What are the radioresistant pathologies?

[thesauce]

When considering your dose and fractionation, what pathologies would you consider radioresistant and possibly give more dose? RCC is the big one that comes to mind, but what others?

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[deleted1116990]

I just treated bulky symptomatic GIST in the pelvis palliatively, which is historically considered radioresistant however the patient had a fantastic and rapid improvement. Hit it hard 6 Gy x 3.

A literature search shows some consider GISTs to be more radiosensitive than previously thought, and my n=1 supports that.

 

[RickyScott]

When considering your dose and fractionation, what pathologies would you consider radioresistant and possibly give more dose? RCC is the big one that comes to mind, but what others?

Rcc and melanoma have traditionally been considered radiation resistant, although maybe it’s partially because they dont radiologically respond as much as other cancers. Colon can sometimes be very radio resistant

 

[BobbyHeenan]

Rcc and melanoma have traditionally been considered radiation resistant, although maybe it’s partially because they dont radiologically respond as much as other cancers. Colon can sometimes be very radio resistant

I've got a hand full of RCC I've done SBRT on. Some like 4 years out now. Basically minimal shrinkage but zero growth or new mets.

 

[BobbyHeenan]

Rcc and melanoma have traditionally been considered radiation resistant, although maybe it’s partially because they dont radiologically respond as much as other cancers. Colon can sometimes be very radio resistant

It's so variable too.
I had an oral cavity case that still haunts me. Dude recurred 1 week after radiation right in field. Like it just laughed at 60 Gy incredibly toxic treatment.

 

[TheWallnerus]

When considering your dose and fractionation, what pathologies would you consider radioresistant and possibly give more dose? RCC is the big one that comes to mind, but what others?

Nothing.

EDIT: bacteremias, like literally the bacteria themselves, are very radioresistant. Otherwise, no human cells (GBM raises hand in back of room).

 

[thesauce]

What about Hepatocellular?

 

[taserlaser]

I just treated bulky symptomatic GIST in the pelvis palliatively, which is historically considered radioresistant however the patient had a fantastic and rapid improvement. Hit it hard 6 Gy x 3.

A literature search shows some consider GISTs to be more radiosensitive than previously thought, and my n=1 supports that.

Our local med onc has been a proponent of RT palliation, either uo front for palliative while awaiting for molecular testing (debatable) or otherwise. I would say we typically see good responses as well. It’s ripe for further inquiry I would think.

 

[taserlaser]

I have some thoughts on melanoma as well. Would also not qualify that as radioresistant - Will probably just add an addendum to the skin rant when I have some time in the next week or two

 

[deleted1116990]

I have some thoughts on melanoma as well. Would also not qualify that as radioresistant - Will probably just add an addendum to the skin rant when I have some time in the next week or two

Yes, just treated a ~1.5 cm melanoma brain met with SRS with complete resolution. Seems like it didn't resist the radiation much. No residual, no necrosis, nothing. Normal brain on follow-up.

 

[evilbooyaa]

So, the concept of 'radioresistant' is more relevant in the pre-SBRT era, talking about conventional fractionation or especially, palliative doses. That being said, most things that are 'historically' radioresistant can be taken care of just fine with SRS/SBRT dose fractionation schemes.

So RCC and Melanoma are resistant to palliative or conventional fractionation schemes. But they both can be controlled just fine with SRS/SBRT doses.

HCC was thought to be radioresistant similarly, but in reality, it's more so the liver couldn't handle the fractionated doses necessary for anything besides pure pallaition, and similarly, SBRT is overall tolerated fine if baseline liver function is reasonable.

Some say colorectal mets are more resistant (and require high doses of SRS/SBRT than other histologies)

GBM is radioresistant to pretty much to all doses of radiation but it still helps more than anything else.

 

[Palex80]

Old docs. Old docs are commonly "radioresistant".
radioresistant = resistant to treat certain histologies.

 

[CaesarRO]

So, the concept of 'radioresistant' is more relevant in the pre-SBRT era, talking about conventional fractionation or especially, palliative doses. That being said, most things that are 'historically' radioresistant can be taken care of just fine with SRS/SBRT dose fractionation schemes.

So RCC and Melanoma are resistant to palliative or conventional fractionation schemes. But they both can be controlled just fine with SRS/SBRT doses.

HCC was thought to be radioresistant similarly, but in reality, it's more so the liver couldn't handle the fractionated doses necessary for anything besides pure pallaition, and similarly, SBRT is overall tolerated fine if baseline liver function is reasonable.

Some say colorectal mets are more resistant (and require high doses of SRS/SBRT than other histologies)

GBM is radioresistant to pretty much to all doses of radiation but it still helps more than anything else.

The discussion is interesting to me because of all the hoops we have to jump through for SBRT authorization. I was just talking about this recently. Would be nice to be able to use a "classically radioresistant histology" as an indication for SBRT even in the clearly palliative setting.

