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"I will choose to irradiate nodes in all N+ women to get the LRR from 7.8% to 4.8% at 10 years" - all Rad Oncs

Sorry it's Monday and I haven't had my tuna fish and cigarettes yet

 

[SneakyBooger]

Then there is also the German OCUM study...

"Oncological outcome after MRI-based selection for neoadjuvant chemoradiotherapy in the OCUM Rectal Cancer Trial"

"The 3- and 5-year local recurrence rates were 1.3 and 2.7 per cent respectively, with no differences between the two treatment protocols."


DOI: 10.1002/bjs.10879

 

[theradiator]

"I will choose to irradiate nodes in all N+ women to get the LRR from 7.8% to 4.8% at 10 years" - all Rad Oncs

Sorry it's Monday and I haven't had my tuna fish and cigarettes yet

In all fairness, does anyone think ascertainment of LRR in breast cancer is accurate? Unlike lung or even rectal, no one is performing restaging MRI or PET on all of these patients to document lymph node recurrence.

 

[RickyScott]

Then there is also the German OCUM study...

"Oncological outcome after MRI-based selection for neoadjuvant chemoradiotherapy in the OCUM Rectal Cancer Trial"

"The 3- and 5-year local recurrence rates were 1.3 and 2.7 per cent respectively, with no differences between the two treatment protocols."


DOI: 10.1002/bjs.10879


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You have to blind not to see that rectal radiation does not have a bright future, regardless of what nccn guidelines stipulate today.

 

[radoncftw]

You have to blind not to see that rectal radiation does not have a bright future, regardless of what nccn guidelines stipulate today.

what about non-operative management?

 

[deleted941485]

what about non-operative management?

Dude it’s clear surgeons and med onc will be taking the reigns for all of GI minus anal. Medoncs don’t care they will be giving chemo either way. And nobody on our end is gonna fight for real nonoperative or if they do it’ll just be ignored with low enrollment.

 

[Mandelin Rain]

what about non-operative management?

Never will be standard. Look at the series above. TME yields about a 2% local failure. Is chemoradiation ever going to do that, in any cancer site?

Will continue to attempt on severely comorbid and those refusing APR.

 

[TheWallnerus]

In all fairness, does anyone think ascertainment of LRR in breast cancer is accurate? Unlike lung or even rectal, no one is performing restaging MRI or PET on all of these patients to document lymph node recurrence.

It’s probably not as accurate as we would like. It’s probably higher than we suspect; but in which case it still doesn’t affect survival. Or it’s lower than we suspect; and in which case it really doesn’t affect survival. Or the values we suspect re LRR in the nodes are from the previous century when staging and systemics are quite different than what we have today; and in which case… well, you know. (I do remember reading an older paper where the IMN positivity rate at autopsy for women dying of metastatic breast cancer was 90%; we will never detect that positivity rate in living Stage IV patients I suspect.)

 

[theradiator]

It’s probably not as accurate as we would like. It’s probably higher than we suspect; but in which case it still doesn’t affect survival. Or it’s lower than we suspect; and in which case it really doesn’t affect survival. Or the values we suspect re LRR in the nodes are from the previous century when staging and systemics are quite different than what we have today; and in which case… well, you know. (I do remember reading an older paper where the IMN positivity rate at autopsy for women dying of metastatic breast cancer was 90%; we will never detect that positivity rate in living Stage IV patients I suspect.)

All true but for rhetorical purposes, we need to play the surrogate endpoint game like oncology pharma and cardiology trials do. If electively lymph nodes reduces distant metastases and breast cancer mortality, then LRR is irrelevant. If prostate RT achieves equivalent freedom from disease progression as surgery, then PSA is irrelevant. My point is to not diminish trials that we actually won fair and square.

 

[SneakyBooger]

what about non-operative management?

Looking at the International Watch and Wait database:

The 2-year cumulative incidence of local regrowth was 25.2%.

In patients with local regrowth, the proportion of patients with distant metastasis was 18% (38 of 213), whereas the proportion of patients with a sustained complete response was 5% (33 of 634).

Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study

 

[RickyScott]

Looking at the International Watch and Wait database:

The 2-year cumulative incidence of local regrowth was 25.2%.

In patients with local regrowth, the proportion of patients with distant metastasis was 18% (38 of 213), whereas the proportion of patients with a sustained complete response was 5% (33 of 634).

Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study

Nonoperative approach is only realistic for those pts facing an apr. zero chaNce of buy in for lar candidates.

 

[RadRadRad]

Nonoperative approach is only realistic for those pts facing an apr. zero chaNce of buy in for lar candidates.

Agree
And the demand may be patient driven (rather than surgeon or Medonc).
Patients facing apr seem very motivated to avoid

 

[TheWallnerus]

I don't know why this sort of test wouldn't make its way into the rectal space of the colorectal space...

