Going beyond 45 / 1.5 bid in SCLC

[Palex80]

Hi, I was wondering if any of you have tried going beyond 45 /1.5 bid in limited disease SCLC.

I have been trying to do this in patients with N1 or limited N2 disease, usually with a stereotactic boost to the affected sites after adaptive planning (for example 1-2 x 5 Gy SBRT after the 45/1.5) or simply adding more fractions (usually up to 51-54 Gy bid) in patients who can tolerate it. I avoid it if the esophagus is in the PTV (so involvement of station 7 is a no-go). I've seen a tiny Japanese series a couple years ago reporting good results:
http://abstract.asco.org/176/AbstView_176_161478.html

I never did 66/2 or 70/2 and after CONVERT results came out, I was happy that I stuck to Turrisi.

Any thoughts?


And since we are already on it:
How do you manage N1 SCLC in terms of target volume delineation of the nodes? Elective nodal irradiation is not necessary in SCLC if you do PET-based planning (probably due to incidental dose), but I am not sure if this can be safely done in N1 disease, since incidental dose to N2 nodes is less if you only treat N1. I've been doing "tailored" volumes (mostly including station 4 & 7 if N1), but that's not really evidence based...

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[medgator]

I never did 66/2 or 70/2 and after CONVERT results came out, I was happy that I stuck to Turrisi.

I didn't interpret convert to be so damning against 66-70 daily and personally have no problems continuing to recommend it to patients where BID is logistically impossible

 

[Palex80]

I didn't interpret convert to be so damning against 66-70 daily and personally have no problems continuing to recommend it to patients where BID is logistically impossible

Sure, but would you push to a higher dose? Bearing in mind that quite a sizable portion of the recurrences are local with 45/1.5 (or 66/2), do you go higher? 66/2 + boost?

 

[medgator]

Sure, but would you push to a higher dose? Bearing in mind that quite a sizable portion of the recurrences are local with 45/1.5 (or 66/2), do you go higher? 66/2 + boost?

I try to go to 70 when OARs allow. Personally, I see distant disease relapse continuing to be the bigger issue, even in limited stage patients.

Hopefully there is pdl1 inhibitor on the horizon, similar to durvulumab that will address that issue better

 

[Gfunk6]

I have started doing SABR for N0 small cell lung cancers. Short treatment course, 100% local control, very little toxicity and most importantly does not delay systemic therapy.

SCLC is fundamentally a systemic disease. There is little mileage to be gained by dumping more dose into the target or expanding elective contours.


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[nkmiami]

Agree with the post above, but fwiw Jeremic in some of the European trials extensive stage went to 54 1.5 bid.
I still give bid and ask for the GTV to be 5% hotter.

 

[medgator]

I have started doing SABR for N0 small cell lung cancers. Short treatment course, 100% local control, very little toxicity and most importantly does not delay systemic therapy.

SCLC is fundamentally a systemic disease. There is little mileage to be gained by dumping more dose into the target or expanding elective contours.


Sent from my iPhone using SDN

Any data? Or extrapolating from surgery?

 

[KHE88]

I have wondered about the situation where you have a very small primary small cell tumor and a single N2 or N3 node and the node completely disappears after first cycle of chemotherapy, nothing in hilum, and there is a tiny primary left, say < 1 cm,

Why not just give SBRT to the residual primary? Should we really be giving 30+ fractions to a tiny primary and the original involved site where there isn't even a node? You'd already be bypassing the hilum since trials aren't including elective nodal coverage anymore. So clearly we believe in chemotherapy in handling microscopic hilar and mediastinal disease all by itself.

 

[radiaterMike]

Data .... https://www.ncbi.nlm.nih.gov/m/pubmed/28011047/

 

[radiaterMike]

I would treat the involved nodal sites. There are no data to suggest otherwise and we know that chemo alone is is insufficient for SCLC.

I have wondered about the situation where you have a very small primary small cell tumor and a single N2 or N3 node and the node completely disappears after first cycle of chemotherapy, nothing in hilum, and there is a tiny primary left, say < 1 cm,

Why not just give SBRT to the residual primary? Should we really be giving 30+ fractions to a tiny primary and the original involved site where there isn't even a node? You'd already be bypassing the hilum since trials aren't including elective nodal coverage anymore. So clearly we believe in chemotherapy in handling microscopic hilar and mediastinal disease all by itself.

