ASCO 2020 - Interesting abstracts

[Palex80]

This year's ASCO is virtual.

Any interesting abstracts seen?

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Proven benefit of IMRT to spare swallowing function in H&N cancer

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Randomized dose deescalation after TORS for P16 H&N cancer

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Weekly vs. 3-weekly cisplatinum for postoperative H&N cancer

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Dose escalation for LD-SCLC. Perhaps the first trial after 20+ years showing that the only thing better than Turrisi is MORE Turrisi. Perhaps we can "steal" the terminology from the med. oncs (BEACOPP-> BEACOPP escalated). Let's call 60/1.5 bid "Turrisi - escalated".

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Sequential vs. Simultaneous RCT for resected cervical cancer. Potentially practice changing.

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[scarbrtj]

Dose escalation for LD-SCLC. Perhaps the first trial after 20+ years showing that the only thing better than Turrisi is MORE Turrisi. Perhaps we can "steal" the terminology from the med. oncs (BEACOPP-> BEACOPP escalated). Let's call 60/1.5 bid "Turrisi - escalated".

In response Drew told me something like "Wonder where the CALGB/RTOG is? 70Gy, 45 BID, and a 5 wk with 1.8 BID to 61 Gy hybrid" a few days ago. And then said something I didn't quite suss, "Norse* study had 18% gr3 esophagitis in both." But hey, 40 IMRT fractions for lung cancer; Evicore willing and the APM creek don't rise.

* Oh, it's a Norwegian study. I like Norwegian lung studies.

 

[GI_RadOnc]

Here's my favorite three in the land of lower GI:

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chemoXRT->chemo has more organ preservation than chemo->chemoXRT

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Induction FOLFIRINOX-chemoXRT > chemoXRT

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SCRT->chemo > chemoXRT for high risk rectal cancer

We are making RAPIDO style treatment our standard of care here; even post pandemic. But either way; these abstracts can be summarized as...

 

[RadOncMegatron]

Keep it coming! Appreciate the posts.

 

[medgator]

Here's my favorite three in the land of lower GI:

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chemoXRT->chemo has more organ preservation than chemo->chemoXRT

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Induction FOLFIRINOX-chemoXRT > chemoXRT

Meeting Library | Meeting Library

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SCRT->chemo > chemoXRT for high risk rectal cancer

We are making RAPIDO style treatment our standard of care here; even post pandemic. But either way; these abstracts can be summarized as...
View attachment 307736

Is rapido really a fair study, they got more chemo preop in the short course arm compared to the conventional course arm... a lot of places are moving towards TNT so i don't see why they don't just give it all upfront and keep the short vs long course issue as the trial question.

 

[Mandelin Rain]

Is rapido really a fair study, they got more chemo preop in the short course arm compared to the conventional course arm... a lot of places are moving towards TNT so i don't see why they just give it all upfront and keep the short vs long course issue as the trial question.

Bingo. Events in question were distant mets, likely higher because surgery delayed/compromised the multi agent chemo to a greater extent. Nothing to do with radiation.

TNT with CRT first is the way to go IMO.

 

[BobbyHeenan]

In response Drew told me something like "Wonder where the CALGB/RTOG is? 70Gy, 45 BID, and a 5 wk with 1.8 BID to 61 Gy hybrid" a few days ago. And then said something I didn't quite suss, "Norse* study had 18% gr3 esophagitis in both." But hey, 40 IMRT fractions for lung cancer; Evicore willing and the APM creek don't rise.

* Oh, it's a Norwegian study. I like Norwegian lung studies.

Where the heck is the CALGB trial - I agree.

I put one patient on it three years ago in practice and used to put them on in residency all the time. We closed it here and opened up the NRG LU005 study instead....though pitfalls here with needing more path to get people on trial then what they initially get at EBUS needle biopsy.

 

[CaesarRO]

Currently embargoed, but looking forward to this plenary session:

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ECOG-ACRIN E2108: Systemic + BCT vs Systemic + palliation only for Stage 4 Breast.

I'm hoping that since it's a plenary it'll be good news. OS primary endpoint.

