ASCO 2020 - Interesting abstracts

[RadOncMegatron]

Because the dutch (and most europeans) have a hard-on for the 5Gy x 5 regimen, because (at least most) oncologists don't get paid per fraction, like us money-grubbing US rad oncs do.

Also being picked up by Academic attendings in the US (see all the trials of finding out how to give less radiation treatments).

Your last sentence is correct - this will hopefully make TNT standard of care, but whether you do short course or long-CRT will be physician preference.

I prefer to give patients the option of watchful waiting so I'll likely be doing long-course, at least until APM hits.

I think TNT is the way to go at least for future studies. Aren't there a bunch of RCT showing post-op chemo does not work? Nice review article here: Postoperative Chemotherapy in Patients With Rectal Cancer Receiving Preoperative Radio(chemo)therapy: A Meta-Analysis of Randomized Trials Comparing Surgery ± a Fluoropyrimidine and Surgery + a Fluoropyrimidine ± Oxaliplatin - PubMed " Conclusion: The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence. "

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[evilbooyaa]

Most criticisms of historical post-op chemo trials in rectal cancer is that not enough patients actually receive any chemo, or receive sufficient doses of chemo, so the ITT analysis was always negative.

This was different in the recent ADORE trial (comparing 5-FU to FOLFOX) where somehow 93% of Oxali dose was successfully given in post-op settings, and showed DFS benefit of FOLFOX compared to 5-FU

https://ascopubs.org/doi/full/10.1200/JCO.19.00016

Prevoius retrospective series have shown equivalence of pre-op chemo vs post-op chemo in terms of oncologic outcomes, although TNT does get "more of the chemo in" than post-op: Adoption of Total Neoadjuvant Therapy for Locally Advanced Rectal Cancer

Maybe that difference magnified at multi-institutional (more than just the MSKCC retrospective) enough to cause a DFS benefit with neoadjuvant chemo?

Regardless, agree that some form of TNT (whether that be with long-course CRT or short-course 5x5) is probably most ideal option for rectal cancer patients going forward.

 

[Palex80]

Not sure why they chose 5 fxn instead of full dose CRT plus adding more chemo though...maybe lack of machines/resources etc?

Less acute toxicity.
I am aware that 5x5 Gy are not popular in the US, but it's quite popular in several European countries.

I fully agree however with the statement that long course CRT is the only proven way to get away without surgery. So, if that is your goal, do long course CRT (and actually boost beyond the typical 50/2).

 

[Palex80]

Someone still can't get over the fact that CONVERT failed to show superiority of 66/2 over 45/1.5 bid


Turrisi FTW!

 

[medgator]

View attachment 308772

Someone still can't get over the fact that CONVERT failed to show superiority of 66/2 over 45/1.5 bid


Turrisi FTW!

45 qd was never an appropriate standard in the original turrisi trial.... Still 66/33 for me and many out IRL i imagine

 

[Palex80]

45 qd was never an appropriate standard in the original turrisi trial.... Still 66/33 for me and many out IRL i imagine

Which still puzzles me... Why do you choose 66/33 over 45/1.5 bid?

 

[medgator]

Which still puzzles me... Why do you choose 66/33 over 45/1.5 bid?

Logistically difficult for those of us who have to be physically present and cover multiple offices. I don't believe you have the same physical presence requirements in Europe. I've seen some worse esophagitis with it as well, and no clear data indicating 66/33 is worse (which is why you see both endorsed in the nccn guidelines)

 

[OTN]

Which still puzzles me... Why do you choose 66/33 over 45/1.5 bid?

Patients uniformly hate BID treatment in my area

 

[medgator]

Patients uniformly hate BID treatment in my area

If you live in an area with traffic, it's pretty much a day killer to do bid

 

[Mandelin Rain]

Patients uniformly hate BID treatment in my area

Your area is everywhere.

 

[scarbrtj]

it won’t change anybody’s minds but... I was raised on BID. So when a patient comes to see me I explain that’s the choice and don’t mention alternative fractionations. I get about 90% on BID. But I’m not in LA or NYC. On other hand, when logistics are bad for BID, we just babysit the patient for ~7hrs with TV food and beverage and chit chat. This used to be 15 “wasted days” and now promises to be 20. Although it should always be said that the second best anti-cancer treatment a patient will take is better than the best treatment they won’t.

