Anal Cancer UC patient

[Haybrant]

Got a 70 year old patient with distant history of ulcerative colitis not active in 20 years that is presenting with anal SCC. Had a colonoscopy that showed anal ulceration and about 7 polyps in different areas of the colon. Path was benign for the polyps. There was one area at 80cm that was erythematous and biopsied and positive for chronic inflammation and microabcesses. Surgery did a biopsy on 4.5 cm anal lesion that was positive for SCC, the thing is invading the sphincter and he has mild incontinence. Awaiting imaging right now. Appreciate the thoughts on this one

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[evilbooyaa]

Not on medications for it? Does he have to follow a certain diet for it?

I mean discussion of risks of RT in IBD patients, offer him APR, but if it were me or my family I'd say let's try organ preservation. Especially if IBD isn't wildly uncontrolled.

Would discuss higher risk of toxicity from radiation treatment than most (first hit on quick google search: Radiation therapy in patients with inflammatory bowel disease and colorectal cancer: risks and benefits. - PubMed - NCBI)

Never really seen a guy with UC who isn't on medications/diet and hasn't had a flare in 20 years FWIW who then also needed RT

 

[ramsesthenice]

If he wants to keep his sphincter and you think he will have decent function there isn't a lot to think about. Even with active IBD most patients do fine. Acute toxicity may be higher and sure his risk of wound healing, fistula, etc will be higher but the absolute risk is still pretty low. Just consent and make sure they are making an informed decision. But I agree with evilbooyaa, I'd do it for a member of my family in a heartbeat.

 

[OTN]

It's certainly worth a try, although toxicity will be higher. Worst-case scenario you have to do an APR for XRT complications, but then you're right back to where you would have been from the get-go.

 

[nkmiami]

had several pts with anal ca and ibd, and did fine. I would get a p16 stain to see if this is virally driven- rather than from subclincal inflammation from UC- and would treat to around 50 if p16+. If p16 neg, local control may be an issue. Even if pt was going to get surgery, would still need to radiate preop as has high likelihood of having positive ln in mesorectum, which is first echelon drainage for anal ca.

 

[ramsesthenice]

although toxicity will be higher.

Certainly could be but it’s not a given. In my experience toxicity differences are not as obvious as one might expect.

At the end of the day though, your second point is spot on. Worst thing that happens is you do an APR because of toxicity down the road. If he is like most patients and strongly motivated to avoid a bag, he only has one option.

 

[scarbrtj]

A times B times C equals X.
A is the heightened toxicity risk of the radiotherapy due to patient's medical condition, B is the risk of the patient successfully suing for applying a known standard of care after informed consent, and C is the worst-case maximum potential malpractice settlement. If X is less than the cost of your most prominent local malpractice attorney's boat, do the treatment. #imkidding (but seriously, do the tx)

 

[Palex80]

I'd treat.

If he's cN0 on staging, I'd consider to treat less lymphatics both in terms of dose and volume.

 

[Radiator20]

The risk of toxicity in this specific case may not be high enough to merit it, but one other thing that could be considered in situations like this is a temporary diverting colostomy.

 

[seper]

I'd radiate now. APR on a 4.5 cm tumor will report very close margin, LVI, maybe positive nodes... You'll be back discussing adjuvant radiation.

 

[nguyencuong9102]

It's certainly worth a try, although toxicity will be higher. Worst-case scenario you have to do an APR for XRT complications, but then you're right back to where you would have been from the get-go.

 

[seper]

As the original Nigro paper showed, even 30 Gy is worth it, if you can get that in.

 

[nkmiami]

As the original Nigro paper showed, even 30 Gy is worth it, if you can get that in.

Exactly. Something like 5/6 patients had pathological responses? There probably is a diminishing return in terms of dose above 30-40 Gy.

 

[Radiator20]

As the original Nigro paper showed, even 30 Gy is worth it, if you can get that in.

Great point. While dose certainly escalated quite a bit after Nigro, I'm not sure what data actually supported that move at the time. That said, even in the dose-escalated era, both RTOG 98-11 and ACT II found LF rates around 25%, so I would worry a little bit about long-term local control with lower doses.

 

[OTN]

Anyone else notice my comment was copied word for word by another user? Looks like a website error but it’s kind of strange.

 

[evilbooyaa]

Anyone else notice my comment was copied word for word by another user? Looks like a website error but it’s kind of strange.

User did that for each of his/her 5 posts across multiple threads in this forum. I'll keep an eye on it. If you notice it happening again please feel free to report. Suspicion of spam bot.

