hypofractionation for post-op GYN cancers?

[ramsesthenice]

Got a call from our head of gyn oncology who heads our GOG steering committee about a trial coming through NRG/GOG. Randomizing post-op cervical and endometrial patients to 45-50 Gy in 25 fractions vs 30 Gy in 5 fractions. I clarified and they plan to use the same treatment volumes for both. Looks like this is something they are trying at a few centers but there is really not much if any data that I can find yet for the ongoing Spartacus-1 trial. I've done this 2x weekly for melanomas etc and reactions tend to be brisk. Sounds a little out there to me for these volumes.

And before anyone points out 30/5 isn't much more than short course for rectal cancer recall that we usually take the rectum out after short course and we don't routinely cover external iliac nodes for rectal tumors (which is where the great majority of your small bowel dose will come from). This really is a different animal IMHO.

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[RadRadRad]

Sounds like a bad idea
Is there no phase 1 dose escalation study?
25 in 5
27.5 in 5
30 in 5

 

[ramsesthenice]

Sounds like a bad idea
Is there no phase 1 dose escalation study?
25 in 5
27.5 in 5
30 in 5

There is but I can’t find the data. I have no sense of what it looks like.

Sounds like a bad idea
Is there no phase 1 dose escalation study?
25 in 5
27.5 in 5
30 in 5

 

[scarbrtj]

Got a call from our head of gyn oncology who heads our GOG steering committee about a trial coming through NRG/GOG. Randomizing post-op cervical and endometrial patients to 45-50 Gy in 25 fractions vs 30 Gy in 5 fractions. I clarified and they plan to use the same treatment volumes for both. Looks like this is something they are trying at a few centers but there is really not much if any data that I can find yet for the ongoing Spartacus-1 trial. I've done this 2x weekly for melanomas etc and reactions tend to be brisk. Sounds a little out there to me for these volumes.

And before anyone points out 30/5 isn't much more than short course for rectal cancer recall that we usually take the rectum out after short course and we don't routinely cover external iliac nodes for rectal tumors (which is where the great majority of your small bowel dose will come from). This really is a different animal IMHO.

Are we that far away from a day where "I really question a 5 fraction approach here" gets one banned from the rad onc club? 'Til then, here's "data" that would suggest ~6 Gy times 5 is OK:

Thus, yes, 6 Gy (6.454 Gy more precisely) per fraction is at the upper limit of being acutely normoequivalent to 45/25.
30/5 a bit more for late effects...

But not by much.

Anyways...

 

[seper]

Got a call from our head of gyn oncology who heads our GOG steering committee about a trial coming through NRG/GOG. Randomizing post-op cervical and endometrial patients to 45-50 Gy in 25 fractions vs 30 Gy in 5 fractions. I clarified and they plan to use the same treatment volumes for both. Looks like this is something they are trying at a few centers but there is really not much if any data that I can find yet for the ongoing Spartacus-1 trial. I've done this 2x weekly for melanomas etc and reactions tend to be brisk. Sounds a little out there to me for these volumes.

And before anyone points out 30/5 isn't much more than short course for rectal cancer recall that we usually take the rectum out after short course and we don't routinely cover external iliac nodes for rectal tumors (which is where the great majority of your small bowel dose will come from). This really is a different animal IMHO.

Bad idea, IMO. Volumes are large and patients are long-term survivors in whom fecal incontinence is already an issue

 

[evilbooyaa]

This should not be a national trial without robust phase I/II data. I am aware of no such data in this space. Jumping to ph3 is irresponsible IMO.

 

[Chartreuse Wombat]

Got a call from our head of gyn oncology who heads our GOG steering committee about a trial coming through NRG/GOG. Randomizing post-op cervical and endometrial patients to 45-50 Gy in 25 fractions vs 30 Gy in 5 fractions. I clarified and they plan to use the same treatment volumes for both. Looks like this is something they are trying at a few centers but there is really not much if any data that I can find yet for the ongoing Spartacus-1 trial. I've done this 2x weekly for melanomas etc and reactions tend to be brisk. Sounds a little out there to me for these volumes.

And before anyone points out 30/5 isn't much more than short course for rectal cancer recall that we usually take the rectum out after short course and we don't routinely cover external iliac nodes for rectal tumors (which is where the great majority of your small bowel dose will come from). This really is a different animal IMHO.

Hmmm. Glad that we aren't discussing m**ks.

First I haven't treated a GYN case in more than 2 decades.
Second at the risk of doxxing myself I am intimately familiar with NRG and more importantly the NCI Steering Committees (SC) that approve cooperative group trials.

