Is there any evidence Whipple's is better than doing nothing?

[Palex80]

I do not think there's a role for RT in resectable, small cT1-2 cN0 pancreatic cancer. These patients should get surgery and perioperative chemotherapy. It will be impossible to prove that RT plays a role here, noone will peform a randomized trial and some would even suggest that randomizing patients between the standard of care and "experimental RT" would be unethical, actually.

The problem is that many physicians, mainly surgeons, extrapolate from these results and advocare for surgery as a must in cT3-cT4 or cN+ disease. Whether or not surgery truly improves survival in these patients or these patients are basically doomed to reccur and die anyway, with surgery adding very little in terms of OS and even then with significant morbidity, is debateable. This is the space, where perhaps RT together with systemic therapy can play a role. The problem here however is, that many of these patients are not eligible for "Crane"-approaches, since these tumors are big and one cannot meet constraints for duodenum without underdosing the GTV.


It's a complicated matter...

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[evilbooyaa]

You can treat with 75/25 basically in any situation maybe besides where tumor is directly abutting duodenum. There's a paper out there where CC documents what percentage of tumor has to get the Rx dose to have any potential benefits. I would offer that for locally unresectable after no evidence of mets on chemo.

RT for resectable pancreatic cancer is not going to be a thing until we can get every locally unresectable patient to this first. I think it will happen in time (parag parikh has a series, and many including myself offer it off protocol currently) but some prospective validation even if single arm will be helpful.

The planning is VERY intricate however and is not for those lackadaisical with IGRT.

 

[Palex80]

You can treat with 75/25 basically in any situation maybe besides where tumor is directly abutting duodenum. There's a paper out there where CC documents what percentage of tumor has to get the Rx dose to have any potential benefits. I would offer that for locally unresectable after no evidence of mets on chemo.

I have the feeling that the tumors of all my patients are abutting duodenum or are within <5mm of duodenum. How am I supposed to drop the dose from edge of the GTV to the duodenum by around 30%, while still having some kind of ITV/PTV-margin?

RT for resectable pancreatic cancer is not going to be a thing until we can get every locally unresectable patient to this first.

The problem is that unresectable pancreatic cancers do miserably. I am talking about unresectable, not unoperable due to patients not being fit for a Whipple. Unresectable pancreatic tumors are big, come with involved nodes most of the times and bear a high risk for distant relapse. Local relapse is not the issue most of the times, which is the reason why numerous attempts to make RT a firm component of borderline resectable tumors have not been successful so far.

The planning is VERY intricate however and is not for those lackadaisical with IGRT.

An MR-linac is probably the best tool for this, I would imagine?

 

[evilbooyaa]

I have the feeling that the tumors of all my patients are abutting duodenum or are within <5mm of duodenum. How am I supposed to drop the dose from edge of the GTV to the duodenum by around 30%, while still having some kind of ITV/PTV-margin?
View attachment 359292


The problem is that unresectable pancreatic cancers do miserably. I am talking about unresectable, not unoperable due to patients not being fit for a Whipple. Unresectable pancreatic tumors are big, come with involved nodes most of the times and bear a high risk for distant relapse. Local relapse is not the issue most of the times, which is the reason why numerous attempts to make RT a firm component of borderline resectable tumors have not been successful so far.

An MR-linac is probably the best tool for this, I would imagine?

Many a patient I meet are borderline resectable... looking for some downstaging after FOLFIRINOX x 8. But yes, definitive RT to HoP is difficult, but they are also less likely to be locally unresectable.

There isn't an ITV or PTV margin for the 75Gy. If you're someone who believes in 95/95 or higher or bust, you're not gonna have a good time with 75/25. But if you can stomach a plan that's like 80% of volume getting 95-99% of Rx dose.... you can have a shot. Think of it like the FLAME trial. Goal is to be isotoxic to traditional 45Gy in 25Fx while SIBbing the **** out of gross tumor as much as possible.

I would not put a confirmed N+ pancreas patient through 75/25 because I agree with you.

Local relapse is a frequent occurence for people who don't get RT, see the results from LAP-07. Not as frequent as distant mets, yes, but that's why you test their biology by making sure they get through chemo first without metting out. Local recurrence is frequently painful and can be the cause of a patient's demise (although not enough to translate to OS benefit)

I've heard very good things about MR-Linac in this space. CT-guided adaptive is unfortunately useless for a HoP primary due to inability to not **** itself over bowel gas in the duodenum.

 

[OTN]

Many a patient I meet are borderline resectable... looking for some downstaging after FOLFIRINOX x 8. But yes, definitive RT to HoP is difficult, but they are also less likely to be locally unresectable.

There isn't an ITV or PTV margin for the 75Gy. If you're someone who believes in 95/95 or higher or bust, you're not gonna have a good time with 75/25. But if you can stomach a plan that's like 80% of volume getting 95-99% of Rx dose.... you can have a shot. Think of it like the FLAME trial. Goal is to be isotoxic to traditional 45Gy in 25Fx while SIBbing the **** out of gross tumor as much as possible.

I would not put a confirmed N+ pancreas patient through 75/25 because I agree with you.

Local relapse is a frequent occurence for people who don't get RT, see the results from LAP-07. Not as frequent as distant mets, yes, but that's why you test their biology by making sure they get through chemo first without metting out. Local recurrence is frequently painful and can be the cause of a patient's demise (although not enough to translate to OS benefit)

I've heard very good things about MR-Linac in this space. CT-guided adaptive is unfortunately useless for a HoP primary due to inability to not **** itself over bowel gas in the duodenum.