 

[Haybrant]

It's certainly worth a try, although toxicity will be higher. Worst-case scenario you have to do an APR for XRT complications, but then you're right back to where you would have been from the get-go.

Is that really the worst thing though. What about possibility of adhesions/fistula/sbo etc

 

[seper]

Any large-field pelvic RT patient is at risk of RT-induced SBO, LBO, need for surgery during their lifetimes. I always consent patients for it.

Is that really the worst thing though. What about possibility of adhesions/fistula/sbo etc

 

[evilbooyaa]

Any large-field pelvic RT patient is at risk of RT-induced SBO, LBO, need for surgery during their lifetimes. I always consent patients for it.

Agreed, and I would counsel that this patient's risk may be a bit higher than the standard population.

 

[Haybrant]

Related questions .

1)What are you fields for this patient with 5cm node negative anal SCC

2) What are your fields for a 45 year M old with positive margin after attempted trans anal excision for small 1.5 cm anal SCC, no further surgery was feasible.

 

[Palex80]

1) I presume you mean "this patient" with ulcerative colitis?
I would only treat the mesorectum and the inguinal nodes electively. I'd leave out classical pelvis RT to limit the risk of problems with the bowel.
I'd only do that though if I had a good MRI and PET-CT showing cN0.

2) Standard RT. I'd treat inguinal nodes up to 36 Gy only, the rest up to 45 Gy electively. I'd "drop" the cranial border of the fields down to the internal/external iliac junction after 36 Gy, it's probably safe to do that.

 

[nkmiami]

if pt is p16+, elective fields can receive 3060 cGy then cone down to anal lesion to 55 Gy.

 

[Palex80]

if pt is p16+, elective fields can receive 3060 cGy then cone down to anal lesion to 55 Gy.

Do you have evidence for 30.60 Gy for all elective fields being safe?

 

[nkmiami]

Do you have evidence for 30.60 Gy for all elective fields being safe?

no, just what i have done in past. I think your approach is very reasonable as well. I figure with ulcerative colitis, radiation morbidity, if it occurs will come from treating rectum, which obviously have to include, so thats why I would lean to treating the pelvic lymph nodes in this case as UC shouldnt effect small bowel

 

[scarbrtj]

Do you have evidence for 30.60 Gy for all elective fields being safe?

historically, and certainly purely empirically, the RTOG was wont to treat the biggest (initial) elective field(s) to only 30.6 Gy... so that plus Nigro 30 Gy Rx dose... there's precedent (and a documented response/failure rate at ~30 Gy)

 

[Palex80]

True, true!

So, 30.6 Gy for the area above the SI-joints, right?

 

[evilbooyaa]

Related questions .

1)What are you fields for this patient with 5cm node negative anal SCC

2) What are your fields for a 45 year M old with positive margin after attempted trans anal excision for small 1.5 cm anal SCC, no further surgery was feasible.

Like Palex, assuming that you have UC to worry about. If not, I'd treat them both definitively.

I think treating per 9811 per scarbrtj is certainly reasonable. I'm not sure if treating low pelvis (below SI joint) to 30.6 alone even in a cN0 patient is legally defensible in court (if patient recurs). Yes, Nigro told us that 30Gy to 5 out of 6 patients or whatever eradicates gross disease, but we know that LRR aren't 0 with current dose schedules.

2) Treat him like he didn't get surgery - maybe boost to just 54 or 56 instead of 59.

 

[Haybrant]

Thanks All.

Focusing on the second patient with positive margin I’m a bit confused. So 0529 for T2N0 treats all elective nodal to 42 in 1.5 then boosts the gross to 50.4, doesn’t even mention anything about dropping the border to low SI joint. If I wanted to do what Palex is saying and ucsf handbook then I would treat from l5-S1 to low SI and inguinals to 36 in 1.8 and everything else to 45 in 1.8 then boost to 54? Why should the inbetween elective volume go higher to 45? Or should all elective go to 36 then the mesorectal (+primary) go to 45 and then boost to 54? Not sure why anal is always so confusing, appreciate the help. Thanks

1) I presume you mean "this patient" with ulcerative colitis?
I would only treat the mesorectum and the inguinal nodes electively. I'd leave out classical pelvis RT to limit the risk of problems with the bowel.
I'd only do that though if I had a good MRI and PET-CT showing cN0.

2) Standard RT. I'd treat inguinal nodes up to 36 Gy only, the rest up to 45 Gy electively. I'd "drop" the cranial border of the fields down to the internal/external iliac junction after 36 Gy, it's probably safe to do that.

