T2?N1? NSCLC Case - any suggestions?

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BobbyHeenan

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I have a 77 year old male, long time smoker with COPD (FEV1 ~35% of predicted, DLCO 20% of predicted, on O2 prn). Not a surgical candidate. He was diagnosed with what was initially thought to be a ~4 cm peripheral left upper lobe squamous cell. CT C/A/P negative for nodal or distant mets (non contrast).

For whatever reason he had EBUS before PET. All nodes "looked small" so none sampled. Then came PET and a small L hilar ?node? is hot (PET done without IV contrast, so no node was seen in the midst of vasculatuar) with primary tumor SUV 16, L hilar node SUV 9. Contrasted CT then shows node at 1 cm in greatest dimension...radiology says "suspicious" and anatomically correlates with where PET is hot.

I send him back for repeat EBUS and tell pulmonologist to try to get that L hilar node. They sampled 4L and "think" they got the right node in the L hilum but admittedly it was a very tough stick/angle through the vasculature. Both biopsies negative with lymphocytes in the specimen...

However, I'm not convinced. I'm not sure if I should SBRT the known cancer and watch this node or treat as T2N1. He is not a chemo candidate (not concurrent or sequential). If treating as T2N1 what dose/fractionation would you use?

I rarely go outside standard of care, but I'm thinking about maybe giving ~60 Gy in 10 fractions to the larger tumor and ~45 Gy in 10 to the L hilar area with a dose painting stereotactic fractionated approach. The lung tumor is about 6 cm from the hilum, so if alignment and motion is congruent on 4D ct sim. However with these odd hypofractionated techniques it's hard to know a lung constraint(s). I have a pretty good idea of esophagus, cord, etc at these doses, but lung toxicity data/dosimetry is more difficult.

Any input is appreciated.

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If using stereotactic approach, the dose fall off is sharp and Lung v20 is still probably relevant. Most SBRT recommendations are MLD<10 Gy and V20<10%. If you are using 10 fractions this would be overly conservative. So probably something in between SBRT and conventional fractionation is acceptable. MDACC published their 10 fraction constraints. Off the top of my head I don't recall their Lung constraints though and don't have access on my iPhone. PMID 25108807


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I'd SBRT too. Both volumes.
You consider to give a third "elective" dose level, for example 10 x 4 Gy to entire hilar lymph nodes and go up to 10 x 5 Gy on the involved node. There is quite a risk of adjacent failure, if this is truly N1 disease and I presume you are not going to give chemo to the patient...
 
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I would not do separate 2 SBRT's. I would give 15 treatment fractions treating both targets with the one field.
 
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I would not do separate 2 SBRT's. I would give 15 treatment fractions treating both targets with the one field.

Yeah, I'm starting to lean this way too. I'm thinking 60 Gy in 15 fractions with 4D/gated treatment and tighter margins than I would traditionally do in something like stage III NSCLC.

Really hard to know what to do here. I feel like standard fractionation is too weak in this situation, though I wouldn't fault anyone for just doing that.
 
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Yeah, I'm starting to lean this way too. I'm thinking 60 Gy in 15 fractions with 4D/gated treatment and tighter margins than I would traditionally do in something like stage III NSCLC.

Really hard to know what to do here. I feel like standard fractionation is too weak in this situation, though I wouldn't fault anyone for just doing that.

Did they sample left hilum or 4L (lower paratracheal) or both? I didn't understandard

If you're treating it as real, than treat it to a real dose - i.e. it's not elective. 60 in 10 sounds pretty good, and if off 'gus and cord, should be pretty straightforward. If you guy tight margins and SBRT-ish approach lung dose will be reasonable.
 
Really tuff with no great answer.

Since it sounds like the patient was properly staged and is technically N0 (although a SUV of 9 does not look good), you could just do SBRT on the primary and then do a short f/u imaging/PET for the hilar node and if there is progression then treat the involved mediastinum. I don't think the patient would loose anything with this approach and it may subject them to less treatment.
 
45/10 is kinda weak for gross disease. 70/35 would be estimated to be up to 33% "stronger." 60/10 would be "stronger" than 70/35. My mental gestalt in cases like these where radoncs give 60/10 to a 4cm primary and 45/10 to a 1cm tumor is that's EXACTLY similar to giving 60/10 to 80% of a 5cm mass and 45/10 to 20% of the same 5cm mass. "That's stupid," you'd say. Yet what's the difference? Not much. So I vote 60/10 or 70/35 to both sites. Why no chemo?
 
Canadian data on 52.5/15 or 60/15 looks very good, and they had some N1 cancers.
 
