borderline pancreas volumes

[Ray D. Ayshun]

Wondering how people are doing volumes in BR pancreas when using conventional chemorads. The recently published Preopanc trial based volumes strictly off of gross disease, albeit using a different dose schema. On the other hand, we've historically treated a large volume with ENI from above the celiac down to L2 and into the porta, including the para-aortic, portal venous, celiac, and SMA in the case of head tumors. Based strictly on tolerability, I suspect more people complete the more conservative plans altogether, or without breaks. On the other hand, I would suspect LC is better if treating a larger area, though I'm not aware of the two approaches being compared. It seems the move in unresectable has been towards treating gross disease plus margin alone (if not always that way given the LAP 07 approach), so in my estimation, it also makes sense to treat BR this way as only about 33% should ever undergo a Whipple. In any case, I suspect most are using larger volumes, and haven't really seen the preopanc approach adopted, though perhaps some are using SBRT to gross disease plus margin in BR.

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[Palex80]

Wondering how people are doing volumes in BR pancreas when using conventional chemorads. The recently published Preopanc trial based volumes strictly off of gross disease, albeit using a different dose schema. On the other hand, we've historically treated a large volume with ENI from above the celiac down to L2 and into the porta, including the para-aortic, portal venous, celiac, and SMA in the case of head tumors. Based strictly on tolerability, I suspect more people complete the more conservative plans altogether, or without breaks. On the other hand, I would suspect LC is better if treating a larger area, though I'm not aware of the two approaches being compared. It seems the move in unresectable has been towards treating gross disease plus margin alone (if not always that way given the LAP 07 approach), so in my estimation, it also makes sense to treat BR this way as only about 33% should ever undergo a Whipple. In any case, I suspect most are using larger volumes, and haven't really seen the preopanc approach adopted, though perhaps some are using SBRT to gross disease plus margin in BR.

The reason you are treating borderline resectable pancreatic cancer with neoadjuvant chemo-RT is to facilitate surgery. ENI never made much sense to me in that context.

 

[Ray D. Ayshun]

The reason you are treating borderline resectable pancreatic cancer with neoadjuvant chemo-RT is to facilitate surgery. ENI never made much sense to me in that context.

I don't disagree. Iow, eni never makes sense...

 

[TheWallnerus]

Wondering how people are doing volumes in BR pancreas when using conventional chemorads. The recently published Preopanc trial based volumes strictly off of gross disease, albeit using a different dose schema. On the other hand, we've historically treated a large volume with ENI from above the celiac down to L2 and into the porta, including the para-aortic, portal venous, celiac, and SMA in the case of head tumors. Based strictly on tolerability, I suspect more people complete the more conservative plans altogether, or without breaks.

Definitely.

On the other hand, I would suspect LC is better if treating a larger area, though I'm not aware of the two approaches being compared.

No data either way.

It seems the move in unresectable has been towards treating gross disease plus margin alone

Especially in SABR/high dose hypofx approaches.

(if not always that way given the LAP 07 approach), so in my estimation, it also makes sense to treat BR this way as only about 33% should ever undergo a Whipple.

Agree!

In any case, I suspect most are using larger volumes,

Pure 20th century traditions.

As the years go by, and the systemics (and stagings) improve, we will find in rad onc that many traditional ENI teachings need to be untaught.

 

[Ray D. Ayshun]

Definitely.

No data either way.

Especially in SABR/high dose hypofx approaches.

Agree!

Pure 20th century traditions.

As the years go by, and the systemics (and stagings) improve, we will find in rad onc that many traditional ENI teachings need to be untaught.

I know someone here does eni, and has good reason. And if you're not, how do you define volumes when using conventional?

Edit:. These aren't the answers I was expecting.

 

[TheWallnerus]

I know someone here does eni, and has good reason. And if you're not, how do you define volumes when using conventional?

Edit:. These aren't the answers I was expecting.

If you’ve been out practicing long enough you realize, and it seems you have, giving those big Reginian/Gundersonian volumes from T12 to L3 to 50.4 Gy with chemo was a good way to give people toxicity without a lot of cancer benefit. BR pancreas has dismal outcomes but big volume RT never helped much IRL or in the literature. Thus the ever increasing eschewment of RT by chemotherapists in BR. Wasn’t someone recently talking about how some of the biggest unasked and unanswered questions in rad onc have to do with treatment volumes. Here is an excellent example of that.

