Going beyond 45 / 1.5 bid in SCLC

[NotMattSpraker]

I am doing SIB now with BID regimen. 45 Gy/30 BID to traditional volume. 54 Gy SIB to gross disease.

Avoid increasing esophageal toxicity.

https://www.redjournal.org/article/S0360-3016(17)32871-7/fulltext

I just completed my first case. It went great. I did chose 60/40 over the SIB approach because I convinced myself that was better for this person's large volume. Did 1 adaptive replan. It is interesting this isn't culturally "standard". I know more people that dose escalate NSCLC to 66 Gy based on basically nothing than do dose escalated small cell BID treatment despite 2 positive trials.

My question is if anyone is reserving this for fit patients and hesitating to do it on less fit patients, or if functional status has little/no impact on curative dosing (like NSCLC)

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[MidwestRadOnc]

I just completed my first case. It went great. I did chose 60/40 over the SIB approach because I convinced myself that was better for this person's large volume. Did 1 adaptive replan. It is interesting this isn't culturally "standard". I know more people that dose escalate NSCLC to 66 Gy based on basically nothing than do dose escalated small cell BID treatment despite 2 positive trials.

My question is if anyone is reserving this for fit patients and hesitating to do it on less fit patients, or if functional status has little/no impact on curative dosing (like NSCLC)

Covered esophagus with any significant amount of PTV? I would be curious and bring these patients back at 1 and 2 weeks after EOT to see how the esophageal toxicity really shakes out.

Practices don't do BID because of logistics with therapists and more importantly issues with billing for OTVs and IGRT. So they argue for daily because "it's easier for the patient" Even if the patient is well into chemo. Cognitive dissonance. 66/33 is more efficient for $$$ compared to 45/30. Wonder if an extra 77427 will change the calculus on "doing what's right for the patient"

 

[NotMattSpraker]

Covered esophagus with any significant amount of PTV? I would be curious and bring these patients back at 1 and 2 weeks after EOT to see how the esophageal toxicity really shakes out.

Practices don't do BID because of logistics with therapists and more importantly issues with billing for OTVs and IGRT. So they argue for daily because "it's easier for the patient" Even if the patient is well into chemo. Cognitive dissonance. 66/33 is more efficient for $$$ compared to 45/30. Wonder if an extra 77427 will change the calculus on "doing what's right for the patient"

No, but it was bulkier than usual in the lung. Bigger concern was lung doses. I was able to meet all constraints for 45/30 initially and get below them on the sum plan with the adaptation.

I don't agree that patients would all do BID if it weren't for the biases of their radiation oncologists. I structure my discussion to bias for BID but am clear that daily is unlikely significantly worse (compared to 45/30) so they don't feel bad if they can't do it. They shouldn't. A lot of my patients and often their care giver need to give up basically the full work day for 3 weeks straight when you include the driving and 6 hour spacing of appointments. A lot of people cant do that.

The dose escalation obviously changes this discussion a bit.

My first case was exceptional... a very fit young male patient never smoker. That drove my original question about whether someone would do this for a "little old lady smoker" (stereotype example)

 

[MidwestRadOnc]

I agree and always offer qD if there is even a hint of a logistical problem with BID. However, it seems to be very common the other way, probably the norm, that BID is never discussed at all with these patients. I think it would be pretty unusual that a patient is told BID is their only option, but pretty common they are told qD is.

For your little old lady smoker, I like the SIB option if you want to dose escalate. The gut radiobiological feeling to give more fractions for small cell makes sense, but we know 30 fractions works well, maybe a mild SIB splits the difference?

 

[TheWallnerus]

actices don't do BID because of logistics with therapists and more importantly issues with billing for OTVs and IGRT

Should be zero issues. That is to say, I have never had an issue.

I think it would be pretty unusual that a patient is told BID is their only option

I was a Turrisi trainee. So I do in fact give all my LS-SCLC patients only one option

 

[Palex80]

I was a Turrisi trainee. So I do in fact give all my LS-SCLC patients only one option

Turrisi or Terrorisi?

