Thoracic RT for ES-SCLC: decreased pt volume?

[ProtonElectronNeutron]

Consolidation thoracic RT for ES-SCLC after CR/PR: do you guys see a decrease in referral after the IMPOWER133 Atezo maintenance study came out? Please share your experience? If you get the referral, do you treat concurrently with Atezo?

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[evilbooyaa]

Have seen 2 ES-SCLCs since that trial came out. Both times, med onc didn't want me to do consolidative thoracic RT when discussing the case with them. The patients were referred for discussion of PCI vs MRI surviellance (and to take over MRI surveillance for each of the pts). One guy I treated when he developed oligoprogression in his index lesion.

I think med oncs have a good reason to push against thoracic RT in this population. I don't know that it makes a difference between treating as consolidation vs at oligoprogression.

Not sure what the risk of local recurrence is as I don't see it reported in IMPOWER133

 

[Grubbe-a-dub-dub]

I have consolidated patients who went on to develop horrible pneumonitis, even after only 30 Gy. The patient was on atezo.

This is n of 1, but I am hesitant now to offer consolidation - especially since the pneumonitis delayed further immunotherapy which was actually working.

 

[thecarbonionangle]

Have never run into this so far.

 

[FrostyHammer]

Yes I have, and even with the Slotman trial I was not convinced. The Slotman trial did not meet its primary endpoint (which it was powered for) and many use the 2-year OS as an excuse to offer thoracic RT. Which tells me that thoracic RT benefits the patients who have favorable risk factors and are likely to even make it past ~1.5 years. So overall I was not a big believer of thoracic RT to begin with. I also don't believe in atezo or durva either. The classic case of statistical but questionable (at best) clinical significance. If I had extensive stage SCLC I wouldn't want gobs of money wasted to give me pennies in terms of remaining lifespan...

 

[Palex80]

Yes, less patients are being referred and we debate more often at the tumor board about the value of the treatment.

Two factors triggered that:

1. Immunotherapy is now s.o.c., so patients get Atezolizumab or Durvalumab

2. We probably have a better understanding now of which patients may benefit from consolidative RT (this was one the main weaknesses of the Slotman trial in my opinion - allowing anyone in who had "some" response after chemotherapy, irrelevant of the metastatic burden, with the exception of brain and pleural mets, which were not eligible). But hoping that consolidative RT will be beneficial in a patient who started chemotherapy with 30 liver mets and then showed SD at the end of treatment is illusional...


I do believe that some patients with ES-SCLC will benefit from consolidative RT (and I also think you need more than 10 x 3 Gy to show that), but these patients should be selected. Probably ones with lots of mediastinal disease at baseline and no extensive bone, liver or brain metastasis. Probably less than 30% of all ES-SCLC patients.

 

[seper]

Yes, I see that atezo competes with consolidate RT in this scenario. I guess you can give both, but MedOncs prefer not to

 

[Grubbe-a-dub-dub]

I agree with the above sentiments, it's a horrible disease with few options. I have seen so many die with small cell in my short tenure as an attending, many in pain or debilitated otherwise from mets.

Wish more attention and meaningful clinical trials done in this space, rather than re-hashes of old trials (ie. see RAPTOR trial LU-007 and compare that to RTOG 0937).

 

[radoncopotamus]

My practice is to offer consolidative RT for those with a good PR to chemo-immunotherapy and have not gotten push back yet against doing it concurrently with immunotherapy. They usually get to me after being referred for PCI and I will steer them to address the chest instead and watch the brain.

 

[medgator]

Yes, less patients are being referred and we debate more often at the tumor board about the value of the treatment.

Two factors triggered that:

1. Immunotherapy is now s.o.c., so patients get Atezolizumab or Durvalumab

2. We probably have a better understanding now of which patients may benefit from consolidative RT (this was one the main weaknesses of the Slotman trial in my opinion - allowing anyone in who had "some" response after chemotherapy, irrelevant of the metastatic burden, with the exception of brain and pleural mets, which were not eligible). But hoping that consolidative RT will be beneficial in a patient who started chemotherapy with 30 liver mets and then showed SD at the end of treatment is illusional...


