RTOG 0848 Discussion

[Palex80]

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1. It's a unplanned subset analysis.
2. And most important...

 

[evilbooyaa]

View attachment 387134

1. It's a unplanned subset analysis.
2. And most important...
View attachment 387135

If systeimc therapy improves (Like FOLFIFIRNOX vs Gemcitabine), the distant recurrence rate will decrease and mean higher percentage of patients develop localy primary recurrence.

Just take the damn win when we get it, wtf??

The trial conceived in 2008 JUST resulted. But you want to now immediately re-run the trial and not offer sequential chemoRT because the chemo has changed? Nah, f that. Patients get chemoRT at conclusion of their post-op chemo as a standard now. If GI Med oncs/surgeons want to exclude it, THEY have to run a non-inferiority trial where the standard arm is chemo followed by sequential chemoRT vs an experimental arm of chemo alone and 'demonstrate' non-inferiority.

 

[Mandelin Rain]

Those aren't small differences.

If a drug showed those outcome differences in LN- Pancreatic cancer, it'd be on the cover of Time Magazine

 

[Palex80]

If systeimc therapy improves (Like FOLFIFIRNOX vs Gemcitabine), the distant recurrence rate will decrease and mean higher percentage of patients develop localy primary recurrence.

Just take the damn win when we get it, wtf??

The trial conceived in 2008 JUST resulted. But you want to now immediately re-run the trial and not offer sequential chemoRT because the chemo has changed? Nah, f that. Patients get chemoRT at conclusion of their post-op chemo as a standard now. If GI Med oncs/surgeons want to exclude it, THEY have to run a non-inferiority trial where the standard arm is chemo followed by sequential chemoRT vs an experimental arm of chemo alone and 'demonstrate' non-inferiority.

The only problem is that adjuvant mFOLFIRINOX has demonstrated an OS benefit over adjuvant Gemcitabine for the entire population in a larger trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa1809775

Now, some people try to look at subgroups there too.

But, let’s be frank. If you had a pT2 pN0 pancreatic cancer and (for whatever reason) did not get neoadjuvant chemo, would you go for gemcitabine + RT or for mFOLFIRINOX?

 

[evilbooyaa]

The only problem is that adjuvant mFOLFIRINOX has demonstrated an OS benefit over adjuvant Gemcitabine for the entire population in a larger trial.

https://www.nejm.org/doi/full/10.1056/NEJMoa1809775

Now, some people try to look at subgroups there too.

View attachment 387153


But, let’s be frank. If you had a pT2 pN0 pancreatic cancer and (for whatever reason) did not get neoadjuvant chemo, would you go for gemcitabine + RT or for mFOLFIRINOX?

 

[Palex80]

Because we have no evidence, that „more“ is better. It could even be, that the net benefit of RT shrinks with better chemotherapy. FOLFIRINOX can increase local control too.

 

[medgator]

Because we have no evidence, that „more“ is better. It could even be, that the net benefit of RT shrinks with better chemotherapy. FOLFIRINOX can increase local control too.

Even in localized unresectable, the answer is always more and better chemo? Just odd

 

[evilbooyaa]

Because we have no evidence, that „more“ is better. It could even be, that the net benefit of RT shrinks with better chemotherapy. FOLFIRINOX can increase local control too.

In Table S3 of PRODIGE 24, locoregional alone (13.4) or LR + distant recurrence (9.7%) made up 23% of all the patients (as opposed to 28% having isolated distance recurrence), cumulative 54.2% DFS event

Yes, those numbers are better than Gemcitabine - 18% LR alone, 17.1% LR+ distant, or 35% of all patients, compared to 33% distant recurrence, cumulative 73.2% DFS event.

So let's say that better chemo in pancreatic cancer reduces the global cancer risk, with about half being distant alone, half including recurrent recurrent. 23% of FOLFIRINOX patients have local recurrence. Happy to get post-op RT based on RTOG 0848 to lower that risk ALARA.

