Rapido

[Burt Radnolds]

RAPIDO was an unbalanced trial with much less systemic therapy given in the SOC arm, yet LC still "favored" long course. I'll see what I want to see

View attachment 344624

Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial - PubMed

The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.

pubmed.ncbi.nlm.nih.gov

So 12% vs 8% LRF despite 100 vs 50% receiving full course FOLFOX... Let the spin machine begin!

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[TheWallnerus]

Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial - PubMed

The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.

pubmed.ncbi.nlm.nih.gov

So 12% vs 8% LRF despite 100 vs 50% receiving full course FOLFOX... Let the spin machine begin!

On paper 25/5 shouldn’t be as good as 50.4/28 for local control. The alpha beta of rectal would have to be sub-1.5 for the math to work, lower than the alpha beta of prostate cancer. There wasn’t any great pre-clinical data suggesting that to be the case, yet short course kept showing up with (seeming) real world equivalences and sometimes tiny superiorities. Now, given this clinical data which seems to non-falsify radiobiologic principle, I think we should all cool our collective jets on short course.

As an aside, I cannot think of a single randomized trial asking radiation questions that has ever invalidated radiobiologic principles. We should maybe listen to those principles more often.

 

[OTN]

The data has been telling the story for several years now that LRC is better with long- vs short-course. Good to have more data to push back against the virtue signalers.

 

[Fpg1245]

The data has been telling the story for several years now that LRC is better with long- vs short-course. Good to have more data to push back against the virtue signalers.

Can I go back to my Alma mater and punch my smug faculty in the face?

 

[seper]

B-39 showed that in-breast control was better with WBRT vs. PBI. So what?

With FOLFIRINOX for rectal cancer, these differences in control will no longer be noticeable. Eventually, I bet that RT will not be used in curative setting at all.

 

[medgator]

Eventually, I bet that RT will not be used in curative setting at all.

Except when they never see a surgeon. I think for mismatch-repair deficient though, probably won't get anything except IO

 

[radoncftw]

Can I go back to my Alma mater and punch my smug faculty in the face?

lol

 

[elementaryschooleconomics]

Can I go back to my Alma mater and punch my smug faculty in the face?

I'll stand beside you with a water bottle and towel. Tell me when you need me to cut you:



My version of "faculty face punch" has been "never used short course once as an attending".

 

[TheWallnerus]

I'll stand beside you with a water bottle and towel. Tell me when you need me to cut you:



My version of "faculty face punch" has been "never used short course once as an attending".

As we sit and ponder what our specialty might look like 10, 20, 50 or more years from now, I wonder if we will be doomed to cycle through fashionable and “au courant” treatment approaches only to have them somewhat thinly negated and subsequently abandoned. But later, as new rad oncs continue percolating into the field, the new rad oncs either don’t know history or look at history, misread that history, and say “we can do this better.” Then the different treatment approach becomes “hot” again. People start doing it, and it looks good. But then longer term data emerges casting doubt on the new. The “new” approach is abandoned. But later, as new rad oncs continue percolating into the field…

The Culture of Radiation Oncology. End scene. Repeat scene.

 

[RickyScott]

The data has been telling the story for several years now that LRC is better with long- vs short-course. Good to have more data to push back against the virtue signalers.

I used to think it was just all about the virtue signaling, but almost every academic center I know, uses long course fractionation for those who live nearby, reserving hypofractionation to capture far away patients.

 

[TheWallnerus]

I used to think it was just all about the virtue signaling, but almost every academic center I know, uses long course fractionation for those who live nearby, reserving hypofractionation to capture far away patients.

This is the best type of virtue signaling!

How Al Gore has made $300m with climate alarmism

Warning the world that it is on the brink of disaster has been lucrative for Al Gore.

www.dailymail.co.uk

 

[medgator]

This is the best type of virtue signaling!

How Al Gore has made $300m with climate alarmism

Warning the world that it is on the brink of disaster has been lucrative for Al Gore.

www.dailymail.co.uk

Kinda like Elon musk taking those 8 min private jet flights. Still better than just flat out denying the issue like Exxon Mobil or the koch brothers i guess

 

[elementaryschooleconomics]

As we sit and ponder what our specialty might look like 10, 20, 50 or more years from now, I wonder if we will be doomed to cycle through fashionable and “au courant” treatment approaches only to have them somewhat thinly negated and subsequently abandoned. But later, as new rad oncs continue percolating into the field, the new rad oncs either don’t know history or look at history, misread that history, and say “we can do this better.” Then the different treatment approach becomes “hot” again. People start doing it, and it looks good. But then longer term data emerges casting doubt on the new. The “new” approach is abandoned. But later, as new rad oncs continue percolating into the field…

The Culture of Radiation Oncology. End scene. Repeat scene.

