“Even in fabled Atlantis, the night that the ocean engulfed it,The drowning still cried out for their slaves. “
Yea folks we have many questions. Many questions, indeed! the field is sinking. The Chairs are ignoring truth in their fake Dubai-esque parody of reality. As the final parts of the atlantis sink, the chairs are still thirsty for warm bodies. Medical students please don’t leave! Who will do my work? Who will write my stupid retrospective reviews? Who will wipe my chin when i drool? Who will boost my ego after i look in the mirror in the morning?
Many questions into the sinking, a silent harmonious answer to our fabled end as the haggard daylight steers toward a deep monotone.
RIP
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- Apr 3, 2019
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Honestly I am not sure why I've not shoved all in on 5 fraction rectal.
Oh I know why. When I send my patients back to the academic place for surgery the patient gets told I might have given them unsafe radiotherapy.
Is it really good data, though? A 90-person, single-arm, single-institution trial? Is that even remotely good enough to move the field? Sure, it's hypothesis-generating, but I would say that's about it.
Rapido study had many patients that didn’t undergo surgery for whatever reason, and their outcome mirrors other non-operative management studies. There is a study running at WashU I think for non-operative with short course as the RT component.
25/5 is gonna take religious style conversion. I would bet if a person did 5 cases on people they’d do long course typically on, they would see the outcome and likely utilize it more. It’s just too much of a jump for many people.
We tend to do SCRT for most rectal cases, with caveat being for those who “need heroic downstaging” being considered for long course. And we do for non-operative, but the data doesn’t isn’t better one way than the other. People tend to mood affiliate and lean towards long or short depending on their priors.
Which, at the end of the day, is completely fine! Both lead to great outcomes. Modern treatment of rectal cancer is fantastic and continues to improve.
- Nov 2, 2019
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For me, in my community, it's more about managing expectations of the referring docs. I'm currently trying to get everyone who has been practicing for 20 years on the TNT train, I shudder to think about trying to convince them that 25/5 is OK.
On the RadOnc side, I think those of us who trained in a more modern era can adopt this more easily, but the pre-IMRT RadOncs will fight me on it. Obviously this is just local politics for me, and my experience might not be generalizable to the rest of you.
I led a group meeting of all members that would be treating rectal cancer in the area, which included my private practice RO competitors (who are wonderful - every region needs hospital folks and private folks - it’s better for the community). The data spoke to the group. It was actually really helpful to go through it detail with the multi D team. It made sense for our patients.
- Apr 3, 2019
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But goshdangit galdarnit 25/5 is not "new" by a long shot, antedates IMRT, and was one of a vanishing few trials of the 20th century to show a survival advantage from radiotherapy application (and maybe unless I'm forgetting something one of the most significant p-value survival advantages from RT of all time). I like to quote this trial from time to time to hint that US docs don't read, or hate non-US data (they used to hate it very much so), and/or are hypocritical.
- Nov 2, 2019
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That's a good idea. I feel like this is a "herding cats" situation for me right now, but I'm probably being unfairly pessimistic about it.
It’s really too bad academic centers work this way. I wonder if there would be a way to have an open conversation about this. Or @OTN and MDACC to have it out and listen at how damaging and one-sided the relationship feels. I felt that way with JHH when I worked in DC area, but UMaryland was an excellent partner. Truly collegial. In AZ, there was no academic center. Allegedly, we were “Banner University Medical Center” but not really academic.
I'm a huge fan of 25 / 5; and participated in the RAPIDO trial. Easier on the patient, good results; easier for the patient and the oncologists, and has level 1 evidence from at least TWO prospective, randomized studies that it's either better or not worse (RAPIDO, Polish-2). It does take different communication with the patient due to the proctitis happening after the radiation is complete...
This latest WashU report builds on a long WashU legacy to let people know that there isn't something magical about US rectal cancer patients as opposed to European ones! After doing SCRT -> immediate surgery for several years there, a nice prospective, phase II study with SC-TNT came out (Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer - PubMed)
I don't think the WashU report on it's own moves the needle; but it continues to investigate the regimen for organ preservation, and has patients with less advanced disease than RAPIDO. It includes the population that may be recommended for NO RADIATION after PROSPECT reports out. And it shows that this population may have good organ preservation with SC-TNT. That's going to keep radiation therapy involved in these 'bi-modality' patients; who may do equally well with RT+chemo; chemo+surgery; or maybe even RT+surgery.