 

[thecarbonionangle]

Here's my favorite three in the land of lower GI:

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chemoXRT->chemo has more organ preservation than chemo->chemoXRT

Meeting Library | Meeting Library

meetinglibrary.asco.org

Induction FOLFIRINOX-chemoXRT > chemoXRT

Meeting Library | Meeting Library

meetinglibrary.asco.org

SCRT->chemo > chemoXRT for high risk rectal cancer

We are making RAPIDO style treatment our standard of care here; even post pandemic. But either way; these abstracts can be summarized as...
View attachment 307736

whats your theory on why chemo first Is “worst” (First link you have)?

 

[evilbooyaa]

Here's my favorite three in the land of lower GI:

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chemoXRT->chemo has more organ preservation than chemo->chemoXRT

Meeting Library | Meeting Library

meetinglibrary.asco.org

Induction FOLFIRINOX-chemoXRT > chemoXRT

Meeting Library | Meeting Library

meetinglibrary.asco.org

SCRT->chemo > chemoXRT for high risk rectal cancer

We are making RAPIDO style treatment our standard of care here; even post pandemic. But either way; these abstracts can be summarized as...
View attachment 307736

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.

 

[ramsesthenice]

Is rapido really a fair study, they got more chemo preop in the short course arm compared to the conventional course arm... a lot of places are moving towards TNT so i don't see why they don't just give it all upfront and keep the short vs long course issue as the trial question.

In isolation RAPIDO is not a great question. They really were asking TNT vs not and when they designed the trial there was not much data. They used the only real control arm they had at the time.

Collectively though, it is yet another price of data suggesting SC with delayed therapy is an effective therapy. 27% pCR in the TNT setting which is identical to what WashU/Stanford published with their phase 2 data. That’s as good as the TNT with LC studies. Look at the “control” arm from NRG GI002. FOLFOX -> LC CRT CR 21%. Phase 2 studies range from 22-31% with LC TNT.

 

[Doctorer]

In isolation RAPIDO is not a great question. They really were asking TNT vs not and when they designed the trial there was not much data. They used the only real control arm they had at the time.

Collectively though, it is yet another price of data suggesting SC with delayed therapy is an effective therapy. 27% pCR in the TNT setting which is identical to what WashU/Stanford published with their phase 2 data. That’s as good as the TNT with LC studies. Look at the “control” arm from NRG GI002. FOLFOX -> LC CRT CR 21%. Phase 2 studies range from 22-31% with LC TNT.

I’ll counter this with the superior organ preservation rates seen with long course chemo rt-> chemo in the other Asco abstract. Organ preservation is not path CR, but 58% is still fairly impressive. I wonder if that’s beginning to tease out the effect of a higher EQD2 equivalent versus 5x5, especially with more time given for the full effects of RT to be seen.

 

[ramsesthenice]

I’ll counter this with the superior organ preservation rates seen with long course chemo rt-> chemo in the other Asco abstract. Organ preservation is not path CR, but 58% is still fairly impressive. I wonder if that’s beginning to tease out the effect of a higher EQD2 equivalent versus 5x5, especially with more time given for the full effects of RT to be seen.

Fair question. Time will tell. Personally, I think the data says no. If you look at Stockholm 3 or any of the RCTs with a delayed surgery arm after SC (of which there are 3) the pCR is consistently 15% which is identical to every preop LC CRT ever done. If you go by EQD2 alone it shouldn’t be as good but if you compare the apples to apples data that exists (pCR with a 4-6 week delay to surgery) there is no measurable difference in the literature. All that being said, it’s still not my go to either.

As someone said above, how happy is a normal rectum if you hypofrac then leave it in place for organ preservation? I think that’s a great question we simply don’t know. Late toxicity is hugely important if OP is the goal. Would saving 4 weeks of treatment justify a lifetime of functional loss? Absolutely not. I’m a fan of SC but without more data on this issue it’s not what I use if OP is the goal. We have used something very similar to LC for anal cancer with OP for decades and we know people have great function. For now, it’s still my standard until I see data to convince me otherwise.

 

[BobbyHeenan]

Fair question. Time will tell. Personally, I think the data says no. If you look at Stockholm 3 or any of the RCTs with a delayed surgery arm after SC (of which there are 3) the pCR is consistently 15% which is identical to every preop LC CRT ever done. If you go by EQD2 alone it shouldn’t be as good but if you compare the apples to apples data that exists (pCR with a 4-6 week delay to surgery) there is no measurable difference in the literature. All that being said, it’s still not my go to either.