Oh - so treating nodes electively in prostate cancer?

*screams*

 

[Palex80]

Oh - so treating nodes electively in prostate cancer?

*screams*

BREAST! The 25 year update of the EORTC trial is going to astonish you!

 

[sirspamalot]

Ya'll made me snort. Good stuff. Data Bros be damned, I'm doing what feels good, because in the end, nobody knows for sure.

 

[pikachu]

Wonder if we'll ever see outcomes from true believers that raced to do short course --> watch and wait for clinical complete responders. In RAPIDO, local recurrence was 12% with 90+% of patients going to TME...

Would anyone now offer short course + watch and wait?

 

[RickyScott]

Wonder if we'll ever see outcomes from true believers that raced to do short course --> watch and wait for clinical complete responders. In RAPIDO, local recurrence was 12% with 90+% of patients going to TME...

Would anyone now offer short course + watch and wait?

No

 

[evilbooyaa]

Wonder if we'll ever see outcomes from true believers that raced to do short course --> watch and wait for clinical complete responders. In RAPIDO, local recurrence was 12% with 90+% of patients going to TME...

Would anyone now offer short course + watch and wait?

I think Wash U group have something higher N and prospective potentially cooking in this space: Nonoperative Rectal Cancer Management With Short-Course Radiation Followed by Chemotherapy: A Nonrandomized Control Trial

But to answer the question, off-protocol, no I would not at the current time. That was also true prior to most recent data coming out.

 

[TheWallnerus]

Would anyone now offer short course + watch and wait?

On paper 25/5 shouldn’t be as good as 50.4/28 for local control.

25/5 seemed REALLY not as good on paper as 50.4 (or a bit higher) for rectal organ preservation

 

[StIGMA]

Wonder if we'll ever see outcomes from true believers that raced to do short course --> watch and wait for clinical complete responders. In RAPIDO, local recurrence was 12% with 90+% of patients going to TME...

Would anyone now offer short course + watch and wait?

This is being done with higher dose sib’s to tumor, not simple 25/5 though

 

[radoncftw]

This is being done with higher dose sib’s to tumor, not simple 25/5 though

like 30Gy to primary?

 

[StIGMA]

like 30Gy to primary?

Yes, as optionally offered here:

Clinical Complete Response in Patients With Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Nonoperative Management - PubMed

Short-course radiation therapy followed by consolidation chemotherapy may be a feasible organ preservation strategy in rectal cancer. Additional prospective studies are necessary to evaluate the safety and efficacy of this approach.

pubmed.ncbi.nlm.nih.gov

and Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum - Full Text View - ClinicalTrials.gov

Would also boost nodes threatening CRM (30-35Gy) or involved lateral pelvic LNs (35-40 Gy)

They don't specify how many patients had 25 vs 30 Gy to primary tumor (most have to be 25 Gy as max 20 patients could have even been eligible on separate trial to have received 30 Gy)

"Among 86 patients with an evaluable initial clinical response, the initial cCR rate after consolidation chemotherapy was 50% (43 of 86). ....
With a median follow-up of 30.1 months, the persistent cCR rate was 79% (30 of 38 patients) in the [non-operative management] cohort. "
These patients primary treated with short course RT (25 Gy) + consolidative chemo.

These are not bad numbers. There are differences in rapido volumes and treatment style compared to modern US approaches. Interesting the RAPIDO update suggesting SCRT vs. LCRT has same LRR if treated with VMAT (but not with 3DCRT). "Patients treated with 3D-CRT more often had [a locoregional recurrence] in the EXP group (12%) than in the STD group (6%) whereas no such difference was seen in patients treated with IMRT/VMAT (6% vs. 5%, respectively)."

So yes, WW is still being offered in select contexts. Still too early to be advocating for this routinely off study (I treat as written above, and always advise resection) but it is reasonable to counsel patients.