The standard for T2N1 would be 60 in 2's with chemo. The left hilar lesion certainly sounds concerning. Why go outside of standard, I mean even 400 x 15 can lead to airway issues centrally (I get it, that risk is low and we certainly all feel better about it than 10 x 5 centrally but the Canadian study didn't have many central lesions if I remember correct?) but this is a node, its not a primary mass either. I think you need to go chemo/RT otherwise be ready to justify this decision if any issues at all.
 
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The standard for T2N1 would be 60 in 2's with chemo. The left hilar lesion certainly sounds concerning. Why go outside of standard, I mean even 400 x 15 can lead to airway issues centrally (I get it, that risk is low and we certainly all feel better about it than 10 x 5 centrally but the Canadian study didn't have many central lesions if I remember correct?) but this is a node, its not a primary mass either. I think you need to go chemo/RT otherwise be ready to justify this decision if any issues at all.

Well... sort of trying to thread a needle. If it's true T1N1 dz and medically inoperable and we assume the original poster is not lying about patient not being a chemo candidate (seems like multiple people keep harping on giving chemo, I think it's clearly stated above that he's not a candidate; you can't just change the case and say "GIVE THE JUICE"; seems rather DJT-like). We know that a stage I lung cancer will laugh at beam alone, unless you believe this study, then 60/30 without chemo to a T1N1 lesion seems like aggressive palliation. If it's actually T1 and end up accidentally overtreating the hilum, we know that patients with central tumors do fine with 60/8-10. Why not give the guy a chance with a curative dose? And, I don't think we are that far away from treating T1-T2N1 non-operable cases with SBRT like approach.
 
The standard for T2N1 would be 60 in 2's with chemo. The left hilar lesion certainly sounds concerning. Why go outside of standard, I mean even 400 x 15 can lead to airway issues centrally (I get it, that risk is low and we certainly all feel better about it than 10 x 5 centrally but the Canadian study didn't have many central lesions if I remember correct?) but this is a node, its not a primary mass either. I think you need to go chemo/RT otherwise be ready to justify this decision if any issues at all.

And TBH, carbo/taxol has to be one of the less toxic concurrent regimens out there, but when talking about efficacy, well I digress.
 
And TBH, carbo/taxol has to be one of the less toxic concurrent regimens out there.....

4th person saying give chemo. @BobbyHeenan - come clean, are you lying about the chemo? Are you holding back the fact that this person can take chemo? ANSWER ME NOW! Because the majority of the people do not believe you.
 
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Thanks everyone for the responses. Further info:

- Yes, the patient had biopsies of both 4L and 11L. Like I said, pulm *thinks* they got the right node at 11L but amidst vasculature it was a "tough stick."
- The patient was seen in our multi-D thoracic clinic. CT surgeon said no way to surgery. Med Onc didn't want to give chemo either sequentially or concurrently. I think I could possibly twist their arm for chemo, but they are good and I respect their opinion.
- I've had a chance to sit down and contour and plan. The lung tumor is closer to the node than I originally thought. About 3.5 cm away on our 4D sim. I'm afraid that if I just treat SBRT on the lung tumor then re-treating a failure at the hilum would be more problematic than just treating them both.
 
What's wrong with the standard hypofractionated RT regimen (45/15 or whatever else people are using now) in medically inoperable patients who can't get concurrent chemoRT?

What is this, IMO, nonsense about SBRTing the primary lesion and the hilar lesion separately?

Although what I don't understand, is that the patient really should be staged as a T2N0 based off the repeat EBUS. What was the point of an EBUS if the answer from it wasn't going to change your management? They got lymphoid tissue so it's not like they missed lymph node entirely. Yeah hilar SUV of 9 is concerning, but a false positive in PET in lung cancer isn't unheard of.

If you feel super strongly that it's a cT2N1 (ignoring the EBUS) then hypofractionated RT to primary and nodal region, same dose. Gross disease gets gross disease dose, not something elective.

If you're OK going with a PET-avid lymph node (maybe) that was EBUS negative per Pulm, then it's T2N0 and you SBRT it how you see fit.

Those to me are the only defensible options. It's a tough case, and regardless of what you do you're probably going to be blamed.
 
60/15 if chemo not an option. To both primary and nodal disease. It's reasonable to assume involved at SUV9 despite negative biopsy, and the additional morbidity with treating that node would be mild-moderate but not crazy. Wouldn't treat elective nodes.
 
What's wrong with the standard hypofractionated RT regimen (45/15 or whatever else people are using now) in medically inoperable patients who can't get concurrent chemoRT?

What is this, IMO, nonsense about SBRTing the primary lesion and the hilar lesion separately?

Although what I don't understand, is that the patient really should be staged as a T2N0 based off the repeat EBUS. What was the point of an EBUS if the answer from it wasn't going to change your management? They got lymphoid tissue so it's not like they missed lymph node entirely. Yeah hilar SUV of 9 is concerning, but a false positive in PET in lung cancer isn't unheard of.