 

[theradiator]

I don't know why this sort of test wouldn't make its way into the rectal space of the colorectal space...

Surgery only for ctDNA positive after chemoRT?

 

[radoncftw]

Agree
And the demand may be patient driven (rather than surgeon or Medonc).
Patients facing apr seem very motivated to avoid

i don't think it will gain widespread traction rapidly, but i think there is a real potential for organ preservation (like for anal cancer). our colorectal surgeons are on board and push for non-op mgmt when feasible (regardless of APR/LAR) if locally advanced.

 

[grenz]

i don't think it will gain widespread traction rapidly, but i think there is a real potential for organ preservation (like for anal cancer). our colorectal surgeons are on board and push for non-op mgmt when feasible (regardless of APR/LAR) if locally advanced.

I’ve always been impressed by general surgeons’ willingness to give up indications for surgery. Lumpectomy, omitting ALND, non-op mgmt of trauma, NOM for rectal…list goes on.

 

[medgator]

Agree
And the demand may be patient driven (rather than surgeon or Medonc).
Patients facing apr seem very motivated to avoid

Just saw another low rectal pt today trying to avoid an apr.... Rectal ain't going away

 

[Mandelin Rain]

Just saw another low rectal pt today trying to avoid an apr.... Rectal ain't going away

Not all rectal for sure. But I could see a greatly diminished/no role for T3 N0/1 proximal/mid without threatened CRM on MRI in the next decade.

 

[jondunn]

I’ve always been impressed by general surgeons’ willingness to give up indications for surgery. Lumpectomy, omitting ALND, non-op mgmt of trauma, NOM for rectal…list goes on.

Agree. Urologists also drove active surveillance. It rings false fo me when people say rad oncs are the only ones who try to reduce burdens of care

 

[jondunn]

Not all rectal for sure. But I could see a greatly diminished/no role for T3 N0/1 proximal/mid without threatened CRM on MRI in the next decade.

I think it’s a guarantee.

Do we really think high T3N0 benefits from RT? But that’s where it’s good to have 25/5 as an option. Similar fo
Shorter courses of breast treatment, observation becomes less of an attractive option when the treatment is short and Easy.

 

[radoncftw]

I think it’s a guarantee.

Do we really think high T3N0 benefits from RT? But that’s where it’s good to have 25/5 as an option. Similar fo
Shorter courses of breast treatment, observation becomes less of an attractive option when the treatment is short and Easy.

no there is data to suggest you don't neoadjuvant treatment for these cases. Of course you need to have good pre-op staging w/MRI.
We routinely will have these patients with T3N0 disease get upfront TME. You do sometimes get the whoopsies and end up with pN+ or + margins and end up needing adjuvant chemoRT which sucks for the patients.

 

[medgator]

Agree. Urologists also drove active surveillance.

All those repeat ultrasounds and biopsies? Sure

Cost-Effectiveness of Active Surveillance, Radical Prostatectomy and External Beam Radiotherapy for Localized Prostate Cancer: An Analysis of the ProtecT Trial - PubMed

Although active surveillance represents a cost-effective strategy to manage localized prostate cancer during the initial several years after diagnosis, the relative cost-effectiveness of treatment emerges with extended followup.

pubmed.ncbi.nlm.nih.gov

 

[grenz]

Agree. Urologists also drove active surveillance. It rings false fo me when people say rad oncs are the only ones who try to reduce burdens of care

Not sure AS is the best example. They’re clearly just trying to replace the volume by operating on more high risk patients

 

[Mandelin Rain]

no there is data to suggest you don't neoadjuvant treatment for these cases. Of course you need to have good pre-op staging w/MRI.
We routinely will have these patients with T3N0 disease get upfront TME. You do sometimes get the whoopsies and end up with pN+ or + margins and end up needing adjuvant chemoRT which sucks for the patients.

{Spoiler Alert}
NCCN 2030:
Neoadjuvant FOLFIRI > TME > If ypN+ > Immunotherapy

 

[madchemist89]

Non op for colorectal means lots of scopes for the surgeon down the road

 

[RickyScott]

I don't know why this sort of test wouldn't make its way into the rectal space of the colorectal space...

It absolutely will, and ultimately breast cancer as well. Within 10-15 years we will probably be able to eliminate adjuvant xrt in breast cancer based on mrd. Mdacc hard at work on this for breast ca- charline goodMan well published on this. Local nci center is already using this to eliminate chemo in crc.

 

[ramsesthenice]

Local nci center is already using this to eliminate chemo in crc.

