Stampede: RT for M1 PCA—> OS benefit

[evilbooyaa]

I was going to start a new thread but found this previously posted....

Just curious... have people been able to get this approved? I have a patient with GS8 primary and one single sacral met.

Evicore is reviewing... so I know there's no way it will be approved. But was curious as to other's experiences....

Even if they don't this is a scenario that I would go P2P with, and threaten documentation in the chart if they continue to not allow.

Are you doing the 20 fractions done in the trial?

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[dieABRdie]

Even if they don't this is a scenario that I would go P2P with, and threaten documentation in the chart if they continue to not allow.

Are you doing the 20 fractions done in the trial?

Another good question I would like to hear other's opinions...

I was leaning toward recommending 55/20 as done in the trial... not so sure how I feel about 6Gy x 6 fractions delivered once weekly...

 

[deleted1002574]

6 x 6 Gy is very gentle and well tolerated. Was there a difference in outcome based on dose? I don’t recall.

The problem with these doses is that if the goal is cure (or, long term control) of the disease in the prostate / pelvis, then for comfort’s sake, I just don’t love these doses. 60/20 provided severe post-acute toxicity in a patient I treated in the last several weeks. Another patient with M1 disease treated also got 60/20 and did fine toxicity-wise. Think I’d rather do 70/28 if going for cure, because I’m much more comfortable with that.

Been getting insurance approval if they fit criteria for STAMPEDE. I would fight hard.

 

[RadOncMegatron]

6 x 6 Gy is very gentle and well tolerated. Was there a difference in outcome based on dose? I don’t recall.

The problem with these doses is that if the goal is cure (or, long term control) of the disease in the prostate / pelvis, then for comfort’s sake, I just don’t love these doses. 60/20 provided severe post-acute toxicity in a patient I treated in the last several weeks. Another patient with M1 disease treated also got 60/20 and did fine toxicity-wise. Think I’d rather do 70/28 if going for cure, because I’m much more comfortable with that.

Been getting insurance approval if they fit criteria for STAMPEDE. I would fight hard.

6 Gy was given weekly and I have personally never done that regimen. From the paper:

"There was some evidence of heterogeneity in the effect on failure-free survival by nominated radiotherapy schedule (interaction p=0·072; appendix p 8). Prespecified analyses in 1082 patients who nominated the daily schedule before randomisation (55 Gy in 20 fractions over 4 weeks) found strong evidence of a failure-free survival advantage with radiotherapy compared with control (HR 0·69, 95% CI 0·59–0·80; p<0·0001). Among these 1082 patients, 212 deaths were reported in the control group and 188 in the radiotherapy group (stratified logrank p=0·123; HR 0·86, 95% CI 0·71–1·05; p=0·128). There was insufficient evidence of a difference in failure free survival in 979 patients who nominated the weekly radiotherapy schedule (36 Gy in six fractions over 6 weeks; HR 0·85, 95% CI 0·73–0·99; p=0·033) to report on survival."

Seems like daily was slightly favored though not statistically significant. (Side note: was anyone else confused by the "nominated" verbiage and by the 1082 pts in the daily and 979 in the weekly arm? I didn't realize the 1082 and 979 until I really probed that those numbers included the SOC arm that did not have XRT...)

Table for FFS:

Table below OS:

 

[CaesarRO]

6 x 6 Gy is very gentle and well tolerated. Was there a difference in outcome based on dose? I don’t recall.

The problem with these doses is that if the goal is cure (or, long term control) of the disease in the prostate / pelvis, then for comfort’s sake, I just don’t love these doses. 60/20 provided severe post-acute toxicity in a patient I treated in the last several weeks. Another patient with M1 disease treated also got 60/20 and did fine toxicity-wise. Think I’d rather do 70/28 if going for cure, because I’m much more comfortable with that.

Been getting insurance approval if they fit criteria for STAMPEDE. I would fight hard.

Not that Evicore follows NCCN, but it's in the NCCN now for <5 Mets based on the STOPCAP meta-analysis from HORRAD and STAMPEDE. You can at least use that for P2P

Late Edit: somehow half my post was missing and didn't say what I thought it did.

 

[SneakyBooger]

I was going to start a new thread but found this previously posted....

Just curious... have people been able to get this approved? I have a patient with GS8 primary and one single sacral met.

Evicore is reviewing... so I know there's no way it will be approved. But was curious as to other's experiences....

Same scenario here. Evicore denied.

I am treating according to (currently enrolling) SWOG 1802 protocol as far as fractionation is concerned.

 

[dieABRdie]

Same scenario here. Evicore denied.

I am treating according to (currently enrolling) SWOG 1802 protocol as far as fractionation is concerned.

View attachment 283500

Confused.... so Evicore denied STAMPEDE but approves 79.2Gy in 1.8s???

I'm filling out their worksheet now. I'm thinking of asking for 6Gyx6 just because I anticipate them denying 20 fractions....