 

[TheWallnerus]

Yes, as optionally offered here:

Clinical Complete Response in Patients With Rectal Adenocarcinoma Treated With Short-Course Radiation Therapy and Nonoperative Management - PubMed

Short-course radiation therapy followed by consolidation chemotherapy may be a feasible organ preservation strategy in rectal cancer. Additional prospective studies are necessary to evaluate the safety and efficacy of this approach.

pubmed.ncbi.nlm.nih.gov

and Non-Operative Radiation Management of Adenocarcinoma of the Lower Rectum - Full Text View - ClinicalTrials.gov

Would also boost nodes threatening CRM (30-35Gy) or involved lateral pelvic LNs (35-40 Gy)

They don't specify how many patients had 25 vs 30 Gy to primary tumor (most have to be 25 Gy as max 20 patients could have even been eligible on separate trial to have received 30 Gy)

"Among 86 patients with an evaluable initial clinical response, the initial cCR rate after consolidation chemotherapy was 50% (43 of 86). ....
With a median follow-up of 30.1 months, the persistent cCR rate was 79% (30 of 38 patients) in the [non-operative management] cohort. "
These patients primary treated with short course RT (25 Gy) + consolidative chemo.

These are not bad numbers. There are differences in rapido volumes and treatment style compared to modern US approaches. Interesting the RAPIDO update suggesting SCRT vs. LCRT has same LRR if treated with VMAT (but not with 3DCRT). "Patients treated with 3D-CRT more often had [a locoregional recurrence] in the EXP group (12%) than in the STD group (6%) whereas no such difference was seen in patients treated with IMRT/VMAT (6% vs. 5%, respectively)."

So yes, WW is still being offered in select contexts. Still too early to be advocating for this routinely off study (I treat as written above, and always advise resection) but it is reasonable to counsel patients.

To be blunt, I wonder how turds pass through anorectums (patient reported outcomes and experience) irradiated to 6 Gy a day times 5 days versus 1.8 Gy a day times 28 to 30 days… 5 years or more after RT.

 

[metallica81788]

To be blunt, I wonder how turds pass through anorectums (patient reported outcomes and experience) irradiated to 6 Gy a day times 5 days versus 1.8 Gy a day times 28 to 30 days… 5 years or more after RT.

But but but but but we have 30 month follow up!

 

[TheWallnerus]

But but but but but we have 30 month follow up!

Or butt butt butt butt

 

[RickyScott]

Or butt butt butt butt

We have a mix of hypofractionated and conventional prostate over the past 10 years. We have had only a handful of rectal issues - most bleeding resolved with steroid enema and one cauterization. Every single one was in the hypofractionated group. I am sure if we analyzed the data, given the small number of cases, it would be non inferior.

 

[StIGMA]

To be blunt, I wonder how turds pass through anorectums (patient reported outcomes and experience) irradiated to 6 Gy a day times 5 days versus 1.8 Gy a day times 28 to 30 days… 5 years or more after RT.

the anal canal should not be part of the volume, in long or short course, for most of these cases. For the 6x5, it's to tumor with small margin, not the entire rectum. Definitely would be higher risk in WW with larger tumor perhaps with lower response rate vs. smaller tumor (ie: strongly advise resection), and if not resected, concern with larger tumor long term rectal toxicity due to larger volume. I'd avoid that.

 

[evilbooyaa]

To be blunt, I wonder how turds pass through anorectums (patient reported outcomes and experience) irradiated to 6 Gy a day times 5 days versus 1.8 Gy a day times 28 to 30 days… 5 years or more after RT.

We don't know yet. I think people doing it off protocol are likely doing it to capture people from a far distance. On-protocol, very reasonable thing to evaluate.

 

[TheWallnerus]

the anal canal should not be part of the volume, in long or short course, for most of these cases. For the 6x5, it's to tumor with small margin, not the entire rectum. Definitely would be higher risk in WW with larger tumor perhaps with lower response rate vs. smaller tumor (ie: strongly advise resection), and if not resected, concern with larger tumor long term rectal toxicity due to larger volume. I'd avoid that.

None of the anal canal will get radiation in a very low lying rectal cancer in which you’re trying to do NOM? This is radiotherapy not frickin lasers But anyway can we change the name of rectal cancer to anorectal cancer. Sure would help at the prior auth stage.