I find it very hard to believe that this sort of trial would past muster at the Steering Committee level. After all what is the hypothesis? The NCI is interested in survival outcomes and it is not plausible that there would a survival outcome. It is possible that this is a (G_d forbid) non-inferiority trial with a disease-specific outcome but this is not something that Steering Committee would endorse.

The Steering Committees are charged with setting strategic priorities in their respective disease area. For GYN the most recent priorities are here.

I don't see how this trial has a chance of ever being approved by the Steering Committee.

 

[scarbrtj]

Hmmm. Glad that we aren't discussing m**ks.

yeah that'd be highly inappropriate

 

[medgator]

yeah that'd be highly inappropriate

Speak for yourself

 

[ramsesthenice]

Hmmm. Glad that we aren't discussing m**ks.

First I haven't treated a GYN case in more than 2 decades.
Second at the risk of doxxing myself I am intimately familiar with NRG and more importantly the NCI Steering Committees (SC) that approve cooperative group trials.

I find it very hard to believe that this sort of trial would past muster at the Steering Committee level. After all what is the hypothesis? The NCI is interested in survival outcomes and it is not plausible that there would a survival outcome. It is possible that this is a (G_d forbid) non-inferiority trial with a disease-specific outcome but this is not something that Steering Committee would endorse.

The Steering Committees are charged with setting strategic priorities in their respective disease area. For GYN the most recent priorities are here.

I don't see how this trial has a chance of ever being approved by the Steering Committee.

I will certainly follow up when I know more. I was asked for my general thoughts on the dose and fractionation as it didn’t make sense to this particular surgeon. I was honestly too busy to ask many questions at the time (I assumed he paged next about a patient). I got the sense it is a non inferiority randomized phase 2 study but again I did not specifically ask. I did not get the sense he was overly thrilled about the concept and I doubt my reaction fostered a lot of faith.

To Scar, you know how I feel about biological calculations . In truth, I would not be surprised if this went ok for most people. My issue here is 2 fold. First, having used this scheme a number of times for cutaneous tumors, it’s not the acute toxicity that scares me. It’s the late complications that we frankly are not great at tracking that concern me. Second, this is a huge jump. If the volumes are as big as described (admittedly an important if) conceptually I think it would be nice to start with something a little more modest in terms of hypofrac schemes (more akin to 3-3.5 Gy/day). I may well turn out to be wrong but as of today, I would be very nervous signing a 6 Gy/fx plan in this setting without better data telling me it is reasonable. Admittedly, the list of things I have been wrong about in terms of tolerance, for good or for bad, is long and in other settings I have advocated things people think sound crazy aggressive. But I am not a fan of opening a trial with a randomization I wouldn’t feel good about offering my mom or sister. It may be a reasonable question worth studying, I just don’t plan to be an early participant.

 

[ramsesthenice]

This should not be a national trial without robust phase I/II data. I am aware of no such data in this space. Jumping to ph3 is irresponsible IMO.

Your sentiment is correct but these are smart people. I’m sure they are discussing a randomized phase 2. Possibly even a 1b/2 expansion trial. As I responded to wombat above I was not in a place to ask for more details at the time. Will follow up later.

 

[Palex80]

This is not going to be trivial... I am thinking of all that small bowel in the pelvis receiving high doses...

 

[evilbooyaa]

Your sentiment is correct but these are smart people. I’m sure they are discussing a randomized phase 2. Possibly even a 1b/2 expansion trial. As I responded to wombat above I was not in a place to ask for more details at the time. Will follow up later.

OK - I mean it's strange to see it as a NRG trial with zero institutional data, since UCLA did a version of this in sarcoma basically by themselves, but if they're doing a phase I lead in and then doing a randomized phase II then.... OK I guess.

 

[GI_RadOnc]

Coming from someone who's a huge proponent of SCRT for rectal cancer; I also share some of the concerns for this topic. However, with modern XRT techniques; one could feel safer scooping out the small bowel and keeping it to 25 Gy or lower even when chasing the external iliac chain. Devil will be in the details...

It is good to know that, thus far, in the FEW rectal cancer studies looking at QOL between short course and long course, there doesn't seem to be any difference. I do wish we were better at that in the USA!

Long-Term Health-Related Quality of Life in Patients With Rectal Cancer After Preoperative Short-Course and Long-Course (Chemo) Radiotherapy - PubMed

This analysis of HRQL in patients who received CRT shows no clinically relevant differences in long-term HRQL and symptoms between patients who received CRT and SC-PRT, apart from less satisfaction with urinary function reported by patients who received CRT. These results indicate that both...

pubmed.ncbi.nlm.nih.gov

 

[evilbooyaa]

Big difference between rectum that will be resected getting 25/5 and rectum not going to be resected getting 30/5, at least IMO.