 

[MidwestRadOnc]

Should be zero issues. That is to say, I have never had an issue.

I mean collecting all the charges for 30 fractions of BID is harder than for daily. You don't miss any and you get 3 extra days.

I was a Turrisi trainee. So I do in fact give all my LS-SCLC patients only one option

So when a patient says they don't want to, or even won't/can't come in twice a day (which happens probably half the time in my experience, at least), what do you say? You really send these people back to the referring saying patient refused RT, give palliative chemo?

 

[Palex80]

So when a patient says they don't want to, or even won't/can't come in twice a day (which happens probably half the time in my experience, at least), what do you say?

 

[communitydoc13]

The BID data is a little weird. Hypofractionated accelerated regimens haven't really shown a benefit and there is no difference in the BID escalation trial regarding response rates, including CRs.

Also, no big trials. So either a little real magic going on or we are getting fooled. If there is magic (e.g. chemosensitizing radiation...reassortment), we really need to find out what it is.

 

[NotMattSpraker]

The BID data is a little weird. Hypofractionated accelerated regimens haven't really shown a benefit and there is no difference in the BID escalation trial regarding response rates, including CRs.

Also, no big trials. So either a little real magic going on or we are getting fooled. If there is magic (e.g. chemosensitizing radiation...reassortment), we really need to find out what it is.

The trialists are weird, not the fractionation

But also, if LU-005 is positive, get ready to question all your dogma about limited stage small cell lung cancer because thats exactly what happened with extensive stage. qD vs. BID was dealers choice on that trial haha.

If LU-005 is not positive, people gonna lose their minds about chemo-immuno-radiotherapy for lung cancers.

 

[Palex80]

The BID data is a little weird. Hypofractionated accelerated regimens haven't really shown a benefit and there is no difference in the BID escalation trial regarding response rates, including CRs.

Also, no big trials. So either a little real magic going on or we are getting fooled. If there is magic (e.g. chemosensitizing radiation...reassortment), we really need to find out what it is.

I‘ve said this before:

One main benefit of accelerated treatment in SCLC is that you complete treatment and give your dose before the patient had to stop due to toxicity or the patient stopped.
This was also the case in CONVERT; more patients completed treatment in the bid group than in the normofractionated group.

 

[evilbooyaa]

The BID data is a little weird. Hypofractionated accelerated regimens haven't really shown a benefit and there is no difference in the BID escalation trial regarding response rates, including CRs.

Also, no big trials. So either a little real magic going on or we are getting fooled. If there is magic (e.g. chemosensitizing radiation...reassortment), we really need to find out what it is.

The pretzels people twist themselves into to ignore multiple trials simply because it's BID....

 

[communitydoc13]

The pretzels people twist themselves into to ignore multiple trials simply because it's BID....

I do offer BID. The Convert trial was enough. The Norwegian and Chinese data follows a pattern.

It's just that it is not as simple as accelerated fractionation (Norwegian hypofractionation trial was negative) or local response or even local control IMO.

BID must be interacting with the chemo better IMO and more protracted BID even more so. This is exciting but still a murky sort of thing that I am not seeing applied in other disease sites.

I do not believe that 60/40 is equitoxic to 45/15 in real life. Prior is too strong and toxicity too hard of an outcome to measure well for me to believe that.

But I will start offering 60/40.

 

[evilbooyaa]

Small cell is more radioresponsive to small but frequent doses of RT given the speed in which it divides. That's why Turrisi did the Turrisi regimen in the first place...

Converting 45Gy from 30fx BID to 15fx qD doesn't work as well because it ignores that component.

Decent number of folks still have interest in accelerated hyperfractionation (BID) for rapidly growing tumors (including H&N SCC). Would love to see a chemoRT trial where it was 70/35 qD vs the BID hyperfractionation regimen where both arms got chemo. IIRC the chemoRT arms looking at accelerated just did the one random day of BID to folks done in 6 weeks rather than BID throughout.