 

[taserlaser]

Prior to stampede, for a lot of the elderly gentlemen <10 year life expectancy and wouldn’t be suitable for AS (eg not favorable disease) that would be nice to limit toxicity (not that there’s much anyways from external beam but there’s some), I gave a lot of 50/20 to the prostate. Had good results with that. I’m out of GU practice now for the most part now, though.

 

[evilbooyaa]

Another good question I would like to hear other's opinions...

I was leaning toward recommending 55/20 as done in the trial... not so sure how I feel about 6Gy x 6 fractions delivered once weekly...

I personally think putting somebody through the toxicity of 78-81/39 or similar is not worth it for someone who is metastatic.

I would personally do 55/20. I would avoid 60/20 (just like I'd avoid standard fx) because regardless of what I do for their local disease, their prostate is not going to be what kills them the vast majority of the time. It's aggressive palliation the same way we'd consider 45/15 treatment for the primary in oligometastatic NSCLC.

 

[deleted1002574]

I would never do 45/15 for oligometastatic NSCLC.

If you’re going for cure, go for cure. There are plenty of experienced rad oncs that have 3, even 5 years survivors of limited M1a lung cancer.

Curious to know why that would be your approach when you enter the real world?

I personally think putting somebody through the toxicity of 78-81/39 or similar is not worth it for someone who is metastatic.

I would personally do 55/20. I would avoid 60/20 (just like I'd avoid standard fx) because regardless of what I do for their local disease, their prostate is not going to be what kills them the vast majority of the time. It's aggressive palliation the same way we'd consider 45/15 treatment for the primary in oligometastatic NSCLC.

 

[medgator]

I would never do 45/15 for oligometastatic NSCLC.

If you’re going for cure, go for cure. There are plenty of experienced rad oncs that have 3, even 5 years survivors of limited M1a lung cancer.

Curious to know why that would be your approach when you enter the real world?

What would you do? 60/15?

- American Society for Radiation Oncology (ASTRO) - American Society for Radiation Oncology (ASTRO)

www.astro.org

Not sure I would sbrt the mediastinum.

I think 45/15 is just fine for oligometastatic in situations where sbrt cannot be done. Many, including turisi, like it for consolidative trt in es sclc too (per mednet).

I've also done 50/20 for es sclc consolidation.

 

[evilbooyaa]

I would never do 45/15 for oligometastatic NSCLC.

If you’re going for cure, go for cure. There are plenty of experienced rad oncs that have 3, even 5 years survivors of limited M1a lung cancer.

Curious to know why that would be your approach when you enter the real world?

Because the majority of patients on the published Gomez trial and the ongoing LU-002 are going to be getting 45/15? I mean 45/15 in patients who cannot get SBRT to the primary (usually b/c of mediastinal LNs) in case it was unclear. If they have N0 disease and I can SBRT it then I will do that.

Until there's data saying "Man the local recurrence rate (and not distant metastasis rate as expected) in these oligometastatic patients is like sooooooooooo high" I'm going to use 45/15 as a standard, even in the real world.

I mean if they can tolerate 60/15 then great but again, consolidating the mediastinum is where I meant 45/15.

Are you doing 60/30 with concurrent chemo for your oligomet stage IV NSCLCs?

 

[deleted1002574]

Hmm. Sounds like more variation then I thought.

In the pre-stage IV data area (all these new studies showing benefit with RT consolidation). If a patient had a single met or just a few in the brain, a bone met or just a liver lesion.. 4-6 cycles platinum doublet and if CR, then treat with curative dose. 45/15 feels really low.

What would you do? 60/15?

- American Society for Radiation Oncology (ASTRO) - American Society for Radiation Oncology (ASTRO)

www.astro.org

Not sure I would sbrt the mediastinum.

I think 45/15 is just fine for oligometastatic in situations where sbrt cannot be done. Many, including turisi, like it for consolidative trt in es sclc too (per mednet).

I've also done 50/20 for es sclc consolidation.

 

[dieABRdie]

I don't have a machine commissioned for SBRT, just static IMRT.

I have one patient with metastatic EGFR positive NSCLC who has only one known lesion in her body (1.6cm left upper lobe)... as well as one patient with cT1cN0 NSCLC non-surgical candidate. I'm giving both 60/15.

I was going to give the metastatic patient 45/15... but after talking with the patient and the med onc we decided to be more aggressive. I think 45/15 would have been reasonable...

 

[xrthopeful]

45/15 is a great proven definitive dose. Perfect for patients with stage III disease not getting concurrent chemo, as is 60/15

 

[deleted1002574]

Got it.

I don’t mean to go all “Scarbtj” on you, I really don’t. But BED of 45/15 is less than 60 for ab = 2.

To aim for cure for stage III lung, the minimum dose was around 60/2 to 70/2 (with variation) and that was with chemo. And this is in the era (70s to 90s) where the cure rate was about 5-10% at 5 years.

