Logic behind different concurrent chemotherapy regimens

[TurboTesla]

Hello everyone,

As I'm studying for boards (on GI cancers now), I have been noticing the plethora of concurrent chemotherapy regimens that have been tried over the years and I'm trying to make sense of this information.

As general rules of thumb, do we expect certain concurrent chemotherapy regimens to work better in adenocarcinoma compared to SCC or vice versa? (5FU/cisplatin/carboplatin/etoposide/xeloda/epirubicin/leucovorin)

For example, why would you treat both SCC and adenocarcinomas of the anus or cervix with cisplatin over other regimens?

If a combination is used, is it typically driven by relatively independent toxicity profiles with potential additive/synergistic tumoricidal activities? (aka widening the therapeutic index)

If anyone has a paper/resource that helps clarify this it would be greatly appreciated.

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[elementaryschooleconomics]

Also studying for boards, also annoyed by this.

I don't have a single paper/resource tying this together, so if someone could show us, that would be great.

My general impression is everything has to do with 1) era of trial, 2) country of trial, 3) institution(s) within said country, 4) any other "convention" that has developed for whatever reason.

For example, head and neck. There's the GORTEC trials. GORTEC is done in France. Evidently, in France, they like(d) carbo/5FU for H&N. They also like(d) CDDP/5FU for GI malignancies. It's France, I guess that's what they do. We're expected to know the GORTEC stuff because...we're American RadOncs and we love trivia (they're also valuable trials). So, we normally do cisplatin for head and neck in America. However, we need to know about the Tata Memorial Trial comparing once a week to once every 3 week cisplatin. It's a good trial. But in India, they use 30 mg/m^2 of cis, while we (and others) use 40 mg/m^2 of cis. That trial asks (and answers) an interesting question, which is why we should know it, but it's hard to generalize to American medicine.

So, I've basically started paying attention to that. Whenever I come across a trial that does something different than what we're doing right now, I look for the timeline, the country, and the institution ("there's the right way, the wrong way, and the MD Anderson way"). Almost every time a trial deviates from something I consider "normal", one of those 3 factors comes into play.

Not a real answer, I know, but it helps me be less annoyed.

 

[ramsesthenice]

Chemo is largely a bonus on our oral boards and not something you need to worry too much about honestly. The only sections that really require much are peds and lymphoma since timing and use of specific regimens can affect RT. For all other sections you just have to be able to name an acceptable choice if asked. And know what drugs don’t go with RT

 

[TurboTesla]

This is more for the written exam, but these are actually questions I have been wanting to understand for a while now, especially the SCC vs adenocarcinoma concurrent chemo and whether certain chemo agents work better with one vs the other.

 

[RadOncDoc21]

If med onc had oral boards I’m sure the right answer pertaining to radiation would be to “omit radiation.”

 

[RadOncMegatron]

If med onc had oral boards I’m sure the right answer pertaining to radiation would be to “omit radiation.”

Guess how much push back I get from med Onc when I want to omit 50 Gy to the abdomen for anything. I’ll give you a hint rhymes with “hero.”

 

[ramsesthenice]

This is more for the written exam, but these are actually questions I have been wanting to understand for a while now, especially the SCC vs adenocarcinoma concurrent chemo and whether certain chemo agents work better with one vs the other.

Exactly. You are spot on: details on the written exams will be no where to be found on orals. On my oral boards they were all on the level of what is ABVD? How many cycles for X stage lymphoma? Ditto for pediatrics. At the end of my GU section (which I know I was crushing) they asked me what chemo I thought they would use if the seminoma were stage 2 instead of stage 1 and then followed it up with what does BEP stand for. Honestly I think they only did it because it was easier than starting a new case with only a few minutes left. I know a few examiners who confirmed my suspicion I would have been fine no matter what I said by that point. That said, your goal on orals is to avoid saying something straight up wrong. You can’t punt when they ask you what dose to give a stage 1 seminoma patient as an adjuvant, and you can’t punt on what chemo you would give someone with RT for cervical cancer, but you can say you don’t know what chemo they use for advanced testicular cancer. Probably better than taking a blind shot in the dark if you honestly don’t know. At one point someone showed me a pathology slide and asked me for the diagnosis and I straight up said it’s one of 2 diagnoses and I’d ask pathology for help. Didn’t seem to hurt me 🙂

 

[ramsesthenice]

Hello everyone,

As I'm studying for boards (on GI cancers now), I have been noticing the plethora of concurrent chemotherapy regimens that have been tried over the years and I'm trying to make sense of this information.