 

[drowsy12]

I think the point is more the total package time, not the BID. Based on Turrisi principles, 3 Gy a day, whether BID or single fraction, should have same efficacy. If you were concerned about late toxicity that’s a different point, IMO

 

[communitydoc13]

Converting 45Gy from 30fx BID to 15fx qD doesn't work as well because it ignores that component.

I don't think that's true. What it would ignore is any favorable reassortment that may make the cancer cells more sensitive to a second dose roughly 6 hours later.

As @drowsy12 states, the hyperfractionation does allow for preferential sparing of "late" toxicity based on a/b considerations.

 

[Palex80]

What it would ignore is any favorable reassortment that may make the cancer cells more sensitive to a second dose roughly 6 hours later.

 

[CaesarRO]

What kind of constraints are folks using for the 60 Gy in 40 fraction regimens?

Just following the trial protocol? Have seen grumblings they were lax

 

[NotMattSpraker]

What kind of constraints are folks using for the 60 Gy in 40 fraction regimens?

Just following the trial protocol? Have seen grumblings they were lax

Ive been using the LU-005 protocol for all my small cell cases and want to meet those constraints on the dose escalated regimen.

(I treat everyone with IMRT)

 

[seper]

A lot of people have been doing 60/40 BID. I want to see some real world retrospective data on efficacy

 

[evilbooyaa]

A lot of people have been doing 60/40 BID. I want to see some real world retrospective data on efficacy

For what purpose? Would you trust a retrospective analysis more so than a randomized, controlled, clinical trial?

 

[Palex80]

For what purpose? Would you trust a retrospective analysis more so than a randomized, controlled, clinical trial?

 

[MidwestRadOnc]

Would be interesting to see a multi arm trial

60/40 BID
50/40 BID
66/33 qD
66/33 6 fx/week

my hunch is there’s some complicated questions with regards to #fractions vs. total dose vs. dose per fraction vs. time to completion given unique radio sensitivity of sclc.

I get funny feelings when I see people doing 5 fraction sbrt to sclc in the lung and single fraction srs to brain Mets.

 

[drowsy12]

I get zero funny feelings about SBRT for stage 1 SCLC. Same for SRS.

 

[Palex80]

I get zero funny feelings about SBRT for stage 1 SCLC.

I do not feel that the evidence is adequate to say that SBRT is the way to go in early SCLC.
The main issue I have is that ENI is omitted. One can argue, that chemo will take care of any microscopic deposits in N1/N2 lymph nodes and that we have data that we can treat only PET-avid nodes.
However, it feels funny that we ask our surgery colleagues to carry out a comprehensive lymphadenectomy if they even operate on an early SCLC, yet we think that skipping it in SBRT is fine.
Of course, we don't see any issue omitting ENI when doing SBRT for stage I NSCLC. On the other hand, the affinity for nodal involvement in a T1 central SCLC is considerably higher than in a peripheral T1 adenocarcinoma. This is my only concern, since we are speaking about a treatment with curative intent. I have little doubt that SBRT will lead to a local control rate that is comparable to surgery.

Same for SRS.

I feel very comfortable giving SRS for SCLC.

 

[communitydoc13]

The main issue I have is that ENI is omitted.

I assume you are referring to ipsilateral hilum plus PET positive disease in this era.

I get funny feelings

It is interesting that the Norwegian outcomes for extended BID treatment are better than published outcomes for surgery plus chemo for T1-T2N0 disease.

Acknowledging the caveats regarding comparing across studies, I think there is enough aggregate data regarding timing and fractionation of XRT in the concurrent setting to indicate that these things matter and may impact outcomes outside of the treatment field. (I'm still holding on to the chemosensitizing radiotherapy concept).