If all the disease is gone, and it’s an aim to cure, I just “feel” it’s low.

But, yeah, I guess Oli-Gomez trial suggests 45/15. “There’s the right way, the wrong way, and the MD Anderson way”.

Everyone in rad onc says, “as systemic treatment gets better, then local control becomes more important”. 45/15 after a CR (or near CR) seems to violate that principle. Seem to be a bummer if after all that the local disease came back. Would be really limited as to what dose you could give.

 

[Palex80]

Think I’d rather do 70/28 if going for cure, because I’m much more comfortable with that.

The problem I have with 70/2.5 is that this regime was tested against 73.8/1.8 in low-risk patients and found to be equivalent.

Now:
1. I don't treat low-risk patients any more with EBRT, these patients get active surveillance nowadays. Drawing conclusions on efficacy of radiation therapy regimes in a population where AS may also result to comparable results is tricky.
2. I would never consider 7.3/1.8 as a "modern" normofractionated regime. It's too low in terms of BED (the 1.8 Gy dose/day makes it even worse).

Even the 60/3 as per CHHiP was tested against 74/2 (albeit in all-risk patients) and I believe all of us can agree that 74/2 is at the lowest end of what one would consider adequate normofractionated dose nowadays.


Thus...

I think pushing the dose higher, for example with 72.5-75/2.5 or 63/3 will rather reflect a treatment that is closer to nowadays, dose-escalated normofractionated regimes (like 78-80+/2). Do I have data to back it up? Nope. But you can do the math yourself.

Thoughts?

 

[Palex80]

45/15 is a great proven definitive dose. Perfect for patients with stage III disease not getting concurrent chemo, as is 60/15

Replace "definitive" with "palliative" please.

 

[evilbooyaa]

Hmm. Sounds like more variation then I thought.

In the pre-stage IV data area (all these new studies showing benefit with RT consolidation). If a patient had a single met or just a few in the brain, a bone met or just a liver lesion.. 4-6 cycles platinum doublet and if CR, then treat with curative dose. 45/15 feels really low.

I don't think it's wrong to do 60/30 with chemo but I don't think it's wrong to 45/15. Most patients on Gomez got 45/15 to the primary but a small proportion did get 60/30 with chemo.

As always, variation of practice. To each his own, IMO. I would personally not routinely offer 60/30 with chemo to an oligometastatic patient. If they had one solitary brain met (published historical cure potential) then I would potentially consider, especially if med-onc was really aggressive about giving chemo. No chemo with 45/15.

 

[evilbooyaa]

I don't have a machine commissioned for SBRT, just static IMRT.

I have one patient with metastatic EGFR positive NSCLC who has only one known lesion in her body (1.6cm left upper lobe)... as well as one patient with cT1cN0 NSCLC non-surgical candidate. I'm giving both 60/15.

I was going to give the metastatic patient 45/15... but after talking with the patient and the med onc we decided to be more aggressive. I think 45/15 would have been reasonable...

I would personally refer both of these patients out for SBRT, doubly so on the early stage NSCLC that is in an obviously curative state. I'm not familiar with where you work, but would refer either to the mothership (if you are an academic satellite) or to the local academic practice (if you're in PP). Obviously easy for me to say this as I am not the one losing out on the money doing so. If the patient would be a candidate for truly ablative dosing (54/3, 50-60/5, even 60/8) I would not like 60/15 as BED > 100 (which 60/15 is not) has been proven to be instrumental in control rates across multiple studies.

 

[evilbooyaa]

Replace "definitive" with "palliative" please.

Googling '45Gy in 15 fractions'

Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer

While conventionally fractionated radiation therapy alone is an acceptable option for poor prognostic patients with unresectable stage III NSCLC, we hypothesized that accelerated hypofractionated radiotherapy will have similar efficacy without increasing ...

www.ncbi.nlm.nih.gov

Just a note that even the 60/30 patients did not receive chemo.

Is 45/15 worse than 60/30 with chemo in terms of local control? Sure.

However, is 45/15 worse than 60/30 without chemo? I don't know of any evidence that says that, and there are multiple evaluations saying that it isn't. There may even be clinical trials on this but I put the onus of proof on you. Ball in your court.

Local recurrence rate less than 30% in that study at 5 years. We call GBM dosing definitive so I'm going to call this definitive.

 

[deleted1002574]

Yes, both definitely are reasonable, but 45/15 is the “board answer”. Even though it “feels” palliative, especially without chemo. It’s a bias of being out for a while.

73 in 1.8s to PTV is 76-77 to isocenter if comparing to past dose escalation studies. But that’s been debated in the past, and won’t get much agreement about that.

Truly a better and more civil discussion than jobs and the market! Carry on, boys and girls.

 

[medgator]

Replace "definitive" with "palliative" please.

