Oral mucositis

[scarbrtj]

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Guess no one commented much yesterday because of Mueller Report. Left you with a bad taste in your mouth? Magic mouthwash to the rescue. Or not.

Does magic mouthwash help cancer patients with oral mucositis (OM)? No, it's useless and should "vanish into thin air." But now one trial shows magic mouthwash had statistically significant reductions in OM... but not clinically significant. Even so, the authors said the results would/should change practice guidelines.

It's a polarized world filled with fake news. Creams, rinses, etc., treat the treatment team as much as the patient. "Don't just stand there... do something." Not that there's anything wrong with that. Amifostine was supposed to work; no offense to Hall writing about it in his textbook but does ANYONE use it anymore? (It reimburses for less than it costs, which is problematic.) The greatest ameliorator of XRT side effects, ever, is removing oneself from XRT exposure. The second best: making Rx doses lower. Third best: IMRT. Everything else is a distant fourth.

Also it's suspicious the ads that run on the site after the redesign. There is right now, below, an ad on this page for "Chuy's World Famous Tex-Mex." Oral mucositis... Chuy's... it's clear-cut collusion.

 

[medgator]

MM is nice to throw at OM and esophagitis before you have to bring out narcotics

 

[evilbooyaa]

MM and formulations like it (topical lidocaine essentially) seem to help in the early stages when the majority of pain is due to the inflamed mucosa touching things (usually food), before they develop constant pain (which tylenol and advil, co-morbidities allowing, seem to control briefly).

I agree that MM is not going to help a patient more than intelligent planning and reduction of RT dose will. This is why some academic (AFAIK, maybe there's PP folks too) H&N attendings are getting away from CTVs to their GTV70 and going straight from GTV to PTV for the gross tumor dose. Along with dose reduction (rather than 70-60-50 sequentially or 70-63-56, a lot of people are now doing 70-56 only for nodal volumes). Also depends on the integrity of a plan and the dose constraints you give to your dosimetrists. If you're not pushing the oral cavity/FOM region as much as you possibly can (assuming it's feasible, like not an oral cavity tumor) then MM isn't going to magically save you.

We also do glutamine for all H&Ns as a preventative which seems to help.

 

[thecarbonionangle]

Guess no one commented much yesterday because of Mueller Report. Left you with a bad taste in your mouth? Magic mouthwash to the rescue. Or not.

Does magic mouthwash help cancer patients with oral mucositis (OM)? No, it's useless and should "vanish into thin air." But now one trial shows magic mouthwash had statistically significant reductions in OM... but not clinically significant. Even so, the authors said the results would/should change practice guidelines.

It's a polarized world filled with fake news. Creams, rinses, etc., treat the treatment team as much as the patient. "Don't just stand there... do something." Not that there's anything wrong with that. Amifostine was supposed to work; no offense to Hall writing about it in his textbook but does ANYONE use it anymore? (It reimburses for less than it costs, which is problematic.) The greatest ameliorator of XRT side effects, ever, is removing oneself from XRT exposure. The second best: making Rx doses lower. Third best: IMRT. Everything else is a distant fourth.

Also it's suspicious the ads that run on the site after the redesign. There is right now, below, an ad on this page for "Chuy's World Famous Tex-Mex." Oral mucositis... Chuy's... it's clear-cut collusion.

Chuy’s, fake news... clear link here. “Bad hombres”?

 

[thecarbonionangle]

See PMID 30521105 for intersting data on OM and probiotics.

 

[metallica81788]

Does anybody here use Doxepin rinse?

Doxepin rinse versus placebo in the treatment of acute oral mucositis pain in patients receiving head and neck radiotherapy with or without chemoth... - PubMed - NCBI

 

[Palex80]

I have high hopes in this:
ScienceDirect

Phase 3 running now.
A Study to Investigate the Effects of GC4419 on Radiation Induced Oral Mucositis in Patients With Head/Neck Cancer - Full Text View - ClinicalTrials.gov

The main problem I see, is getting the patient to have a 60-minute infusion on a daily basis. But perhaps once the drug is deemed safe, the duration can be shortened.

 

[scarbrtj]

MM and formulations like it (topical lidocaine essentially) seem to help in the early stages when the majority of pain is due to the inflamed mucosa touching things (usually food), before they develop constant pain (which tylenol and advil, co-morbidities allowing, seem to control briefly).

I agree that MM is not going to help a patient more than intelligent planning and reduction of RT dose will. This is why some academic (AFAIK, maybe there's PP folks too) H&N attendings are getting away from CTVs to their GTV70 and going straight from GTV to PTV for the gross tumor dose. Along with dose reduction (rather than 70-60-50 sequentially or 70-63-56, a lot of people are now doing 70-56 only for nodal volumes). Also depends on the integrity of a plan and the dose constraints you give to your dosimetrists. If you're not pushing the oral cavity/FOM region as much as you possibly can (assuming it's feasible, like not an oral cavity tumor) then MM isn't going to magically save you.