No Bueno. If you are going to use this to get rid of a therapy, what you need is a really high sensitivity and that these tests don’t have yet. During COVID, Signatera was free for all GI patients at our NCI center. I can tell you first had (and published if you do into the fine details) false negatives post neoadjuvant (chemo or RT depending on disease) and surgery are very common. At least a third of the ctDNA negative patients turn positive within six months. If you look close, the companies hype up their specificity and claim there are essentially zero false positives. Even if you accept that at face value, still doesn’t mean it’s a great test to start excluding therapy. Much better for identifying who should not be de-escalated at this point.

They will get better and eventually play a huge role in post treatment decisions.

 

[RickyScott]

No Bueno. If you are going to use this to get rid of a therapy, what you need is a really high sensitivity and that these tests don’t have yet. During COVID, Signatera was free for all GI patients at our NCI center. I can tell you first had (and published if you do into the fine details) false negatives post neoadjuvant (chemo or RT depending on disease) and surgery are very common. At least a third of the ctDNA negative patients turn positive within six months. If you look close, the companies hype up their specificity and claim there are essentially zero false positives. Even if you accept that at face value, still doesn’t mean it’s a great test to start excluding therapy. Much better for identifying who should not be de-escalated at this point.

They will get better and eventually play a huge role in post treatment decisions.

I don’t have experience with this platform, but like you, see that this kind of tech will play a HUGE role in treatment decisions, most likely to the detriment of xrt.

 

[ramsesthenice]

I don’t have experience with this platform, but like you see that this kind of tech will play a huge role in treatment decisions, and most likely to the detriment of xrt.

With these technologies the losers will be the folks who go last. These tests are useless as long as the primary is in place (if there is residual tumor at least). In the US, I don’t see this really affecting RT utilization for rectal. Breast though…could be another beast. It’s easily foreseeable that we get to a place negative ctDNA after chemo and surgery = observation instead of adjuvant RT.

Not all rectal for sure. But I could see a greatly diminished/no role for T3 N0/1 proximal/mid without threatened CRM on MRI in the next decade.

I disagree. LAR causes waaaaay more long term morbidity than RT or chemo and a lot of high volume centers routinely use TNT with selective w/w for essentially all mid rectal tumors. It’s not just about avoiding an APR. Word is getting out and patients are (probably too) empowered to try to drive their treatment.

Non op for colorectal means lots of scopes for the surgeon down the road

Bingo! This is precisely why AS became a thing for prostate too. You are not completely giving up surgery, just delaying it for some a decent proportion and keeping yourself quite busy and well paid in the process. And don’t forget, a typical colorectal surgeon does 2-3x as many surgeries for colon as they do rectal. They are not hurting for patients.

 

[elementaryschooleconomics]

With these technologies the losers will be the folks who go last. These tests are useless as long as the primary is in place (if there is residual tumor at least). In the US, I don’t see this really affecting RT utilization for rectal. Breast though…could be another beast. It’s easily foreseeable that we get to a place negative ctDNA after chemo and surgery = observation instead of adjuvant RT.


I disagree. LAR causes waaaaay more long term morbidity than RT or chemo and a lot of high volume centers routinely use TNT with selective w/w for essentially all mid rectal tumors. It’s not just about avoiding an APR. Word is getting out and patients are (probably too) empowered to try to drive their treatment.


Bingo! This is precisely why AS became a thing for prostate too. You are not completely giving up surgery, just delaying it for some a decent proportion and keeping yourself quite busy and well paid in the process. And don’t forget, a typical colorectal surgeon does 2-3x as many surgeries for colon as they do rectal. They are not hurting for patients.

*furiously jots down tumor board talking points from @ramsesthenice posts*

 

[RickyScott]

With these technologies the losers will be the folks who go last. These tests are useless as long as the primary is in place (if there is residual tumor at least). In the US, I don’t see this really affecting RT utilization for rectal. Breast though…could be another beast. It’s easily foreseeable that we get to a place negative ctDNA after chemo and surgery = observation instead of adjuvant RT.


I disagree. LAR causes waaaaay more long term morbidity than RT or chemo and a lot of high volume centers routinely use TNT with selective w/w for essentially all mid rectal tumors. It’s not just about avoiding an APR. Word is getting out and patients are (probably too) empowered to try to drive their treatment.


Bingo! This is precisely why AS became a thing for prostate too. You are not completely giving up surgery, just delaying it for some a decent proportion and keeping yourself quite busy and well paid in the process. And don’t forget, a typical colorectal surgeon does 2-3x as many surgeries for colon as they do rectal. They are not hurting for patients.

Breast is an existential threat to the field.

 

[deleted941485]

Breast is an existential threat to the field.

Breast blows. It keeps the lights on but I hate it more and more.

 

[evilbooyaa]

Breast blows. It keeps the lights on but I hate it more and more.

We don't call it the worst on a weekly basis (and have 3-4 threads about how breast is the worst) for nuthin'

 

[ramsesthenice]

Breast blows. It keeps the lights on but I hate it more and more.