As someone said above, how happy is a normal rectum if you hypofrac then leave it in place for organ preservation? I think that’s a great question we simply don’t know. Late toxicity is hugely important if OP is the goal. Would saving 4 weeks of treatment justify a lifetime of functional loss? Absolutely not. I’m a fan of SC but without more data on this issue it’s not what I use if OP is the goal. We have used something very similar to LC for anal cancer with OP for decades and we know people have great function. For now, it’s still my standard until I see data to convince me otherwise.

I think this is a good take.

I think if someone is 100% needing to eventually go to surgery (you know this up front) then at this point I think there's enough data where I'm comfortable with short course.

But if the approach is "watch and wait" with TNT and possibly holding surgery, then I favor longer course.

 

[Doctorer]

Fair question. Time will tell. Personally, I think the data says no. If you look at Stockholm 3 or any of the RCTs with a delayed surgery arm after SC (of which there are 3) the pCR is consistently 15% which is identical to every preop LC CRT ever done. If you go by EQD2 alone it shouldn’t be as good but if you compare the apples to apples data that exists (pCR with a 4-6 week delay to surgery) there is no measurable difference in the literature. All that being said, it’s still not my go to either.

As someone said above, how happy is a normal rectum if you hypofrac then leave it in place for organ preservation? I think that’s a great question we simply don’t know. Late toxicity is hugely important if OP is the goal. Would saving 4 weeks of treatment justify a lifetime of functional loss? Absolutely not. I’m a fan of SC but without more data on this issue it’s not what I use if OP is the goal. We have used something very similar to LC for anal cancer with OP for decades and we know people have great function. For now, it’s still my standard until I see data to convince me otherwise.

Fair, however Stockholm 3 was done prior to TNT, with the path cr rates similar between arms as you’ve pointed out. I think a fair question is whether there’d be any difference in organ preservation between 5x5 - chemo versus long course CRT - chemo in a TNT/organ preservation paradigm. I think we also don’t know how many patients without a path CR may have ultimately had one given more time.

Sounds like we’re on the same page though: 5x5 is fine when planning on going to surgery, maybe less so when planning on organ preservation.

 

[ramsesthenice]

Fair, however Stockholm 3 was done prior to TNT, with the path cr rates similar between arms as you’ve pointed out. I think a fair question is whether there’d be any difference in organ preservation between 5x5 - chemo versus long course CRT - chemo in a TNT/organ preservation paradigm. I think we also don’t know how many patients without a path CR may have ultimately had one given more time.

Sounds like we’re on the same page though: 5x5 is fine when planning on going to surgery, maybe less so when planning on organ preservation.

I think we basically agree. I brought up pre-TNT because that is the setting in which we have a clear baseline with LC CRT. The pCR is 15% give or take a few percentage points. In that setting (not TNT), SC with delayed surgery (at least 4 weeks) give similar results so its hard to know what to make of the BED predictions.

What happens with TNT is much less clear. RAPIDO suggests that SC -> Chemo is probably similar to Chemo -> LC (from GI002). I think a more subtle (and important) question is why was LC -> chemo better than Chemo -> LC in the other abstract? Are we operating too soon? Is rectal cancer like anal SCC in that we can wait a little longer for regression? I bet it is and if that is the case we have absolutely no idea what the true baseline pCR or cCR will really look like with either modality. I bet they will ultimately be similar and I doubt 5x5 proves to be more toxic in the long run but until I have data supporting it I won't personally be using it off trial unless there are extenuating circumstances.

 

[evilbooyaa]

Fair question. Time will tell. Personally, I think the data says no. If you look at Stockholm 3 or any of the RCTs with a delayed surgery arm after SC (of which there are 3) the pCR is consistently 15% which is identical to every preop LC CRT ever done. If you go by EQD2 alone it shouldn’t be as good but if you compare the apples to apples data that exists (pCR with a 4-6 week delay to surgery) there is no measurable difference in the literature. All that being said, it’s still not my go to either.