We also do glutamine for all H&Ns as a preventative which seems to help.

Taken to a logical extreme, XRT toxicity correlates with treatment volumes more so than tx site or dose. The perfect volume is 1) minimized for toxicity's sake and 2) maximized for tumor coverage in the realm of uncertainties. There's been too much #2 and not enough #1 in HNSCC IMRT. Also, "two phasing" the plan helps. One, it provides for re-orientation of dose delivery based on patient weight loss/tumor shrinkage (which there always is). Two, it provides for smaller fields in the latter part of treatment and completely "coming off" certain parts of the anatomy with any dose at all. I do approximately 50/25 to gross & elective (rescan and replan at about 45 Gy) and then ~20 Gy boost to the gross disease using a new scan/plan. (Grossly summarizing and over-simplifying.) An old-style approach with the new technology which avoids gauchely kludgy and essentially rigorously untested (against the previous standard) schemes, e.g. 1.6 Gy/day (56/35) which we use in no other solid tumor definitive tx circumstance.

 

[thecarbonionangle]

Taken to a logical extreme, XRT toxicity correlates with treatment volumes more so than tx site or dose. The perfect volume is 1) minimized for toxicity's sake and 2) maximized for tumor coverage in the realm of uncertainties. There's been too much #2 and not enough #1 in HNSCC IMRT. Also, "two phasing" the plan helps. One, it provides for re-orientation of dose delivery based on patient weight loss/tumor shrinkage (which there always is). Two, it provides for smaller fields in the latter part of treatment and completely "coming off" certain parts of the anatomy with any dose at all. I do approximately 50/25 to gross & elective (rescan and replan at about 45 Gy) and then ~20 Gy boost to the gross disease using a new scan/plan. (Grossly summarizing and over-simplifying.) An old-style approach with the new technology which avoids gauchely kludgy and essentially rigorously untested (against the previous standard) schemes, e.g. 1.6 Gy/day (56/35) which we use in no other solid tumor definitive tx circumstance.

Doesnt 1.6 come from cobalt? Basically, they went back and looked at what that area was actually getting and it was about 1.6. They were prescribing a higher dose.

If SIB approach were inferior, wouldnt we see it in outcomes?

 

[xrthopeful]

If SIB approach were inferior, wouldnt we see it in outcomes?

+1

I think scarbtj's approach is fine, presuming he's able to avoid excessive additive hot spots from a sequential plan BUT I have zero concern about 1.6 Gy/fx for elective especially in the HPV era given super low rates of failure in elective volumes.

 

[Palex80]

50 Gy to the elective neck in 2 Gy/d is probably an overtreatment. There is randomized evidence showing that 40 Gy may be sufficient. When treating with chemo I am comfortable with 40 Gy, especially for HPV positive disease.
https://www.thegreenjournal.com/article/S0167-8140(16)34247-5/pdf

 

[scarbrtj]

50 Gy to the elective neck in 2 Gy/d is probably an overtreatment. There is randomized evidence showing that 40 Gy may be sufficient.

Everybody's got an opinion😉 50/25 to ENI is still NCCN ok'd obviously. ENI to 40 Gy will doubtless give much better toxicity profiles than 56/35 or 50/25. Even better than 40 Gy: zero Gy ENI dose, when appropriate. These patients are a delight to take care of vs the "typical" HNSCC patient. In the study you cite they did some wacky stuff like 42 Gy in 30 fx of 1.4 Gy a day. Guess it's OK. I wouldn't do it personally but maybe, really, we can do whatever we want as long as it makes radiobiological sense.
EDIT: Also your link cites George Sherouse (he helped make the planning system they used). Another story for another day.

Doesnt 1.6 come from cobalt? Basically, they went back and looked at what that area was actually getting and it was about 1.6. They were prescribing a higher dose.
If SIB approach were inferior, wouldnt we see it in outcomes?

I think scarbtj's approach is fine, presuming he's able to avoid excessive additive hot spots from a sequential plan BUT I have zero concern about 1.6 Gy/fx for elective especially in the HPV era given super low rates of failure in elective volumes.