 

[TheWallnerus]

We have a mix of hypofractionated and conventional prostate over the past 10 years. We have had only a handful of rectal issues - most bleeding resolved with steroid enema and one cauterization. Every single one was in the hypofractionated group. I am sure if we analyzed the data, given the small number of cases, it would be non inferior.

I agree with your predictions. But I think hypofx prostate and 25/5, 30/5 SIB rectal RT are going to have different rectal sequelae.

 

[metview]

Some portion of the anal sphincter/canal is going to receive prescription dose in the majority of rectal cancer cases. The median tumor distance from the anal verge in that washu trial is 4 cm. The anal canal is 4 cm in length. For mid-low lying tumors, it'll be interesting to see what 30 Gy in 5 fractions does to bowel QOL in the long-term.

 

[RickyScott]

Some portion of the anal sphincter/canal is going to receive prescription dose in the majority of rectal cancer cases. The median tumor distance from the anal verge in that washu trial is 4 cm. The anal canal is 4 cm in length. For mid-low lying tumors, it'll be interesting to see what 30 Gy in 5 fractions does to bowel QOL in the long-term.

I really try to avoid the anal canal. Vast majority of recurrences are in the mesorectum.

 

[metview]

I really try to avoid the anal canal. Vast majority of recurrences are in the mesorectum.

How do you treat low lying tumors because CTV (2-3 cm) and PTV (0.5-1cm) margins would include nearly all of the canal?

 

[RickyScott]

How do you treat low lying tumors because CTV (2-3 cm) and PTV (0.5-1cm) margins would include nearly all of the canal?

I typically dont use 2-3 cm ctvs if the tumor is well defined on PET and MRI. typically 1-1.5 cm on mri and pet volume and 0.5 cm for ptv and cbct daily. If trying to get to 56 Gy+ to decrease chance of apr, I do get tight.

 

[sirspamalot]

to the sphincter we go? butt seriously..

 

[TheWallnerus]

I typically dont use 2-3 cm ctvs if the tumor is well defined on PET and MRI. typically 1-1.5 cm on mri and pet volume and 0.5 cm for ptv and cbct daily. If trying to get to 56 Gy+ to decrease chance of apr, I do get tight.

Super low lying tumors, which are not common… you’re gonna have some anal (that’s what she said). But otherwise most of time I agree, we avoid anal (that’s what she said). “I do get tight.” No comment.

 

[sirspamalot]

This reminds me of a recently developed college cheer that you would undoubtedly agree is crossing the (dentate) line...

ps. I win it for today, thank you very much

 

[ramsesthenice]

the anal canal should not be part of the volume, in long or short course, for most of these cases. For the 6x5, it's to tumor with small margin, not the entire rectum. Definitely would be higher risk in WW with larger tumor perhaps with lower response rate vs. smaller tumor (ie: strongly advise resection), and if not resected, concern with larger tumor long term rectal toxicity due to larger volume. I'd avoid that.

N is small, but I have 9 patients treated with SC and no surgery with > 2 years of follow up. For most all of them, the rationale was that they were found to have a more lethal concurrent cancer and we wanted to not totally ignore the rectal cancer but also not delay systemic therapy for the other cancer. Three of them the plan was SC and then delayed surgery (because of OR scheduling) and then when they were NED on MRI they refused surgery. Nothing scary has come up yet. Again, small number and there could be some real differences, but I don't think there is going to be anything crazy high.

The RAPIDO follow up data is interesting. I think it is important but my interpretation is more nuanced. Its important to remember that RAPIDO was restricted to big bad tumors. If you look at the European short course studies with very long-term follow up in more general populations there really is no consistent concerning local recurrence signal. My guess is that SC is probably fine for standard risk patients but RAPIDO suggests there should probably be real pause given before offering it to patients with more locally advanced tumors. I've never personally tried it in that scenario. Im a believer in SC but I have thus far been unwilling to give it for people with an involved CRM or bulky tumors where downstaging was important. Never saw a real reason to risk it.

 

[radoncftw]

N is small, but I have 9 patients treated with SC and no surgery with > 2 years of follow up. For most all of them, the rationale was that they were found to have a more lethal concurrent cancer and we wanted to not totally ignore the rectal cancer but also not delay systemic therapy for the other cancer. Three of them the plan was SC and then delayed surgery (because of OR scheduling) and then when they were NED on MRI they refused surgery. Nothing scary has come up yet. Again, small number and there could be some real differences, but I don't think there is going to be anything crazy high.