As general rules of thumb, do we expect certain concurrent chemotherapy regimens to work better in adenocarcinoma compared to SCC or vice versa? (5FU/cisplatin/carboplatin/etoposide/xeloda/epirubicin/leucovorin)

For example, why would you treat both SCC and adenocarcinomas of the anus or cervix with cisplatin over other regimens?

If a combination is used, is it typically driven by relatively independent toxicity profiles with potential additive/synergistic tumoricidal activities? (aka widening the therapeutic index)

If anyone has a paper/resource that helps clarify this it would be greatly appreciated.

Specific advise to your questions: keep it simple. Most GI cancers get concurrent Xeloda or FU. Just use carbo/tax for esophagus because it’s what most people use and they used it in CROSS. Just give FU/MMC for anal squams. Most of us treat adenos as rectal cancers (even in the anal canal) and SCCs as anal cancers (even if they are in the low rectum). I would be shocked if that was in your boards.

All cervical cancers get concurrent cis regardless of histology because we don’t have any compelling data otherwise even though the biology is probably different.

In short: do what they did in the major trials. If you go off course you may open the door to things that would never have come up organically.

 

[drewdog1973]

Do they ask chemo doses any more?
can you imagine medoncs getting asked RT doses? (I can’t; they ain’t idiots)

 

[HemeOncHopeful19]

Do they ask chemo doses any more?
can you imagine medoncs getting asked RT doses? (I can’t; they ain’t idiots)

As medonc I actually did have a question about dosing radiation for Hodgkin’s on an exam recently (missed it of course). I actually don’t recall any chemo dosing questions even on our exams... I feel like it’s more about recognizing when things need to be adjusted for renal/hepatic function and not the numbers themselves.

I got pimped on what BEP stood for last month (1st year fellow).

If you guys find a good source for concurrent chemoXRT regimens all organized in one place please send it my way

 

[RadOncDoc21]

Haha the radiation dose for a lymphoma question was the critical “omit radiation” one for the med onc.

 

[Palex80]

Haha the radiation dose for a lymphoma question was the critical “omit radiation” one for the med onc.

Correct answer is: "As low as possible".

 

[medgator]

Correct answer is: "As low as possible".

The proper acronym is ALARA

 

[ramsesthenice]

The proper acronym is ALARA

We should all make a concerted effort to get Alara on the top 10 hottest baby names within the next few years. Yep, this is the dark road COVID has led me down

 

[TheWallnerus]

We should all make a concerted effort to get Alara on the top 10 hottest baby names within the next few years. Yep, this is the dark road COVID has led me down

“Covid Alara” as a girls name almost sounds pretty.

 

[RadOncDoc21]

“Covid Alara” as a girls name almost sounds pretty.

Covida Alara... sounds exotic and dangerous!

 

[evilbooyaa]

Correct answer is: "As low as possible".

For lymphoma? Correct answer is zero on Med Onc boards lmao.

I know people may be curious as to the 'history' of stuff, but honestly most chemo is just following what some trial did. Others do something different just because their institution feels strongly about.

Let's just look at variations in practice of H&N:

Just look at what U Chicago did, on a trial, for locally advanced H&N cancer: Final Results of a Randomized Phase 2 Trial Investigating the Addition of Cetuximab to Induction Chemotherapy and Accelerated or Hyperfractionated Chemoradiation for Locoregionally Advanced Head and Neck Cancer - PubMed

weekly Cetux + CarboTaxol with concurrent Cetux/5-FU/HYDROXYUREA (wtf on the HU) with 1.5Gy BID RT that is given every OTHER week to a cumulative dose of 75Gy (like some split course ****)


Here's the thing - if I try to figure out WHY U Chicago picked these agents for chemo, let alone these RT doses and scheduling, my head would literally explode. But, for people at Chicago, this is just 'the norm'. This is how many H&Ns are treated, even off protocol.

Many an institution will have weird 'non-standard' ways of treating X. So deciding between q3 wk cis vs 40mg/m2 weekly cis for H&N (don't do 30/m2 as per Tata) is dealer's choice.

Why Cross did CarboTax but american trials historically did Cis/5-FU for Esophageal cancer is beyond me, and honestly, for purposes of oral boards, just stick with well known published trial in terms of your chemo dosing.