 

[Palex80]

Logistically difficult for those of us who have to be physically present and cover multiple offices. I don't believe you have the same physical presence requirements in Europe. I've seen some worse esophagitis with it as well, and no clear data indicating 66/33 is worse (which is why you see both endorsed in the nccn guidelines)

CONVERT demonstrated identical rates of esophagitis with 66/33 compared to 45/1.5 bid. In fact, 66/33 seemed to produce even more late esophagitis than 45/1.5 bid.

Other than that, CONVERT was designed as a superiority trial for 66/33 over 45/1.5 bid and failed to prove it.
Had you designed CONVERT as a non-inferiority trial (with the same number of patients), you wouldn't be able to prove that 66/33 is non-inferior to 45/1.5 bid.
45/1.5 bid in CONVERT was 5% better in OS than 66/33.
And 5% is a lot when your OS is only 25%.

I understand the logistical issues, however patients actually need to come in more often with 66/33 than with 45/1.5 (10% more to be precise).
We have no major issues, since all machines run at least 6 hours. So the patients get their first fraction around 08:00-09:00 and then next one around 14:00-15:00.

My personal assumption is that it's not the hyperfractionation that does the "trick", but the acceleration. And one can accelerate with hypofractionation too.
So giving something like 53.20 in 2.66 Gy/d should probably also work quite well. That would be 4 weeks of treatment instead of 3 weeks as per Turrisi.
Do I have data to back it up? No. But the Canadians have published 39.9/2.66 with good results.

 

[deleted774703]

it won’t change anybody’s minds but... I was raised on BID. So when a patient comes to see me I explain that’s the choice and don’t mention alternative fractionations. I get about 90% on BID. But I’m not in LA or NYC. On other hand, when logistics are bad for BID, we just babysit the patient for ~7hrs with TV food and beverage and chit chat. This used to be 15 “wasted days” and now promises to be 20. Although it should always be said that the second best anti-cancer treatment a patient will take is better than the best treatment they won’t.

Purist answer is BID,

Not wrong IMO to offer 33 fxn either At moment

Whatever works for practice and patient

Now in future 20 days BID may be the 100% right answer

 

[radiaterMike]

Your area is everywhere.

Sounds like UPMCs expansion plans.

 

[GI_RadOnc]

The German Rectal Cancer Study group has already moved on, freund!

https://ascopubs.org/doi/full/10.1200/JCO.19.00308?af=R

They've already shown the OPRA results (25% with CRT first vs 17% with CT first pCR rates). Will be interesting to see what cCR they're able to achieve as ze germanz love ze zurgery and are still evaluating pCR in all these folks.

In regards to RAPIDO being 'SOC' - nah. I still prefer total TNT with CT + XRT. No benefit of doing 5Gy x 5, no idea if it's safe in those pursuing organ preservation (which should be the next SOC in this cancer).

I hope the cCR rate in OPRA is high enough we can start pushing for watchful waiting in ALL rectal cancer patients, not just those who may need an APR.

True on the Germans... I have been working on a second meme to the effect of "The germans have moved on, why haven't we?" Many centers in the community (including mine!) still cling to the Sauer NEJM 2004 chemoXRT->surgery->chemo routine. The definite message from ASCO is that you should stop this and head to a TNT approach; with some good data saying that if the goal is downstaging, start with radiation.

No benefit to SCRT? Each one of those patients had ONE LESS MONTH of treatment! What would each of us do with one extra month of vacation? Also, even though RAPIDO had the WORST of the patients (compared with OPRA, Prodige, German AIO-12)l the RAPIDO pCR rate still was higher or equivalent. Maybe something immunological (said by all radiation oncologists when they don't understand something) ?

 

[evilbooyaa]

True on the Germans... I have been working on a second meme to the effect of "The germans have moved on, why haven't we?" Many centers in the community (including mine!) still stick to the chemoXRT->surgery->chemo routine. The definite message from ASCO is that you should stop this.