1.6 Gy per day to ENI didn't really become a thing until the IMRT SIB era. It was maybe some weird homage and/or misreading of the past I always thought. But just look at the novel-ness of dose regimens in Palex's link above (1.4 Gy a day??). "Went back and looked at what the area was actually getting," is a bit hand-waving (doubt they were always off by 25% to make the 1.6 like 2.0). And I'm not saying 56/35 is inferior oncologically; 50/25 and 56/35 have almost same exact Gy10 (w/ time corrections). I'm merely talking side effects. 5 hours of hot sun exposure has a lower "pain AUC" than 7 hours. And for ~5 weeks of XRT (50/25) exposure vs 7 weeks of XRT exposure (56/35), patients experience OM (and skin redness etc) for fewer days for the former vs the latter, in general (depends on how big the "boost" is, but you catch my drift). 50/25 and 56/35 get you to the same acute side effect point, but the 50/25 patient is on her way to recovery faster, "spends less time in the sun." And then all the added dosimetric benefits of treating the right IMRT plan to the right patient; after 5 weeks of CERT (that acronym never caught on), patients don't look like themselves and their initial planning scans sure don't look like their daily CBCTs either in some instances. So replanning seems justified (may save the spit e.g., help better cover targets and so on). Just consider 50/25 the hypofractionated form of 56/35. #eyeroll

somehow managed to coalesce CC Wang, Herman Suit, Gilbert Fletcher, KK Ang, Jay Cooper all in one post....

 

[Palex80]

Everybody's got an opinion😉 50/25 to ENI is still NCCN ok'd obviously. ENI to 40 Gy will doubtless give much better toxicity profiles than 56/35 or 50/25. Even better than 40 Gy: zero Gy ENI dose, when appropriate. These patients are a delight to take care of vs the "typical" HNSCC patient. In the study you cite they did some wacky stuff like 42 Gy in 30 fx of 1.4 Gy a day. Guess it's OK. I wouldn't do it personally but maybe, really, we can do whatever we want as long as it makes radiobiological sense.

Of course it is and the Dutch trial was rather small, so certainly not designed to answer a good non-inferiorioty question. However it is quite provoking, wouldn't you say?

Based on my practice (but that's heavily biased) I have rarely seen recurrence within elective irradiated areas with 50 Gy. To be frank, I cannot actually recall a single case. Most of the patients with a recurrence, failed in the primary tumor area or the affected nodes (so within the boost volumes) and then there were some odd recurrences occuring outside the elective volumes, like recurrences in the contralateral supraclavicular area in patient with a oral cavity pT2 pN1 primary or high level II contralateral recurrence in a patient with a cT2 cN0 laryngeal cancer with subglottic extension.

To me it remains odd, that we will keep the dose the same irrespective of systemic treatment.

For example:

You are presented with a case of oropharyngeal cancer, p16 negative pT2 pN2a cM0 R0. You treat elective nodes to 50 Gy and boost the primary + affected node areas to 60 Gy (or so, some may give 64 Gy). All 2 Gy/d.

Then you are presented with the same case, but this time it's a close margin, so the med onc will give cisplatin 100mg/m2 q3 on top. Why do you still give the same dose to the elective neck (50 Gy) ? This patient is not in a higher risk for recurrence in the nodal areas, simply because he has a close margin. He is in a higher risk for local recurrence.. How much RT dose is cisplatin 100mg/m2 q3 "worth".

 

[scarbrtj]

Of course it is and the Dutch trial was rather small, so certainly not designed to answer a good non-inferiorioty question. However it is quite provoking, wouldn't you say?

Based on my practice (but that's heavily biased) I have rarely seen recurrence within elective irradiated areas with 50 Gy. To be frank, I cannot actually recall a single case. Most of the patients with a recurrence, failed in the primary tumor area or the affected nodes (so within the boost volumes) and then there were some odd recurrences occuring outside the elective volumes, like recurrences in the contralateral supraclavicular area in patient with a oral cavity pT2 pN1 primary or high level II contralateral recurrence in a patient with a cT2 cN0 laryngeal cancer with subglottic extension.

It's provoking, and believable. ENI is likely overkill in the vast majority of patients. Too bad we can't predict the future, smartly, to know on whom to avoid it. Let's face it: modern, or semi-modern, thought on why to treat the neck in HNSCC comes from this old paper.

To me it remains odd, that we will keep the dose the same irrespective of systemic treatment.

Sigh. A lot of what we do is odd.

You are presented with a case of oropharyngeal cancer, p16 negative pT2 pN2a cM0 R0. You treat elective nodes to 50 Gy and boost the primary + affected node areas to 60 Gy (or so, some may give 64 Gy). All 2 Gy/d.

Then you are presented with the same case, but this time it's a close margin, so the med onc will give cisplatin 100mg/m2 q3 on top. Why do you still give the same dose to the elective neck (50 Gy) ? This patient is not in a higher risk for recurrence in the nodal areas, simply because he has a close margin. He is in a higher risk for local recurrence.. How much RT dose is cisplatin 100mg/m2 q3 "worth".

In general I only give postop chemoRT for T4, or N3 or ECE, or positive margin/gross disease left behind patients. However, because we can't predict the future smartly and we just don't have a great intellectual platform off of which to operate, I like you am left ENI-ing to the same doses with/without chemo.