I would consider SBRT to be a reasonable option for primary disease in a frail patient. I do think we have enough real world data to indicate that we are not catastrophically impacting outcomes with this approach and sometimes it's all a patient can tolerate or is willing to do.

https://www.redjournal.org/article/S0360-3016(18)33398-4/fulltext

 

[Palex80]

I assume you are referring to ipsilateral hilum plus PET positive disease in this era.

Well if I have a small primary (cT1) which is not peripheral, but I have zero FDG-avid nodes (cN0) any no suspect node on EBUS, I would still feel inclined to give "some" dose to the ipsilateral hilum and perhaps the first N2 station (for instance 4R for a left upper lobe tumor) if I was treating with 45/1.5 bid together with chemo. I may not give the full 45 Gy, but I would give "some" dose.
I cannot do that, if I am going to simply SBRT that cT1 cN0 SCLC.

I would consider SBRT to be a reasonable option for primary disease in a frail patient. I do think we have enough real world data to indicate that we are not catastrophically impacting outcomes with this approach and sometimes it's all a patient can tolerate or is willing to do.

True, a frail patient that will not qualify for concurrect CRT, can surely have some tailored approach like the one you describe.

 

[Aphtalyfe]

This is a great discussion. In my practice I recommend BID, but do daily for patients who logistically cannot come twice a day. I have one patient who had a focal nodal GTV failure and I do wish I would've given it a little more. I think going forward I'll be SIB'ing GTV(s) to 54.

 

[seper]

For what purpose? Would you trust a retrospective analysis more so than a randomized, controlled, clinical trial?

For what purpose? Would you trust a retrospective analysis more so than a randomized, controlled, clinical trial?

in this case, yes

 

[evilbooyaa]

in this case, yes

Why in this case, and not in other cases? Because the data doesn't stay in line with your pre-conceived notions? Which endpoint do you believe isn't 'real' across two randomized control trials? That there is a improvement in PFS, or that there isn't an increase in toxicity? If the former, why? If the latter, why does it matter? Even if there was an increase in toxicity to dose escalation, are we not supposed to give patients the most effective treatments?

We give 78Gy in 2Gy fxs over 70Gy in 2Gy fxs for a PSA benefit even though there's more toxicity, and that's in a cancer a hundred times less lethal than SCLC....

 

[evilbooyaa]

View attachment 381437

We can give 60Gy in 30 fractions with Platinum/Etoposide without batting an eye for stage III NSCLC

Now we give the same 60Gy but broken up over 40fx BID, with the same chemo, and it's.... too toxic?

We thought 45Gy BID was the maximal effective dose for tumor control?

 

[drowsy12]

I am not so worried about the dose. My hold up is that the OS improved without other things improving, but the Chinese trial showed similar (but not published, and terrible presentation at astro)

I'm open minded to it, just have not done it and no one in my circle has. is it in NCCN I wonder?

but if LU005 is positive, it may make this moot in some people's eyes

 

[evilbooyaa]

I am not so worried about the dose. My hold up is that the OS improved without other things improving, but the Chinese trial showed similar (but not published, and terrible presentation at astro)

I'm open minded to it, just have not done it and no one in my circle has. is it in NCCN I wonder?

but if LU005 is positive, it may make this moot in some people's eyes

I had a similar concern to bolded when Dutch trial was an abstract. The paper for it then gave some additional detail suggesting maybe not sufficiently powered for PFS (which was not the primary end point) numerically being much improved in the high dose arm.

"Median progression-free survival was 18·6 months (95% CI 7·3–30·0) in the 60 Gy group and 10·9 months (8·7–13·1) in the 45 Gy group (HR 0·75 [95% CI 0·52–1·09]; p=0·13; figure 2). There was no difference in progression-free survival between the two dose groups in the multivariable analysis (HR 0·68 [95% CI 0·45–1·03]; p=0·067; appendix p 3)."

The chinese trial then showed a benefit to both PFS and OS in a phIII setting. Granted it's not fully published yet.