The key trial for the organ preservation, of course, is going on in Europe in Germany. They are randomizing patients between long course chemoradiation + chemo VERSUS short course radiation + chemo; essentially OPRA vs RAPIDO with the endpoint of cCR. Short-course Radiotherapy Versus Chemoradiotherapy, Followed by Consolidation Chemotherapy, and Selective Organ Preservation for MRI-defined Intermediate and High-risk Rectal Cancer Patients - Full Text View - ClinicalTrials.gov.
With regards to changing practices... I brought short course radiation and TNT to our practice a few years ago; with many colleagues who had 20 years plus of experience. It took about 1 year to change the practice; and definitely to have some flexibility when starting out. I should collect our path outcomes both before and after the change; but anecdotally patients are doing quite similarly.
And, it's interesting that the two NCCN centers in our area do not use short course radiation routinely! But none have the temerity to point out that the radiation I delivered was 'inappropriate'! Cause, you know, data.
This latest WashU report builds on a long WashU legacy to let people know that there isn't something magical about US rectal cancer patients as opposed to European ones! After doing SCRT -> immediate surgery for several years there, a nice prospective, phase II study with SC-TNT came out (Five fractions of radiation therapy followed by 4 cycles of FOLFOX chemotherapy as preoperative treatment for rectal cancer - PubMed)
I don't think the WashU report on it's own moves the needle; but it continues to investigate the regimen for organ preservation, and has patients with less advanced disease than RAPIDO. It includes the population that may be recommended for NO RADIATION after PROSPECT reports out. And it shows that this population may have good organ preservation with SC-TNT. That's going to keep radiation therapy involved in these 'bi-modality' patients; who may do equally well with RT+chemo; chemo+surgery; or maybe even RT+surgery.
The key trial for the organ preservation, of course, is going on in Europe in Germany. They are randomizing patients between long course chemoradiation + chemo VERSUS short course radiation + chemo; essentially OPRA vs RAPIDO with the endpoint of cCR. Short-course Radiotherapy Versus Chemoradiotherapy, Followed by Consolidation Chemotherapy, and Selective Organ Preservation for MRI-defined Intermediate and High-risk Rectal Cancer Patients - Full Text View - ClinicalTrials.gov.
With regards to changing practices... I brought short course radiation and TNT to our practice a few years ago; with many colleagues who had 20 years plus of experience. It took about 1 year to change the practice; and definitely to have some flexibility when starting out. I should collect our path outcomes both before and after the change; but anecdotally patients are doing quite similarly.
And, it's interesting that the two NCCN centers in our area do not use short course radiation routinely! But none have the temerity to point out that the radiation I delivered was 'inappropriate'! Cause, you know, data.
- Jul 26, 2007
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I was converted by force to 25/5 by my institution upon arrival; they are very aggressive about it.
Initially I hated it, and the short term proctitis is real - generally worse than I see with long course. Seems like patients either do fantastic or terrible shortly after finishing. However, I strongly dislike treating any GI so it moves these patients along quicker and the (anecdotal) post-surgical outcomes have been fantastic. I also don't see too many rectal cancers so it doesn't make a huge impact on my practice metrics.
Our institutional protocol is 25/5 for all with exception of very low tumors or any consideration for watch/wait style. At least I don't have to worry about any surgeons accusing me of "inappropriate" care.
Initially I hated it, and the short term proctitis is real - generally worse than I see with long course. Seems like patients either do fantastic or terrible shortly after finishing. However, I strongly dislike treating any GI so it moves these patients along quicker and the (anecdotal) post-surgical outcomes have been fantastic. I also don't see too many rectal cancers so it doesn't make a huge impact on my practice metrics.
Our institutional protocol is 25/5 for all with exception of very low tumors or any consideration for watch/wait style. At least I don't have to worry about any surgeons accusing me of "inappropriate" care.
- Apr 3, 2019
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To ruminate on RickyScott's point for those reading who aren't in rad onc...
1. 1970's seminoma paper from MDACC:
2. Then we all just sort of decided chest RT for seminoma was a little much.
3. Then the dog leg got eliminated.
4. Then the RT dose got reduced.
5. Then a drug seemed to be better than the RT.
6. Then the options became surveil, risk-adapt w/ chemo, or, according to the NCCN, RT if the patient begs on his hands and knees for it but you have to tell him long-term side effects are greater.
As time went on we did less and less. How'd the B.A.L.L.S. initiative go @Gfunk6?
For GI: 1)gastric xrt eliminated. 2) anal cancer will disappear in 2030s w/vaccine 3) pancreas XRT- large studies continue to disappoint. preop Esophageal XRT= FLOT (one drug away from being eliminated) Rectal cancer: In setting of LAR, absolute benefit of XRT is very low and again one drug away from being eliminated and most pts are now candidate for 5 fractions. Sure, xrt for non operative manangement of rectal cancer is promising, and can also be given in 5 fractions, but minority of rectal cases.