 

[seper]

I treat “borderline” scenario often. Sometimes my surgeons will label patients “borderline” when chance of Whipple happening is like 1%. Then I treat gross tumor only. In true preoperative cases, I use ENI. I feel like isolated nodal failures is a known problem after Whipple. Don’t know of any good data tho

 

[ramsesthenice]

I do less and less ENI for pancreas except for the celiac. My logic there is just how bad a failure there can be and honestly I am more so trying to cover PNI tracts than lymphatics. For me the issue comes down to how many isolated regional nodal failures have I ever seen? Almost none. And that hasn’t changed since backing off of ENI over the last few years.

 

[Ray D. Ayshun]

I do less and less ENI for pancreas except for the celiac. My logic there is just how bad a failure there can be and honestly I am more so trying to cover PNI tracts than lymphatics. For me the issue comes down to how many isolated regional nodal failures have I ever seen? Almost none. And that hasn’t changed since backing off of ENI over the last few years.

With that in mind, how are you defining volumes? Simply GTV/ITV plus 5 mm CTV plus asymmetric sup/inf PTV expansion or symmetric if using an ITV?

 

[pikachu]

Wondering how people are doing volumes in BR pancreas when using conventional chemorads. The recently published Preopanc trial based volumes strictly off of gross disease, albeit using a different dose schema. On the other hand, we've historically treated a large volume with ENI from above the celiac down to L2 and into the porta, including the para-aortic, portal venous, celiac, and SMA in the case of head tumors. Based strictly on tolerability, I suspect more people complete the more conservative plans altogether, or without breaks. On the other hand, I would suspect LC is better if treating a larger area, though I'm not aware of the two approaches being compared. It seems the move in unresectable has been towards treating gross disease plus margin alone (if not always that way given the LAP 07 approach), so in my estimation, it also makes sense to treat BR this way as only about 33% should ever undergo a Whipple. In any case, I suspect most are using larger volumes, and haven't really seen the preopanc approach adopted, though perhaps some are using SBRT to gross disease plus margin in BR.

Take a close look at the adjuvant chemo regimens patterns of failure data vs RTOG 9704

CONKO-001 (gem alone): local failure 34%
PRODIGE (FOLFIRINOX arm): local-only failure 13.4%, local + distant failure 9.7% (sum 23.1%)
RTOG 9704: local recurrence 28%; regional 7.5% (unfortunately they don't clearly delineate the distinction between local and regional recurrence and note that the two categories may overlap so you can't even add the two sites together for an exact total. Regardless est. local/regional failure probably somewhere in the neighborhood of 30%).

So if comprehensive nodal irradiation a la 9704 doesn't seem to provide any LC improvement over chemo alone in the setting of an oncologic resection...why add to toxicity by treating these massive fields? Especially if you are thinking about any sort of altered fractionation.

 

[deleted1111261]

If you look at the ablative unresectable volumes by Crane/Parikh (Parag, unrelated), they have a lower dose ENI volume. I like that approach. And I see what y’all are saying. But, if you are doing 36/15 or whatever to tumor for borderline, then you can probably give the nodes the same dose or a touch lower (30/15 SIB) safely. It’s hard to completely not treat them (for me). Just in case the tumor is sterilized, would hate to see a regional recurrence. With conformal techniques, I don’t see that the elective volume treatment causes that much more toxicity.

 

[Neuronix]

SBRT I always used to do gross disease + small PTV with a precision setup (MR-guided or linac with fiducials and good motion management)

The fad nowadays is to add celiac, SMA, and peri-aortic nodes at those levels to an intermediate or high dose volume. With MR-guidance you can verify safety of this daily, and generally as you go posteriorly you don't hit any dose limiting structures. I'm on the fence about this approach personally given what's already been discussed with low rates of regional failure.

Conventionally fractionated I've always just followed RTOG 0848. It's a big volume, but it's pretty safe with conventional fractionation, so why not? I guess the question is would you save G2/G3 fatigue, nausea, diarrhea, etc by limiting the field a bit. I don't really know the answer. Generally it's the more anterior dose to stomach and bowel that causes issues and that's probably not much of what I'd save on by limiting nodal coverage again since most of the nodal volume is more posterior. Maybe if you restrict the sup/inf aspect a bit and bring in the CTV/PTV...

 

[TheWallnerus]

With conformal techniques, I don’t see that the elective volume treatment causes that much more toxicity

IRL, maybe. But in theory… I got an online board recert question recently. Let’s see if I can recreate it.