 

[elementaryschooleconomics]

I feel like it’s more about recognizing when things need to be adjusted for renal/hepatic function and not the numbers themselves.

Hahahaha

I am not infrequently pimped (or genuinely asked) about dosing and it takes a lot of restraint to not sarcastically fire back "it's not like I can prescribe it"

 

[TheWallnerus]

Hahahaha

I am not infrequently pimped (or genuinely asked) about dosing and it takes a lot of restraint to not sarcastically fire back "it's not like I can prescribe it"

Oh but you can suggest it! For example when a med onc gives thiotepa for lung cancer I can say “Hey... is that right?”

 

[Palex80]

Oh but you can suggest it! For example when a med onc gives thiotepa for lung cancer I can say “Hey... is that right?”

He's the treating the brain mets, silly boy! The ones you missed!

 

[Reaganite]

Hahahaha

I am not infrequently pimped (or genuinely asked) about dosing and it takes a lot of restraint to not sarcastically fire back "it's not like I can prescribe it"

"What chemotherapy should I give this patient, Rad Onc" said no medical oncologist ever.

 

[FrostyHammer]

"What chemotherapy should I give this patient, Rad Onc" said no medical oncologist ever.

But many of them are on such high horses that they routinely tell radoncs what radiation dose to give. SMH.

 

[evilbooyaa]

"What chemotherapy should I give this patient, Rad Onc" said no medical oncologist ever.

Probably not most, but I've had discussions of pros/cons of Xeloda + RT for neoadjuvant pancreas vs Gem + Hypofx RT for same indication (Preopanc) and my (mostly) community med oncs are open to discussions on whether somebody can handle single agent vs multi agent chemo in say concurrent management of bladder cancer... when to skip the weekly cis on the H&N patient that's having a rough go of it, etc.

 

[TheWallnerus]

Hello everyone,

As I'm studying for boards (on GI cancers now), I have been noticing the plethora of concurrent chemotherapy regimens that have been tried over the years and I'm trying to make sense of this information.

As general rules of thumb, do we expect certain concurrent chemotherapy regimens to work better in adenocarcinoma compared to SCC or vice versa? (5FU/cisplatin/carboplatin/etoposide/xeloda/epirubicin/leucovorin)

For example, why would you treat both SCC and adenocarcinomas of the anus or cervix with cisplatin over other regimens?

If a combination is used, is it typically driven by relatively independent toxicity profiles with potential additive/synergistic tumoricidal activities? (aka widening the therapeutic index)

If anyone has a paper/resource that helps clarify this it would be greatly appreciated.

I just remembered this from a long time ago. Sort of applies to what you're asking and echoes @ramsesthenice. Little data. In essence: treat the histology more than the site.



Papagikos M, Crane CH, Skibber J, Janjan NA, Feig B, Rodriguez-Bigas MA, Hung A, Wolff RA, Delclos M, Lin E, Cleary K
Chemoradiation for adenocarcinoma of the anus.
Int J Radiat Oncol Biol Phys 2003 Mar 01;55(3) 669-78

JOEL TEPPER, MD
I did not pick this article for the journal club because it was such an exceptional article, but rather because it raises an issue that I don't think is that rare but on which there is little information regarding management. I also liked it since the conclusions were concordant with my management strategy for this clinical situation. Specifically, there are a moderate number of patients who present with either a rectal histology in the anal canal or an anal canal histology in the rectum and there is little in the literature to guide as to how to manage these patients.

I think that the histology of the tumor is more important than the location of the tumor as far as response to therapy. By “histology” I don't mean just what the tumor looks like under the microscope but what it likely implies regarding the cell and site of origin. Therefore, an anal canal adenocarcinoma, especially one that is mucinous, should respond more like an adenocarcinoma of the rectum and not have a high likelihood of control with primary radiation therapy combined with 5-FU and mitomycin (or platinum). Although it is not addressed in this article, this approach would also suggest that a cloacogenic carcinoma located in the rectum would be successfully managed without surgical resection.

This paper supports the argument regarding adenocarcinomas in the anal canal. The local recurrence rate with non-surgical management was high, with many of the controlled tumors being those which had a previous resection and where the amount of residual disease was likely small. One should keep in mind that it is usually not clear whether the tumor is originating in an anal duct or in rectal mucosa. Sometimes we are surprised when differing histologies respond in a similar manner (esophageal squamous and adenocarcinomas come to mind), but there is no reason to think that the site of origin will determine the radiation and chemotherapy responsiveness. Generally I think these adenocarcinomas should be managed with surgery as the primary therapeutic modality with radiation therapy and chemotherapy used as an adjuvant depending on disease extent. For the tumors with an anal histology in the rectum I have usually treated the patients as if they had anal canal tumors (in terms of radiation and drug delivery, not in terms of fields which are controlled by anatomy), reserving surgery for a salvage procedure or for poor response.

