 50Gy dose is for 2Gy a fraction isn't it? Not 4Gy? I'm assuming nothing in the mucosa on EGD/EUS.

What're you guys advocating for 60/15 allowing as point doses to Esophagus and circumferential dose in this setting?

74 Gy point dose was in 2Gy fractions. At a/b =3, 60Gy in 15 fractions is a higher BED, equal to 84Gy EQD2

I'd consider 'aggressively palliate' him with 45/15 if no chemo.... at those doses I've seen riproaring G2-3 esophagitis in lung patients with close mediastinal LNs.

It's good that it's out of his previous RT field and would consider doing definitive chemoRT again if med-onc is on board to 50-50.4, treating as far down as is safe and elective LNs in the area.
 

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It's good that it's out of his previous RT field and would consider doing definitive chemoRT again if med-onc is on board to 50-50.4, treating as far down as is safe and elective LNs in the area.
That's what we've done in similar cases with chemo, though caveat is we used protons
 

RickyScott

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nsclc stage iii involved subcarinal nodes with margin used to get min 74 gy all time. I am sure esophagus maybe a bit higher full circumf. Had several self limited ulcers and stricture that needed ballooning, but no real significant esophageal toxicity when had a lung service.

Would not do anything elective when 50gy has 25% chance of controlling gross disease,wouldn’t worry about subclinical disease. 75/25 Chris crane is another option.
 
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BobbyHeenan

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I'd be wary of 60/15 TBH. Circumferential 50Gy dose is for 2Gy a fraction isn't it? Not 4Gy? I'm assuming nothing in the mucosa on EGD/EUS.

What're you guys advocating for 60/15 allowing as point doses to Esophagus and circumferential dose in this setting?

74 Gy point dose was in 2Gy fractions. At a/b =3, 60Gy in 15 fractions is a higher BED, equal to 84Gy EQD2

I'd consider 'aggressively palliate' him with 45/15 if no chemo.... at those doses I've seen riproaring G2-3 esophagitis in lung patients with close mediastinal LNs.

It's good that it's out of his previous RT field and would consider doing definitive chemoRT again if med-onc is on board to 50-50.4, treating as far down as is safe and elective LNs in the area.

Concern with 50.4 Gy was that it didn’t have a CR up front at that dose. Elective nodes treated at lower doses still had 4+

After all this treatment highly doubt it controls a stubborn relapse clone.

I’m definitely struggling with this tough case. Agree that distant failure pretty likely, but only 1 site of regional disease now > 1 year out from surgery...so a little glimmer of hope.

Patient is very reasonable and a straight shooter. We’ll obviously discuss “safer” versus more risky options .
 

ramsesthenice

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Concern with 50.4 Gy was that it didn’t have a CR up front at that dose. Elective nodes treated at lower doses still had 4+

After all this treatment highly doubt it controls a stubborn relapse clone.

I’m definitely struggling with this tough case. Agree that distant failure pretty likely, but only 1 site of regional disease now > 1 year out from surgery...so a little glimmer of hope.

Patient is very reasonable and a straight shooter. We’ll obviously discuss “safer” versus more risky options .

These suck. No matter how innocent they look I have yet to be satisfied with the long term results. That being said, if you are going to take a swing, swing for the fences. I agree that 50.4 probably won’t do much for all the reasons you stated. 60/30 or some kind of hypofractionation is the way to go if you want any shot at local control. I personally wouldn’t go nuts with ENI. Keep it tight. No matter how big you make your volumes the risk of distant failure is very high and realistically you are palliating an asymptomatic lesion on the off chance it is curative. Don’t make them sicker than you need to.
 
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Palex80

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nsclc stage iii involved subcarinal nodes with margin used to get min 74 gy all time. I am sure esophagus maybe a bit higher full circumf. Had several self limited ulcers and stricture that needed ballooning, but no real significant esophageal toxicity when had a lung service.

Half of the NSCLC stage III patients which "used to get min 74 gy all time" were dead within a year due to tumor progression.
We do not really have long follow-up of data showing that dose escalation in this setting is safe. I have concerns of esophageal doses beyond 66/2.

And 60/15 translates in higher BEDs than that when talking about late effects.
 
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FrostyHammer

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Isolated nodal failures for NSCLC are often treated with 45/15 and chemo (I would not waste healthcare/patient money on offlabel immunotherapy), for which there are some data albeit retrospective. I'm not sure the point of doing RT to this node without chemo TBH, since second recurrences in this very setting for NSCLC are most often distant.
 

BobbyHeenan

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Thanks all for the discussion/input.