No benefit to SCRT? Each one of those patients had ONE LESS MONTH of treatment! What would each of us do with one extra month of vacation? Also, even though RAPIDO had the WORST of the patients (compared with OPRA, Prodige)l their pCR rate still was higher or equivalent.

I have no issues with people using 5x5 as their default dose and will feel more comfortable offering it as an option primarily for patients with transportation issues or who are 100% motivated to undergo surgery based on results of RAPIDO. We currently offer it primarily to metastatic patients looking for quick treatment before synchronous liver and colon resections.

However, I do think that long-course CRT has a higher chance of allowing the patient to avoid surgery, without having to worry about functionality of the irradiated area.

I just think WW is the future of rectal cancer treatment and know that 5x5 is not working us towards that goal.

I hope that, when I am an attending, I do not have to butt heads with med-oncs/surgeons stuck in the old ways of doing XRT --> Surgery --> Chemo.

 

[deleted774703]

I have no issues with people using 5x5 as their default dose and will feel more comfortable offering it as an option primarily for patients with transportation issues or who are 100% motivated to undergo surgery based on results of RAPIDO. We currently offer it primarily to metastatic patients looking for quick treatment before synchronous liver and colon resections.

However, I do think that long-course CRT has a higher chance of allowing the patient to avoid surgery, without having to worry about functionality of the irradiated area.

I just think WW is the future of rectal cancer treatment and know that 5x5 is not working us towards that goal.

I hope that, when I am an attending, I do not have to butt heads with med-oncs/surgeons stuck in the old ways of doing XRT --> Surgery --> Chemo.

BINGO!!!!

Short course better for surgeons

Long course CRT better for WW and ultimately the patient

 

[GI_RadOnc]

I'm not sure about the 'benefit much less clear in the adj CTX subgroup'; in fact I think this forest plot from the author would say otherwise. This shows that benefit was HIGHER in patients treated with a hospital policy of adjuvant therapy (ie, everyone in the US).

I feel that it's counterintuitive; but it may be related to the idea that not only do many patients not receive adjuvant chemotherapy; but also the toxicity is much higher, so perhaps it's less effective? Thoughts?

 

[GI_RadOnc]

I just think WW is the future of rectal cancer treatment and know that 5x5 is not working us towards that goal.

Glad this discussion was so lively!

I found an interesting pattern happen after a move to SC-TNT. The surgeon/medical oncology team was much less interested in getting rid of radiation for T3N0 or other patients that would be eligible for the PROSPECT; as that the SCRT didn't seem much of a burden and could be done quickly and still get the chemotherapy in. It will be interesting to see what the referral pattern after PROSPECT comes out... which is likely going to show equivalency with the delayed radiation; or a small effect size that the medical oncologists will make the decision for us.

If there is much better pCR with SC-TNT; there could be better cCR with it as well. Agree that longer term data is necessary to see how well that turns out in a W+W setting. I think we will see it coming in the next several years...

And for your last comment... as rad oncs; we read a lot. Probably because we don't ever round on patients. And so you will spend your career talking to med/surg onc colleagues about new and old ways....

 

[evilbooyaa]

Don't get me started on PROSPECT and how that trial is written to make radiation seem like a loser nearly regardless of what the results end up being.

In regards to high rectal cT3N0 - if patients truly don't need it (like there's no outcomes detriment from not doing RT in this population) I'd rather just skip the RT altogether rather than do 'some' RT.

Of course, you worry that other people will over extrapolate any of the (realtively) low-quality data that I've seen for this and negatively affect outcomes, but if there was a well-defined "lower edge of disease must be at minimum x cm from AV and patient must be 100% interested in surgical resection with no consideration of watchful waiting" to consider omitting RT in cT3N0, I'd be OK with it.


But yes, the last line is likely wishful thinking.

In regards to SC-TNT and WW - I would worry about functional outcomes after 5x5 and no surgery to that big of a field. We have no late-term toxicity data in an unresected patient after 5x5. I would not consider WW in a patient who got 5x5.

 

[RadOncMegatron]

Glad this discussion was so lively!