The RAPIDO follow up data is interesting. I think it is important but my interpretation is more nuanced. Its important to remember that RAPIDO was restricted to big bad tumors. If you look at the European short course studies with very long-term follow up in more general populations there really is no consistent concerning local recurrence signal. My guess is that SC is probably fine for standard risk patients but RAPIDO suggests there should probably be real pause given before offering it to patients with more locally advanced tumors. I've never personally tried it in that scenario. Im a believer in SC but I have thus far been unwilling to give it for people with an involved CRM or bulky tumors where downstaging was important. Never saw a real reason to risk it.

I think this is a very reasonable approach. There have been a fair amount of studies (Polish, Australian) that show equipoise for your average T3, N+ in patients getting resection.

I think for non-operative mgmt or the "ugly" tumors, LC-CRT is a reasonable approach.

 

[Haybrant]

Locoregional Failure During and After Short-course Radiotherapy Followed by Chemotherapy and Surgery Compared With Long-course Chemoradiotherapy and Surgery: A 5-Year Follow-up of the RAPIDO Trial - PubMed

The EXP treatment was associated with an increased risk of LRR, whereas the reduction in disease-related treatment failure and distant metastases remained after 5 years. Further refinement of the TNT in rectal cancer is mandated.

pubmed.ncbi.nlm.nih.gov

So 12% vs 8% LRF despite 100 vs 50% receiving full course FOLFOX... Let the spin machine begin!

For those of us not up to date can you just clarify. The long course standard of care arm only 50% got full systemic therapy and all patients completed full chemo in the short course arm? Update of Rapido showed the long course group had better local control by 50% or 8 vs 12% so despite inferior chemo the local control was improved with long course RT

 

[sirspamalot]

I guess I'm just confused now. I'll stick with LC-CRT and call it a win... for the majority of my patients anyway. I think for early stage patients, maybe SC if they are coming from a long way. My old skool medonc .. I had to tell him about TNT. Boom.

 

[evilbooyaa]

For those of us not up to date can you just clarify. The long course standard of care arm only 50% got full systemic therapy and all patients completed full chemo in the short course arm? Update of Rapido showed the long course group had better local control by 50% or 8 vs 12% so despite inferior chemo the local control was improved with long course RT

Yes, because the long course arm was NOT TNT, but rather the more 'traditional' style of rectal Ca management (neoadj chemoRT --> surgery --> adjuvant chemo).

RAPIDO showed an increase in DM in the non-TNT group, likely because their receipt of full systemic chemo was only 50% (vs close to 100%) and potentially any delays in receipt of full dose systemic leading to development of early mets.

Showing that SC + chemo maybe potentially less effective in very high-risk (lots of T4, N2 patients) in terms of local recurrence. So, at current time LC-RT --> chemo --> surgery vs NOM probably the most defensible approach for most patients.

 

[medgator]

Game over, surgery?

 

[CaesarRO]

Game over, surgery?

Anybody in the US doing contact brachy for that boost?

 

[seper]

Anybody in the US doing contact brachy for that boost?

Never heard of a case. An absurd idea, IMO, since rectal mucosa is the most important avoidance structure. An you are putting source next to it.

 

[OTN]

Never heard of a case. An absurd idea, IMO, since rectal mucosa is the most important avoidance structure. An you are putting source next to it.

That data is tremendous, though. I've done contact brachy postop after T1 anal resection.

 

[sirspamalot]

Never heard of a case. An absurd idea, IMO, since rectal mucosa is the most important avoidance structure. An you are putting source next to it.

You ever see a giant 50 kVp gun inserted in the anus for low rectal cancer?

Because until you've seen that, you haven't lived.

 

[medgator]

You ever see a giant 50 kVp gun inserted in the anus for low rectal cancer?

Because until you've seen that, you haven't lived.

Many decent gifs to post here but I'll refrain

 

[CaesarRO]

Never heard of a case. An absurd idea, IMO, since rectal mucosa is the most important avoidance structure. An you are putting source next to it.

That data is tremendous, though. I've done contact brachy postop after T1 anal resection.

Just don't see how to translate that data to the US with nobody here doing the same technique. It's exciting data but technique seems to be a (literal) PITA

 

[Doctorer]

Is anyone (in Europe, maybe?) doing HDR brachy (with a multichannel cylinder, maybe?) for these rectal boosts?