As someone said above, how happy is a normal rectum if you hypofrac then leave it in place for organ preservation? I think that’s a great question we simply don’t know. Late toxicity is hugely important if OP is the goal. Would saving 4 weeks of treatment justify a lifetime of functional loss? Absolutely not. I’m a fan of SC but without more data on this issue it’s not what I use if OP is the goal. We have used something very similar to LC for anal cancer with OP for decades and we know people have great function. For now, it’s still my standard until I see data to convince me otherwise.

Stockholm III was long course RT alone, which is not SOC currently. I do believe in the need for radiosensitization when giving 1.8-2Gy/day.

Otherwise agree.

I think pCR/cCR depends on time from end of radiation to surgery. I think the comparison to anal cancer and the 26 week threshold before considering something (that is not obviously growing) for biopsy is a reasonable one.

This is my personal opinion as to WHY ze Germans (see link above) and OPRA both show higher rates with CRT first followed by chemotherapy rather than vice-versa. May also be why Rapido showed very similar pCR rates with 5x5 followed by chemo.

 

[ramsesthenice]

Stockholm III was long course RT alone, which is not SOC currently. I do believe in the need for radiosensitization when giving 1.8-2Gy/day.

Otherwise agree.

I think pCR/cCR depends on time from end of radiation to surgery. I think the comparison to anal cancer and the 26 week threshold before considering something (that is not obviously growing) for biopsy is a reasonable one.

This is my personal opinion as to WHY ze Germans (see link above) and OPRA both show higher rates with CRT first followed by chemotherapy rather than vice-versa. May also be why Rapido showed very similar pCR rates with 5x5 followed by chemo.

Agree with your OPRA interpretation. Now if we can just get med onc to play ball. Ours are still largely hung up on the idea that we need to give the chemo first so that we can "see how they are responding to it" and "risk of metastasis is high...blah blah blah." Hopefully this will move the needle in the direction of RT first in TNT. The data is pretty clear.

Also agree ignore the LC arm from Stockholm 3. No one does RT alone. Only useful information is the results from the delayed SC arm.

 

[evilbooyaa]

Same "risk of metastasis blah blah" on my end.

To their point, they're probably waiting for PFS/OS data before changing their practice. While my preference for CRT first was tempered by 'lol its a phase II with an 8% rate of pCR who cares", if the numbers from OPRA look good in terms of cCR rates I will be pushing much harder, especially for those who are in strong favor of WW.

 

[Palex80]

What happens with TNT is much less clear. RAPIDO suggests that SC -> Chemo is probably similar to Chemo -> LC (from GI002). I think a more subtle (and important) question is why was LC -> chemo better than Chemo -> LC in the other abstract? Are we operating too soon? Is rectal cancer like anal SCC in that we can wait a little longer for regression? I bet it is and if that is the case we have absolutely no idea what the true baseline pCR or cCR will really look like with either modality.

Well, the French have looked into that.

Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6) - PubMed

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the...

pubmed.ncbi.nlm.nih.gov

7 vs. 11 week waiting time didn't enhance pCR.

 

[scarbrtj]

Well, the French have looked into that.

Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6) - PubMed

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the...

pubmed.ncbi.nlm.nih.gov

7 vs. 11 week waiting time didn't enhance pCR.

Counterpoint:
Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Have to be careful when saying "in theory," but yes, in theory, the longer one waits (esp, IMHO, in adenoCA, which has a longer tumor doubling time, in general), the more opportunity the irradiated cells have for a mitotic catastrophe. A 7w vs 11w comparison may be a little "tight," esp in a trial with only about ~130 pts in either arm, to figure out which cells are mortal "Dead Men Walking" and which are immortal. I will hold on to this notion for a loooong time

 

[Palex80]

Counterpoint:
Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Have to be careful when saying "in theory," but yes, in theory, the longer one waits (esp, IMHO, in adenoCA, which has a longer tumor doubling time, in general), the more opportunity the irradiated cells have for a mitotic catastrophe. A 7w vs 11w comparison may be a little "tight," esp in a trial with only about ~130 pts in either arm, to figure out which cells are mortal "Dead Men Walking" and which are immortal. I will hold on to this notion for a loooong time

I knew you would post that!