 

[Ray D. Ayshun]

Data .... https://www.ncbi.nlm.nih.gov/m/pubmed/28011047/

That's stage I. Question was about stage iii. Eni is treating nodes that were always negative, not nodes that are now negative. And I haven't heard of downstaging the cancer after chemo.

 

[radiaterMike]

That's stage I. Question was about stage iii. Eni is treating nodes that were always negative, not nodes that are now negative. And I haven't heard of downstaging the cancer after chemo.

That was in response to medgator who was responding to Gfunks post about N0 disease. My second post was in response to the question about SBRT for N2 disease that disappeared. I wouldn’t do it.

 

[scarbrtj]

FWIW I trained w/ Turrisi and ate a nice breakfast w/ him a few weeks ago. He's well. If there's anything that's surpassed 45/30 bid for XRT for SCLC I am not aware of it. The reason one can ponder "going beyond" 45 bid in LS-SCLC is the same reason one can not ponder going beyond a few weeks of whole breast RT in early stage breast ca: none of our societies, and none of the physicians in our societies evidently, have written any stentorian commandments re: what thou shalt or shalt not do. Thus one can stand about and pontificate. Guidelines prevent this

 

[scarbrtj]

I have wondered about the situation where you have a very small primary small cell tumor and a single N2 or N3 node and the node completely disappears after first cycle of chemotherapy, nothing in hilum, and there is a tiny primary left, say < 1 cm,

Why not just give SBRT to the residual primary? Should we really be giving 30+ fractions to a tiny primary and the original involved site where there isn't even a node? You'd already be bypassing the hilum since trials aren't including elective nodal coverage anymore. So clearly we believe in chemotherapy in handling microscopic hilar and mediastinal disease all by itself.

There's data for those who have CRs to chemo that XRT adds something, so even when a node "disappears after first cycle" w/ chemo I treat it. In real life, the only disappearance would be one in which I would judge the disappearance because, again, in real life, no one is really going for another diagnostic CT (or PET) after just one cycle of chemo. And we should be doing the XRT as close in time as possible to that first chemo anyways. So a "disappearance" is perhaps vaporware-ish (I'm not a radiologist!). Perhaps I wouldn't trust a disappearance w/o biopsy. We know that'd be fruitless.

 

[evilbooyaa]

All of the below is for LS-SCLC. Agree that most people met out, and role of intensifying local therapy with dose escalation is, IMO, minimal.

1) If a node 'disappears' after chemo (since we should be starting with cycle 1 or 2 anyways so this shouldn't be an issue) you always treat the Pre-chemo GTV. Always. If it's a mediastinal lymph node that shrunk yeah you can pull volumes out of the lung but you have to treat where that LN was. consolidative volume RT is being evaluated in lymphoma trials, and is not (IMO) a reasonable option for LS-SCLC.
2) IMO, while CONVERT was not a non-inferiority trial, the results were similar enough that 66/33 is a reasoanble fractionation scheme to offer to patients who cannot or do not want to come for twice daily treatment.
3) I have no great data saying push it past 45Gy. Majority of failures are still distant.
4) No role for elective nodal irradiation (IMO, beyond where the disease is). If they have N1 disease, treat the N1 disease. I don't think it's unreasoanble to cover level 7. I don't see a need to cover level 4 in N1 patients. I don't think there's any reason to cover level 4 or 2 if it's truly N1 disease. If it is N2 disease say in level 2, then I generally treat 4 as well (as like the intransit method). Usually 7 as well. If they have ipsi level 4 N2 disease, I don't cover level 2 or anything contralateral.
5) NCCN guidelines support surgery in early stage N0 LS-SCLC, and if felt to be inoperable, SBRT. Both followed by adjuvant chemo.

 

[scarbrtj]

All of the below is for LS-SCLC. Agree that most people met out, and role of intensifying local therapy with dose escalation is, IMO, minimal.