I found an interesting pattern happen after a move to SC-TNT. The surgeon/medical oncology team was much less interested in getting rid of radiation for T3N0 or other patients that would be eligible for the PROSPECT; as that the SCRT didn't seem much of a burden and could be done quickly and still get the chemotherapy in. It will be interesting to see what the referral pattern after PROSPECT comes out... which is likely going to show equivalency with the delayed radiation; or a small effect size that the medical oncologists will make the decision for us.

If there is much better pCR with SC-TNT; there could be better cCR with it as well. Agree that longer term data is necessary to see how well that turns out in a W+W setting. I think we will see it coming in the next several years...

And for your last comment... as rad oncs; we read a lot. Probably because we don't ever round on patients. And so you will spend your career talking to med/surg onc colleagues about new and old ways....

Anyone have the RAPIDO trial protocol. I'd like to see what they used for their 5x5 arm. Heck, what do you all use as constraints for 5x5?

 

[ramsesthenice]

In regards to SC-TNT and WW - I would worry about functional outcomes after 5x5 and no surgery to that big of a field. We have no late-term toxicity data in an unresected patient after 5x5. I would not consider WW in a patient who got 5x5.

Agree that we should get toxicity data (as I said above) before regularly doing this but I do have to point out it kinda feels like you are trying to have it both ways with regards to SC and BED calcs. Lets assume the rectum has an a/b 3 and tumor has an a/b 10. No question, the BED for SC is much different for the tumor (roughly 40 vs 60 in favor of LC). I see why that math might make you uncomfortable (even though the data we have suggests it doesn't pan out in terms of pathologic responses). If you do the calculations for SC vs LC and normal tissues you get the opposite (66 vs 83). The BED is significantly higher for LC. What about the calculations would make you predict rectal function will be worse after SC? If BED calcs are important for guiding decisions regarding tumor fractionation shouldn't they be the same for normal tissues? I personally take them all with a grain of salt as they require so many assumptions its hard to know how to trust what gets spit out.

On a more encouraging note, I don't think you are going to have to fight surgeons and med oncs over TNT and WW. Adoption has been pretty good and even the cooperative groups are moving to add WW arms of existing trials.

I would also like to share one of the best pieces of advise I ever got. You have a lot of energy and are very knowledgeable. Don't come out swinging right out of the gates as a new attending. Spend the first 6 months or so learning the culture of your surgeons and med oncs. Understand why they do what they do. Show them that you know what you are talking about, that you know the literature, and gain their trust before you go trying to convince them to change their ways. If you push too soon you may lose them forever.

 

[Palex80]

In regards to SC-TNT and WW - I would worry about functional outcomes after 5x5 and no surgery to that big of a field. We have no late-term toxicity data in an unresected patient after 5x5. I would not consider WW in a patient who got 5x5.

Are you concerned about rectal function after 5 x 5 Gy in a non-resected patient?

 

[salubalu]

I would also like to share one of the best pieces of advise I ever got. You have a lot of energy and are very knowledgeable. Don't come out swinging right out of the gates as a new attending. Spend the first 6 months or so learning the culture of your surgeons and med oncs. Understand why they do what they do. Show them that you know what you are talking about, that you know the literature, and gain their trust before you go trying to convince them to change their ways. If you push too soon you may lose them forever.

gold

 

[Ray D. Ayshun]

I knew you would post that!

But you know what? I have the randomized trial, you have a retrospective bias-infested study...

I suspect I'm wrong, but this seems like a scenario where a randomized trial is also potentially unreliable. While it may do a good job controlling for disease and patient-specific factors at the outset, as RCTs are wont to do, analyzing based on intention-to-treat, or a potentially problematic definition of per-protocol, might cover up the truth when length-of-time between two events is the variable. For instance, median time to surgery was 7.4 +/- 1 week vs 11.0 +/- 0.9 wk, as opposed to 7 vs 11 weeks on the head.