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We have a surg onc that is really into watch and wait. So I've been very reluctant to use 5 fraction for these.
Maybe I need to revisit this?
I'm very comfortable with 5 fraction for patients surely going to surgery...but for these cases where surgeon is on board (and hoping) not to operate, I've stuck with long course.
Maybe I need to revisit this?
I'm very comfortable with 5 fraction for patients surely going to surgery...but for these cases where surgeon is on board (and hoping) not to operate, I've stuck with long course.
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Feel exactly the same way. One question I have is TNT with significant nodal disease. I remember Chris Crane on mednet discussing what is actually taken out with TME and noting that pelvic sidewall nodes and higher nodes near iliac bifurcation not typically removed. I like to dose escalate these nodes with standard fractionation close to 60 Gy (or some dose painted equivalent).
Is there an equivalent strategy with 5 fxn treatment?
I am very skeptical of 25/5, especially for NOM. Based on what we know/believe about BED and alpha/beta, LC has significantly higher BED than SC. If SC does prove to be equivalent to LC for in NOM for big T3 tumors, I will have an existential crisis and throw my Hall book in a dumpster fire.
It's gone great! I have not treated a seminoma in 10 years. I can only assume this means that these insanely complex and high-dose treatments are being performed using IMPT on a registry trial at academic medical centers.
Please, don’t be ridiculous, hyperbole like this isn't helpful!
They’re not on a registry.
Findings from Rapido study:
Probability at three years of distant metastasis and locoregional failure were, in the experimental and standard arms, 19.8% vs 26.6% (HR 0.69 [0.53 – 0.89]; p = 0.004) and 8.7% vs 6.0% (HR 1.45 [0.93 – 2.25]; p = 0.10), respectively.
Reception of more systemic therapy in the exp arm may have also reduced LRF a little more as well. In any case, possibly a 3% improvement in LRF for an extra 4 weeks of RT.
Probability at three years of distant metastasis and locoregional failure were, in the experimental and standard arms, 19.8% vs 26.6% (HR 0.69 [0.53 – 0.89]; p = 0.004) and 8.7% vs 6.0% (HR 1.45 [0.93 – 2.25]; p = 0.10), respectively.
Reception of more systemic therapy in the exp arm may have also reduced LRF a little more as well. In any case, possibly a 3% improvement in LRF for an extra 4 weeks of RT.
Like I said, possibly. We are a specialty good at powering trials for one thing to conclude other things. Kinda like powering a trial comparing breast schemes for local control in order to conclude toxicity equivalence.
That's the big issue many of us have with that study, not a pure sc vs LC comparison. Hopefully data from those more recently accruing trials will clear things up
The European trial will, of course, tell us the answer. Do we even bother to try RCTs anymore in the US?
- Apr 3, 2019
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I would marry alpha beta if I could! It always tells the whole story, if you use the right alpha beta. The BED of 25/5 is bigger than 50.4/28... with the right alpha beta.*† (And sometimes all the cells in the same tumor refuse to tell the same alpha beta story.)
* and time correction factors
† α/β≤~3.8 (with ~0.5 per day BED-lessening correction factor), α/β≤~1.3 (with no time correction)
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- Oct 10, 2011
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As a not very common user of 25/5, the Wash U study is interesting to me.
RAPIDO told me that TNT is probably better than ChemoRT/SC RT alone --> Surgery --> Chemo in an unselected population.
I agree with @elementaryschooleconomics that trying to get non-academic CRS on TNT can be a struggle on it's own.
Historically, my concern with watch and wait was whether LC was better than SC. I'd be intersted in seeing OPRA results compared to this Wash U paper.
@OTN , It's not the highest quality data to suggest that short course for non-op management is MANDATORY, but it does provide data (at least to me) that it's a reasonable tx paradigm.
As APM approaches closer and closer for the general population, we should all be ready to be willing to pivot to a shorter, equal fractionation. Not mandatory, but an option.
RAPIDO told me that TNT is probably better than ChemoRT/SC RT alone --> Surgery --> Chemo in an unselected population.
I agree with @elementaryschooleconomics that trying to get non-academic CRS on TNT can be a struggle on it's own.
Historically, my concern with watch and wait was whether LC was better than SC. I'd be intersted in seeing OPRA results compared to this Wash U paper.
@OTN , It's not the highest quality data to suggest that short course for non-op management is MANDATORY, but it does provide data (at least to me) that it's a reasonable tx paradigm.