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

 

[mheat3]

bias-infested

Now this is a term I can get behind. Why don't we see this in more editorials and response to the authors?

 

[evilbooyaa]

I knew you would post that!

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

Are 250 patients randomized enough to believe negative results? They assumed a doubling of pCR (12% to 26%) with an extra 4 weeks of waiting in their power/sample size calculation.

I think that would have been incredibly unlikely.

 

[ramsesthenice]

Well, the French have looked into that.

Effect of Interval (7 or 11 weeks) Between Neoadjuvant Radiochemotherapy and Surgery on Complete Pathologic Response in Rectal Cancer: A Multicenter, Randomized, Controlled Trial (GRECCAR-6) - PubMed

Purpose A pathologic complete response (pCR; ypT0N0) of a rectal tumor after neoadjuvant radiochemotherapy (RCT) is associated with an excellent prognosis. Several retrospective studies have investigated the effect of increasing the delay after RCT. The aim of this study was to evaluate the...

pubmed.ncbi.nlm.nih.gov

7 vs. 11 week waiting time didn't enhance pCR.

I figured someone might mention this. I don't think it really answers the question in this context. In the CRT -> FOLFOX arm you are talking about a difference of months, not 4 weeks. The French RCT doesn't really rule out the possibility there could be more of a difference if you wait longer. Admittedly, there are other reasons radiation first might be better than chemo first in the TNT setting. Chemosensitization, revascularization, etc. Its all hypothetical at this point.

I'll be the first to admit that I didn't think there was going to be any difference in outcomes between the two arms. I thought radiation first made sense for logistical and tolerability reasons (not to mention faster resolution of presenting symptoms). But I would have bet exactly $0 it was going give a better clinical response rate. So my track record on the subject is admittedly not great

 

[Palex80]

Are 250 patients randomized enough to believe negative results? They assumed a doubling of pCR (12% to 26%) with an extra 4 weeks of waiting in their power/sample size calculation.

I think that would have been incredibly unlikely.

You can critisize that, but that's how the trial was designed. What difference would you consider "worthy"?

I understand however that the questions asked by the French group is not as relevant in the current discussion of sequencing CRT->CT or CT->CRT.

 

[evilbooyaa]

You can critisize that, but that's how the trial was designed. What difference would you consider "worthy"?

I understand however that the questions asked by the French group is not as relevant in the current discussion of sequencing CRT->CT or CT->CRT.

I would've thought that giong from 15 to 20% in 4 weeks would've been reasonable. Or 12 to 20%. I agree that it's nitpicking - what I'm saying is that I don't agree with their power calculation and thus don't feel that this closes the door on increasing waiting times leading to cCR.

Whether 250 prospective randomized patients are "equal" to 2000+ retrospective patients is immaterial to me.

It is tangentially related to the CRT--> CT vs CT-> CRT discussion IMO, as we're asking whether prolonged time from end of RT prior to surgery matters. I agree with you that, thus far, the data is mixed, but we do have prospective data that the answer is "maybe not"

 

[Chartreuse Wombat]

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No OS observed for LRT in Stage IV breast but the hypothesized effect size was enormous. 3Y OS in standard arm 30% with SOC INCREASING to 49.3% with the addition of LRT. The observed 3Y OS was 67-68% in both arms. Talk about missing with your a priori hypotheses.

 

[Krukenberg]

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No OS observed for LRT in Stage IV breast but the hypothesized effect size was enormous. 3Y OS in standard arm 30% with SOC INCREASING to 49.3% with the addition of LRT. The observed 3Y OS was 67-68% in both arms. Talk about missing with your a priori hypotheses.

it’s pretty incredible how off they were with their expected survival

 

[taserlaser]

When is their plenary? Would be interesting to hear the in depth discussion.

 

[ramsesthenice]

I would've thought that giong from 15 to 20% in 4 weeks would've been reasonable. Or 12 to 20%. I agree that it's nitpicking - what I'm saying is that I don't agree with their power calculation and thus don't feel that this closes the door on increasing waiting times leading to cCR.

Whether 250 prospective randomized patients are "equal" to 2000+ retrospective patients is immaterial to me.