Stop by your local endocrinology office and ask them how they feel about type 2 diabetes.

 

[deleted941485]

Stop by your local endocrinology office and ask them how they feel about type 2 diabetes.

What office? Those guys have been virtual for a year and brush it off on the APN.

 

[RickyScott]

Stop by your local endocrinology office and ask them how they feel about type 2 diabetes.

I follow the diabetes space. Like medical oncology, it is in a golden age w/sglt2 inhibitors and glp1 agonists. In fact, sglt2 inhibitors should be in the water supply- they improve cardiac outcomes in non diabetics (every pt with chf should be on), kidney disease in non diabetics and and made healthy mice live longer in the nia national intervention testing program. Who doesn’t want to pee out 300kcal of glucose a day? Wegovy/ozempic and successors could end obesity, depriving us of more cancer pts.(since obesity is the number one cause of cancer)

(It can be really sad to compare radonc to some other random field)

 

[temujim]

I don’t have experience with this platform, but like you, see that this kind of tech will play a HUGE role in treatment decisions, most likely to the detriment of xrt.

It will be a re-sorting. But can see how all adjuvant therapies of any type could be impacted.

 

[radoncftw]

I follow the diabetes space. Like medical oncology, it is in a golden age w/sglt2 inhibitors and glp1 agonists. In fact, sglt2 inhibitors should be in the water supply- they improve cardiac outcomes in non diabetics (every pt with chf should be on), kidney disease in non diabetics and and made healthy mice live longer in the nia national intervention testing program. Who doesn’t want to pee out 300kcal of glucose a day? Wegovy/ozempic and successors could end obesity, depriving us of more cancer pts.(since obesity is the number one cause of cancer)

(It can be really sad to compare radonc to some other random field)

so i could pee out an ipa a day w/a pill. sign me up.

 

[jondunn]

No Bueno. If you are going to use this to get rid of a therapy, what you need is a really high sensitivity and that these tests don’t have yet. During COVID, Signatera was free for all GI patients at our NCI center. I can tell you first had (and published if you do into the fine details) false negatives post neoadjuvant (chemo or RT depending on disease) and surgery are very common. At least a third of the ctDNA negative patients turn positive within six months. If you look close, the companies hype up their specificity and claim there are essentially zero false positives. Even if you accept that at face value, still doesn’t mean it’s a great test to start excluding therapy. Much better for identifying who should not be de-escalated at this point.

They will get better and eventually play a huge role in post treatment decisions.

my assumption is that the NCI center is doing it on trial? Isnt there an NRG trial like this right now?

 

[ramsesthenice]

my assumption is that the NCI center is doing it on trial? Isnt there an NRG trial like this right now?

There are a lot of trials looking at this. And that’s how it should be done. It’s not all clear how to use these with respect to adjuvant therapies and that needs to be answered before just giving it the old college try off trial.

 

[RickyScott]

There are a lot of trials looking at this. And that’s how it should be done. It’s not all clear how to use these with respect to adjuvant therapies and that needs to be answered before just giving it the old college try off trial.

I went to a sponsored dinner with speaker from Mayo. They were doing it off trial for stage 3 colon.

 

[ramsesthenice]

I went to a sponsored dinner with speaker from Mayo. They were doing it off trial for stage 3 colon.

Yikes. Thats an impressive risk appetite. The idea has merit but man, withholding standard therapy without demonstrated evidence it is safe to do so...if someone came back and sued you would have no real defense. It also does nothing to help the rest of us figure out how to use this fancy new stuff either.

 

[RickyScott]

Yikes. Thats an impressive risk appetite. The idea has merit but man, withholding standard therapy without demonstrated evidence it is safe to do so...if someone came back and sued you would have no real defense. It also does nothing to help the rest of us figure out how to use this fancy new stuff either.

They made the point that in a few instances would show no mrd but then turn positive several months later. Somehow they felt that chemo would not have helped those pts anyway. Didn’t really follow because I was more interested in the dessert.

 

[ramsesthenice]

They made the point that in a few instances would show no mrd but then turn positive several months later. Somehow they felt that chemo would not have helped those pts anyway. Didn’t really follow because I was more interested in the dessert.

Oh boy. I have heard this before and I think it’s a very precarious position to take as a med Onc. What they are saying is that it probably wouldn’t have cured the folks who eventually turned positive and delaying chemo was unlikely to alter their overall disease course. On the whole, it benefitted the group because a lot of folks avoided chemo they never needed. Which could all be true! But this hypothesis (inadvertently) implies something fairly profound: Adjuvant chemo is palliative, not curative. Is that the montra med oncs have been selling for decades? Oh right, the argument has been we need to get it in as soon as possible to control micrometastatic disease and improve cure rates. So…which is it???