"Aggressive" palliation in my book

 

[dieABRdie]

I would personally refer both of these patients out for SBRT, doubly so on the early stage NSCLC that is in an obviously curative state. I'm not familiar with where you work, but would refer either to the mothership (if you are an academic satellite) or to the local academic practice (if you're in PP). Obviously easy for me to say this as I am not the one losing out on the money doing so. If the patient would be a candidate for truly ablative dosing (54/3, 50-60/5, even 60/8) I would not like 60/15 as BED > 100 (which 60/15 is not) has been proven to be instrumental in control rates across multiple studies.

Oh.... I definitely tried to send them out. The response.... "I ain't driving to that thar big city!!!"

 

[medgator]

I don't have a machine commissioned for SBRT, just static IMRT.

I have one patient with metastatic EGFR positive NSCLC who has only one known lesion in her body (1.6cm left upper lobe)... as well as one patient with cT1cN0 NSCLC non-surgical candidate. I'm giving both 60/15.

I was going to give the metastatic patient 45/15... but after talking with the patient and the med onc we decided to be more aggressive. I think 45/15 would have been reasonable...

70/17 gets you close to a BED of 100 and can be done on any linac

Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904 - PubMed

Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further...

www.ncbi.nlm.nih.gov

 

[dieABRdie]

70/17 gets you close to a BED of 100 and can be done on any linac

Phase I study of accelerated conformal radiotherapy for stage I non-small-cell lung cancer in patients with pulmonary dysfunction: CALGB 39904 - PubMed

Accelerated conformal radiotherapy was well tolerated in a high-risk population with clinical stage I NSCLC. Outcomes are comparable to prospective reports of alternative therapies, including stereotactic body radiation therapy and limited resection, with less apparent severe toxicity. Further...

www.ncbi.nlm.nih.gov

Thanks! I had not seen that before.....

 

[Palex80]

Googling '45Gy in 15 fractions'

Accelerated hypofractionated radiation therapy compared to conventionally fractionated radiation therapy for the treatment of inoperable non-small cell lung cancer

While conventionally fractionated radiation therapy alone is an acceptable option for poor prognostic patients with unresectable stage III NSCLC, we hypothesized that accelerated hypofractionated radiotherapy will have similar efficacy without increasing ...

www.ncbi.nlm.nih.gov

Just a note that even the 60/30 patients did not receive chemo.

Is 45/15 worse than 60/30 with chemo in terms of local control? Sure.

However, is 45/15 worse than 60/30 without chemo? I don't know of any evidence that says that, and there are multiple evaluations saying that it isn't. There may even be clinical trials on this but I put the onus of proof on you. Ball in your court.

Local recurrence rate less than 30% in that study at 5 years. We call GBM dosing definitive so I'm going to call this definitive.

60/30 is not curative for stage III NSCLC, not without chemo (&Durva). Have a look at the Kaplan–Meier curves of your quoted article. 5–y–OS looks like 10% and PFS is at 5%... which is more or less GBM–level of survival.
And any GBM treatment is palliative, but then again, it‘s a matter of perception and how you call things.

A patient newly diagnosed with GBM asked me this summer what the chance is the tumor will not come back. I said „practically 0%“. What would you say?

 

[scarbrtj]

I don’t mean to go all “Scarbtj” on you, I really don’t. But BED of 45/15 is less than 60 for ab = 2.

Great I'm a meme. It's scarbrtj. Get it right.
Let's correct for time, see what happens. Shorter courses by their nature have more BED. My rough time factor correction is 0.5*[total elapsed tx days], or [total elapsed tx days]/2.* I'm plus/minus on time factor corrections. I'm into it today.

You want α/β=2? For tumor BED? Everyone has typically used 10.

45/15 = 45*(1+(3/10))-(19/2) = 49 BED Gy10

Yes. Much less than 60 BED Gy10. (Goal is 100+ BED Gy10 as we all know.) Someone mentioned Turrisi. Way back when he was doing 80.5 Gy/35fx for Stage I NSCLC. He was also one of first people in the world to abandon mediastinal ENI for all stages of lung cancer, small and non-small. He was also chided as a young attending by older attendings with such taunts as "The game is not how small you can make the treatment field, Andrew."

80.5/35 = 80.5*(1+(2.3/10))-(47/2) = 76 BED Gy10

80.5 Gy sounded like a lot in the "old days." It wasn't that hot, literally and figuratively.

* ([ln 2]*days)/(α*Tpot)

 

[scarbrtj]

60/30 is not curative for stage III NSCLC, not without chemo (&Durva). Have a look at the Kaplan–Meier curves of your quoted article. 5–y–OS looks like 10% and PFS is at 5%... which is more or less GBM–level of survival.
And any GBM treatment is palliative, but then again, it‘s a matter of perception and how you call things.

A patient newly diagnosed with GBM asked me this summer what the chance is the tumor will not come back. I said „practically 0%“. What would you say?

