Colorectal ADK in 95 yo patient

[Kroll2013]

Dear colleagues,

I have a 95 yo female patient, very well conserved, ambulant . No severe comorbidities.
She presented for low rectum ademocarcinoma invading partially the internal anal sphincter with no fecal incontinence.
She complains of post defecation pain and rectorrhagia.
Pelvic MRI showed no LNs.
She is not operable.
She will receive xeloda with concomitant radiation.
What would you propose as for dose and fractionation?
-45/25 with boost to small pelvis and tumor
- 25 in 5 even if no following surgery
- palliative RT : 30/10 or 37.5 in 15


Thank you


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[medgator]

You wouldn't go higher than 45 at all? Generally 50.4 is the standard/conventional fractionation dose with chemo in the U.S. for preoperative therapy.

I'd prob push for 59.4-63 Gy if I knew surgery wasn't happening and the pt was in reasonable shape.

Xeloda isn't a walk in the park either, that will probably be tougher to get her through than the radiation

 

[Palex80]

I'd also push for a higher dose: 54-59.4 Gy.
I'd consider doing "limited field" RT in her case, meaning I would only irradiate the mesorectal LN and leave out the iliac LN.
The risk of isolated nodal failure in this areas is probably small and you would certainly spare her toxicity. She is cN0 after all.
You could consider to hypofractionate in the boost phase if she tolerates treatment well: 45/25 + 10/2.5 for example?

 

[nkmiami]

I have had a couple cases like this and treated just the tumor + margin to 60 gy. Usually I get a pet, and put 1-1.5 cm margin, and daily image guidance to avoid treating too much inferiorly as perianal skin toxicity is the main acute toxicity (which can lead her to quit treatment).

 

[nkmiami]

the problem with 30/10 etc is it will just be back within 6 months to a year, and her performance status can't be that bad if they offered her xeloda.

 

[napoleondynamite]

I like 25/5 no chemo or surgery. Likely will control the disease the rest of her life without hurting or killing her.

If she's super fit & active, I agree with above push to 60Gy. But she should understand definitive treatment probably has a 50/50 chance of killing her

 

[seper]

I would treat her with small field, to 55-60 Gy. Going over 60 Gy risks anal sphincter toxicity.

 

[evilbooyaa]

Would consider at least 54Gy w/ conventional fractionation, sequential boosts. You could start with 45/25 to standard rectal fields (consider IMRT or prone positioning to spare bowel), and if there's toxicity you could shrink fields early.

I wouldn't do a palliative course if she's going to live more than 6 months.

 

[BobbyHeenan]

Agree with others. I would do 3-D conformal, maybe skimp some on upper coverage to spare small bowel just like Palex has said - don't worry about covering those upper internal iliacs at the expense of giving her small bowel dose..especially if she's getting xeloda. Boost to 55.8ish. Wouldn't go over 60.

 

[OTN]

59.4 Gy with concurrent Xeloda. IMRT/daily CBCT should help dramatically with tolerance. I've treated several octo- and nonagenarians with this regimen with good results, well-tolerated, etc.

 

[Reaganite]

I like Palex's approach. For these patients where I question tolerance, I'll often start with the boost instead of the bigger pelvic field. This gives me some time to gauge their response. So I'd probably do 14.4-19.8Gy-ish to the tumor alone and if doing okay, expand to some sort of mini-pelvic field mainly to target the perirectal nodes another 40-45 depending on the boost dose I gave.

 

[napoleondynamite]

I'm intrigued by the majority opinion on here being to treat with chemoRT to 54-60Gy.

(*braces self)

Are you guys saying you think local control (or heck, survival too?) with that approach will be better than just treating with RT alone 25/5?

I just don't see a reason to put a 95 year-old through standard chemoRT when you have a much less toxic option on the table that will be much easier for all involved.. help me see the light

 

[medgator]

I'm intrigued by the majority opinion on here being to treat with chemoRT to 54-60Gy.

(*braces self)

Are you guys saying you think local control (or heck, survival too?) with that approach will be better than just treating with RT alone 25/5?

I just don't see a reason to put a 95 year-old through standard chemoRT when you have a much less toxic option on the table that will be much easier for all involved.. help me see the light

Honestly I think you bring up a good point. I wouldnt treat conventional fx unless the med onc felt the pt was fit enough for xeloda..... but if the pt really could tolerate xeloda (and 95 is pretty darn old, even in FL), wouldn't you want to give them the benefit of the doubt?