I'm circling back around and re-presenting at our thoracic oncology tumor board to re-visit possibility for a mediastinoscopy with a simple node excision (not a full dissection) potentially followed by treating the operative bed with XRT.

If that's off the table 100% (was previously declined by one of our CT surgeons, we'll see what the other three say) then seeing what kind of dose I can give this node...
 

BobbyHeenan

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Half of the NSCLC stage III patients which "used to get min 74 gy all time" were dead within a year due to tumor progression.
We do not really have long follow-up of data showing that dose escalation in this setting is safe. I have concerns of esophageal doses beyond 66/2.

And 60/15 translates in higher BEDs than that when talking about late effects.

FWIW, I suspect the survival curves for this situation are similar or worse than a stage III lung. An esophageal stricture requiring dilation wouldn't hurt us, but tracheoesohpageal fistula or a bleeding ulcer that doesn't really have a fix keeps me up at night.
 
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CptCrunch

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I've treated 45/15 with Xeloda in an older gentleman. Node is controlled 2 years out but he progressed elsewhere.
 
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Palex80

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FWIW, I suspect the survival curves for this situation are similar or worse than a stage III lung. An esophageal stricture requiring dilation wouldn't hurt us, but tracheoesohpageal fistula or a bleeding ulcer that doesn't really have a fix keeps me up at night.
Indeed that may be true, but options in the metastatic setting are getting better both in NSCLC and esophageal cancer.
We may need to rethink about some of the regimes we have used in the past, because some late effects may become more visible with longer follow up if the patients live longer.
 

BobbyHeenan

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Indeed that may be true, but options in the metastatic setting are getting better both in NSCLC and esophageal cancer.
We may need to rethink about some of the regimes we have used in the past, because some late effects may become more visible with longer follow up if the patients live longer.

As a corollary to this, I'm seeing more and more late brain met failures in lung and melanoma patients...I think the notion that these high radiosurgery local control numbers really aren't applicable when you're > 12- 18 months out is a thing now, because all of our control data is in an era when people weren't this long.
 
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I get nervous about esophagus. I've seen serious toxicity and even death with 5 fraction SBRT for adjacent lung cancer.

So for me: 60/30 +/- chemo? Some moderate hypofractionation probably ok like 45/15. I personally wouldn't go nuts.
 
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radoncgrad2019

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I've treated 45/15 with Xeloda in an older gentleman. Node is controlled 2 years out but he progressed elsewhere.

This is a good approach too.

I would just do 15 fractions, give most of it a high dose, undercover the part near esophagus, you choose what dose max you want. 50, 45 whatever

I just don’t like the idea of making someone come in for 6 weeks
 
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RickyScott

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Half of the NSCLC stage III patients which "used to get min 74 gy all time" were dead within a year due to tumor progression.
We do not really have long follow-up of data showing that dose escalation in this setting is safe. I have concerns of esophageal doses beyond 66/2.

And 60/15 translates in higher BEDs than that when talking about late effects.
Large segments of esophagus 10 cm or more routinely used to routinely get 60 Gy for treatment of esophageal cancer. 70 gy to nodes in lung cancer is still given at places like moffitt, and this would be a circumferential dose in subcarinal area. In RTOG 74 Gy NSCLC study, no mention of any fistulas? A small point dose 10-20% above this is highly unlikely to cause significant toxicity. lastly PTV dose not need to extend into esophagus. Fall off with stereo like plan for this volume can be 8-10% per mm so that if your treated ptv is 2mm away from esophagus, point esophageal dose is getting 10-20% less per fraction.

can get some idea of fistulas and toxicity from old rtog studies (no ct sims, no 3d!) with hdr- some of these guys were really well known in their time. Fistulas occurred when had no spacing/small diameter applicators (think of difference in surface dose 1 cm cylcinder vs 3 cm) so surface dose much higher. also combined hdr with c chemo. Treating huge segments of esophagus and large segments of esophageal wall compromised by tumor.

 
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Neuronix

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Yeah that's true. I'm probably being too chicken. 70 Gy EQD2 (alpha/beta=2) hot spot on esophagus seems reasonable. Just a question of how much do you feel comfortable hypofractionating that.
 

evilbooyaa

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Concern with 50.4 Gy was that it didn’t have a CR up front at that dose. Elective nodes treated at lower doses still had 4+

After all this treatment highly doubt it controls a stubborn relapse clone.

I’m definitely struggling with this tough case. Agree that distant failure pretty likely, but only 1 site of regional disease now > 1 year out from surgery...so a little glimmer of hope.

Patient is very reasonable and a straight shooter. We’ll obviously discuss “safer” versus more risky options .