1) If a node 'disappears' after chemo (since we should be starting with cycle 1 or 2 anyways so this shouldn't be an issue) you always treat the Pre-chemo GTV. Always. If it's a mediastinal lymph node that shrunk yeah you can pull volumes out of the lung but you have to treat where that LN was. consolidative volume RT is being evaluated in lymphoma trials, and is not (IMO) a reasonable option for LS-SCLC.
2) IMO, while CONVERT was not a non-inferiority trial, the results were similar enough that 66/33 is a reasoanble fractionation scheme to offer to patients who cannot or do not want to come for twice daily treatment.
3) I have no great data saying push it past 45Gy. Majority of failures are still distant.
4) No role for elective nodal irradiation (IMO, beyond where the disease is). If they have N1 disease, treat the N1 disease. I don't think it's unreasoanble to cover level 7. I don't see a need to cover level 4 in N1 patients. I don't think there's any reason to cover level 4 or 2 if it's truly N1 disease. If it is N2 disease say in level 2, then I generally treat 4 as well (as like the intransit method). Usually 7 as well. If they have ipsi level 4 N2 disease, I don't cover level 2 or anything contralateral.
5) NCCN guidelines support surgery in early stage N0 LS-SCLC, and if felt to be inoperable, SBRT. Both followed by adjuvant chemo.

1) Totally agree. TL;DR: 45 Gy bid ISRT for LS-SCLC.
2) In practice the operated-upon SCLC patient is usu an "accident." And there's enough data out there to hint at inferiority of surgery for SCLC that when it's not an accident, I recommend standard-of-care chemoRT instead of surgery.
3) I was a little surprised at SABR for SCLC being NCCN OK'd but you are right. Cursory googling showed me a 2016 review article--that equivocated like few articles ever have--about SABR for SCLC and said "Based on thorough PubMed and EMBASE searches, there have been three published case series, with a total of 22 patients, examining SABR for stage I SCLC." And it's NCCN OK'd?! Alrighty then.
4) PCI

 

[radiaterMike]

I agree with everything you said except to treat pre-chemo GTV. I'd treat those sites but not the volume.

While it may not apply to 2018, there is level 1 evidence saying you can reduce your target volume after response to chemo ...

Multimodal therapy for limited small-cell lung cancer: a randomized study of induction combination chemotherapy with or without thoracic radiation ... - PubMed - NCBI

All of the below is for LS-SCLC. Agree that most people met out, and role of intensifying local therapy with dose escalation is, IMO, minimal.

1) If a node 'disappears' after chemo (since we should be starting with cycle 1 or 2 anyways so this shouldn't be an issue) you always treat the Pre-chemo GTV. Always. If it's a mediastinal lymph node that shrunk yeah you can pull volumes out of the lung but you have to treat where that LN was. consolidative volume RT is being evaluated in lymphoma trials, and is not (IMO) a reasonable option for LS-SCLC.
2) IMO, while CONVERT was not a non-inferiority trial, the results were similar enough that 66/33 is a reasoanble fractionation scheme to offer to patients who cannot or do not want to come for twice daily treatment.
3) I have no great data saying push it past 45Gy. Majority of failures are still distant.
4) No role for elective nodal irradiation (IMO, beyond where the disease is). If they have N1 disease, treat the N1 disease. I don't think it's unreasoanble to cover level 7. I don't see a need to cover level 4 in N1 patients. I don't think there's any reason to cover level 4 or 2 if it's truly N1 disease. If it is N2 disease say in level 2, then I generally treat 4 as well (as like the intransit method). Usually 7 as well. If they have ipsi level 4 N2 disease, I don't cover level 2 or anything contralateral.
5) NCCN guidelines support surgery in early stage N0 LS-SCLC, and if felt to be inoperable, SBRT. Both followed by adjuvant chemo.

 

[evilbooyaa]

To clarify, I would treat it like ISRT in lymphoma. If the mediastinal LN is no longer bulging 4cm laterally, then you don't need to treat normal lung, but the mediastinal space should be covered.

 

[KHE88]

1) If a node 'disappears' after chemo (since we should be starting with cycle 1 or 2 anyways so this shouldn't be an issue) you always treat the Pre-chemo GTV. Always. If it's a mediastinal lymph node that shrunk yeah you can pull volumes out of the lung but you have to treat where that LN was. consolidative volume RT is being evaluated in lymphoma trials, and is not (IMO) a reasonable option for LS-SCLC.

As far as I can tell, the CONVERT protocol had you only cover the residual gross post-chemo disease. So, unless I'm reading it wrong, if you had a very small biopsy or PET proven node, say 0.8 cm, that disappeared after one cycle, then you shouldn't cover it. And if that were the only N2 or N3 node, then you would be left covering only whatever is left of the primary.

In any case, I was trained to only cover the post-chemo residual (typically after 1-2 cycles), NOT fuse the original PET/CT and cover the original GTV volume as you could very well be including lung, muscle, nerve, or vessel in your GTV. So I just contour whatever else I see left of the original positive node(s) and add an expansion. Then I will typically add a little bit of elective coverage nearby "because it feels right."