 

[Gfunk6]

I'm intrigued by the majority opinion on here being to treat with chemoRT to 54-60Gy.

(*braces self)

Are you guys saying you think local control (or heck, survival too?) with that approach will be better than just treating with RT alone 25/5?

I just don't see a reason to put a 95 year-old through standard chemoRT when you have a much less toxic option on the table that will be much easier for all involved.. help me see the light

I personally treat 39/3 with Xeloda based on a few published Phase I/II trials in elderly patients. 25/5 is pretty explicitly a preop dose so may be no better than 30/10.


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[evilbooyaa]

Honestly I think you bring up a good point. I wouldnt treat conventional fx unless the med onc felt the pt was fit enough for xeloda..... but if the pt really could tolerate xeloda (and 95 is pretty darn old, even in FL), wouldn't you want to give them the benefit of the doubt?

This. If med-onc feels she's good enough for Xeloda, I'm not going to short change her chances. 25/5 is not a dose that will give her any significant chance of pCR, and I disagree that it won't cause side effects.

It's hard to make this judgement call without the patient directly in front of us. Multiple options are certainly worth a discussion with her.

I personally treat 39/3 with Xeloda based on a few published Phase I/II trials in elderly patients. 25/5 is pretty explicitly a preop dose so may be no better than 30/10.


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I would be very interested in those studies names, or links to pubmed, if you got 'em. Always good to have some stuff in your back pocket for a scenario like this.

 

[OTN]

I'm intrigued by the majority opinion on here being to treat with chemoRT to 54-60Gy.

(*braces self)

Are you guys saying you think local control (or heck, survival too?) with that approach will be better than just treating with RT alone 25/5?

I just don't see a reason to put a 95 year-old through standard chemoRT when you have a much less toxic option on the table that will be much easier for all involved.. help me see the light

25/5 has data only for preop - for definitive treatment, chemoRT has the only available data. I do believe fractionated chemoRT would provide better local control and survival compared with 25/5.

 

[evilbooyaa]

As an aside, can I ask what ADK means? Does it mean AdenoKarcinoma? I feel like that's what folks in Mortal Kombat get. Or, maybe, germany?

 

[napoleondynamite]

Honestly I think you bring up a good point. I wouldnt treat conventional fx unless the med onc felt the pt was fit enough for xeloda..... but if the pt really could tolerate xeloda (and 95 is pretty darn old, even in FL), wouldn't you want to give them the benefit of the doubt?

Benefit of the doubt meaning try for definitive treatment? Personally - I would not. Granted, it is a judgement call. But to me, putting this patient through chemoRT with plans for surgery is more likely to do harm than good.

Unless we aren't talking about surgery afterward? But if we are not - then what is the point of chemoRT? Wouldn't we all agree that barring surgery, this is palliative treatment?

In my mind, the least harm with the biggest bang for the buck is 25/5 - which seems at least comparable to a much more aggressive course of (palliative!) chemoRT.

I admit I am clearly in the minority opinion. Cases like these have been presented in tumor boards in the past with 4-5 radoncs there and I have been the outlier recommending this approach with everyone looking at me cross-eyed.

I wonder what a European tumor board would recommend if this were presented?

I guess part of the issue boils down to how likely you think surgery would be. To me, surgery in most 95 year-olds probably has more risk to their life than the cancer.

 

[napoleondynamite]

I personally treat 39/3 with Xeloda based on a few published Phase I/II trials in elderly patients. 25/5 is pretty explicitly a preop dose so may be no better than 30/10.


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I am interested in these trials too.. Do those trials suggest 39/3 with Xeloda is potentially curative in patients who are not surgical candidates or you just believe in a more durable palliation with that approach?

 

[medgator]

Benefit of the doubt meaning try for definitive treatment? Personally - I would not. Granted, it is a judgement call. But to me, putting this patient through chemoRT with plans for surgery is more likely to do harm than good.

Unless we aren't talking about surgery afterward? But if we are not - then what is the point of chemoRT? Wouldn't we all agree that barring surgery, this is palliative treatment?

In my mind, the least harm with the biggest bang for the buck is 25/5 - which seems at least comparable to a much more aggressive course of (palliative!) chemoRT.

I admit I am clearly in the minority opinion. Cases like these have been presented in tumor boards in the past with 4-5 radoncs there and I have been the outlier recommending this approach with everyone looking at me cross-eyed.

I wonder what a European tumor board would recommend if this were presented?

I guess part of the issue boils down to how likely you think surgery would be. To me, surgery in most 95 year-olds probably has more risk to their life than the cancer.