I do believe that some patients with ES-SCLC will benefit from consolidative RT (and I also think you need more than 10 x 3 Gy to show that), but these patients should be selected. Probably ones with lots of mediastinal disease at baseline and no extensive bone, liver or brain metastasis. Probably less than 30% of all ES-SCLC patients.

Had a pt we successfully salvaged with chemo RT for medistinal recurrence 2-3 years after chemo and PCI for es-sclc with a CR after initial chemo on pet... Guy is still alive 5 years later

 

[FrostyHammer]

We're still offering PCI for ES-SCLC???

 

[medgator]

We're still offering PCI for ES-SCLC???

In 2012? Yeah

 

[drewdog1973]

2012 is modern for some people

 

[Neuronix]

We're still offering PCI for ES-SCLC???

I'm offering MAVERICK trial.

 

[evilbooyaa]

We're still offering PCI for ES-SCLC???

I mean I am technically 'offering' it the same way I 'offer' WBRT to a patient with 1-3 brain mets from NSCLC but I haven't had a patient take me up on it ever since Takahashi trial came out.

I'm getting away from even doing PCI for LS-SCLC at the current time clinically, although my boards answer will be to do PCI. Hope MAVERICK completes enrollment for the LS-SCLC population soon.

 

[FrostyHammer]

I mean I am technically 'offering' it the same way I 'offer' WBRT to a patient with 1-3 brain mets from NSCLC but I haven't had a patient take me up on it ever since Takahashi trial came out.

I'm getting away from even doing PCI for LS-SCLC at the current time clinically, although my boards answer will be to do PCI. Hope MAVERICK completes enrollment for the LS-SCLC population soon.

I totally agree. I have been routinely offering the choice of PCI vs no PCI for limited stage off protocol. I trust the existing data that much and I don't think it's that much of a stretch to extrapolate the Takahashi trial to limited stage.

 

[ProtonElectronNeutron]

I am not in favor doing PCI whether its ES or LS - SCLC. Of course I discuss the PCI option with the patient and let them decide. And definitely the board answer is yes to PCI for LS-SCLC.
Is it just me? I hope I got company in my thought process.

 

[medgator]

I am not in favor doing PCI whether its ES or LS - SCLC. Of course I discuss the PCI option with the patient and let them decide. And definitely the board answer is yes to PCI for LS-SCLC.
Is it just me? I hope I got company in my thought process.

The answer is we don't know and the pro PCI folk believe we are sterilizing subclinical disease in the brain that chemo can't get to, so could go either way imo. Data for es sclc is weaker but some of the original PCI trials did use CT imaging

 

[Palex80]

The answer is we don't know and the pro PCI folk believe we are sterilizing subclinical disease in the brain that chemo can't get to, so could go either way imo. Data for es sclc is weaker but some of the original PCI trials did use CT imaging

I believe it is quite clear that omitting PCI in LD-SCLC will lead to higher rates of isolated brain recurrence. There are enough data to back up that point.
Thus, it is clear that giving PCI will decrease rates of disease recurring in the brain later on. The same has actually been shown for stage III NSCLC.

The main argument of those who advocate against PCI is that these metachronous brain metastases will not have an impact on OS as long as MRI is done at regular intervals and disease is treated upon progression (whenever possible with RC).

I have said that before and I will state it again. Although MAVERICK is a trial looking at a very important question, its design is flawed.
2-years-OS a primary endpoint is simply too early.

 

[Lamount]

I still do a fair bit of consolidators TRT for ES SCLC. I also will TRT for oligoprogressive disease in the chest.

For consolidation I focus on mediastinal disease and stay out of the parenchyma as I feel the mediastinum is the biggest driver of morbidity. I usually don’t have the med onc hold atezo and really haven’t had much pneumonitis except one case (which could have been COVID). I usually try to get in 37.5-45/15 with dose paining to minimize dose to the esophagus.

with atezo, some patients do really well and I find myself spot welding for a while.

 

[evilbooyaa]

I believe it is quite clear that omitting PCI in LD-SCLC will lead to higher rates of isolated brain recurrence. There are enough data to back up that point.
Thus, it is clear that giving PCI will decrease rates of disease recurring in the brain later on. The same has actually been shown for stage III NSCLC.