So, in either case, you are skipping the hilum and going straight to a 2nd or 3rd level echelon. My question is, why do this if the node is gone after 1-2 cycles of chemo? I know there's usually something left, but I've seen a situation where it's not. If we don't believe in chemo doing the job alone for non-visualized disease, then why are we skipping the hilum since we know it has to go through there? And you guys are already saying it's typically a systemic disease. So why not spare the mediastinal toxicity and give a short SBRT course to ablate a tiny primary if it's all that's left then carry on with chemo +/- PCI?

But I'm just an unprofessional resident from a cow college who failed the rad bio boards so what the hell do I know?

 

[scarbrtj]

As far as I can tell, the CONVERT protocol had you only cover the residual gross post-chemo disease... My question is, why do this if the node is gone after 1-2 cycles of chemo?

Best practices would have you never giving XRT post-chemo. Only giving intra-chemo. Very soon after first cycle chemo. So soon after first cycle chemo you wouldn't get to a disappeared node or primary situation. If you've let chemo "disappear" disease before you come in with XRT you have waited too long. (OK, OK. Sometimes it disappears pretty quickly.) However, as Rumsfeld said "You go to war with the army you have, not the army you want." So in the case of where you get to the patient late, after the second cycle which is not great, then attempt to cover the subclinical disease which is separate and distinct from microscopic disease. Don't ever think that chemo "disappeared" gross disease. There is always microscopic-to-subclinical residual disease in a previously visible carcinoma site after 4 cycles of chemo. Always. Enough disease that XRT on top will have an impact. Two aphorisms come to mind. When Turrisi started fiddling with XRT fields for lung cancer, and he was one of the first to abandon elective nodal coverage in general (for SCLC and NSCLC), Eli Glatstein told him "The game is not how small you can make the fields, Andrew." And today, that kinda is the game. Kinda. Second, Rusty Marcus said, "I prefer the tumor-within-the-field technique versus the field-within-the-tumor technique." If you think there's tumor outside your field, cover it. I think there's residual tumor cells in previous radiographically positive sites after chemo renders them radiographically negative. Keep in mind the "resolving resolution" of a modern CT is about 1 millimeter. There can be a million tumor cells within a 1 mm voxel... something a CT would miss. (And FWIW I would not let CONVERT establish any new standards of care.)

 

[KHE88]

Oh, I agree. I would still cover the area where the original node was, but it would be a fairly small site, certainly not an entire nodal station. But it has me wondering. Would you really bypass the hilum and mediastinum to cover a tiny little site where a ~1 cm supraclav node used to be for 33 fractions? Would you still treat that tiny primary for 33 fractions when the <1 cm level 7 thing disappeared? I mean, yes I would. But I am suspicious that there is a better way to do this. Slotman's trial had us covering bilateral mediastinum electively. And I am just thinking technically about the CONVERT protocol, if the node went away, you could be left covering only the primary per protocol.

I am not making this argument by any means, but I am just wondering. N2, N3 disease with small cell. Just how curable is that that we need to be treating <1mm disease for 33 fractions?

 

[Palex80]

One major problem with the concept of covering only involved disease and abandoning ENI is the data that this evidence is based on.
Some of it are from the PET era, like the Dutch trial, but an additional problem arises from the techniques that were used back then.

Multi field conformal 3D-techniques allowed to raise the dose to the mediastinum by sparing out the spinal cord but also led to increased incidental irradiation of the neighboring stations for example in the contralateral mediastinum. That's how people treated in the 90s. Nowadays we use IMRT/VMAT and sometimes the dose drops remarkably fast to the contralateral side, allowing us to spare out the ersophagus for example. This is great but it also lowers the dose. I have recently retreated a patient with an initial N2 disease on the right side who failed on station 2L; the dose dropped really fast at the midline, although we were treating 2R and 4R. IMRT/VMAT leads to "dose bath" to the contralateral side, but those doses are too low to control metastatic spread to the contralateral side. The V10 or V5 may be higher to the contralateral side, but we need is the V30 to control microscopic disease.

 

[radiaterMike]

FWIW the ongoing RTOG trial requires coverage of the hilum even if not involved, so this is what I do off protocol.