I would say the chance of it not coming back is directly related to the chance of pathological mis-diagnosis (Gr IV vs Gr III)... which is not 0% But in seriousness 0% may be a bit harsh...

I think it was "Tyler Durden" who said on a long enough timeline the survival for everyone drops to zero. So I can't totally argue with you. This obv a graph of survivors, not recurrers.

 

[Palex80]

You are right, BUT the curves stop at 5 years.
I do not believe there is a plateau effect there, this is not immunotherapy.

All GBM patients die from GBM-progression, unless something else kills them earlier.

I recall two patients that survived quite a long time, both of them very young and fit. They died 8 & 9 years after diagnosis, both progressing after X lines of treatment. I do not believe you can actually cure someone with GBM.

 

[medgator]

. I do not believe you can actually cure someone with GBM.

Technically we don't really cure diabetes or htn but just manage them as chronic diseases, although a few of my head and neck patients have done that after we took off 30-40 lbs during tx

I think optune may do that for some gbm pts eventually the way immunotherapy may also be keeping metastatic tumors at bay/in a stalemate

 

[deleted1002574]

All cancer patients die from cancer, unless something kills them earlier

You are right, BUT the curves stop at 5 years.
I do not believe there is a plateau effect there, this is not immunotherapy.

All GBM patients die from GBM-progression, unless something else kills them earlier.

I recall two patients that survived quite a long time, both of them very young and fit. They died 8 & 9 years after diagnosis, both progressing after X lines of treatment. I do not believe you can actually cure someone with GBM.

 

[Palex80]

I think optune may do that for some gbm pts eventually the way immunotherapy may also be keeping metastatic tumors at bay/in a stalemate

I have seen absolutely no data showing that Optune results in a plateau in OS-curves.

Please bear in mind that we are talking about very small numbers in those OS curves Scarbtj posted, something like 20 patients out of initial 900+.
It reminds me of a wonderful poster I saw on Ipilimumab several years ago (sorry it's in German):

What is written in orange: The first immunotherapy for melanoma with long-term survival data of over 10 years.

Look at the graph and the number at risk at 10 years...

 

[evilbooyaa]

60/30 is not curative for stage III NSCLC, not without chemo (&Durva). Have a look at the Kaplan–Meier curves of your quoted article. 5–y–OS looks like 10% and PFS is at 5%... which is more or less GBM–level of survival.
And any GBM treatment is palliative, but then again, it‘s a matter of perception and how you call things.

A patient newly diagnosed with GBM asked me this summer what the chance is the tumor will not come back. I said „practically 0%“. What would you say?

These are patients who have such bad co-morbidities that they cannot get chemotherapy. While a majority of those patients are likely dying of their disease, the local and distant metastasis free additions don't equal the pure survival numbers. There is a competing risk here and K-M does not illustrate that well.

 

[OTN]

You are right, BUT the curves stop at 5 years.
I do not believe there is a plateau effect there, this is not immunotherapy.

All GBM patients die from GBM-progression, unless something else kills them earlier.

I recall two patients that survived quite a long time, both of them very young and fit. They died 8 & 9 years after diagnosis, both progressing after X lines of treatment. I do not believe you can actually cure someone with GBM.

In neuro-onc tumor board, the conclusion on these patients is usually that it wasn't quite as high grade at diagnosis as originally thought. Such a miserable disease.

 

[taserlaser]

In neuro-onc tumor board, the conclusion on these patients is usually that it wasn't quite as high grade at diagnosis as originally thought. Such a miserable disease.

Thats the understanding I got from the neuro oncs from where I trained as well, whether those were ‘true’ GBMs. Certainly now molecular markers are driving treatment decisions in the low grade population more than ever these days.

 

[scarbrtj]

There will be new treatments that will produce "cures." I'm a pessimist. But I'm not 100% a pessimist.

60/30 is not curative for stage III NSCLC, not without chemo (&Durva).

What I'm saying is... never say never.
Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy.

 

[thaddeus]

I don't think it's wrong to do 60/30 with chemo but I don't think it's wrong to 45/15. Most patients on Gomez got 45/15 to the primary but a small proportion did get 60/30 with chemo.

As always, variation of practice. To each his own, IMO. I would personally not routinely offer 60/30 with chemo to an oligometastatic patient. If they had one solitary brain met (published historical cure potential) then I would potentially consider, especially if med-onc was really aggressive about giving chemo. No chemo with 45/15.

Agree with this. In my view, there are two equivalent paradigms: Address mets (e.g. SRS for a solitary brain met), then do upfront chemoRT with 60/30, or do upfront chemotherapy, with consolidation to primary and any metastatic disease (45/15 to the primary without chemo). While we might argue BEDs until were blue in the face, the fact remains that the large majority of these patients will fail distantly regardless of what dose we give thoracic disease. I have treated a number of patients with 45/15 as consolidative therapy - none have failed locally and (almost) all have failed distantly. I personally favor upfront chemo for most of these cases, because 1) I think they should start maximally effective systemic therapy as early as possible in their disease course (especially now with highly effective chemo/immunotherapy regimens that cannot be combined with RT) and 2) I want to see how they respond to therapy before exposing them to toxicity from thoracic radiation.