The main argument of those who advocate against PCI is that these metachronous brain metastases will not have an impact on OS as long as MRI is done at regular intervals and disease is treated upon progression (whenever possible with RC).

I have said that before and I will state it again. Although MAVERICK is a trial looking at a very important question, its design is flawed.
2-years-OS a primary endpoint is simply too early.

I don't necessarily buy this. If there was a single study that regularly used brain MRI for staging in PCI, then maybe I'd agree. AFAIK, none of the PCI studies in the Auperin meta-analysis mandated this. I would be happy to be proven wrong on this.

I submit that patients who received PCI were having disease that would have been visible on MRI but not visible on CT staging.

That being said, your second paragraph (basically a re-hash of adjuvant vs salvage) is also an important point, in terms of 'microscopic subclinical brain mets' as somewhat of a possibility in this patient population.

 

[Palex80]

That's interesting. You really think

I don't necessarily buy this. If there was a single study that regularly used brain MRI for staging in PCI, then maybe I'd agree. AFAIK, none of the PCI studies in the Auperin meta-analysis mandated this. I would be happy to be proven wrong on this.

Well, the Japanese trial with ES-SCLC proved quite well that the rate of brain failure without PCI is higher than with PCI.
And that was in ES-SCLC, where patients often die due to other metastasis quite early during follow up.
If this is the case in ES-SCLC, why shouldn't it be the case in LD-SCLC with a controlled primary and no other metastasis?

We already have data on NSCLC on exactly the same question - RTOG 0214

Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial - PubMed

ClinicalTrials.gov identifier: NCT00048997.

pubmed.ncbi.nlm.nih.gov

9% vs 21% isolated brain recurrence with vs. without PCI in NSCLC stage III following CRT (with no impact on OS).
I would say that LD-SCLC (with the exception of very-limited disease probably) bears the same risk of recurrence in the brain as stage III NSCLC.


But, formally, you are correct. We do not have a randomized trial testing PCI after MRI staging for LD-SCLC. Why? Because PCI is s.o.c. (still).

 

[evilbooyaa]

That's interesting. You really think

Well, the Japanese trial with ES-SCLC proved quite well that the rate of brain failure without PCI is higher than with PCI.
And that was in ES-SCLC, where patients often die due to other metastasis quite early during follow up.
If this is the case in ES-SCLC, why shouldn't it be the case in LD-SCLC with a controlled primary and no other metastasis?

We already have data on NSCLC on exactly the same question - RTOG 0214

Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial - PubMed

ClinicalTrials.gov identifier: NCT00048997.

pubmed.ncbi.nlm.nih.gov

9% vs 21% isolated brain recurrence with vs. without PCI in NSCLC stage III following CRT (with no impact on OS).
I would say that LD-SCLC (with the exception of very-limited disease probably) bears the same risk of recurrence in the brain as stage III NSCLC.


But, formally, you are correct. We do not have a randomized trial testing PCI after MRI staging for LD-SCLC. Why? Because PCI is s.o.c. (still).

Fair point, that patients with metastatic disease at diagnosis are more likely to develop additional metastases at some time point in the future than somebody without any metastases.

We may see those same numbers, but I expect the difference will be smaller than what was seen in Takahashi (more like the 9 vs 21% in NSCLC). Thanks for linking the NSCLC paper, that even if more mets are seen, without OS benefit, PCI isn't SOC!

 

[thecarbonionangle]

I hate PCI. I think this is caveman stuff. It makes no sense to patients. It makes me feel dirty. I don’t do PCI most of the time.

 

[medgator]

.

I submit that patients who received PCI were having disease that would have been visible on MRI but not visible on CT staging.

There is also a population of pts with negative brain MRIs upfront who still end up developing brain mets from subclinical disease in the brain, @Palex80 alluded to the 0214 study that closed early, I'd wager the small cell rates will be even more disparate

 

[StIGMA]

For arguments sake, subclinical disease in the brain (when present) represents incurable metastatic disease and is in fact ES-SCLC. So the OS benefit is for (perhaps less aggressive/advanced) ES-SCLC. Everyone else, who is truly non-metastatic, is receiving brain irradiation for nothing. The cells have either attained a metastatic phenotype or not and the long-term outcome will reflect that.