 

[taserlaser]

As an aside, I love short course sarcoma RT. Where I trained we did a modified Eiber protocol, and where I’m working now there’s a phase II dose escalation of 35/5 to the GTV I’m enrolling patients on. Time to surgery is much quicker, treatment burden much less on patients, need less replanning as compared to 25 fractions. Definitely my preference on trial if it’s an option. SARC-032 during the pandemic temporarily allowed one of the hypofractionated Eiber protocols to be done to minimize treatment burden for patients, which was also nice, but I think they’re going to/have mandated standard fractionation for the remainder of the trial ongoing (ok I understand that for trial purposes). But short course is certainly convenient for many patients (and practitioners).

 

[evilbooyaa]

I am on board with evaluating sarcoma pre-op SBRT in a randomized fashion because we have phase I data suggesting its reasonable. Not the case in post-op pelvic patients. IMO this should be done at an institutional level first not on the national level.

 

[ramsesthenice]

Hmmm. Glad that we aren't discussing m**ks.

First I haven't treated a GYN case in more than 2 decades.
Second at the risk of doxxing myself I am intimately familiar with NRG and more importantly the NCI Steering Committees (SC) that approve cooperative group trials.

I find it very hard to believe that this sort of trial would past muster at the Steering Committee level. After all what is the hypothesis? The NCI is interested in survival outcomes and it is not plausible that there would a survival outcome. It is possible that this is a (G_d forbid) non-inferiority trial with a disease-specific outcome but this is not something that Steering Committee would endorse.

The Steering Committees are charged with setting strategic priorities in their respective disease area. For GYN the most recent priorities are here.

I don't see how this trial has a chance of ever being approved by the Steering Committee.

No body question the wombat. Ever. I don’t know for sure how things turned out (and it really wouldn’t be proper to say if I did) but my contact echoed everything above heading into the meeting.

 

[evilbooyaa]

Hmmm. Glad that we aren't discussing m**ks.

First I haven't treated a GYN case in more than 2 decades.
Second at the risk of doxxing myself I am intimately familiar with NRG and more importantly the NCI Steering Committees (SC) that approve cooperative group trials.

I find it very hard to believe that this sort of trial would past muster at the Steering Committee level. After all what is the hypothesis? The NCI is interested in survival outcomes and it is not plausible that there would a survival outcome. It is possible that this is a (G_d forbid) non-inferiority trial with a disease-specific outcome but this is not something that Steering Committee would endorse.

The Steering Committees are charged with setting strategic priorities in their respective disease area. For GYN the most recent priorities are here.

I don't see how this trial has a chance of ever being approved by the Steering Committee.

Are the goals of NCI/NRG alliance different from the goals of RTOG? We've had non-inferiority trials to reduce number of fractions for prostate cancer (0415) in the past, so on the bolded, unless the goals have radically changed, I'm not sure that this is a valid criticism? I still stand by all my other issues with the trial, but the one mentioned here doesn't make a whole lot of sense to me.

 

[Chartreuse Wombat]

0415 was the end of the line. The NCI sees how the results haven't changed practice dramatically and they are not keen to subsidize research that doesn't change practice (or save lives).

Priorities of NRG don't matter. It's the Steering Committee priorities that matter

Underutilization of hypofractionation in prostate cancer found (in yet another) paper.

 

[evilbooyaa]

0415 was the end of the line. The NCI sees how the results haven't changed practice dramatically and they are not keen to subsidize research that doesn't change practice (or save lives).

Priorities of NRG don't matter. It's the Steering Committee priorities that matter

Underutilization of hypofractionation in prostate cancer found (in yet another) paper.

Well, glad to see that focus of nationwide clinical trials will now be on improving outcomes, not finding ways to do our treatments less.

Still can't stop the Europeans from doing all of that research, however.

I suppose then, a 25/5 vs 50/25 pre-op sarcoma trial would be dead in the water at the national level for similar reasons?

 

[Chartreuse Wombat]

I am not familiar with the NCI priorities for sarcoma. I don't there is a sarcoma (adult) steering committee)

 

[taserlaser]

Well, glad to see that focus of nationwide clinical trials will now be on improving outcomes, not finding ways to do our treatments less.

Still can't stop the Europeans from doing all of that research, however.

I suppose then, a 25/5 vs 50/25 pre-op sarcoma trial would be dead in the water at the national level for similar reasons?

Tangential, but the single arm 25 Gy study that I have in the back of my memory has a higher local recurrence rate then some of the other hypo fractionated doses and protocols; likely any trial would look at around the 30 Gy dose level I think. No idea on what's going on with sarcoma trial leadership.

 

[Radonc90]

Also,

Remember that postop GYN (after rad hyst +/- BSO), quite a bit of small bowel sits in the pelvis.
What is the hurry for 5 fx?
Why hurry and get more small bowel complications?