 

[evilbooyaa]

Anal is confusing, IMO, because there are multiple ways to do it and no one way is more right than the other. 9811 is one option. 0529 is another option and is not wrong. Just depends on attending preference. If you wanted to 42 at 1.5 and dose paint to 50.4 to 'gross' then go for it. Obviously 0529 is a phase II trial so the argument is that 9811 was phase III data but in reality it doesn't matter.

There's a 'sequential boost' camp and a 'simultaneous boost' camp, and which way you do depends on which one of those options you prefer. Then of course all the stuff that people do that is in-between (like 30.6-36 to the entire elective nodal volume).

 

[Haybrant]

Makes sense evilB. Are people doing 98-11 technique with IMRT? If so is it all nodal volumes to 36 then mesorectal volume to 45 then anal volume to 54-59 assuming n zero patient?

 

[evilbooyaa]

Yeah you can do sequential boosts with IMRT as well, which is generally how they're done now at my institution (if sequential boosts are the attending preference) I personally think the plans look cleaner with single plan techniques using dose painting/SIB, but it honestly doesn't matter that much for an anal IMRT plan.

 

[Haybrant]

Yeah you can do sequential boosts with IMRT as well, which is generally how they're done now at my institution (if sequential boosts are the attending preference) I personally think the plans look cleaner with single plan techniques using dose painting/SIB, but it honestly doesn't matter that much for an anal IMRT plan.

So if you SIB then do you do 3600 and 4500 simultaneous and do 1.8s to 4500 and 1.44 to the 3600 in 25 fractions then boost the gross

 

[evilbooyaa]

No, SIB would be doing 0529 doses (42 and 50.4). If you're going to do 36Gy you have to do at 1.8Gy/fx, IMO. I don't have data that says its absolutely necessary to do that, but whenever you decrease the fraction size you generally have to increase the total dose (see 50 vs 54/56 or 60 vs 63 in H&N between sequential boost plans and SIB plans)

 

[scarbrtj]

True, true! So, 30.6 Gy for the area above the SI-joints, right?

Moreso, 30.6 Gy to everything elective in this patient. TxN0 anal patients have a 5-20% isolated inguinal relapse rate--and that's probably the elective region at highest risk in anal (not pelvic nodes)--this is a relapse rate right at the border of where we think ENI affects outcomes. I have seen retrospective series where the relapse rates are super-low in contralateral nodes in well-lateralized primaries... and where ENI has been omitted outright in other series. (And I do not think inguinals got a reliable elective dose in the "old days" of electron strips and non-3D planning.) Couple all that with the risk/benefit ratio in an UC patient... I say use your noggin and concentrate on local control here, rely on locoregional control with ~30Gy ChemoRT (if he is TxN0); 30 Gy is pretty close to 36 Gy ha. People do anal so many different ways (double ha); re: IMRT, SIB and sequential boosting seems to have similar outcomes. I personally think plans are cleaner with two separate plans (cleaner "IRL"... on the screen, perhaps not as clean but I'd rather "diversify my risks and doses" across time with multiple plans versus a single sim snapshot in time).

but whenever you decrease the fraction size you generally have to increase the total dose

You must. Alpha/beta, and time factor, etc. E.g., 50/25 for ENI (60Gy-10 BED) in HNSCC became 56/35 (65Gy-10) with IMRT, sans time factor. However, with time correction, 50/25 is actually slightly more BED at 42.5Gy-10 and 56/35 is 40.5Gy10. Thus, as I am a bit of a traditionalist and/or like to predict future occurrence based on past dose data, I am not a big SIB guy (although it is far more laborious and tedious not to be so).

I wouldn't ever test for p16 in anal. Of course p16+ do better but the pre-test positive likelihood is about 95% and p16 sensitivity/specificity is only about 90% so the negative predictive value is <50% in the case of a negative p16. So odds-wise, out in the wild for us average MDs, negative p16's in anal are more often wrong than right. Positive p16 has about a 100% positive predictive value though 🙂

 

[Krukenberg]

This thread on The MedNet is enlightening about the varying practice for anal cancer dosing.

theMednet - Login

 

[scarbrtj]

This thread on The MedNet is enlightening about the varying practice for anal cancer dosing.

theMednet - Login

Myerson:
"With Nigro style chemotherapy, the elective nodal control is excellent with 30-36 Gy at 1.8-2Gy /fx followed, sequentially, by a boost to macroscopic disease."
Tepper:
"I think the doses that are standardly used to treat microscopic disease, such as those recommended by Chris Crane, are too high. One needs to remember that the original Nigro regimen used doses of 30 Gy to gross disease and had good control. Subsequently the dose to microscopic disease has been escalated without, to my knowledge, ANY data to suggest that it is needed... The best way to minimize dose to normal tissues is not to use a fancier technique, it is to use the lowest dose that gets the job done."
Crane:
"To clarify the microscopic dose issue, I would add that we also have never seen a recurrence in a microscopically treated area with 30.6 Gy in 17 fractions with 2 agent chemotherapy... There was also was never any data to justify having 2 microscopic doses in the 2D era (30.6 and 45 Gy)... Like the microscopic doses in IMRT, that was empirically established... The other way to do it is to do sequential IMRT plans at standard fractions for the 30.6Gy and for the subsequent volume reductions. Some people do prefer that option, but it is more resource intensive."