That's true, and a reasonable thought. I agree with something like 45/15. Never done it with concurrent Xeloda and would worry about even worse esophagitis but if you keep volumes small you could probably get away with grade 2 acute esophagitis and acceptable late-toxicity risk.
 
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BobbyHeenan

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Thanks for everyone's input. Confirmed with CT surgery not a candidate for a node excision.

At this point in time still planning, but I'm looking at 60 Gy in 15 (*without xeloda) and using the constraints from the Timmerman 60 Gy in 15 fraction lung trial (esophagus max is around 54 and tracheal max around 47-50). So will have to under cover PTV medially, but I'm still getting GTV min at at least 45.

Everyone was helpful.
 
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FrostyHammer

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Can I inquire into what the point of RT would be if chemo isn't given? Dude's going to fail distantly for sure. Can he not tolerate chemo?
 

BobbyHeenan

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Can I inquire into what the point of RT would be if chemo isn't given? Dude's going to fail distantly for sure. Can he not tolerate chemo?

He just recently completed chemo. When he failed in that node I (and tumor board) rec'd chemo first due to high risk of distant disease.

No distant mets seen over 6 months now (initial suspicioun that this node grew was in 10 to 11/2019, one year after surgery). Only site of disease is this node, which only minimally responded to recent chemo. He did complete all planned chemo, but last cycle got very rough with a big bump in LFT's and clinical decline, but no hospitalization.

Agree distant failure is highest risk, that's why I'm not going crazy with 50/5 or something more radical.

It's not unreasonable to say just give it a smaller palliative dose, but patient wants to be aggressive and so given only 1 site of disease.
 
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ramsesthenice

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It's not unreasonable to say just give it a smaller palliative dose, but patient wants to be aggressive and so given only 1 site of disease.

If it is asymptomatic, what would you be palliating with a lower dose? Unless a met is in a location that has a reasonable chance of becoming problematic with local progression, I personally don't see the point in giving palliative dosing to asymptomatic lesions. Even if all you are trying to do is buy a chemo holiday you should at least use a dose high enough you have a reasonable chance at a decent disease free interval.
 
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If it is asymptomatic, what would you be palliating with a lower dose? Unless a met is in a location that has a reasonable chance of becoming problematic with local progression, I personally don't see the point in giving palliative dosing to asymptomatic lesions. Even if all you are trying to do is buy a chemo holiday you should at least use a dose high enough you have a reasonable chance at a decent disease free interval.

That's the plan.
 

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He just recently completed chemo. When he failed in that node I (and tumor board) rec'd chemo first due to high risk of distant disease.

No distant mets seen over 6 months now (initial suspicioun that this node grew was in 10 to 11/2019, one year after surgery). Only site of disease is this node, which only minimally responded to recent chemo. He did complete all planned chemo, but last cycle got very rough with a big bump in LFT's and clinical decline, but no hospitalization.

Agree distant failure is highest risk, that's why I'm not going crazy with 50/5 or something more radical.

It's not unreasonable to say just give it a smaller palliative dose, but patient wants to be aggressive and so given only 1 site of disease.
So this would be classified as oligorecurrent and nonmet oligoprogressive disease. Makes sense to not throw the kitchen sink in that case given the unclear benefit of local therapy in these cases.
 
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evilbooyaa

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It is a metastatic (M1) recurrence. Oligometastatic, but metastatic. I would call a mediastinal LN for a GEJ primary a metastatic (M1) recurrence.

He got upfront chemotherapy, did not progress in that lesion (or in any others) and is now getting consolidative RT.

Just some info I guess on what I would call each stage of his treatment since his recurrence.

I would have considered this oligoprogressive if the LN in question grew while on chemotherapy (but still no other sites of disease).

That being said, I do think this could cause symptoms if untreated and continues growing given proximity to esophagus and trachea. I would prefer treatment now one way or the other regardless of what dosing is picked.
 

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It’s not metastatic. And AJCC concurs.

It’s literally a regional peri esophageal node that is abutting the esophagus. Doesn’t get more regional Than that!
 
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evilbooyaa

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It’s not metastatic. And AJCC concurs.

It’s literally a regional peri esophageal node that is abutting the esophagus. Doesn’t get more regional Than that!

Guy has a GEJ primary, he has a LN above the level of the carina. Given normal esophageal anatomy, the LN is let's say at least 15cm (and I'm underselling it here) from the primary.

You calling him M0?

I'm not asking if you're going to treat him definitively or not in the absence of other disease.

I just want to know what you're going to call him on staging.