 

[Mandelin Rain]

Because we have no evidence, that „more“ is better. It could even be, that the net benefit of RT shrinks with better chemotherapy. FOLFIRINOX can increase local control too.

2+2 = 2?

Only in rad onc.

 

[Mandelin Rain]

If this was a trial of Gem +/- elective hip arthroplasty and had the same results, Stryker would already have bill boards on every high way in America.

Meanwhile in rad onc land: But.... the chemo, while standard then, is no longer standard. Would not bang.

 

[communitydoc13]

2+2 = 2?

Only in rad onc.

Well to be fair, in radonc...

2+2+2+2 < 4+4

 

[RadOncDoc21]

Well to be fair, in radonc...

2+2+2+2 < 4+4

Academic rad onc:

2+2=protons

 

[drowsy12]

Well to be fair, in radonc...

2+2+2+2 < 4+4

2+2 is non inferior to 4.

 

[TheWallnerus]

Two plus two…

The number of clinical years and research years for our Holman scholars?

 

[StIGMA]

But, let’s be frank. If you had a pT2 pN0 pancreatic cancer and (for whatever reason) did not get neoadjuvant chemo, would you go for gemcitabine + RT or for mFOLFIRINOX?

If good PS, I anticipate we will move in the direction of chemoRT -> folfirinox as one option in that setting.
And if neoadjuvant folfirinox, addition of chemoRT post-op is viable given these trial results.

 

[lilshopta]

I feel like the majority of pancreatic cancer patients (resectable and BRPC) are getting neoadjuvant mFFX 4-6 mos and then surgery. You can justify neoadjuvant radiation (per PREOPANC, Korean trial) or adjuvant now for pN0 (RTOG 0848). I think adjuvant may be easier to sell now with RTOG 0848 and because surgeons won't whine about operating in a radiated field.

 

[ramsesthenice]

I feel like the majority of pancreatic cancer patients (resectable and BRPC) are getting neoadjuvant mFFX 4-6 mos and then surgery. You can justify neoadjuvant radiation (per PREOPANC, Korean trial) or adjuvant now for pN0 (RTOG 0848). I think adjuvant may be easier to sell now with RTOG 0848 and because surgeons won't whine about operating in a radiated field.

I doubt it. For years, we have pointed to large retrospective studies that suggested pN+ was likely an indication for adjuvant RT. Now we have a subset analysis from a trail suggesting the exact opposite? And whether you agree with Palex or not, plenty of med oncs are surgeons are going to go right to the gem issue and argue any benefit seen in 0848 is just making up for inadequate chemo. I don't personally see it making many converts.

Personally, I continue to feel that if you believe radiation is beneficial, neoadjuvant is likely the better way to go. It typically is better tolerated and you are not leaving as much radiated intestinal tissues in place. I've also known more than one high volume Whipple surgeon who feel that radiation firms up the pancreas and makes it easier to work with, no harder.

 

[BobbyHeenan]

I doubt it. For years, we have pointed to large retrospective studies that suggested pN+ was likely an indication for adjuvant RT. Now we have a subset analysis from a trail suggesting the exact opposite? And whether you agree with Palex or not, plenty of med oncs are surgeons are going to go right to the gem issue and argue any benefit seen in 0848 is just making up for inadequate chemo. I don't personally see it making many converts.

Personally, I continue to feel that if you believe radiation is beneficial, neoadjuvant is likely the better way to go. It typically is better tolerated and you are not leaving as much radiated intestinal tissues in place. I've also known more than one high volume Whipple surgeon who feel that radiation firms up the pancreas and makes it easier to work with, no harder.

Agree.

It is going to be a hard sell in my neck of the woods to treat N0. I'm ok with it, but convincing our GI team will be tough.

Plus, our surgeons usually prefer pre op as well (if it is recommended at all), as there is data it decreases post op fistula rates. They don't mind operating with pre op XRT at least for our two high volume surg oncs and say just what you say - they are working with a firmer pancreas and in some ways that’s easier.

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