 

[evilbooyaa]

Agree that we should get toxicity data (as I said above) before regularly doing this but I do have to point out it kinda feels like you are trying to have it both ways with regards to SC and BED calcs. Lets assume the rectum has an a/b 3 and tumor has an a/b 10. No question, the BED for SC is much different for the tumor (roughly 40 vs 60 in favor of LC). I see why that math might make you uncomfortable (even though the data we have suggests it doesn't pan out in terms of pathologic responses). If you do the calculations for SC vs LC and normal tissues you get the opposite (66 vs 83). The BED is significantly higher for LC. What about the calculations would make you predict rectal function will be worse after SC? If BED calcs are important for guiding decisions regarding tumor fractionation shouldn't they be the same for normal tissues? I personally take them all with a grain of salt as they require so many assumptions its hard to know how to trust what gets spit out.

On a more encouraging note, I don't think you are going to have to fight surgeons and med oncs over TNT and WW. Adoption has been pretty good and even the cooperative groups are moving to add WW arms of existing trials.

I would also like to share one of the best pieces of advise I ever got. You have a lot of energy and are very knowledgeable. Don't come out swinging right out of the gates as a new attending. Spend the first 6 months or so learning the culture of your surgeons and med oncs. Understand why they do what they do. Show them that you know what you are talking about, that you know the literature, and gain their trust before you go trying to convince them to change their ways. If you push too soon you may lose them forever.

Thanks for the last paragraph, and I whole-heartedly agree. Much easier to be loud and (some may say) obnoxious on an anonymous internet forum. That is something that I need to remain cognizant of as I transition to attending practice, 100%.

I see your and @Palex80 point in regards to the BED calcs. I suppose I'm trying to have my cake and eat it too. I do agree with you on the bolded. I just don't want to do 5x5 and WW off-protocol without somebody evaluating that patient population and saying that they do OK. Would I never do it in a specific patient scenario? I wouldn't say that, but not something that I want to consider as a normal option for patients like 5x5 with surgery.

 

[scarbrtj]

We now out of the adj XRT in Stage III EGFR+ game?

Adjuvant Osimertinib Exceeds Expectations in EGFR-Positive NSCLC - The ASCO Post

www.ascopost.com

"In patients with stage II to IIIA NSCLC, osimertinib improved disease-free survival by 83% vs placebo (P < .0001). The 2-year disease-free survival rate in patients with stage II to IIIA disease was 90% with osimertinib vs 44% with placebo."
(It's my understanding RT not allowed on trial.)

 

[taserlaser]

We now out of the adj XRT in Stage III EGFR+ game?

Adjuvant Osimertinib Exceeds Expectations in EGFR-Positive NSCLC - The ASCO Post

www.ascopost.com

"In patients with stage II to IIIA NSCLC, osimertinib improved disease-free survival by 83% vs placebo (P < .0001). The 2-year disease-free survival rate in patients with stage II to IIIA disease was 90% with osimertinib vs 44% with placebo."
(It's my understanding RT not allowed on trial.)

That being said, I’ll take a page out of Prasad’s book and just link directly to his tweet criticisms of the trial as I enjoy my morning coffee.

 

[scarbrtj]

That being said, I’ll take a page out of Prasad’s book and just link directly to his tweet criticisms of the trial as I enjoy my morning coffee.

if I'm understanding/viewing correctly, the 2y relapse rate in the placebo arm would be 56% (DFS was 44% in placebo arm), but even so with the high rate of relapse the OS was 93%. (Many people can survive relapses of EGFR+ disease and just hold the osi in abeyance, is that VP's point?) And thus the placebo arm OS was not different than a 2y OS of 100%(!) in the osi arm.

We quotin' ~100% 2y OS in Stage II-IIIA NSCLC EGFR+ here on out? Neat.
EDIT: maybe we can convince the med oncs not to give osi upfront after stage III surgery and instead do some lite chemoRT and hold the osi until recurrence.

 

[deleted774703]

if I'm understanding/viewing correctly, the 2y relapse rate in the placebo arm would be 56% (DFS was 44% in placebo arm), but even so with the high rate of relapse the OS was 93%. (Many people can survive relapses of EGFR+ disease and just hold the osi in abeyance, is that VP's point?) And thus the placebo arm OS was not different than a 2y OS of 100%(!) in the osi arm.

We quotin' ~100% 2y OS in Stage II-IIIA NSCLC EGFR+ here on out? Neat.
EDIT: maybe we can convince the med oncs not to give osi upfront after stage III surgery and instead do some lite chemoRT and hold the osi until recurrence.