If you feel super strongly that it's a cT2N1 (ignoring the EBUS) then hypofractionated RT to primary and nodal region, same dose. Gross disease gets gross disease dose, not something elective.

If you're OK going with a PET-avid lymph node (maybe) that was EBUS negative per Pulm, then it's T2N0 and you SBRT it how you see fit.

Those to me are the only defensible options. It's a tough case, and regardless of what you do you're probably going to be blamed.

Really appreciate everyone's thoughts.

These mirror my thoughts as well. I'm not worried about blame, I just want to do right by the patient. If I hurt him I'll take the blame. If he fails I take the blame. But if he does well I'll take the credit :).

The point of the repeat EBUS was to direct attention to the L hilar node and *hope* pulm feels they got a good sample. They aren't confident they got a good sample, though to their credit there were lymphocytes in the specimen, so they got A node, maybe not THE node though.

My tentative plan is 60 Gy in 15 to both the lesion and node. Working on trying to meet the MD Anderson constraints for their 70 Gy in 10 fraction regimen as posted above.
 
ok cool cool cool I didn't read the whole thing. Fine No chemo. Would say the standard is 70 in 35 but ya just talk to him say hey I want to be a touch more aggressive to give you a better chance, you down with that too? Then do what you plan
 
If it was a large node and minimally avid and biopsy was negative I would consider it less suspicious. However, this is a small node that is VERY hot on PET and Pulm wasn't certain about the biopsy (despite getting lymphoid tissue). I would still consider this to be disease and would treat accordingly with whatever you're comfortable treating T2N1 disease with. I would also rule out brain mets, especially if it's adeno.
 
60/15 if chemo not an option. To both primary and nodal disease. It's reasonable to assume involved at SUV9 despite negative biopsy, and the additional morbidity with treating that node would be mild-moderate but not crazy. Wouldn't treat elective nodes.

Are people routinely doing 60/15 for hypofractionated RT without chemo? I would be very interested in a link in terms of dose constraints, outcomes, etc.
 
I believe they are in the article- don't have it right now- maybe someone can post it.

http://www.redjournal.org/article/S0360-3016(15)00505-2/pdf

Thanks for posting. Here's the supplemental table about their dose constraints.

upload_2017-7-3_16-53-40.png


I think an awful lot of those constraints could be extremely difficult for a T2N1 lung cancer, with a hilar lymph node. Treating to 60Gy with great vessel point dose of 54.3? V18 depends on location of primary, like always. Large bronchus point dose of 45.6Gy with a hilar lymph node? What N1 disease could these constraints realistically apply to?
 
Some of the constraints really dont make a lot of sense. 45 GY/15 fractions -with chemo-is not that uncommon in the rest of the world for small cell for small to moderate volumes and significant portions of the trachea and bronchus get this dose.
 
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Some of the constraints really dont make a lot of sense. 45 GY/15 fractions is not that uncommon in the rest of the world for small cell for small to moderate volumes and significant portions of the trachea and bronchus get this dose.
That's what I've been doing....
 
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Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904. - PubMed - NCBI

I use the hypofractionated regimen from the calgb trial several times year and never had any toxicity, although it is for stage I- it was not geographically limited ie. hilum carina etx and there was no central toxicity and they had 90% local control.

By definition there were no mediastinal/carina lesions in that study. I use it for central lesions quite often but I wouldn't treat N2 disease with it...
 
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Thanks for posting. Here's the supplemental table about their dose constraints.

View attachment 220916

I think an awful lot of those constraints could be extremely difficult for a T2N1 lung cancer, with a hilar lymph node. Treating to 60Gy with great vessel point dose of 54.3? V18 depends on location of primary, like always. Large bronchus point dose of 45.6Gy with a hilar lymph node? What N1 disease could these constraints realistically apply to?

They are very difficult or impossible to meet. It appears that many patients didn't meet these goals for certain "non critical" structures like great vessels or trachea.

Within the methods it outlines that they only made sure to meet the goals (ie compromise tumor coverage) for what they deemed the critical structures of the plexus, cord, heart, and lung. For instance, it appears from table 4 that ?most? patients in the 60 Gy arm had trachea and rib doses above those in the goals above...while the spinal cord doses and plexus doses appear to have been met the majority of the time.
 
When you hypofractionate, do you utilize stereotactic type hetereogeneity- ie do significant portions of the target get +20% prescription dose that allows for very rapid fall off, or because it is more than 5 fractions, you are somehow obligated to keep your hotspot below 10%...(your planner is trying to achieve homogeneity at the expense of fall off.)

Personally, I think it makes sense to contour airways in the PTV and limit hot spot to no more than 5-10% here and who cares how hot the rest of the PTV /excluding critical structutres?
 
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