One other point: we consider 45 Gy delivered over 15 days (BID) to be "curative" treatment in the SCLC setting, so not sure why we don't here.

 

[deleted1002574]

Agree with this. In my view, there are two equivalent paradigms: Address mets (e.g. SRS for a solitary brain met), then do upfront chemoRT with 60/30, or do upfront chemotherapy, with consolidation to primary and any metastatic disease (45/15 to the primary without chemo). While we might argue BEDs until were blue in the face, the fact remains that the large majority of these patients will fail distantly regardless of what dose we give thoracic disease. I have treated a number of patients with 45/15 as consolidative therapy - none have failed locally and (almost) all have failed distantly. I personally favor upfront chemo for most of these cases, because 1) I think they should start maximally effective systemic therapy as early as possible in their disease course (especially now with highly effective chemo/immunotherapy regimens that cannot be combined with RT) and 2) I want to see how they respond to therapy before exposing them to toxicity from thoracic radiation.

One other point: we consider 45 Gy delivered over 15 days (BID) to be "curative" treatment in the SCLC setting, so not sure why we don't here.

Yes, most patients fail distantly, if locally advanced (stage III) or metastatic. Yet, with no major changes in therapy the median survival of stage III NSCLC has gone from 16 months (RTOG 9410) to 24 months (RTOG 0617). Why? PET-CT staging/stage migration? Or did the radiation technique actually get better and the old line "local control becomes more meaningful as systemic therapy improves". I don't know, but nobody has a great answer for this.

Saying it doesn't matter what dose (and I know you're just saying it to make a point) would mean that the optimal dose could be zero, as well, right?
But, 45/15 helps to improve survival. And we do know from older studies that 60/30 was considered "the dose" and nothing has really shown to be better otherwise. It is a lower BED than 60-66/30-33 with chemo, no doubt about that. It's a matter of how much you weigh the risk of distant vs local recurrence - and so the dose can be anywhere from 0 to 66 Gy. Most people, at this point in time, feel that 0 is the wrong dose. My logic is that some of these people will be cured. And to give them 45/15, to me, seems very low.

How about this scenario ...

54 yo attorney who smoked in her 20s for 5 years presents with cough/hemoptysis and 10lb wt loss (that she thought was intentional because she began to run 4 miles a day, 4 days a week). CT - 3cm suprahilar mass, and 2.4cm subcarinal node. EBUS and bx of subcarinal node proves to be NSCLC, adenocarcinoma. PET-CT shows the disease mentioned above, plus a 1.5 cm FDG avid left superior iliac lesion, MRI brain negative. Iliac lesion is biopsied and proven to be adenocarcinoma. She starts standard chemotherapy and after 4 cycles, PET-CT shows metabolic resolution, but the suprahilar mass is still 2cm and the subcarinal nodes is 1.5cm. You'd stop at 45 on this lady? And feel like you have given her best possible chance?

It seems pessimistic. Medical oncologists absolutely FLOG their patients. An extra 3 weeks of RT with good technique and minor excess toxicity compared to 45/15 seems reasonable... (don't worry, I have not forgotten the bone met).

 

[medgator]

54 yo attorney who smoked in her 20s for 5 years presents with cough/hemoptysis and 10lb wt loss (that she thought was intentional because she began to run 4 miles a day, 4 days a week). CT - 3cm suprahilar mass, and 2.4cm subcarinal node. EBUS and bx of subcarinal node proves to be NSCLC, adenocarcinoma. PET-CT shows the disease mentioned above, plus a 1.5 cm FDG avid left superior iliac lesion, MRI brain negative. Iliac lesion is biopsied and proven to be adenocarcinoma. She starts standard chemotherapy and after 4 cycles, PET-CT shows metabolic resolution, but the suprahilar mass is still 2cm and the subcarinal nodes is 1.5cm. You'd stop at 45 on this lady? And feel like you have given her best possible chance?

It seems pessimistic. Medical oncologists absolutely FLOG their patients. An extra 3 weeks of RT with good technique and minor excess toxicity compared to 45/15 seems reasonable... (don't worry, I have not forgotten the bone met).

I'm sure plenty of us do 60-66 with chemo on oligometastatic stage III pts with a single brain met that gets srs/srt.... Don't think anything should be different if that single met was in the bone instead

 

[Mandelin Rain]

I've seen a person die of metastatic GBM about 5 years after primary diagnosis with a completely NED brain.

Now THAT'S some awful/frustrating stuff.