There’s been a lot of back and forth going on amongst med oncs at least on Twitter RE ADAURA

Half say not ready bc no OS data yet and cost

Will be interesting what happens in real world

Would say EGFR+ Stage IIIA (where we would be primarily involved) Pretty small subset

 

[scarbrtj]

There’s been a lot of back and forth going on amongst med oncs at least on Twitter RE ADAURA

Half say not ready bc no OS data yet and cost

Will be interesting what happens in real world

Would say EGFR+ Stage IIIA (where we would be primarily involved) Pretty small subset

Small subset for sure.
However it opens the eyes that if biology is further and further and more and more effectively elucidated/manipulated in lung CA... or any other cancer... radiation begins to play a shrinking role. Back in a more oncologically stupid and barren era, e.g 10 short years ago, they'd have laughed you out of tumor board if you predicted a ~100% 2y OS for any Stage IIIA NSCLC.

 

[deleted774703]

Small subset for sure.
However it opens the eyes that if biology is further and further and more and more effectively elucidated/manipulated in lung CA... or any other cancer... radiation begins to play a shrinking role. Back in a more oncologically stupid and barren era, e.g 10 short years ago, they'd have laughed you out of tumor board if you predicted a ~100% 2y OS for any Stage IIIA NSCLC.

You’re right about that. Amazing progress!

 

[Palex80]

EHA 25 abstracts are also out...

Web App

eha25-eha.web.indrina.com

2x BEACOPP escalated --> PET-negative --> 2x ABVD --> no need for RT in early unfavorable Hodgkins

 

[radoncgrad2019]

not so fast Palex - US Med Oncs don't like BEACOPP. they better be willing to give it if they want to drop RT

 

[Palex80]

I absolutely agree with you. Our med oncs do not give BEACOPP to all early-unfavorable Hodgkins, but some patients do get it.
And with HD17 out, I presume that many med oncs will push for this all-chemo/no-RT approach.

However:
If I was a 28 year old female with a big mediastinal Hodgkin's with some axillary involvement, I would opt to ommit RT and go for 2x BEACOPP esc +2x ABVD (and freeze my oocytes, while I am at it) rather than 4x ABVD + 30 Gy RT.

Mediastinal irradiation in young females (especially when you need to treat the axilla too) will lead to high doses to the breasts, unless you are lucky to get protons.

Do remember: In early-unfavorable HD you still need to give 30 Gy of RT, not 20 Gy.
Non-inferiority of 30 Gy over 20 Gy was never proven in HD11 in the pre-PET-era and no trial has tried 20 Gy in early-unfavorable HD since.

 

[ramsesthenice]

I presume that many med oncs will push for this all-chemo/no-RT approach.

Either that or they will keep using the ABDV x 6 with no RT approach they have been doing for years

 

[scarbrtj]

Last thing Americans need to discuss right now is a chemo regimen pronounced "be a cop"

 

[evilbooyaa]

I absolutely agree with you. Our med oncs do not give BEACOPP to all early-unfavorable Hodgkins, but some patients do get it.
And with HD17 out, I presume that many med oncs will push for this all-chemo/no-RT approach.

However:
If I was a 28 year old female with a big mediastinal Hodgkin's with some axillary involvement, I would opt to ommit RT and go for 2x BEACOPP esc +2x ABVD (and freeze my oocytes, while I am at it) rather than 4x ABVD + 30 Gy RT.

Mediastinal irradiation in young females (especially when you need to treat the axilla too) will lead to high doses to the breasts, unless you are lucky to get protons.

Do remember: In early-unfavorable HD you still need to give 30 Gy of RT, not 20 Gy.
Non-inferiority of 30 Gy over 20 Gy was never proven in HD11 in the pre-PET-era and no trial has tried 20 Gy in early-unfavorable HD since.

Reasonable to have as AN option for a case as described, but hematologists will run with this as the SOC that nets them more money and not having to share with dirty radiation oncologists. Even if it's a neck or waldeyer's ring mass without mediastinal disease in a man.

I think butterfly technique with IMRT for posterior masses or rainbow for anterior masses would still be a very reasonable treatment option.