You are doing lung SBRT. You see a tumor moves 2cm inf/sup. If you did free breathing vs gating, there would be
A More tox
B More LC
C Less LC
D Better Regional control

Guess what right answer was

 

[deleted1111261]

IRL, maybe. But in theory… I got an online board recert question recently. Let’s see if I can recreate it.

You are doing lung SBRT. You see a tumor moves 2cm inf/sup. If you did free breathing vs gating, there would be
A More tox
B More LC
C Less LC
D Better Regional control

Guess what right answer was

Different body part/anatomic considerations.

 

[TheWallnerus]

Different body part/anatomic considerations.

Maybe radiation’s truest truism is volume ∝ toxicity (I think proton docs carry a card in their wallet with this saying). Re: the question, it was just a small amount of increased treatment volume (off in the lung) and the question writer was trying to say even that would increase toxicity. (FWIW I thought it a crappy question)

 

[ytcmrr]

Here is very recent data comparing comparing hypofractionated RT to GTV+ENI vs GTV with improvement in LC with GTV+ENI but increase in G1-2 nausea and no increase in severe acute/late toxicity. At my residency, we used to treat just GTV+margin but for the past 2 years we have been including elective nodal regions with SBRT.

Pancreatic Stereotactic Body Radiation Therapy With or Without Hypofractionated Elective Nodal Irradiation - PubMed

Pancreatic SBRT + ENI was tolerable and did not increase late or serious acute toxicity relative to a matched cohort undergoing SBRT alone, but did increase acute grade 1 to 2 nausea. The addition of ENI to SBRT was associated with decreased locoregional progression but not improved survival...

pubmed.ncbi.nlm.nih.gov

 

[GI_RadOnc]

For borderline patients who are going to go for surgery (good PS, surgeon is already asking when to see them afterwards), I have been using the 36 Gy / 15 fraction PREOPANC volumes with GTV and inclusion of LN (prechemotherapy) of greater than 1 cm. Patients fly through this; it is clearly easier than the 50 Gy / 25 fraction that I used to do routinely.

In borderline patients who are not clearly going to surgery; I treat them like locally advanced patients with 50 Gy / 5 fractions to the tumor, celiac, SMA and retroperitoneal as @RealSimulD Simul mentioned.

I think Dan's paper listed by @ytcmrr here is an excellent rationale to consider 'full (ie porta hepatis) ENI'; but they didn't ever go to a step with the limited LN coverage; and the details of the paper show that the practice became a little more aggressive with dose; and of course there could have been some changes in systemic therapy in that time period.

But, I think you would be justified either way in this 'data-less' area.

 

[dieABRdie]

If you look at the ablative unresectable volumes by Crane/Parikh (Parag, unrelated), they have a lower dose ENI volume. I like that approach. And I see what y’all are saying. But, if you are doing 36/15 or whatever to tumor for borderline, then you can probably give the nodes the same dose or a touch lower (30/15 SIB) safely. It’s hard to completely not treat them (for me). Just in case the tumor is sterilized, would hate to see a regional recurrence. With conformal techniques, I don’t see that the elective volume treatment causes that much more toxicity.

Planning one of these now...

Would you add concurrent xeloda for one of these hypofractionated regimens like 67.5/15? Looks like they did in their publications, but don't have experience with this myself.

 

[deleted1111261]

Planning one of these now...

Would you add concurrent xeloda for one of these hypofractionated regimens like 67.5/15? Looks like they did in their publications, but don't have experience with this myself.

It scares me! But I have

 

[ramsesthenice]

Planning one of these now...

Would you add concurrent xeloda for one of these hypofractionated regimens like 67.5/15? Looks like they did in their publications, but don't have experience with this myself.

I typically do and have not seen any issues.

Take a close look at the adjuvant chemo regimens patterns of failure data vs RTOG 9704

CONKO-001 (gem alone): local failure 34%
PRODIGE (FOLFIRINOX arm): local-only failure 13.4%, local + distant failure 9.7% (sum 23.1%)
RTOG 9704: local recurrence 28%; regional 7.5% (unfortunately they don't clearly delineate the distinction between local and regional recurrence and note that the two categories may overlap so you can't even add the two sites together for an exact total. Regardless est. local/regional failure probably somewhere in the neighborhood of 30%).

So if comprehensive nodal irradiation a la 9704 doesn't seem to provide any LC improvement over chemo alone in the setting of an oncologic resection...why add to toxicity by treating these massive fields? Especially if you are thinking about any sort of altered fractionation.