That's not been my experience with CBCT for IGRT for HoP SBRT. While it's not quite as good as MRI, I've been confident in our ability to identify the duodenum on daily imaging with CBCT, and (knocks on all available wood within a 3-mile radius) no duodenal injury thus far.

 

[ramsesthenice]

That's not been my experience with CBCT for IGRT for HoP SBRT. While it's not quite as good as MRI, I've been confident in our ability to identify the duodenum on daily imaging with CBCT, and (knocks on all available wood within a 3-mile radius) no duodenal injury thus far.

I personally use the MR for this space but I will say, I have talked to some of the folks at a different center who have both Ethos and Unity and they don't universally opt for the MR. I have never tried to use any kind of CT-based adaptive imaging so I can't really comment. But I think its important to clarify that the real strength of the MRI is not the visualization but the ability to adapt and allow the optimizer to try to increase (or decrease) tumor coverage based on time of treatment bowel positioning. When using no to minimal margins it can make a pretty big difference in coverage. Will it end up translating into something meaningful? No one knows yet. But as you said, you can do high dose SBRT (45-50/5) with CBCT IGRT. Most people use fiducials and breath hold. Seems to work pretty well.

 

[evilbooyaa]

That's not been my experience with CBCT for IGRT for HoP SBRT. While it's not quite as good as MRI, I've been confident in our ability to identify the duodenum on daily imaging with CBCT, and (knocks on all available wood within a 3-mile radius) no duodenal injury thus far.

I mean CT-based adaptive ablative treatment (whethe rit be SBRT or not), not static SBRT, to get doses of 50/5 or equivalent ablative doses. Are you going higher than 33/5 for your SBRT?

Trying to adapt to where pancreas tumor ends on a CBCT does not work nearly as well as what at least is published with MR guidance simply because of ability to see the tumor. I say this as someone who has looked at it on an Ethos. Maybe an aggressive gas regimen would help minimize artifact on the Ethos CBCT.

 

[OTN]

I mean CT-based adaptive ablative treatment (whethe rit be SBRT or not), not static SBRT, to get doses of 50/5 or equivalent ablative doses. Are you going higher than 33/5 for your SBRT?

Trying to adapt to where pancreas tumor ends on a CBCT does not work nearly as well as what at least is published with MR guidance simply because of ability to see the tumor. I say this as someone who has looked at it on an Ethos. Maybe an aggressive gas regimen would help minimize artifact on the Ethos CBCT.

50 in 5. No adapting. Keep duodenal dose to < 30 Gy. I overestimate GTV/CTV but fanatically protect the duodenum.

 

[evilbooyaa]

50 in 5. No adapting. Keep duodenal dose to < 30 Gy. I overestimate GTV/CTV but fanatically protect the duodenum.

Nice. Same questions about feasibility that I think palex had. 95/95+ coverage to 50Gy?

If not.... I wonder if you translated that same practice to 15-25 fractions ablative dosing and expanded your therapeutic window.

 

[OTN]

Nice. Same questions about feasibility that I think palex had. 95/95+ coverage to 50Gy?

If not.... I wonder if you translated that same practice to 15-25 fractions ablative dosing and expanded your therapeutic window.

Highly dependent on anatomy- when the tumor is close to the duodenum, we naturally underdose in that area, so 95 to 95 isn't feasible. However, there has been some interesting data suggesting dose heterogeneity for SBRT doesn't lead to decreased local control like we would assume. I haven't had much in the way of local recurrences with that strategy.

I do the Chris Crane 70 Gy in 20 fx style fractionated SBRT for central hepatobiliary tumors a fair bit and have had good success with both control and toxicity. I haven't seen as much data for pancreas, though, so I haven't yet made the switch. Has there been a decently-sized series looking at it?

 

[RickyScott]

I have the feeling that the tumors of all my patients are abutting duodenum or are within <5mm of duodenum. How am I supposed to drop the dose from edge of the GTV to the duodenum by around 30%, while still having some kind of ITV/PTV-margin?
View attachment 359292


The problem is that unresectable pancreatic cancers do miserably. I am talking about unresectable, not unoperable due to patients not being fit for a Whipple. Unresectable pancreatic tumors are big, come with involved nodes most of the times and bear a high risk for distant relapse. Local relapse is not the issue most of the times, which is the reason why numerous attempts to make RT a firm component of borderline resectable tumors have not been successful so far.

An MR-linac is probably the best tool for this, I would imagine?

Gtv is not covered by 75 gy. I think cc said on average about 70% of gtv gets prescription dose.

 

[Doctorer]

Ablative radiation therapy for locally advanced pancreatic cancer: techniques and results - Radiation Oncology

Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest...

ro-journal.biomedcentral.com

Here’s the technique paper for 67.5/15 and 75/25 that I’ve used to guide contouring/planning.

 

[TheWallnerus]

Gtv is not covered by 75 gy. I think cc said on average about 70% of gtv gets prescription dose.

I begin glossing over and/or losing interest when people start “educating” me on techniques like this. Is it the children or is it me…….

 

[StIGMA]

There isn't an ITV or PTV margin for the 75Gy.

Don't need to get into nuances here and assuming you are describing the way you do it, but per CC the lack of ITV is because this technique is recommended to be done with breath hold, and there can be a PTV margin as noted in that linked paper by Doctorer (that is then subtracted from PRV & also meets toxicity constraints). Would highly recommend those interested look into how the daily CBCTs are analyzed/used for adaptive planning as needed.

 

[evilbooyaa]

I begin glossing over and/or losing interest when people start “educating” me on techniques like this. Is it the children or is it me…….

Well... given that edges of his tumor are getting 45Gy and he's seeing outcomes much better than 45-54Gy in the locally advanced setting, I think it may be worth challening some of the assumptions of 'required coverage' of GTV/PTV.