 

[medgator]

I've seen a person die of metastatic GBM about 5 years after primary diagnosis with a completely NED brain.

Now THAT'S some awful/frustrating stuff.

Drop mets?

 

[Mandelin Rain]

Nope. Started as lung. Biopsied multiple times, all consistent.

 

[evilbooyaa]

Yes, most patients fail distantly, if locally advanced (stage III) or metastatic. Yet, with no major changes in therapy the median survival of stage III NSCLC has gone from 16 months (RTOG 9410) to 24 months (RTOG 0617). Why? PET-CT staging/stage migration? Or did the radiation technique actually get better and the old line "local control becomes more meaningful as systemic therapy improves". I don't know, but nobody has a great answer for this.

Saying it doesn't matter what dose (and I know you're just saying it to make a point) would mean that the optimal dose could be zero, as well, right?
But, 45/15 helps to improve survival. And we do know from older studies that 60/30 was considered "the dose" and nothing has really shown to be better otherwise. It is a lower BED than 60-66/30-33 with chemo, no doubt about that. It's a matter of how much you weigh the risk of distant vs local recurrence - and so the dose can be anywhere from 0 to 66 Gy. Most people, at this point in time, feel that 0 is the wrong dose. My logic is that some of these people will be cured. And to give them 45/15, to me, seems very low.

No, that is not supported by the data. In Gomez trial, in the non-consolidative local therapy arm, the MAJORITY of recurrences included in the index lesion. In the consolidative local therapy arm, the majority of recurrences were distant lesions only. Local therapy absolutely changes the patterns of failure in oligometastatic NSCLC.

Just to get the numbers from the initial Gomez paper (showing improvement in PFS) - 13 patients in LCT arm progressed, 10 were DM only, 1 was LR only, 2 were both. 3/13 patients failed locally. In contrast, in the no LCT arm, 6 had DM only, 4 had LR only, and 7 had both. 11/17 patients failed locally.

Granted, that is with median f/u of ~ 1 year, so the number of patients experiencing local failure is likely to go up. However, the issue at hand here is generally the development of isolated locoregional failure.

It's a balance of benefits of therapy vs the risks. Are patients who get upfront systemic therapy (which I generally favor before I put them through the toxicity of thoracic RT at any dose), especially with IT as front line in all patients, going to be at a higher risk of grade 3+ pneumonitis with 60-66 with chemo? I would argue, well yeah of course. Is there data that suggests patients who get 60-66 with chemo are doing better than patients getting 45/15? No. Is there data suggesting that these patients are recurring at such high rates locally with 45/15 (remember that they are getting maintenance systemic therapy) that dose escalation in this setting is warranted? Dose-escalation doesn't matter even in stage III NSCLC, but you're telling me it's going to matter in stage IV?

How about this scenario ...

54 yo attorney who smoked in her 20s for 5 years presents with cough/hemoptysis and 10lb wt loss (that she thought was intentional because she began to run 4 miles a day, 4 days a week). CT - 3cm suprahilar mass, and 2.4cm subcarinal node. EBUS and bx of subcarinal node proves to be NSCLC, adenocarcinoma. PET-CT shows the disease mentioned above, plus a 1.5 cm FDG avid left superior iliac lesion, MRI brain negative. Iliac lesion is biopsied and proven to be adenocarcinoma. She starts standard chemotherapy and after 4 cycles, PET-CT shows metabolic resolution, but the suprahilar mass is still 2cm and the subcarinal nodes is 1.5cm. You'd stop at 45 on this lady? And feel like you have given her best possible chance?

It seems pessimistic. Medical oncologists absolutely FLOG their patients. An extra 3 weeks of RT with good technique and minor excess toxicity compared to 45/15 seems reasonable... (don't worry, I have not forgotten the bone met).

The toxicity of doing this is quite real. 45/15 to a big chunk of mediastinum and esophagus is toxic. 60/30 to the same amount of disease would also be quite toxic. The patients you are seeing may be different than the patient's I'm routinely seeing that are in their 60s/70s with 10 mets at diagnosis, 3-4 left after chemo, with confluent mediastinal disease extending to contralateral mediastinum or SCV, and we're being asked to treat oligometastatic disease.

In your theoretical scenario, sure I would have a discussion of increased likelihood of toxicity with desire to be more aggressive, and given that she is the absolute best of the best I would probably go with 60/30. I've treated these patients with 60/30 with chemo if they only have say one site of disease and are healthy otherwise.

All I'm saying is that the vast majority of patients we're seeing for this are not the scenario you described, they have morbidities, more significant disease, or we're extrapolating Gomez to oligoprogressive patients as well, and I would not default to 60/30 with chemo for all of them. Would I treat unique scenarios with 60/30 with chemo? Sure, but that would not be my default dosing.

 

[Palex80]

What I'm saying is... never say never.
Long-term survival in patients with non-small cell lung cancer treated with palliative radiotherapy.