 

[ramsesthenice]

I just remembered this from a long time ago. Sort of applies to what you're asking and echoes @ramsesthenice. Little data. In essence: treat the histology more than the site.



Papagikos M, Crane CH, Skibber J, Janjan NA, Feig B, Rodriguez-Bigas MA, Hung A, Wolff RA, Delclos M, Lin E, Cleary K
Chemoradiation for adenocarcinoma of the anus.
Int J Radiat Oncol Biol Phys 2003 Mar 01;55(3) 669-78

JOEL TEPPER, MD
I did not pick this article for the journal club because it was such an exceptional article, but rather because it raises an issue that I don't think is that rare but on which there is little information regarding management. I also liked it since the conclusions were concordant with my management strategy for this clinical situation. Specifically, there are a moderate number of patients who present with either a rectal histology in the anal canal or an anal canal histology in the rectum and there is little in the literature to guide as to how to manage these patients.

I think that the histology of the tumor is more important than the location of the tumor as far as response to therapy. By “histology” I don't mean just what the tumor looks like under the microscope but what it likely implies regarding the cell and site of origin. Therefore, an anal canal adenocarcinoma, especially one that is mucinous, should respond more like an adenocarcinoma of the rectum and not have a high likelihood of control with primary radiation therapy combined with 5-FU and mitomycin (or platinum). Although it is not addressed in this article, this approach would also suggest that a cloacogenic carcinoma located in the rectum would be successfully managed without surgical resection.

This paper supports the argument regarding adenocarcinomas in the anal canal. The local recurrence rate with non-surgical management was high, with many of the controlled tumors being those which had a previous resection and where the amount of residual disease was likely small. One should keep in mind that it is usually not clear whether the tumor is originating in an anal duct or in rectal mucosa. Sometimes we are surprised when differing histologies respond in a similar manner (esophageal squamous and adenocarcinomas come to mind), but there is no reason to think that the site of origin will determine the radiation and chemotherapy responsiveness. Generally I think these adenocarcinomas should be managed with surgery as the primary therapeutic modality with radiation therapy and chemotherapy used as an adjuvant depending on disease extent. For the tumors with an anal histology in the rectum I have usually treated the patients as if they had anal canal tumors (in terms of radiation and drug delivery, not in terms of fields which are controlled by anatomy), reserving surgery for a salvage procedure or for poor response.

Joel Tepper is one of the more thoughtful rad oncs you will ever meet but yes that is a way more detailed way of saying the same thing.

Since this thread was about oral boards I’ll echo this is the nice thing about the oral format: you get a chance to explain your thinking. As long as you acknowledged that the local failure rate is going to be higher for an adenocarcinoma and that they are likely to need surgery you would pass either way. Unlike on written exams when the only thing that matters was the intent of the question writer.

 

[TheWallnerus]

Joel Tepper is one of the more thoughtful rad oncs you will ever meet but yes that is a way more detailed way of saying the same thing.

Since this thread was about oral boards I’ll echo this is the nice thing about the oral format: you get a chance to explain your thinking. As long as you acknowledged that the local failure rate is going to be higher for an adenocarcinoma and that they are likely to need surgery you would pass either way. Unlike on written exams when the only thing that matters was the intent of the question writer.

Very thoughtful guy. Have got to speak to him many times. Here's tonight's trivia. First, he oversaw the first use of real 3DCRT and "virtual simulation" and digitally reconstructed radiographs in the U.S. Second, he became a gastric cancer expert. And then he got gastric cancer. That was a very long time ago. Thus he is therefore definitely the longest term survivor of gastric cancer I know.

 

[RickyScott]

Very thoughtful guy. Have got to speak to him many times. Here's tonight's trivia. First, he oversaw the first use of real 3DCRT and "virtual simulation" and digitally reconstructed radiographs in the U.S. Second, he became a gastric cancer expert. And then he got gastric cancer. That was a very long time ago. Thus he is therefore definitely the longest term survivor of gastric cancer I know.

I don’t think he got radiation!