It doesn't really matter what we call him in the posted scenario or in my hypothetical scenario, but I think it's important to think about what regionally means in a logical sense when one is attempting to prognosticate patients.

If you are going to call him M0, are you going to cover the esophagus and its periesophageal LNs in its entirety up from the GEJ tumor to where this LN is?
 
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It’s a regional failure by definition. Of course he is going to fail both locally and distantly. But it’s a regional failure.
 

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Guy has a GEJ primary, he has a LN above the level of the carina. Given normal esophageal anatomy, the LN is let's say at least 15cm (and I'm underselling it here) from the primary.

You calling him M0?

I'm not asking if you're going to treat him definitively or not in the absence of other disease.

I just want to know what you're going to call him on staging.

It doesn't really matter what we call him in the posted scenario or in my hypothetical scenario, but I think it's important to think about what regionally means in a logical sense when one is attempting to prognosticate patients.

If you are going to call him M0, are you going to cover the esophagus and its periesophageal LNs in its entirety up from the GEJ tumor to where this LN is?
I agree with radoncgrad. This is by definition a regional node. Yes, it's farther than most nodes for GEJs but in the non recurrence setting this is still labeled as a regional node by the AJCC. Thus, in the recurrent setting this is no different. The distance between the GEJ and the node simply portends a higher rate of distant metastases, a'la multi station (including "farther away") nodal involvement in NSCLC.
 

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OK I guess you guys can call it whatever you want, but to me regional means that if there is a LN there I am covering all in-transit lymphatics.

Example - Stage III NSCLC with an ipsi level 4 LN gets coverage of, at minimum, ipsilateral hilum and level 4. NSCLC with ipsi level II involvement gets hilum, level, and level 2. Etc.

Lower esophageal (but not GEJ, squarely within Siewert I) tumor with + Celiac LN, gets in-transit coverage of all of esophagus (even if > 3-5cm) to celiac axis.

Lower esophageal tumor with a mediastinal LN gets a gap between the fields. Hence why I asked the question - are you guys treating the 8-10cm of extra esophagus to cover the in-transit lymphatics between the primary and this upper thoracic (again, above level of carina) LN? Because god knows I'm definitely not.
 

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Why would anyone re-irradiate what’s already been radiated?

Treat the Gross disease that’s outside the prior RT field, give some small elective above it if you wish, and call it.
 

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OK I guess you guys can call it whatever you want, but to me regional means that if there is a LN there I am covering all in-transit lymphatics.

Example - Stage III NSCLC with an ipsi level 4 LN gets coverage of, at minimum, ipsilateral hilum and level 4. NSCLC with ipsi level II involvement gets hilum, level, and level 2. Etc.

Lower esophageal (but not GEJ, squarely within Siewert I) tumor with + Celiac LN, gets in-transit coverage of all of esophagus (even if > 3-5cm) to celiac axis.

Lower esophageal tumor with a mediastinal LN gets a gap between the fields. Hence why I asked the question - are you guys treating the 8-10cm of extra esophagus to cover the in-transit lymphatics between the primary and this upper thoracic (again, above level of carina) LN? Because god knows I'm definitely not.
Doesn’t really matter what stage you call it, this is a theoretically potentially curable situation -probably 10% of the time is my best guess. I am sure that there are tumor cells at a distance from the disaese in any oligo presentation, but just have to hope the body can take care of them.
 

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OK I guess you guys can call it whatever you want, but to me regional means that if there is a LN there I am covering all in-transit lymphatics.

Example - Stage III NSCLC with an ipsi level 4 LN gets coverage of, at minimum, ipsilateral hilum and level 4. NSCLC with ipsi level II involvement gets hilum, level, and level 2. Etc.

Lower esophageal (but not GEJ, squarely within Siewert I) tumor with + Celiac LN, gets in-transit coverage of all of esophagus (even if > 3-5cm) to celiac axis.

Lower esophageal tumor with a mediastinal LN gets a gap between the fields. Hence why I asked the question - are you guys treating the 8-10cm of extra esophagus to cover the in-transit lymphatics between the primary and this upper thoracic (again, above level of carina) LN? Because god knows I'm definitely not.
Treatment of in-transit lymphatics in the oligorecurrent/oligoprogressive setting is questionable at best. Simply because in that setting, your goal is not to eradicate all areas of suspected at-risk disease. The principle, like that for oligomets, is to address all known (visible) areas of disease.