Are you trolling Scarbtj?

From the paper you quoted...

The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction.

So, never say never, because 1.3% of all patients treated with palliative raditiotherapy for NSCLC are alive at 5 years?
1.3% 5-years-OS!!! That's what I call cure!

Half of them had stage I/II and only 70% of them had a proven cancer in the first place...

 

[radoncgrad2019]

Are you trolling Scarbtj?

To quote Eli Glatstein - 'Baby if you have to ask, you already know'

 

[scarbrtj]

Are you trolling Scarbtj?

From the paper you quoted...

The aim of palliative thoracic radiotherapy in patients with advanced non-small cell lung cancer (NSCLC) is to alleviate symptoms. This study was designed to determine whether any patients achieved long-term survival after this treatment. In Edinburgh, between 1974 and 1993, 4531 patients were treated with palliative radiotherapy for NSCLC, receiving ten fractions or fewer. We reviewed the case notes of the long-term survivors. Sixty-one (1.3%; 95% confidence interval (CI) 1.0-1.6) patients survived for more than 5 years; 43 (70%) had histological confirmation of cancer; 28 (46%) had stage Stage I or II, 28 (46%) Stage III and one Stage IV disease; 53 (87%) patients were treated with doses of 30-35 Gy in ten daily fractions, seven (12%) received 20 Gy in five daily fractions and one received a 10 Gy single fraction.

So, never say never, because 1.3% of all patients treated with palliative raditiotherapy for NSCLC are alive at 5 years?
1.3% 5-years-OS!!! That's what I call cure!

Half of them had stage I/II and only 70% of them had a proven cancer in the first place...

I didn't call it cure, the two articles I referenced from thousands of patients called it cure

In one episode of Breaking Bad, Gale and Gus are talking after setting up their lab and Gale had synthesized 96% pure meth whereas Walt's blue meth values were coming out to like 99%. And Gus is like what's the big deal. And Gale was like "There's a vast difference between that 96% and 99%." There's a vast difference between 0% cure (LC) and anything that's not 0%. Even as miniscule as a single percentage point. Zero percent (ie "uncontrollable") cures harken back to the "forbidden tumors" of old where radiotherapy was thought to be as good as holy water for some cancers. We are taught in radiobiology that the D-zero (surviving fraction, SF) for many tumor cells is about 1/e after 2 Gy. Thus with a palliative dose of 30 Gy, SF = x*(1/e^15). If x<3E6 or so (which is at least in the realm of possibility for large macroscopic tumors), or if the Dzero is lower following the law of Bergonié and Tribondeau, even palliative radiotherapy can theoretically be curative in certain situations and there's data to show that. There's also data to show cures in GBM. They're rare, yes. But technically in science all it takes is one verifiable conflicting data point to falsify an entire theory. Theories: GBM is never cured, or 60/30 is not a curative dose in lung cancer. There are falsifying data for both of these.

 

[medgator]

I didn't call it cure, the two articles I referenced from thousands of patients called it cure

In one episode of Breaking Bad, Gale and Gus are talking after setting up their lab and Gale had synthesized 96% pure meth whereas Walt's blue meth values were coming out to like 99%. And Gus is like what's the big deal. And Gale was like "There's a vast difference between that 96% and 99%." There's a vast difference between 0% cure (LC) and anything that's not 0%. Even as miniscule as a single percentage point. Zero percent (ie "uncontrollable") cures harken back to the "forbidden tumors" of old where radiotherapy was thought to be as good as holy water for some cancers. We are taught in radiobiology that the D-zero (surviving fraction, SF) for many tumor cells is about 1/e after 2 Gy. Thus with a palliative dose of 30 Gy, SF = x*(1/e^15). If x<3E6 or so (which is at least in the realm of possibility for large macroscopic tumors), or if the Dzero is lower following the law of Bergonié and Tribondeau, even palliative radiotherapy can theoretically be curative in certain situations and there's data to show that. There's also data to show cures in GBM. They're rare, yes. But technically in science all it takes is one verifiable conflicting data point to falsify an entire theory. Theories: GBM is never cured, or 60/30 is not a curative dose in lung cancer. There are falsifying data for both of these.

Or, as they say, the only certainty in life is death and taxes?

 

[Ray D. Ayshun]

Is anyone having trouble with medoncs believing the stampede data? I get it was a subgroup, but it matches perfectly with horrad more or less, and was prespecified. In any case, do we really need to wait until 2030 for a large trial asking this specific question to result? Obviously, the whole hammer/nail argument fits here, but the data is pretty convincing.

 

[medgator]

Is anyone having trouble with medoncs believing the stampede data? I get it was a subgroup, but it matches perfectly with horrad more or less, and was prespecified. In any case, do we really need to wait until 2030 for a large trial asking this specific question to result? Obviously, the whole hammer/nail argument fits here, but the data is pretty convincing.

Maybe talk to your urologists?