As APM approaches closer and closer for the general population, we should all be ready to be willing to pivot to a shorter, equal fractionation. Not mandatory, but an option.
- Nov 2, 2019
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- Oct 10, 2011
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I've been using short course TNT for just about everyone with locally advanced rectal cancer, including W&W since 2014... helps that my job has a Polish med onc; so he's totally on-board! But I do support the equipoise that we don't know for sure in the W&W setting the SC-TNT vs the LC-TNT.
The alpha/beta arguments and the non-statistically significant difference in local control are boomer arguments! That Hall textbook is about as relevant as the decay curve of a Co-60 teletherapy unit by now; and should be limited to the ABR board hazing only! And to not offer a patient 4 weeks of their life back for a numerical difference in local control that has a p=.10 is also silly.
The better argument for long course rectal cancer chemoradiation is the lack of W&W data; and lack of integration of SC-TNT with the rest of your treatment team (med onc, surgery).
Has anyone tried the FOLFOXIRI -> long course in the French study? I don't have the cajones to do it for locally advanced rectal cancer; but have seen some young patients with metastatic disease with a good response who have been referred in for the radiation...
The alpha/beta arguments and the non-statistically significant difference in local control are boomer arguments! That Hall textbook is about as relevant as the decay curve of a Co-60 teletherapy unit by now; and should be limited to the ABR board hazing only! And to not offer a patient 4 weeks of their life back for a numerical difference in local control that has a p=.10 is also silly.
The better argument for long course rectal cancer chemoradiation is the lack of W&W data; and lack of integration of SC-TNT with the rest of your treatment team (med onc, surgery).
Has anyone tried the FOLFOXIRI -> long course in the French study? I don't have the cajones to do it for locally advanced rectal cancer; but have seen some young patients with metastatic disease with a good response who have been referred in for the radiation...
- Nov 2, 2019
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I have a dream,
that one day future residents will practice in a specialty,
where they are not tested on their ability to memorize and regurgitate irrelevant trivia,
but on their ability to practice compassionate and and effective medicine.
The issue I have with 5 x 5 in w&w is that sometimes it works, and in this setting, that's good enough, because there's always surgery. Not much pressure to do any more than work every now and then. Is 54-56 gy plus xeloda more likely to cure rectal cancer than 5x5? I'll do a side bet for a really expensive bourbon at the next astro I attend.
Sometimes it works? Why do you say sometimes?
Your baseline belief is that 25/5 is ‘less than’ in terms of efficacy. As long as you have that bias, the rest of the conversation is hard to have
Because sometimes it does. Sometimes long course dose too. Only an rct will determine which does it better, and one rct hints that a lower dose long course regimen (50.4 vs 54-56) is slightly better at controlling residual microscopic disease than short course. The idea that a five fx regimen thats barely more aggressive than a 5 fx palliative regimen would be used in the definitive setting seems weird. I'll trust the data, and buy the bourbon, if I'm wrong.
This is mood affiliation in action. The pCr rate in rapido trial is impressive, amongst highest reported. As the honorable alligator asks, is it the chemotherapy or the SCRT? I answer - “yes”.
Give it a try. But beware the pelvic and abdominal spasms in week 1-2 after treatment. We have a handout made for this, with some people pre writing RXs
It’s not bad to do LCRT, I’m not judging anybody. I think the problem, personally, is this is an advance for patients but we get punished to do it. This is a big problem in RO, in general.
sometimes I think about what I would/will want as a patient. changes from time to time. how I feel right now:
I would actively demand/want 5 fraction partial breast
would want prostate sbrt
I would lean towards wanting 25/5 but would be fine with either. 5.5 weeks is a long time to deal with the worsening acute toxicity, having to be on the table with it, etc
I would be fine with any of 1,5,or 10 fraction for my bone mets. would prob pick 5, but that's not data based, just a little bit of wishful thinking.
I would prefer 54/3 or 50/5 over 34/1 for my stage 1 lung cancer.
I would actively demand/want 5 fraction partial breast
would want prostate sbrt
I would lean towards wanting 25/5 but would be fine with either. 5.5 weeks is a long time to deal with the worsening acute toxicity, having to be on the table with it, etc
I would be fine with any of 1,5,or 10 fraction for my bone mets. would prob pick 5, but that's not data based, just a little bit of wishful thinking.
I would prefer 54/3 or 50/5 over 34/1 for my stage 1 lung cancer.
Pcr in SC double lc, 27% vs 13%, yet somehow trending towards worse lrf, or equivalent... In any case, using the results of a trial comparing the short course regimen to a long course regimen nobody uses in the definitive setting doesn't seem right.