From my perspective,we know from decades old data that chemo and RT is better than chemo alone, so I would not opt to not treat a site with known disease involvement even if it disappears on imaging. The number of cell in a several mm tumor is on the order of several million (though only a small percentage may be malignant). So the sensitivity of imaging is not great.

 

[seper]

Yes, CALGB 30610 irradiates ipsilateral hilum, to either 46 Gy or 45 Gy depending on the arm. That's what I do in practice.

 

[evilbooyaa]

I wouldn't skip the intransit path of developed mediastinal mets - if there's a level 4 LN I'm probably covering hilum and level 7.

I wouldn't bypass it as is being suggested - for me ENI means coverage PAST where the max extent of nodal disease is.

I get the concerns about it, but given that we're in a data-free space, I'd lean towards sticking with what we know, or trying to shrink fields (to not include CR nodal stations after 1 or 2 cycles of chemo) only on a protocol.

 

[Radonc90]

This thread is from Nov. 2018.

What you you guys/girls do these days with volume/dosing/fraction for Limited Stage SCLC?
- How much expansion (how many mm) beyond PET-based GTV, CTV?
- 2Gy/fx?
- Total = ____ Gy?

 

[radOresident]

Also interested in this question - is anyone doing high dose BID treatment to 60/40 based on the ASCO abstract? Meeting Library | Meeting Library

 

[scarbrtj]

Because I have always done 45/30 bid, with the new data I’m doing 60/40 bid.

 

[evilbooyaa]

Also interested in this question - is anyone doing high dose BID treatment to 60/40 based on the ASCO abstract? Meeting Library | Meeting Library

That abstract makes zero sense to me. No difference in response rate (fine, maybe the durability of response is the issue). But, no difference in median PFS? How does one improve OS but not PFS and claim it to be due to the treatment and not a confounding variable?

This thread is from Nov. 2018.

What you you guys/girls do these days with volume/dosing/fraction for Limited Stage SCLC?
- How much expansion (how many mm) beyond PET-based GTV, CTV?
- 2Gy/fx?
- Total = ____ Gy?

I offer BID but would more often treat 66/33 per CONVERT as patients frequently don't like BID and there is no advantage to BID.

For gross disease I personally think 1cm off a 4DCT-based ITV is overkill but probably what I'll say on boards, with at least 0.5cm PTV margin, more if not using 4DCT.

 

[Palex80]

I offer BID but would more often treat 66/33 per CONVERT as patients frequently don't like BID and there is no advantage to BID.

Being a purist: CONVERT failed to prove non-inferiority of 66/33 versus 45/1.5 bid.

From the manuscript.
"In CONVERT, 2-year survival for twice-daily and once-daily radiotherapy was 56% and 51%, versus 47% and 41% in the Intergroup 0096 study.4
CONVERT was not an equivalence study (and was not powered for equivalence) so it cannot be concluded that the two regimens have the same efficacy."

 

[scarbrtj]

Breast ENI trials show mild LRC benefits; and in fact, a proven lack of survival benefit from doing it... yet that's standard of care (in many's minds).

BID in SCLC keeps showing survival improvements; it's one of the few randomized style-of-XRT interventions in the pantheon of radiation oncology to show survival improvements in fact. But lots o' people are like "there is no advantage to BID."

Folks, rad oncs are neurotic.

 

[evilbooyaa]

Being a purist: CONVERT failed to prove non-inferiority of 66/33 versus 45/1.5 bid.

From the manuscript.
"In CONVERT, 2-year survival for twice-daily and once-daily radiotherapy was 56% and 51%, versus 47% and 41% in the Intergroup 0096 study.4
CONVERT was not an equivalence study (and was not powered for equivalence) so it cannot be concluded that the two regimens have the same efficacy."

Yes, yes, I know. But I also consider 5-FU/Cis to be a reasonable option for anal cancer rather than 5-FU/MMC based on ACT-II (which had a very similar conclusion that it was not an equivalence or non-inferiority trial).

Breast ENI trials show mild LRC benefits; and in fact, a proven lack of survival benefit from doing it... yet that's standard of care (in many's minds).

BID in SCLC keeps showing survival improvements; it's one of the few randomized style-of-XRT interventions in the pantheon of radiation oncology to show survival improvements in fact. But lots o' people are like "there is no advantage to BID."

Folks, rad oncs are neurotic.