Ditto.

 

[thecarbonionangle]

do you guys ever boost anal primary >54 Gy? if so in which cases would you consider it? to what dose?

 

[medgator]

do you guys ever boost anal primary >54 Gy? if so in which cases would you consider it? to what dose?

I do.... Large T3/T4 lesions. Burned a couple of times only going to 54

 

[Palex80]

I do.... Large T3/T4 lesions. Burned a couple of times only going to 54

Me too, usually up to 59.4 Gy. "Burned" a couple of patients going that high though too... :-(

 

[evilbooyaa]

59 or 59.4 for large primaries 100% of the time. Maximize homogeneity, try to avoid hotspots in the sphincter. Obviously depends on the lesion size/location above all else. If they already haev a lesion crossing sphincter I want to make sure they don't recur above any toxicity concerns.

 

[seper]

Poor local control for T3/T4 with 54 Gy is well known. The trouble is, there are no data to support dose escalation. I personally started to doubt value of treating to 60 Gy.

 

[thecarbonionangle]

Yeah thats why I ask because some consider these patients incurable/difficult to cure so adding a few extra grey is it just making us feel better? Evidence? Thoughts on induction chemo?

 

[evilbooyaa]

Yeah thats why I ask because some consider these patients incurable/difficult to cure so adding a few extra grey is it just making us feel better? Evidence? Thoughts on induction chemo?

Induction chemo has been exclusively evaluated and shown to have zero benefit. What's the last RT dose escalation trial was done? Maybe the answer is adjuvant therapy, like adjuvant nivolumab (Nivolumab after Combined Modality Therapy in Treating Patients with High Risk Stage II-IIIB Anal Cancer - NCT03233711)

 

[Burt Radnolds]

Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized U... - PubMed - NCBI

Somewhat complicated study of advanced anal cancer patients. Double randomization to 1) +/- induction 2) 45 Gy + either 15 Gy boost or 20-25 Gy boost. Induction did nothing, again. This is not very applicable to the current question of 54 vs 60Gy as everyone got at least 60Gy, but it is interesting to see the trend in favor of the boost dose in regards to colostomy free survival (p = .067). At least that dose did not appear to increase colostomies, which is what I might guess would happen with such a high boost dose!

 

[nkmiami]

Induction chemo has been exclusively evaluated and shown to have zero benefit. What's the last RT dose escalation trial was done? Maybe the answer is adjuvant therapy, like adjuvant nivolumab (Nivolumab after Combined Modality Therapy in Treating Patients with High Risk Stage II-IIIB Anal Cancer - NCT03233711)

I also expect trials to be positive for adjuvant immuno in multiple cancer after definitive chemorads including head and neck and ge junction in the next couple of years.

 

[ramsesthenice]

Induction chemotherapy and dose intensification of the radiation boost in locally advanced anal canal carcinoma: final analysis of the randomized U... - PubMed - NCBI

Somewhat complicated study of advanced anal cancer patients. Double randomization to 1) +/- induction 2) 45 Gy + either 15 Gy boost or 20-25 Gy boost. Induction did nothing, again. This is not very applicable to the current question of 54 vs 60Gy as everyone got at least 60Gy, but it is interesting to see the trend in favor of the boost dose in regards to colostomy free survival (p = .067). At least that dose did not appear to increase colostomies, which is what I might guess would happen with such a high boost dose!

I never know what to do with this study. On its face, it looks like a higher dose boost might be better but it only trended to make a difference in the patients who also got induction chemo (70 vs 82% for standard and high dose boost). If anything, the trend was the opposite for the non-induction arm (77 vs 72%). I will always be one of the first to caution people from abusing 2x2 studies, but I do feel like it is kind of hard to look at this data and say maybe there something to increasing the boost dose but induction is dead. Neither one looks all that promising really. Agree with the above point though, it doesn't look like the boost is as harmful as I would have expected. I would have predicted more sphincter dysfunction and palliative colostomies with boost doses that high.