It is tangentially related to the CRT--> CT vs CT-> CRT discussion IMO, as we're asking whether prolonged time from end of RT prior to surgery matters. I agree with you that, thus far, the data is mixed, but we do have prospective data that the answer is "maybe not"

You are right that if you are not careful when you design and power your study you can set yourself up to make type 2 errors. It is good to look at these kinds of details when you interpret studies and make sure that you believe negative studies are convincingly negative.

In fairness, this was a negative study. They just flat didn’t see a meaningful difference. Once you start designing your own trials you will have the unfortunate pleasure of realizing how most studies are powered. You would like to think you pick a reasonable goal and have your statisticians come up with a number needed to enroll. But unless you are blessed with endless patient volumes and funding, more often than not you end up doing the opposite. You tell them how many patients you can accrue and they tell you what it’s powered to find. I highly doubt the authors of this study actually thought an additional 4 weeks would slightly more than double the pCR. In residency we do train residents to be very critical assessing study details. It’s a critical skill to have. Just be careful not to miss the forest through the trees.

 

[Palex80]

I would've thought that giong from 15 to 20% in 4 weeks would've been reasonable. Or 12 to 20%. I agree that it's nitpicking - what I'm saying is that I don't agree with their power calculation and thus don't feel that this closes the door on increasing waiting times leading to cCR.

Ok, sure. I can understand that. You probably need something like 2000 patients in the trial for that, but yes, understandable.

 

[evilbooyaa]

You are right that if you are not careful when you design and power your study you can set yourself up to make type 2 errors. It is good to look at these kinds of details when you interpret studies and make sure that you believe negative studies are convincingly negative.

In fairness, this was a negative study. They just flat didn’t see a meaningful difference. Once you start designing your own trials you will have the unfortunate pleasure of realizing how most studies are powered. You would like to think you pick a reasonable goal and have your statisticians come up with a number needed to enroll. But unless you are blessed with endless patient volumes and funding, more often than not you end up doing the opposite. You tell them how many patients you can accrue and they tell you what it’s powered to find. I highly doubt the authors of this study actually thought an additional 4 weeks would slightly more than double the pCR. In residency we do train residents to be very critical assessing study details. It’s a critical skill to have. Just be careful not to miss the forest through the trees.

I certainly sympathize with clinical trialists on issues of funding. Me reading this study does not make me want to wait an additional 4 weeks, so I agree with the conclusion. It's more than just the power, though. As others have said adding chemo to CRT in TNT adds MONTHS to post-RT timing. I'm not surprised that 7 to 11 weeks didn't show a significant difference in pCR, even if the study was underpowered for what is a reasonable conclusion.

Not to say this study is 'worthless' or anything as at the time of its inception that's what people were interested in, and now we know. Adds to the body of literature on this topic.

 

[scarbrtj]

Radiation and surgery do not prolong survival in newly diagnosed metastatic breast cancer

Up to now, women who present with a new diagnosis of breast cancer that is already in an advanced stage (stage IV) face an unanswered question about whether surgery and radiation to the tumor in the breast (local therapy) will prolong survival compared to the traditional treatment of systemic...

www.news-medical.net

 

[Palex80]

Radiation and surgery do not prolong survival in newly diagnosed metastatic breast cancer

Up to now, women who present with a new diagnosis of breast cancer that is already in an advanced stage (stage IV) face an unanswered question about whether surgery and radiation to the tumor in the breast (local therapy) will prolong survival compared to the traditional treatment of systemic...

www.news-medical.net

No breast-STAMPEDE!
However: a far smaller trial and with a rather very "ambitious" goal, wouldn't you say?

 

[scarbrtj]

Would this be the biggest statistical OS benefit from XRT seen in any ±XRT study in medical history? Gotta be in top 5 (median OS 26 w/ XRT vs 17 mos w/o, p<0.001)?
First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS)


No more neck dissections (upfront) in early stage cN0 oral/OP sq c ca.
Equivalence randomized trial comparing treatment based on sentinel node biopsy versus neck dissection in operable T1-T2N0 oral and oropharyngeal cancer.

No more "traditional" chemo in some stage IV colon CAs.
Pembrolizumab versus chemotherapy for microsatellite instability-high/mismatch repair deficient metastatic colorectal cancer: The phase 3 KEYNOTE-177 study.

