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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.

I have not heard of that in almost 10 years. Is this really the practice where you are at? Interesting. NCCN does not say one way or the other - as far as ENI or not. Dealer's choice, appears.
 

evilbooyaa

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I have not heard of that in almost 10 years. Is this really the practice where you are at? Interesting. NCCN does not say one way or the other - as far as ENI or not. Dealer's choice, appears.

Yes. I'm not aware that it is 'mandated' but all lung attendings do something similar. If Level 4 is involved, ipsi hilum gets covered. If level 2 is covered, ipsi hilum and level 4 get covered as. Very interesting to see that I am apparently the outlier.
 
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scarbrtj

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Yes. I'm not aware that it is 'mandated' but all lung attendings do something similar. If Level 4 is involved, ipsi hilum gets covered. If level 2 is covered, ipsi hilum and level 4 get covered as. Very interesting to see that I am apparently the outlier.
Local control of the primary, and distant progression, is such a big (depressing and humbling) competing risk vs the ENI regions, ENI fell out of favor for many. Prior to your entering rad onc there was a big fascination with dose esc in NSCLC. This had some data behind it despite 0617 etc. Dose escalation was a bit fraught affair tox wise with ENI in NSCLC. (There are sections in old rad onc textbooks about ENI for Stage I lung!) Re ENI in SCLC, the competing risk as you know is not only local but also distant (ie cranially) vs doing the ENI. It’s just tough to get much clinical use out of ENI in any lung cancer. Isolated nodal relapses have been shown as rare with no ENI.
 
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FrostyHammer

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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.
You got it. Like I wrote above, individual practice patterns vary. But I gander that what you're describing in the first paragraph is what most do. Now, a lot will hedge and cover the whole level of what is involved rather than just the involved node itself, and this is also individual variation in practice (I also don't to this apart from CTV expansion and educated additional expansion/trimming based on CT findings).
 
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A little late, but would consider lower dose SBRT (i.e. 30-35 in 5) to this node, prioritizing esophagus constraints over PTV coverage. Almost certain he will fail elsewhere. This would likely provide the best balance between durable local control and side effect profile.

Would not do 60/15.
 
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scarbrtj

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epilogue on the lung ENI...

Less is more in radiotherapy target volume planning: lessons from the PET-plan trial
...target volume reduction based on 18F-FDG PET alone was not inferior to traditional large volume radiotherapy with elective nodal irradiation with regard to locoregional control, with a suggestion of improvement in locoregional control; allowed further escalation of the radiation dose; and was not associated with a substantial reduction or increase in toxicity... In view of the result of this study, target volume reduction based on 18F-FDG PET alone could be considered standard of care. International guidelines already recommend the omission of elective nodal irradiation guided by 18F-FDG PET/CT in locally advanced non-small-cell lung cancer, making this study practice confirming.
 

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epilogue on the lung ENI...

Less is more in radiotherapy target volume planning: lessons from the PET-plan trial
...target volume reduction based on 18F-FDG PET alone was not inferior to traditional large volume radiotherapy with elective nodal irradiation with regard to locoregional control, with a suggestion of improvement in locoregional control; allowed further escalation of the radiation dose; and was not associated with a substantial reduction or increase in toxicity... In view of the result of this study, target volume reduction based on 18F-FDG PET alone could be considered standard of care. International guidelines already recommend the omission of elective nodal irradiation guided by 18F-FDG PET/CT in locally advanced non-small-cell lung cancer, making this study practice confirming.
The PET-plan trial is an interesting trial, but I do have some ... issues with its interpretation.

First of all, let's have a look at one of its results:

1587889777329.png

What we have here is a almost 20% higher risk of locoregional progression in patients who received ENI (conventional target group).


Now this may have happened because:

a) the patients in the non-ENI (FDG-PET-based) group received higher doses?
Perhaps. But the dose difference was merely 2 Gy
"The mean escalated total radiotherapy reference dose was significantly higher in the ¹⁸F-FDG PET-based target group (67·3 Gy [SD 5·2]) than in the conventional target group (65·3 Gy [5·3]; appendix p 7)."
2 Gy more of RT won't result in a 20% absolute reduction of locoregional failures.

b) adherence to treatment may have been better in the non-ENI group?
Perhaps, but doesn't seem so.