I love your eye for detail and as I said I don’t use big ENI fields. That said, your argument is a bit flawed. I don’t know how it is where you practice but everyone at my institution gets gem/abraxane or FOLFIRINOX before radiation. Given the robust difference in disease control with these compared to single agent gem, outcomes in 9704 are a little irrelevant. I agree, 9704 certainly draws into question the benefit of regional radiation. But to be fair, the door is still open to the possibility that RT after multiagent chemo may work better than expected.

 

[pikachu]

I typically do and have not seen any issues.

I love your eye for detail and as I said I don’t use big ENI fields. That said, your argument is a bit flawed. I don’t know how it is where you practice but everyone at my institution gets gem/abraxane or FOLFIRINOX before radiation. Given the robust difference in disease control with these compared to single agent gem, outcomes in 9704 are a little irrelevant. I agree, 9704 certainly draws into question the benefit of regional radiation. But to be fair, the door is still open to the possibility that RT after multiagent chemo may work better than expected.

I agree...we really don't know how better control of distant disease will affect indications for both definitive or postop RT with these new and better chemo regimens. my point was really not that we should hang our hat on the 9704 results permanently but more that we shouldn't assume larger fields are better...and the 9704 patterns of failure data is just one example of why these huge ENI fields may not be necessary. this is perhaps more relevant with the use of more active chemo regimens which may theoretically help to control low volume nodal disease; could then leverage smaller fields to facilitate dose escalation as indeed many are doing following G/A or FOLFIRINOX. It would be great to have the 0848 results to inform this discussion too...after all, it's only been 13 years!

There are a few small studies of preop SBRT incorporating ENI with modern chemo regimens and while there may be a marginal difference compared with 9704 in terms of local control, they are still reporting about 1/4 patients with local failure at 2 years. Possibly the doses used are not high enough to control pre-existing subclinical disease in lymph nodes in pancreas cancer. Regardless the LC numbers with RT and surgery + RT are probably going to have to improve substantially before we can ever expect RT to move the needle in outcomes in pancreas cancer.

 

[deleted1111261]

RTOG 0848 still not published ???

 

[evilbooyaa]

RTOG 0848 still not published ???

Not the phase III part (just the phase II "erlotinib doesn't work, lol" part)
I really am wondering where the hell the results of 0848 are. Wondered like 3 years ago too.

I would do ENI for bordelrine resectable getting fractionated.

 

[deleted1111261]

Not the phase III part (just the phase II "erlotinib doesn't work, lol" part)
I really am wondering where the hell the results of 0848 are. Wondered like 3 years ago too.

I would do ENI for bordelrine resectable getting fractionated.

This is like the 9410 fiasco.

gonna be hard to find eager students to help with this …

 

[Ray D. Ayshun]

Can't believe I started this a year ago. In any case, this seemed like good thread to ask. Is there anyone out there doing Preopanc in borderline cases? Not necessarily even true Preopanc, but maybe something like neoadjuvant FOLFIRINOX or Gem/Abrax followed by restaging and then preopanc if still borderline. I feel like I' may have asked this before, but just had an opportunity to talk with GI Surgery about preopanc and preopanc-2. It sounds like GI_Radonc is, just wondering if there's buy-in from surgery/medonc.

 

[evilbooyaa]

I am still offering 45-50Gy for any pancreas cases still referred to me. Most of the med oncs still prefer to give Xeloda which pushes me to give 5-5.5 weeks of RT. If someone wanted to give concurrent Gem, then I would drop the dose to the 36Gy as seen in the trial. But I wouldn't feel great about 36 with Xeloda given differences in chemosensitization.

And yes, generally after chemo showing stability, still unresectable, perhaps poor tolerance of ongoing chemo, etc. but it's likely a subset of borderline resectable cases.

 

[BobbyHeenan]

Can't believe I started this a year ago. In any case, this seemed like good thread to ask. Is there anyone out there doing Preopanc in borderline cases? Not necessarily even true Preopanc, but maybe something like neoadjuvant FOLFIRINOX or Gem/Abrax followed by restaging and then preopanc if still borderline. I feel like I' may have asked this before, but just had an opportunity to talk with GI Surgery about preopanc and preopanc-2. It sounds like GI_Radonc is, just wondering if there's buy-in from surgery/medonc.

In my neck of hte woods it's surg onc specific. We almost always would start with multi agent chemo...then re-assess. Two of three surg oncs like then to go on for pre op XRT. I'm kind of ambivalent. If they are worried about a margin and want pre op I go for it. LIke evilbooyaa above, most med oncs want xeloda so it's 28 fractions I typically give.