I am referring to nonsurgical tx with chemo/xrt

There are studies out there regarding deferring surgery...

http://ascopubs.org/doi/abs/10.1200/JCO.2011.37.7176

I think there is a chance the pt would be cured without surgery and if she is medically fit and willing to proceed, it's a worth a shot

 

[Burt Radnolds]

I would advocate for definitive chemoradiation unless you are fairly sure she has a very limited life expectancy and/or the patient isn't interested in the logistics and toxicity of it.

Unless we aren't talking about surgery afterward? But if we are not - then what is the point of chemoRT? Wouldn't we all agree that barring surgery, this is palliative treatment?

No, I do not entirely agree with this. There is an evolving paradigm that we can manage some of these patients nonsurgically (Local recurrence after complete clinical response and watch and wait in rectal cancer after neoadjuvant chemoradiation: impact of salvage therapy o... - PubMed - NCBI). While she may not be a complete responder, she would still get more durable palliation than 30/10 or 25/5.

I have seen several very fit metastatic patients get treated with palliative radiation to a rectal mass, in addition to FOLFOX etc, and still recur within 2 years with very morbid difficult to treat local failures.

If you do not choose to do full dose conventional chemoradiation, I think some of the other mentioned approaches may buy you more efficacy. Also, you can always abort treatment if it ends up being too much, and what you have done with still likely amount to high dose palliation, more durable than 30/10, 25/5, etc.

 

[OTN]

I was talking about definitive chemoRT without surgery. I think short-course RT has too great of a potential for pelvic failure, which would be disastrous.

 

[evilbooyaa]

As others have stated, I would think that most people suggesting conventional fractionation mean for it in a definitive setting, hence the higher doses than standard 45 or 50.4 neoadjuvant doses of radiation.

I doubt that many (if any) of us are recommending a LAR or APR for a 95-year old.

The Habr-Gama group (per radmonckey above) out of Brazil were (I think) the first ones to publish on watch and wait after what was originally planned as neoadjuvant chemoradiation, and it's being done more frequently now (seems like at least 1 or maybe more groups out of Netherlands now). I'm not familiar with any phase 3 trials of it comparing to non-surgical management, and I'm not sure if we'll ever definitively see those trials in patients with a cCR.

 

[napoleondynamite]

Ok, I see where you guys are coming from. I just don't see the evidence that chemoRT is any better than 25/5. You can choose to 'defer surgery' after either chemoRT or 25/5.

We're not talking about systemic chemo. We're talking about radiosensitizing chemo since you're only using 1.8Gy per fraction. And this package comes at a significant toxicity price in most elderly patients. This package was designed in an era when radiation technology needed the help of chemo - before CBCT capability and our ability to safely dose escalate. Knowing what we know about SBRT or other dose escalated packages, do you believe we need a radiosensitizer in this situation to provide what is very likely just durable palliation and local control?

I personally believe you're just as likely to control this using 5Gy per fraction to 25Gy. Again, I know I am in the minority opinion here - but I see this less as an area of applying data like we are used to doing and more of an oncologic common sense situation. Patient has a local problem and cure without surgery is very unlikely. I do not see any convincing data that chemoRT offers better local control than RT alone.

I would love to be proven wrong - if there is any data, show me. But I would need to be pretty positive that I'm offering a superior option with chemoRT - and I'm just not convinced that is the case. I would bet that CR rates are comparable with 25/5 and chemoRT - we don't know because the timing of surgery in the pre-op trials.

 

[nkmiami]

Ok, I see where you guys are coming from. I just don't see the evidence that chemoRT is any better than 25/5. You can choose to 'defer surgery' after either chemoRT or 25/5.

We're not talking about systemic chemo. We're talking about radiosensitizing chemo since you're only using 1.8Gy per fraction. And this package comes at a significant toxicity price in most elderly patients. This package was designed in an era when radiation technology needed the help of chemo - before CBCT capability and our ability to safely dose escalate. Knowing what we know about SBRT or other dose escalated packages, do you believe we need a radiosensitizer in this situation to provide what is very likely just durable palliation and local control?

I personally believe you're just as likely to control this using 5Gy per fraction to 25Gy. Again, I know I am in the minority opinion here - but I see this less as an area of applying data like we are used to doing and more of an oncologic common sense situation. Patient has a local problem and cure without surgery is very unlikely. I do not see any convincing data that chemoRT offers better local control than RT alone.