Do most of us think metastatic disease is really different for small cell? And isn’t it against radbio principles that low dose treatment would really sterilize huge numbers of (imaging inapparent) cells?

 

[Palex80]

For arguments sake, subclinical disease in the brain (when present) represents incurable metastatic disease and is in fact ES-SCLC. So the OS benefit is for (perhaps less aggressive/advanced) ES-SCLC. Everyone else, who is truly non-metastatic, is receiving brain irradiation for nothing. The cells have either attained a metastatic phenotype or not and the long-term outcome will reflect that.

Do most of us think metastatic disease is really different for small cell? And isn’t it against radbio principles that low dose treatment would really sterilize huge numbers of (imaging inapparent) cells?

I am sorry but that makes no sense.

If you look at the old trials of PCI vs. no-PCI in LD-SCLC (and in some mixed cohorts of LD & ES) you will find a "tail" in the OS-curves that is still there, 3-5 years post treatment and shows superiority of PCI over no PCI. It's not a lot, perhaps only 5%, perhaps even less. But it's there.

We know that these trials did not use MRI for staging, so there were 3 sets of patients in both arms randomized to PCI and no-PCI.
a) Patients with macroscopic metastasis, which would have been visible on MRI.
b) Patients with microscopic metastasis, that would not have been visible on MRI.
c) Patients with no disease in the brain at all.

So where does the "tail" of higher OS come from? a), b) or c)?

Can 10 x 2.5 Gy PCI cure macroscopic metastasis to the brain and result in a superior OS 3-5 years later? Nope. --> A is not the answer.
Can 10 x 2.5 Gy PCI improve your survival if you don't have macroscopic or microscopic disease in the brain? Nope. --> C is not the answer.

It's sterilizing microscopic disease in the brain. --> B

Either this or multiple trials were all falsely positive including the associated metaanalysis.

PCI did improve survival in those trials. The question is whether or not that survival can be compensated with regular MRIs and salvage treatment nowadays. And this is why trials like MAVERICK are important.



I am actually surprised that you think subclinical metastatic disease represents incurable disease.

We treat patients on a daily basis for subclinical metastatic disease and have proven over and over again that this kind of treatment can increase survival.
It's called elective nodal irradiation, which we practice with OS benefit in head&neck cancer for instance.
And here's another example for treating non-nodal, metastatic, microscopic disease: CSI for localized, average-risk medulloblastoma.
We even have randomized evidence showing that if you lower the dose to the "incurable" (as you called it) subliclinical metastatic disease (from 23.4 Gy to 18 Gy), patients die. Oh wait, isn't lowering 5.4 Gy of dose to imaging inapparent cells against radbio principles? (Sorry, didn't mean to be rude).

 

[StIGMA]

I am sorry but that makes no sense.

If you look at the old trials of PCI vs. no-PCI in LD-SCLC (and in some mixed cohorts of LD & ES) you will find a "tail" in the OS-curves that is still there, 3-5 years post treatment and shows superiority of PCI over no PCI. It's not a lot, perhaps only 5%, perhaps even less. But it's there.

We know that these trials did not use MRI for staging, so there were 3 sets of patients in both arms randomized to PCI and no-PCI.
a) Patients with macroscopic metastasis, which would have been visible on MRI.
b) Patients with microscopic metastasis, that would not have been visible on MRI.
c) Patients with no disease in the brain at all.

So where does the "tail" of higher OS come from? a), b) or c)?

Can 10 x 2.5 Gy PCI cure macroscopic metastasis to the brain and result in a superior OS 3-5 years later? Nope. --> A is not the answer.
Can 10 x 2.5 Gy PCI improve your survival if you don't have macroscopic or microscopic disease in the brain? Nope. --> C is not the answer.

It's sterilizing microscopic disease in the brain. --> B

Either this or multiple trials were all falsely positive including the associated metaanalysis.

PCI did improve survival in those trials. The question is whether or not that survival can be compensated with regular MRIs and salvage treatment nowadays. And this is why trials like MAVERICK are important.