 

[medgator]

No more neck dissections in early stage cN0 oral/OP sq c ca.
Equivalence randomized trial comparing treatment based on sentinel node biopsy versus neck dissection in operable T1-T2N0 oral and oropharyngeal cancer.

Still getting a sentinel. Would not observe the neck based on prior data.

https://www.nejm.org/doi/full/10.1056/NEJMoa1506007

 

[medgator]

Would this be the biggest statistical OS benefit from XRT seen in any ±XRT study in medical history? Gotta be in top 5 (median OS 26 w/ XRT vs 17 mos w/o, p<0.001)?
First-line tyrosine kinase inhibitor with or without aggressive upfront local radiation therapy in patients with EGFRm oligometastatic non-small cell lung cancer: Interim results of a randomized phase III, open-label clinical trial (SINDAS)

Egfr+ pts a pretty small group, but the data sure is compelling

 

[scarbrtj]

Immunotx having XRT-like effect levels on brain mets in HER2+ patients; if not locally, at least in terms of OS ...

Tucatinib versus placebo added to trastuzumab and capecitabine for patients with previously treated HER2+ metastatic breast cancer with brain metastases (HER2CLIMB)

Tucatinib Combo Shows Significant Intracranial Responses in HER2+ Breast Cancer Brain Mets

Patients with previously treated HER2-positive metastatic breast cancer and brain metastases achieved significant intracranial responses with a combination of tucatinib plus trastuzumab and capecitabine, according to findings from a subset of patients in the HER2CLIMB trial.

www.onclive.com

 

[Palex80]

Immunotx having XRT-like effect levels on brain mets in HER2+ patients; if not locally, at least in terms of OS ...

Certainly an unmet need.
I recall two patients last year without any disease outside of the brain, dying with Her2 metastatic breast cancer after repeat courses of radiotherapy.

 

[scarbrtj]

 

[medgator]

Again, how relevant is this to most of who are practicing in the TNT era?

 

[Ray D. Ayshun]

Again, how relevant is this to most of who are practicing in the TNT era?

Seems relevant in the sense that if you look at the arms and outcomes you'll come out thinking you should do TNT with long course CRT imho.

 

[deleted774703]

Again, how relevant is this to most of who are practicing in the TNT era?

Doesn’t this count as TNT?

It’s just not WW

 

[RadOncMegatron]

This trial is nicely done with lots to think about, but one thing I'm always bothered by are these new fashionable combination primary endpoints. I know it's prb for power and all, but don't think much of it. Why not all death? Why colon primary? Why not traditional PFS?

Does anyone have answer?

With that said I like what they were trying to do.

 

[ramsesthenice]

This trial is nicely done with lots to think about, but one thing I'm always bothered by are these new fashionable combination primary endpoints. I know it's prb for power and all, but don't think much of it. Why not all death? Why colon primary? Why not traditional PFS?

Does anyone have answer?

With that said I like what they were trying to do.

Its basically DFS plus a new colon primary. I would bet it’s because on long term follow up of the original Dutch trial they did see increased secondary cancers. Maybe that’s why?

 

[RadOncMegatron]

Its basically DFS plus a new colon primary. I would bet it’s because on long term follow up of the original Dutch trial they did see increased secondary cancers. Maybe that’s why?

That's a good thought, but isn't the endpoint in the ball park of only 3-5 years? I don't think the difference in new colon primaries could attributed to the different XRT (or chemo?) doses at that early time point. The difference would be very small and need a lot of power? Am I wrong?

 

[evilbooyaa]

Doesn’t this count as TNT?

It’s just not WW

TNT historically means full dose CT and long-course CRT, but it's not wrong to call 5x5 and chemotherapy TNT as well.

 

[deleted774703]

TNT historically means full dose CT and long-course CRT, but it's not wrong to call 5x5 and chemotherapy TNT as well.

Thanks. Yeah, that's how I interpreted this trial

Essentially just a chemo trial to me: Adjuvant chemo doesn't work or ppl don't take it

Can we move it upfront so ppl will take it and see if anything improves

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

LC slightly worse (p=.09)

IMO, doesn't answer long-course vs short-course RT in setting of TNT

 

[evilbooyaa]

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.