First off, would quote EORTC or MA-20 not an NCDB. Again, NCDB analyses asking the same questions clinical trials did is silly. But yes, there is only a DFS benefit and not an OS benefit from those trials. Regardless, let's stay on topic and leave the pontificiation to breast ENI to the various other threads where you have brought up this exact same concern.

Getting back to LS-SCLC, I'm all aboard offering BID for SCLC (and fine calling it SOC) but I'm not going to force patients to get it. For the 60/40 BID I'm going to wait on the paper given my concerns with the data noted above.
There is one trial that has documented evidence of BID improving OS in a paper, the original Turrisi, and nobody is doing 45/25 for SCLC anymore. Some have argued that even 45/15 qD would be similar efficacy to 45/30 BID.

 

[Gfunk6]

In community practice, bid treatment is challenging. We've been treating SCLC like NSCLC 60-70 Gy with 2 Gy per fraction. Alternatively, for lung-confined limited stage SCLC, have been doing SBRT followed by PE chemo.

 

[scarbrtj]

Yes, yes, I know. But I also consider 5-FU/Cis to be a reasonable option for anal cancer rather than 5-FU/MMC based on ACT-II (which had a very similar conclusion that it was not an equivalence or non-inferiority trial).



First off, would quote EORTC or MA-20 not an NCDB. Again, NCDB analyses asking the same questions clinical trials did is silly. But yes, there is only a DFS benefit and not an OS benefit from those trials. Regardless, let's stay on topic and leave the pontificiation to breast ENI to the various other threads where you have brought up this exact same concern.

Getting back to LS-SCLC, I'm all aboard offering BID for SCLC (and fine calling it SOC) but I'm not going to force patients to get it. For the 60/40 BID I'm going to wait on the paper given my concerns with the data noted above.
There is one trial that has documented evidence of BID improving OS in a paper, the original Turrisi, and nobody is doing 45/25 for SCLC anymore. Some have argued that even 45/15 qD would be similar efficacy to 45/30 BID.

In community practice, bid treatment is challenging. We've been treating SCLC like NSCLC 60-70 Gy with 2 Gy per fraction. Alternatively, for lung-confined limited stage SCLC, have been doing SBRT followed by PE chemo.

I wonder how many people would cry foul at going above 60/30 in NSCLC to a left lung tumor involving hilum/mediastinum but will unhesitatingly give 66/33 (or "60-70") to the exact same volume in SCLC so as to avoid BID... and I say that sans judgment I promise. In theory it should be difficult to get people to sign up for having radiation blasted into their body at all much less twice a day, yet somehow we all get people to do it. I'm no mesmerist, but believe it or not I get ~100% of my LS-SCLC community patients to come in twice a day for 15 days. (I can't be quite that confident yet re: 20 days.)

 

[seper]

I have not yet treated anyone to 60Gy/40, but expect that to be difficult for many patients with respect to acute tolerance.
Also, atezo or other targeted agents may replace that ”extra XRT effect” that we are hoping for

 

[communitydoc13]

In community practice, bid treatment is challenging. We've been treating SCLC like NSCLC 60-70 Gy with 2 Gy per fraction. Alternatively, for lung-confined limited stage SCLC, have been doing SBRT followed by PE chemo.

Very similar here. I've got an aggressive thoracic surgeon who will take out the true T1-2N0 lesions (very rare and not wrong). The data (particularly the new abstract for extended bid) doesn't quite add up to me and I'll have to think harder about it. This was a small trial powered for and meeting a 15%! OS benefit with prior studies from same investigator looking at accelerated hypo-fractionated regimens not meeting endpoints. The OS reported for the 60/40 arm exceeds selected retrospective data on surgically managed N0 patients given the same chemo? Maybe there is something magical going on (and may in some way be related to the microscopic breast thread? yikes) but I would not go bid to 60 now where I'm at. Anecdotally, I have had worse acute esophagitis with 45 BID than daily fractionation.

 

[scarbrtj]

Anecdotally, I have had worse acute esophagitis with 45 BID than daily fractionation.

This gets mentioned a lot. And I myself do say "anecdotally" this or that from time to time. But keep in mind...

acute effects BED10 45/30 = 45 * (1+1.5/10) = 51.2
acute effects BED10 66/33 = 66 * (1+2/10) = 79.2, or ~50% "hotter"

... that we should see more acute effects (of any sort, volumes being equal etc) w/ dose-escalated once a day (50% hotter is pretty significant I would think). We gotta pass those rad bio exams for a reason!