I am actually surprised that you think subclinical metastatic disease represents incurable disease.

We treat patients on a daily basis for subclinical metastatic disease and have proven over and over again that this kind of treatment can increase survival.
It's called elective nodal irradiation, which we practice with OS benefit in head&neck cancer for instance.
And here's another example for treating non-nodal, metastatic, microscopic disease: CSI for localized, average-risk medulloblastoma.
We even have randomized evidence showing that if you lower the dose to the "incurable" (as you called it) subliclinical metastatic disease (from 23.4 Gy to 18 Gy), patients die. Oh wait, isn't lowering 5.4 Gy of dose to imaging inapparent cells against radbio principles? (Sorry, didn't mean to be rude).

Thanks for the reply. Again this is for arguments sake (not my personal beliefs; I utilize PCI). I think some of these thoughts are part of the reason the subject is so controversial. Primary -> Local -> distant disease require different biological changes to cancer cells.

The brain is a distant site (different biology than nodal spread) for lung cancer. This is different than the H&N and medulloblastoma examples. For H&N, lymphatic spread is local; for medulloblastoma, CNS is local (and spread outside the CNS is distant, so CSI is curing the elective/at-risk volume, equivalent to nodal for H&N).

Data that we can cure metastatic disease in the oligometastatic setting remains weak. To ask a related question, why should we consider microscopic but not macroscopic disease curable if restricted to the brain (where we can eliminate small volume macroscopic disease)? It is possible that the 5% survival curve tail is curing patients with less aggressive distant disease (that is poorly tumorigenic at distant sites). If this is the case, then MRI surveillance is flawed because it would be allowing more tumorigenic variants to evolve/proliferate.

 

[drewdog1973]

Disagree with saying “A” isn’t possible. I’m fairly confident that treating macroscopic disease is why “P”CI is improving survival in those older studies. It’s not prophylactic...

 

[ramsesthenice]

Disagree with saying “A” isn’t possible. I’m fairly confident that treating macroscopic disease is why “P”CI is improving survival in those older studies. It’s not prophylactic...

This really isn’t in doubt. It was only prophylactic in that we didn’t know who already had Mets.

Question for those of you that do lung cancer and CNS: who has started doing SRS instead of WBRT for a limited number of SCLC Mets? I have seen more of this going through chart rounds and I have not taken the time to look up the data. Is there data for this? Our CNS guys claims to be pretty happy with the outcomes. Honestly it seems like pretty much everything I learned not that long ago (aside from thoracic RT for LS disease) is rapidly becoming irrelevant. It’s probably a good thing.

 

[evilbooyaa]

This really isn’t in doubt. It was only prophylactic in that we didn’t know who already had Mets.

Question for those of you that do lung cancer and CNS: who has started doing SRS instead of WBRT for a limited number of SCLC Mets? I have seen more of this going through chart rounds and I have not taken the time to look up the data. Is there data for this? Our CNS guys claims to be pretty happy with the outcomes. Honestly it seems like pretty much everything I learned not that long ago (aside from thoracic RT for LS disease) is rapidly becoming irrelevant. It’s probably a good thing.

I do offer it now with the caveat that WBRT is still 'SOC' in those with SCLC brain mets, just as PCI is 'SOC' in LS-SCLC

Evaluation of First-line Radiosurgery vs Whole-Brain Radiotherapy for Small Cell Lung Cancer Brain Metastases

This cohort study compares the overall survival, disease progression, and other outcomes of stereotactic radiosurgery with those of whole-brain radiotherapy in patients with brain metastases from small cell lung cancer.

jamanetwork.com

Radiosurgery alone is associated with favorable outcomes for brain metastases from small-cell lung cancer - PubMed

To our knowledge, this is the largest dataset of patients treated with SRS alone for SCLC. The observation of favorable OS with SRS alone in this contemporary dataset suggests that SRS alone may be appropriate for some patients with SCLC. Prospective investigations of SRS in SCLC are warranted.

pubmed.ncbi.nlm.nih.gov

Ongoing ENCEPHALON trial evaluating this

MAVERICK allows SRS to limited intracranial disease as part of it's protocol IIRC

 

[Palex80]

Data that we can cure metastatic disease in the oligometastatic setting remains weak.