I would love to be proven wrong - if there is any data, show me. But I would need to be pretty positive that I'm offering a superior option with chemoRT - and I'm just not convinced that is the case. I would bet that CR rates are comparable with 25/5 and chemoRT - we don't know because the timing of surgery in the pre-op trials.

There are multiple institutional series of definitive radiation for rectal cancer to total doses of around 60 Gy concurrent with 5 fu based chemotherapy where the long term local control is around 40-50%.

5gy x5 is not much radiation period. 6gy x 5 is the biological equivalent of 40GY at 2 gy a fraction, hence its use in cervical cancer HDR. Equivalent dose of 5 gy x 5gy is a lot lower than you think and has virtually no chance of a pCR.

 

[Cancerdancer]

Anecdotally I've seen a few very old patients (80+) given 5 x 5 in this fashion, with a question of whether they'd make it to surgery, and crump in the short term, significant bowel/anorexia issues. Surprised me as I thought too this would be more humane.
I've never really used 5 x 5 in young patients so can't say how this compares to 5 x5 in young patients, but it made me question the wisdom of pumping in 40+ GY (EQD2) within a week in a frail elderly pelvis in effort to be more humane. Take the anecdotes as you will.
The 39/3 option sounds like a nice middle ground to me...

 

[Palex80]

Anecdotally I've seen a few very old patients (80+) given 5 x 5 in this fashion, with a question of whether they'd make it to surgery, and crump in the short term, significant bowel/anorexia issues. Surprised me as I thought too this would be more humane.
I've never really used 5 x 5 in young patients so can't say how this compares to 5 x5 in young patients, but it made me question the wisdom of pumping in 40+ GY (EQD2) within a week in a frail elderly pelvis in effort to be more humane. Take the anecdotes as you will.
The 39/3 option sounds like a nice middle ground to me...

We do not grasp the radiobiology behind fatigue induced by radiotherapy. It's cytokine-mediated, but we do not understand yet what will cause a more pronounced fatigue: a several-week long therapy with smaller doses per day vs. a 1-2 week treatment with higher doses per day. Perhaps it's the "weekly dose" that plays a role and not the daily dose? What we do know is that fatigue is more pronounced when we irradiate bigger volumes and abdominal volumes, in my experienced liver too (as sometimes seen in large SBRT-volumes).
It's actually kind of sad, that fatigue has not been looked into that much as other radiation-induced effects.

 

[evilbooyaa]

We do not grasp the radiobiology behind fatigue induced by radiotherapy. It's cytokine-mediated, but we do not understand yet what will cause a more pronounced fatigue: a several-week long therapy with smaller doses per day vs. a 1-2 week treatment with higher doses per day. Perhaps it's the "weekly dose" that plays a role and not the daily dose? What we do know is that fatigue is more pronounced when we irradiate bigger volumes and abdominal volumes, in my experienced liver too (as sometimes seen in large SBRT-volumes).
It's actually kind of sad, that fatigue has not been looked into that much as other radiation-induced effects.

We all have anecdotes about radiation induced fatigue, but I think fatigue is such a multifactorial issue that it'd be hard to pin down 100% of the time whether it's due to radiation or not. Going to the doctors office every weekday for even 1, or up to 5-6 weeks would be fatiguing for most (certainly would be). Most patients who have had other treatments routinely come in with a baseline level of fatigue.

Are there fatigue scales that can be used to trend it? Similar to other symptom surveys?

 

[nkmiami]

I have seen a somewhat dramatic "fatigue syndrome" in very elderly patients (discussed on another thread) where the patient is basically incapacitated in bed all day long from the radiation- sometimes responds to steroids.

 

[scarbrtj]

My two cents is that being a fan of 25/5... there's nothing wrong with that. Can have up to an 11% pCR rate with 25/5. So that has the outside shot of giving the lady a long cNED period. Do I think it's a curative dose? No. I hold firm to the belief that, like in most things we know of, there is a dose-response relationship in rectal cancer. This has not really been borne out for 25/5 vs 50/25... I'll grant you that. I have treated several older patients who presented as Stage IV-- but had excellent responses to chemo -- "definitively" to their rectum. This is a bit of a common clinical entity: patient responds to chemo in all sites except the rectum. So I have treated these patients in the 60-64 Gy dose range. They have tolerated it very well. I saw no downside to doing 45 to the pelvis in these cases, but past that only treated PET+ dz with PTV margin ~1cm to the 60-64 Gy range using IG-IMRT. Evicore allows IG-IMRT for rectal cancer for dose escalation. YMMV. But at the end of the day, I think organ-sparing is great for older rectal patients. There are many papers out there.