1587890228701.png

"Eight (8%) of 99 patients in the conventional target group and ten (10%) of 105 patients in the ¹⁸F-FDG PET-based target group had relevant dose reductions in radiotherapy (seven vs five) or chemotherapy (three vs eight). Two patients (both died) in the conventional target group and four (one died, two had oesophagitis, and one had pneumonitis) patients in the ¹⁸F-FDG PET-based target group discontinued treatment for toxicity. 20 deaths potentially related to study treatment were reported by treating physicians (seven in the conventional target group and 13 in the ¹⁸F-FDG PET-based target group)"

c) some immuno-related event happening because the non-affected nodes were not irradiated in the non-ENI group.
Perhaps, but none of them got adjuvant immunotherapy.


What do I think?


There is a (suspicious) discrepancy in the reported values of GTV/PTV
1587890540208.png

Patients in the non-ENI group seem to have had bigger tumors in terms of volume (GTV). Although these patients did not receive ENI, the resulting PTV was as big as in the ENI group. This makes little sense... 15ml of "extra" GTV do not justify a PTV that's as big as if you were giving ENI. And in fact, this brings up the question, why patients in the non-ENI group were dose escalated more often than in the ENI-group, when their PTVs were actually as big (or slightly bigger)?
"The mean escalated total radiotherapy reference dose was significantly higher in the ¹⁸F-FDG PET-based target group (67·3 Gy [SD 5·2]) than in the conventional target group (65·3 Gy [5·3]; appendix p 7)."
What is even more striking is the fact that in the non-ENI group the GTV of the primary was drawn based on FDG-PET, while in the ENI group the GTV of the primary included atelectasis too. Yet, in the non-ENI groupt the GTVs of the primaries were bigger... Did FDG-PET-based drawing of the primary result in bigger GTVs or was the randomization so flawed?

It simply makes no sense...

What I suspect:
Physicians were not blinded (at least I couldn't find this being described in the publication/protocol) as to which arm the patients were in, when they contoured the volumes and accepted plans. This could have been different. It would have meant they would have to draw two sets of CTV/PTV for each patient and calculate two plans according protocol but then only one set would be used for the actual treatment according to randomization. Extra burden, but manageable IMHO and would eliminate all bias.

This shortcoming may have led to:

a) tighter margins around CTV in the ENI-group and perhaps "less than actually per protocol supposed" elective nodes and tissue around primary tumor contoured (--> smaller than supposed CTVs in the ENI group). This would explain, why the PTVs remained small, although ENI was used.
b) less likely escalation in the non-ENI group decided by the physicians, knowing that the patients where in the ENI group out of fear of toxicities.

The discrepancy becomes even bigger, if you look at the per-protocol analysis...

1587891398813.png

The authors did describe an extensive quality assurance project, but not many details were revealed on what came out of it.


Thoughts on PET-Plan?

P.S. ENI is dead, don't get me wrong.
 
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scarbrtj

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What we have here is a almost 20% (HR 0.64, 95% CI 0.37-1.10, p=0.11) higher risk of locoregional progression in patients who received ENI (conventional target group).
Now this may have happened because:
a) the patients in the non-ENI (FDG-PET-based) group received higher doses?
b) adherence to treatment may have been better in the non-ENI group?
c) some immuno-related event happening because the non-affected nodes were not irradiated in the non-ENI group.
d) random chance*

That said, your points about CTV/PTV volumes... they really aren't significantly different at all between the groups. There are some differences; they aren't glaring IMHO. Tough to read these tea leaves. One would think the differences would've been bigger/smaller/or something. Who knows. It's like sex: you probably would've had to been there to know for sure what happened. Your point on dose I noticed too. **

Prediction: dose escalation isn't dead in LA-NSCLC (despite one randomized U.S. trial trying to overturn loads of previous data).

*altogether the most likely interpretation

**2Gy more dose won’t give 20% reduction in node failure...
remember this is an average metric. I remember one fetal alcohol study where binge drinking in week 4 of pregnancy lowered IQ in a population from like 105 to 104 and the p value was~ 0.001. And people were like how can you even measure 1 IQ point difference??? Well, so, math/stats doesn’t really work like this, or ask questions like this...
 
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