Well, a lot of colorectal cancer patients with limited liver / lung metastases are cured with local treatment following systemic therapy. Long term OS is in the range of 20%.

To ask a related question, why should we consider microscopic but not macroscopic disease curable if restricted to the brain (where we can eliminate small volume macroscopic disease)?

Macroscopic disease to the brain can be curable too, rarely for SCLC though. Generally, it requires surgery, high-dose focal radiation and in some cases can be achieved with excellent performing drugs.
Microscopic disease can however be better controlled with radiation therapy than macroscopic disease. We know that from othe sites too. It's the principle for instance in postoperative RT for breast cancer. Cure rates after RT for breast cancer are lower after R2-resection than R1-resection.

It is possible that the 5% survival curve tail is curing patients with less aggressive distant disease (that is poorly tumorigenic at distant sites). If this is the case, then MRI surveillance is flawed because it would be allowing more tumorigenic variants to evolve/proliferate.

The 5% benefit from PCI results from eliminating microscopic disease in the brain. Disease which was the only disease left in the body of the patients after completion of CRT.

 

[Palex80]

Disagree with saying “A” isn’t possible. I’m fairly confident that treating macroscopic disease is why “P”CI is improving survival in those older studies. It’s not prophylactic...

This really isn’t in doubt. It was only prophylactic in that we didn’t know who already had Mets.

Of course if was therapeutic. But did it cure patients?

10 x 2.5 Gy PCI supposedly CURED macroscopic SCLC brain metastasis? I doubt it.
1 x 25 Gy SRS yes. 10 x 2.5 Gy PCI no.

We all have given 5 x 4 Gy or 10 x 3 Gy as WBRT for patients with macroscopic brain metastases of various histologies. Think of these patients.
Exclude all the patients you treated postoperatively after resection of one brain metastasis, exclude the ones you treated with SRS/FSRT on top of WBRT. Exclude the ones with ALK-, EGFR-mutated NSCLC, Her2+ breast cancer and those performing excellent on immunotherapy (mainly NSCLC, melanoma).

Now think of all the patients that are left. Did you cure anyone with 5 x 4 Gy or 10 x 3 Gy WBRT? I haven't. They all died. Most of them due to the brain mets.

 

[RadOncG]

The 5% benefit from PCI results from eliminating microscopic disease in the brain. Disease which was the only disease left in the body of the patients after completion of CRT.

I think everyone is saying the same thing. But obviously the "amount" of microscopic disease is dependent on the imaging modality.

What you are saying is true for CT definitions of microscopic or microscopic. CT at best. In some of the studies the definition of brain metastasis was clinical symptoms.

Fewer people expected to have microscopic disease given the sensitivity of MRI. So how many people do we need to PCI for a benefit today?

If you were forced to take a bet on MAVERICK outcomes where would you put your money?

 

[medgator]

I think everyone is saying the same thing. But obviously the "amount" of microscopic disease is dependent on the imaging modality.

What you are saying is true for CT definitions of microscopic or microscopic. CT at best. In some of the studies the definition of brain metastasis was clinical symptoms.

Fewer people expected to have microscopic disease given the sensitivity of MRI. So how many people do we need to PCI for a benefit today?

If you were forced to take a bet on MAVERICK outcomes where would you put your money?

The question also becomes whether patients will be compliant with quarterly MRI scans.... I don't see this as the same analogy as seminoma. A recurrence/emergence of brain mets is worse here

 

[Palex80]

The question also becomes whether patients will be compliant with quarterly MRI scans.... I don't see this as the same analogy as seminoma. A recurrence/emergence of brain mets is worse here

No worries, 75% of them are dead by year 5 anyways...

 

[Palex80]

I think everyone is saying the same thing. But obviously the "amount" of microscopic disease is dependent on the imaging modality.

What you are saying is true for CT definitions of microscopic or microscopic. CT at best. In some of the studies the definition of brain metastasis was clinical symptoms.

Fewer people expected to have microscopic disease given the sensitivity of MRI. So how many people do we need to PCI for a benefit today?