Furthermore, your Stage III NSCLC example is not entirely accurate either. If the argument is that there's a high risk that the hilum is involved, then is there not a high enough risk that another mediastinal station is involved too (particularly for multiple nodes in a single station)? Then you go down the ENI hole. The reason why, as backed by good data, that we don't do ENI for III NSCLC is because the risk of an isolated recurrence in those areas is relatively low. Similarly, even accounting for incidental dose to the hilum in your example above, the risk of an isolated failure in the ipsilateral hilum is low compared to the existing areas of disease and distant metastases (even with durva...see patterns of failure data from PACIFIC). This is why most contemporary protocols across the world make no effort to include the hilum in that case. For instance, 0617 never mandated that sort of coverage. Sure, there are individual variations everywhere, but I would not think that it is by any means a "must" to cover the hilum in that setting. Ergo, if in the definitive setting it's questionable, then in the oligo setting it's definitely questionable at very best.
 
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evilbooyaa

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@FrostyHammer Hmm I never analyzed the protocol for 0617. You're saying that if there were ipsi level 2 LNs in a definitive setting, people are treating just the primary and the involved LN? People would spare ipsi hilum? and ipsi level 4? B/c I can say that I would not at all plan to do that in my practice and have never seen that from the various lung attendings I've worked under.

Is anyone else doing that for their definitive NSCLCs?

I was under the impression that 'ENI' was defined as treating beyond the extent of disease - meaning that if patient had ipsi level 4 LN, then with ENI you would cover ipsi level II and say contralateral 4 and station 7 or something.

Interesting. Thanks for the ongoing discussion.
 
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@FrostyHammer Hmm I never analyzed the protocol for 0617. You're saying that if there were ipsi level 2 LNs in a definitive setting, people are treating just the primary and the involved LN? People would spare ipsi hilum? and ipsi level 4? B/c I can say that I would not at all plan to do that in my practice and have never seen that from the various lung attendings I've worked under.

Is anyone else doing that for their definitive NSCLCs?

I was under the impression that 'ENI' was defined as treating beyond the extent of disease - meaning that if patient had ipsi level 4 LN, then with ENI you would cover ipsi level II and say contralateral 4 and station 7 or something.

Interesting. Thanks for the ongoing discussion.
Yes we (maybe not "we" heh) "threw away" ENI in NSCLC a long time ago. I thought this was a fait accompli; yes, read 0617. Esp no ENI since the advent of PET. Just treat the primary and involved lymph nodes in all NSCLC cases. Will leave it to others to quote/cite the vast orgy of data as to why this is so... but first volley would be that from Drew Turrisi e.g. who would used to say "In Stage III lung we can barely locally control what we can see; why try to control what we can't?"

EDIT: also those "in transit" lymphatics may be a bit of a (locoregional) illusion
 
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RickyScott

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I think If you are going to 60 gy, it is reasonable to consider very Hugh risk areas for some elective radiation.
Level 7, 4R and ap window can all be very High risk depending on the
Site of primary. I often don’t deliver eni, but certainly have no issue with it. Also the incidental dose to eni regions is not trivial in most cases, so even if you are not intentionally delivering eni, many of highest risk areas will still receive substantial dose.
 
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radmonckey

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We have a Stage III NSCLC protocol open with various flavors of immunotherapy given concurrently and adjuvantly. In this protocol, they allow coverage of the intervening uninvolved hilum at the discretion of the treating physician. Essentially, this is a dealers choice situation at current time.

In my practice, if the hilum is close and I know I'll meet my desired DVH, I grab it. If they have crappy lung function or it's going to be a tough plan, I'll omit it. Also, if they are younger and perhaps have more curable looking disease (lower tumor burden, ipsi only adenopathy, etc) maybe I'm more likely to cover it. I like to needlessly overcomplicate things though...
 
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PhotonBomb

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Yeah I mean I’ll occasionally throw a little elective here and there in well selected situations but I think you’re in the vast minority, evil. I thought routine ENI had gone the way of the Dodo
 

medgator

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Yeah I mean I’ll occasionally throw a little elective here and there in well selected situations but I think you’re in the vast minority, evil. I thought routine ENI had gone the way of the Dodo
Yes we (maybe not "we" heh) "threw away" ENI in NSCLC a long time ago. I thought this was a fait accompli; yes, read 0617. Esp no ENI since the advent of PET. Just treat the primary and involved lymph nodes in all NSCLC cases. Will leave it to others to quote/cite the vast orgy of data as to why this is so... but first volley would be that from Drew Turrisi e.g. who would used to say "In Stage III lung we can barely locally control what we can see; why try to control what we can't?"

EDIT: also those "in transit" lymphatics may be a bit of a (locoregional) illusion
Eni seems to have been eliminated in SCLC as well despite being in some of the rtog/nrg protocols over the last decade. Now many are doing sbrt in early stage disease
 
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