 

[FrostyHammer]

I wonder how many people would cry foul at going above 60/30 in NSCLC to a left lung tumor involving hilum/mediastinum but will unhesitatingly give 66/33 (or "60-70") to the exact same volume in SCLC so as to avoid BID

Bingo. With this intuitive issue + SCLC's radioresponsiveness to RT, as long as the patient opts for QD RT, I always do 60/30 for LS-SCLC, not more. I would be much more likely to do 66/33 for NSCLC in the durva era. Better systemic therapies mean more emphasis on L(R)C. Right now, LS-SCLC does not have improved systemic therapies (though these are in the works).

 

[communitydoc13]

This gets mentioned a lot. And I myself do say "anecdotally" this or that from time to time. But keep in mind...

acute effects BED10 45/30 = 45 * (1+1.5/10) = 51.2
acute effects BED10 66/33 = 66 * (1+2/10) = 79.2, or ~50% "hotter"

... that we should see more acute effects (of any sort, volumes being equal etc) w/ dose-escalated once a day (50% hotter is pretty significant I would think). We gotta pass those rad bio exams for a reason!

No time factor in those BED calculations.

 

[medgator]

I wonder how many people would cry foul at going above 60/30 in NSCLC to a left lung tumor involving hilum/mediastinum but will unhesitatingly give 66/33 (or "60-70") to the exact same volume in SCLC so as to avoid BID... and I say that sans judgment I promise. In theory it should be difficult to get people to sign up for having radiation blasted into their body at all much less twice a day, yet somehow we all get people to do it. I'm no mesmerist, but believe it or not I get ~100% of my LS-SCLC community patients to come in twice a day for 15 days. (I can't be quite that confident yet re: 20 days.)

My Sclc and nsclc dose are the same.... 66/33, no cognitive dissonance needed

 

[KHE88]

This gets mentioned a lot. And I myself do say "anecdotally" this or that from time to time. But keep in mind...

acute effects BED10 45/30 = 45 * (1+1.5/10) = 51.2
acute effects BED10 66/33 = 66 * (1+2/10) = 79.2, or ~50% "hotter"

... that we should see more acute effects (of any sort, volumes being equal etc) w/ dose-escalated once a day (50% hotter is pretty significant I would think). We gotta pass those rad bio exams for a reason!

I approach these with a BID recommendation but tell the patient that there is no evidence to suggest daily treatment to 66/33 is worse than BID and offer that if they prefer. I consult that esophagitis may be a little worse and occur sooner and that daily treatments may have less esophagitis but drag it out more. I leave it up to the patient. I'd say about 50/50 take BID, especially if coming from a long ways and having to stay in the hotel.

Agree that they tend to get rip-roaring esophagitis, but usually you hear about it at the first follow-up as they are suffering right after their EOT. But they are over it at that point whereas they would still be suffering if they were getting daily.

 

[KHE88]

My Sclc and nsclc dose are the same.... 66/33, no cognitive dissonance needed

I tend to give 66/33 for SCLC to the full field and for NSCLC either stop at 60 or boost to 66/33 with a cone down if large tumor. I don't have a great reason for this, but I also don't have a great reason to escalate beyond 60/30 to the full field for NSCLC either.

 

[evilbooyaa]

I wonder how many people would cry foul at going above 60/30 in NSCLC to a left lung tumor involving hilum/mediastinum but will unhesitatingly give 66/33 (or "60-70") to the exact same volume in SCLC so as to avoid BID... and I say that sans judgment I promise. In theory it should be difficult to get people to sign up for having radiation blasted into their body at all much less twice a day, yet somehow we all get people to do it. I'm no mesmerist, but believe it or not I get ~100% of my LS-SCLC community patients to come in twice a day for 15 days. (I can't be quite that confident yet re: 20 days.)

I think 60-66 in NSCLC is very reasonable. I usually do 60/30 but agree that with Durva my institution, anecdotally, seems to be seeing more isolated local failures. I think if dose constraints permit (mostly lung and esophagus) I may start transitioning to 66/33 for NSCLC.

For SCLC I have a trial that did 66/33. Maybe I'll do 70/35 once that other CALGB or whatever trial for daily SCLC gets published. If they had analyzed 60/30 I'd do that. If I see somebody doing 60/30 for SCLC I think that's reasonable.