If you were forced to take a bet on MAVERICK outcomes where would you put your money?

Actually I expect that you need to irradiate less people nowadays than you did back then to prove the same benefit. Why?
Just like you said, the old PCI studies included patients with CT (or even no) staging. Yet, these trials showed an OS-benefit with PCI, despite the "contamination" of both arms with patients harboring macroscopic metastasis. These patients did not benefit in terms of long-term survival through PCI. They may have profitted short-term-wise (if we think that delivering WBRT for brain metastases prior to the lesions becoming symptomatic does lead to a survival benefit - a matter of debate bearing in mind the results of the QUART trial in NSCLC patients) but they did not get cured because of PCI.
PCI does not cure macroscopic metastases.
One can make the argument that removing patients with macroscopic metastases from the old PCI trials would actually make the difference between PCI and no-PCI eben bigger! This of course applies only for the time setting when those trials were run --> no MRI-surveillance, no salvage options other than WBRT.

I think that Maverick will be able to show same OS-rates at 2 years (primary endpoint). I am not sure however if that benefit will remain valid with longer term follow up. With SRS, WBRT, second line chemo etc, one is probably able to keep the patient alive for 2 years. In other words, MAVERICK may lead to decreased cure rates at 5 years post treatment, but same OS at 2 years.

 

[RadOncG]

The question also becomes whether patients will be compliant with quarterly MRI scans.... I don't see this as the same analogy as seminoma. A recurrence/emergence of brain mets is worse here

I've heard this argument for PCI before but I've never heard anyone tell a patient "some people aren't compliant so I just have to treat you now"

If that was someone's practice pattern then they would have to do whole brain for all metastasis given the quarterly imaging requirements for SRS. The chance of someone with brain metastasis getting more metastasis is higher then someone with limited stage SCLC developing brain metastasis on any given quarterly scan.

 

[RadOncG]

I think that Maverick will be able to show same OS-rates at 2 years (primary endpoint). I am not sure however if that benefit will remain valid with longer term follow up. With SRS, WBRT, second line chemo etc, one is probably able to keep the patient alive for 2 years. In other words, MAVERICK may lead to decreased cure rates at 5 years post treatment, but same OS at 2 years.

Would you personally get PCI or MRI surveillance if you had limited stage SCLC?

 

[medgator]

I've heard this argument for PCI before but I've never heard anyone tell a patient "some people aren't compliant so I just have to treat you now"

If that was someone's practice pattern then they would have to do whole brain for all metastasis given the quarterly imaging requirements for SRS. The chance of someone with brain metastasis getting more metastasis is higher then someone with limited stage SCLC developing brain metastasis on any given quarterly scan.

Yet people use that argument when discussing whether to treat or observe seminoma patients... Usually men who end up getting treated can't comply with the surveillance protocol, have to get deployed overseas etc.

A not insignificant number of patients i see hate getting MRs, esp of the head. The open scanners give crappy images, so usually it's an ativan before each scan, assuming they don't refuse altogether

 

[Palex80]

Would you personally get PCI or MRI surveillance if you had limited stage SCLC?

PCI! I am a true believer.

 

[ramsesthenice]

Yet people use that argument when discussing whether to treat or observe seminoma patients... Usually men who end up getting treated can't comply with the surveillance protocol, have to get deployed overseas etc.

Totally different calculation here.

Seminoma: Excellent long term prognosis. If someone misses surveillance the salvage therapy could be markedly different from the prophylactic therapy (ie, several cycles of BEP +/- RT is a lot more intense than prophylactic RT or carboplatin)

SCLC: Survival is poor even with PCI. And early detection has minimal effect on choice of therapy. Unless you believe in SRS for limited volume brain mets with SCLC (which apparently more people do) it will be WBRT now vs WBRT later

 

[FrostyHammer]

Question for those of you that do lung cancer and CNS: who has started doing SRS instead of WBRT for a limited number of SCLC Mets?

Based on having read FIRE-SCLC, I offer it if there is 1 met, if 2-4 mets I lean towards WBRT or HA-WBRT but assess individually based on systemic disease status and age/PS etc. @evilbooyaa I would be careful with blanket offerings like that based on FIRE-SCLC and the retrospective nature.