 

[Ray D. Ayshun]

In my neck of hte woods it's surg onc specific. We almost always would start with multi agent chemo...then re-assess. Two of three surg oncs like then to go on for pre op XRT. I'm kind of ambivalent. If they are worried about a margin and want pre op I go for it. LIke evilbooyaa above, most med oncs want xeloda so it's 28 fractions I typically give.

that's my neck of the woods as well re med onc. And despite all the arguments surrounding RT in pancreas, I pretty much always irradiate as the ones that make it in the first place are generally special cases. In any case, I'm also interested in making pre-op RT like preopanc a more common approach locally. Not necessarily in place of long course, but rather, in a different patient population.

 

[Radonky]

For borderline cases the GI rad oncs here like 36/15 including ENI, volumes following RTOG 0848

 

[Ray D. Ayshun]

For borderline cases the GI rad oncs here like 36/15 including ENI, volumes following RTOG 0848

Is it basically standardized at this point? Patient does chemo, then rt if no progression, then surgery if no progression/operable?

 

[evilbooyaa]

For borderline cases the GI rad oncs here like 36/15 including ENI, volumes following RTOG 0848

Concurrent Gemcitabine?

 

[medgator]

Concurrent Gemcitabine?

I've seen people do it with tight volumes. Happens in hypo bladder as well

 

[evilbooyaa]

I've seen people do it with tight volumes. Happens in hypo bladder as well

No, I guess I meant that if you're giving 36Gy with Gemcitabine that's reasonable and supported by the trial, just I would be anxious about whether it's effective enough to give 36Gy with say Xeloda as all my med oncs are concerned about concurrent Gem with abdominal RT.

 

[Ray D. Ayshun]

No, I guess I meant that if you're giving 36Gy with Gemcitabine that's reasonable and supported by the trial, just I would be anxious about whether it's effective enough to give 36Gy with say Xeloda as all my med oncs are concerned about concurrent Gem with abdominal RT.

Well also, I don't think the trial did eni.

 

[ramsesthenice]

Concurrent Gemcitabine?

Gem a sensitizer depends wholly on the dose given. Based on my experience, I have no idea how ECOG gave people 750 mg/m2 with 50(ish) Gy for pancreas and didn't see more toxicity than they reported in 4201. When we give it with RT we typically dose it closer to 350-450 mg/m2 and then it is basically equivalent to 5FU. Pretty context dependent.

 

[evilbooyaa]

Gem a sensitizer depends wholly on the dose given. Based on my experience, I have no idea how ECOG gave people 750 mg/m2 with 50(ish) Gy for pancreas and didn't see more toxicity than they reported in 4201. When we give it with RT we typically dose it closer to 350-450 mg/m2 and then it is basically equivalent to 5FU. Pretty context dependent.

I agree with you. They gave Gem at 1,000 mg/m2 weekly along with 36Gy in 15 fractions. That is going to be more potent at radiosensitization than 5-FU/Xeloda. Gem at 1000mg/m2 weekly seems like a pretty high dose to do hypofrac RT with, personally, but I guess not doing ENI helped limit that.

 

[Radonky]

Is it basically standardized at this point? Patient does chemo, then rt if no progression, then surgery if no progression/operable?

At our tumor board this is generally the pathway we follow

 

[Radonky]

Concurrent Gemcitabine?

We do concurrent xeloda. Years back I think the docs used gem per an older William Small trial

Full-Dose Gemcitabine With Concurrent Radiation Therapy in Patients With Nonmetastatic Pancreatic Cancer: A Multicenter Phase II Trial | Journal of Clinical Oncology

Purpose Gemcitabine is effective in the treatment of pancreatic cancer and is a potent radiosensitizer. This study assessed safety and efficacy of full-dose gemcitabine administered before and during concurrent three-dimensional conformal radiation (3D-CRT) in patients with nonmetastatic...

ascopubs.org

 

[RickyScott]

I've seen people do it with tight volumes. Happens in hypo bladder as well

In bladder gem dose is 40 mg/week? Very well tolerated.

 

[ramsesthenice]

In bladder gem dose is 40 mg/week? Very well tolerated.

I haven’t seen that low. More accustomed to 75-100 mg/m2 weekly for bladder. But agree, goes well.

 

[evilbooyaa]

In bladder gem dose is 40 mg/week? Very well tolerated.

Seems kinda low.... this trial did 100mg/ weekly: Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer - PubMed