It'd probably be easier for people who live far (like say 3+ hours away) and are getting a room near the facility to do BID. The issue is much more for the people who need to drive say between 1-2 hours, because it's too long to just wait around but too short to go back home and come back (with a drive that long). For folks that are within say 15-30 minutes I generally try to encourage BID - looking back at the CONVERT data it does appear numerically (although not statistically) that the numbers look slightly better with BID, so I don't think there's any signal that 66/33 is better than BID, but I also don't think there is any real difference between the two regimens.

 

[radiaterMike]

It is painful in the short run.

No time factor in those BED calculations.

I'm not a big advocate of BID for my patients either, but even with time I think the Turrisi BID regimen is a lower equivalent dose.

Accepting that I may have made errors .... with a/b=10 and Tpot=7 (reasonable for esophageal mucosa?)

66 Gy in 33 fractions has an EQD2 of 66 Gy accounting for time and not accounting for time.
45 Gy in 30 fractions has an EQD2 of 45.7 Gy accounting for time and 43.1 Gy not accounting for time

 

[scarbrtj]

No time factor in those BED calculations.

It’s gonna be roughly 60 BED10 once a day and 45 w twice a day. So 50% hotter becomes “just” 33% hotter. Maybe. A lot of this is hand waving I’ll grant you.

 

[Palex80]

Anecdotally, I have had worse acute esophagitis with 45 BID than daily fractionation.

Me too!

You know what the trick is? When the "s**t hits the fan" in patients receiving BID-RT, treatment is over anyway.
No way for the patient to terminate treatment early. Prescribed dose already delivered.
Treatment adherence was higher with BID in CONVERT too and I suspect this higher treatment adherence may also be the reason why patients with BID tend to perform better in terms of PFS.

We have seen that before, for example in rectal cancer.
PFS is better with neoadjuvant than adjuvant treatment and one clear reason for that is that some patients scheduled to undergo adjuvant RCT, never receive the entire intended treatment. Since all randomized trial results were reported as ITT analyses, this is a major factor driving different rates of PFS.

 

[communitydoc13]

Accepting that I may have made errors .... with a/b=10 and Tpot=7 (reasonable for esophageal mucosa?)

66 Gy in 33 fractions has an EQD2 of 66 Gy accounting for time and not accounting for time.
45 Gy in 30 fractions has an EQD2 of 45.7 Gy accounting for time and 43.1 Gy not accounting for time

You know what the trick is? When the "s**t hits the fan" in patients receiving BID-RT, treatment is over anyway.

I would always consider equivalent dose to be outcome specific and there is a spatial component as well. These are tough calcs.

The lower dose by basically any model for traditional bid scheduling, combined with the equivalent or better outcomes, lack of improvement with accelerated only treatments and fairly recent Korean trial with no difference in late admin of XRT makes me think reassortment is the main explanatory mechanism for these good bid outcomes.

Perhaps reassortment is what is allowing for demonstration of meaningful dose effect with the newest Norway data?

The survival outcomes are surprising, especially given discordance with LC outcomes. Is it possible that circulating tumor cells periodically return to niduses of gross disease, are themselves synchronized and in turn there is a radiation as chemosensitizer effect?

Maybe I should reconsider BID more, but in my community practice, concurrent patients taking up space in infusion or being occasionally hospitalized for esophagitis (and not managed by me or medonc) can be a little bit of a disaster.

 

[Palex80]

I am resurrecting this ancient thread for a pressing matter.

After the publication of the Norwegian and now the Chinese data, showing that escalation beyond 45/1.5 b.i.d. is feasible and potentially beneficial for LD-SCLC, we faced the dilemma of how to name this regime.

So far, the 45/1.5 schedule was named "Turrisi". We would say for instance "We are going to do Turrisi for Mrs. Murphy".
We could of course still keep saying that and add if it's going to be 3 or 4 weeks, but we viewed this as a potential safety issue.

After careful consideration, we propose "Terrorisi" as the name for the escalated, 4-weekly b.i.d. schedule.
I would like to thank my colleague, who would like to stay anonymous, for this excellent idea.

In one word, both "Turrisi" and the likely increased (and vastly underreported in the trials) toxicity is combined.

Thank you for your attention.

 

[evilbooyaa]

Escalated BID regimen is my preferred moniker.

Everyone knows BID is 45/30.

Trust the trials! 60/40 BID should be similarly or even potentially less toxic than 60/30 QD which we do all the time!

 

[MidwestRadOnc]

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