 

[FrostyHammer]

If you were forced to take a bet on MAVERICK outcomes where would you put your money?

Quite confident that there will be equipoise between arms. So much so that I've started routinely offering q 3 months MRI surveillance to limited stage now if pt wants it as an option.

 

[evilbooyaa]

I agree with @Palex80 that if you look at an enriched population that has excluded most of those who are unlikely to 'benefit' from PCI (like those with MRI-visible macroscopic brain mets that wouldn't have been found on CT) then you need a smaller sample size to determine benefit. This is similar to POP-RT which showed a benefit of nodal RT, but 80% of patients had PSMA-PET at diagnosis to exclude an unknown percentage of the potential study population.

I have seen at least 2 patients who were 5+ years out from WBRT without recurrence of their disease. One was EGFR NSCLC. Other one was some NSCLC but unclear of molecular status.

That being said, whether freedom from development of brain metastasis will ever correlate with an OS benefit is unclear. Difference between adjuvant (treating microscopic disease) and salvage. Takahashi suggests that no, those two variables do not correlate with one another. We will see what MAVERICK shows.

Based on having read FIRE-SCLC, I offer it if there is 1 met, if 2-4 mets I lean towards WBRT or HA-WBRT but assess individually based on systemic disease status and age/PS etc. @evilbooyaa I would be careful with blanket offerings like that based on FIRE-SCLC and the retrospective nature.

Fair - I don't offer it for all but it at least is a consideration and discussion in every single patient with (for me) 1-3 BMs from SCLC. I am almost guaranteed to just be kicking the WBRT can down the road and that is how I phrase it.

@medgator I discuss need for MRI surveillance when discussing WBRT vs SRS for non-SCLC brain mets. Same for PCI vs no PCI in SCLC. That being said, for me, the surveillance schedule is the same regardless of what I do for each of those situations, so I've never had someone pick WBRT, and very rarely had someone pick PCI (as I do discuss that PCI is SOC for LS-SCLC).

 

[drewdog1973]

again, Palex, I disagree with one of your facts. Some people survive a long time after WBRT. It happens.

in modern days with modern staging, I’d bet the house PCI won’t show a survival improvement.

 

[seper]

I still like PCI for young-ish patients. As Palex noted, 25 Gy/10 to micromets may be curative, while salvage SRS 18 Gy X 1 likely is not.
Still a lot to study in this disease.

 

[ramsesthenice]

I still like PCI for young-ish patients. As Palex noted, 25 Gy/10 to micromets may be curative, while salvage SRS 18 Gy X 1 likely is not.
Still a lot to study in this disease.

Too many questions and not enough patients to really answer them. Let’s say you are right. WBRT can produce cures by treating micromets but SRS is palliative. Sounds like a trial of PPX WBRT vs salvage SRS is in order. But...the absolute benefit is tiny so you will need a lot of patients. Let’s say you do it and see a 5% OS benefit. You still haven’t addressed the idea of over treatment with WBRT. If it cures micromets couldn’t salvage WBRT with an SRS boost hypothetically be as good as PCI while selecting out the patients who fail distantly first and avoiding patient who never fail in the brain? These are all great questions and any could be right. At least in our neck of the woods, systemic therapy trials are eating patients up. I’m not sure we are ever going to get the patients needed to adequately address these questions.

 

[ProtonElectronNeutron]

Wow!! Didn’t realize that PCI is such a ‘touchy’ topic when I started this conversation.

Personally, I don’t like PCI even for LS-SCLC. I would rather have them close MRI surveillance, keep their cognition, memory and QOL as long as they can. With the new FIRE data, I am more comfortable with SRS, (1-3 mets) when they recur in the brain. More than that, better go WBRT.

 

[Palex80]

again, Palex, I disagree with one of your facts. Some people survive a long time after WBRT. It happens.

in modern days with modern staging, I’d bet the house PCI won’t show a survival improvement.

I have never cured a patient with brain relapse from LD-SCLC (who did not get PCI upfront) with WBRT only.

Has anyone, ever?