 

[metallica81788]

The discussion is interesting to me because of all the hoops we have to jump through for SBRT authorization. I was just talking about this recently. Would be nice to be able to use a "classically radioresistant histology" as an indication for SBRT even in the clearly palliative setting.

It's a nice term to have in a peer to peer setting if speaking with someone rational. Had an SBRT approved by Evilcore using the "classically radioresistant histology" logic with borderline indications via their guidelines.

 

[CaesarRO]

It's a nice term to have in a peer to peer setting if speaking with someone rational. Had an SBRT approved by Evilcore using the "classically radioresistant histology" logic with borderline indications via their guidelines.

It just doesn't make sense to palliate 30/10, 20/5, or 8/1 something that doesn't respond to "conventional" doses...

 

[TheWallnerus]

It just doesn't make sense to palliate 30/10, 20/5, or 8/1 something that doesn't respond to "conventional" doses...

Because we can never predict beforehand what will or won’t respond to conventional doses (complete or partial response was ~70% to 30/10 or 8/1 in the 30/10 vs 8/1 trial; 3 out of 10 just didn’t respond), then based on this logic you should never do conventional doses for anything.

Reductio ad absurdum?

 

[RickyScott]

I have seen plenty of melanoma and renal cell respond to 30/10. I don’t know if it is the optimal regimen but more likely than not they will benefit.

 

[NotMattSpraker]

Agree with above, the term is best reserved for insurance calls and letters and you can use it for all the histologies an old doctor would call radioresistant: lung, HCC, sarcoma, RCC, melanoma. This worked for me a lot.

I just treated bulky symptomatic GIST in the pelvis palliatively, which is historically considered radioresistant however the patient had a fantastic and rapid improvement. Hit it hard 6 Gy x 3.

A literature search shows some consider GISTs to be more radiosensitive than previously thought, and my n=1 supports that.

So true, unless they are heavily pre-treated. If you put a GIST on a TKI (or now days many sequential different TKIs) then take them off they explode. I would always argue for earlier palliative RT but it never took. To this day GIST is the only histology Ive had grow through Lattice SBRT treatment. Other highly radiosensitive sarcomas include myxoid liposarcoma (there is a dose de-escalation trial), synovial sarcoma, and angiosarcoma.

I just couldnt resist chiming in with a sarcoma comment

 

[deleted1116990]

I have seen plenty of melanoma and renal cell respond to 30/10. I don’t know if it is the optimal regimen but more likely than not they will benefit.

They really like 39/13.

 

[ramsesthenice]

Some say colorectal mets are more resistant (and require high doses of SRS/SBRT than other histologies)

I hear people say that and think it has more to do with liver vs non-liver mets. There is reasonable (though I wouldn't call it conclusive) data mets to liver may take a little more dose than the classic BED = 100 for similar tumor control as other sites. I treat a lot of colorectal metastases and see no consistent differences between them an most other histologies.

 

[taserlaser]

Theres some other data of variable quality to support better LC with BED>100 for CRC lung mets as well i believe

 

[TheWallnerus]

When a bacteria is antibiotic resistant does that mean the antibiotic doesn’t work for that bacteria at any safe dose of antibiotic, or that the patient needs more milligrams of the same antibiotic

 

[Lamount]

Carcinosarcoma (or sarcomatoid anything), MPNST, mCRC

 

[Palex80]

All of us have seen these patients. We treated with a typical dose of RT and treatment failed its goals, although we have expected otherwise. I have seen that happen in almost any of the "Big-4" (prostate, breast, lung, colorectal) histologies that we often treat with palliative RT.
It can even happen when using ablative doses. Last week we had a patient with a progressive metastasis in the spine, 6 months after having received 2 x 12 Gy on that spot. And yes, it was true progression with tumor progressing beyond the bone now, and not in the area where the PTV was underdosed to meet spinal cord constraints. It was in the area that received the full 2 x 12 Gy. Would I have expected that? No. A perfectly normal case of metastatic NSCLC, nothing "fancy" about the histology. There are factors in the molecular level that we do not yet understand, it may have to do with repopulation or damage repair mechanisms.
Molecular insights will hopefully one day allow us to guide treatment. Perhaps some of these "tough" cases require a certain fractionation schedule or dose per day or combination with systemic agents or even other forms of radiotherapy (perhaps heavy ions, who knows?).
I have high hopes in both these diagnostics and potentially new agents that will modulate the effect of radiotherapy.
One example for one of these new agents is Xevinapant, tested in H&N cancer.

xevinapant

www.debiopharm.com

 

[TheWallnerus]

All of us have seen these patients. We treated with a typical dose of RT and treatment failed its goals, although we have expected otherwise. I have seen that happen in almost any of the "Big-4" (prostate, breast, lung, colorectal) histologies that we often treat with palliative RT.
It can even happen when using ablative doses. Last week we had a patient with a progressive metastasis in the spine, 6 months after having received 2 x 12 Gy on that spot. And yes, it was true progression with tumor progressing beyond the bone now, and not in the area where the PTV was underdosed to meet spinal cord constraints. It was in the area that received the full 2 x 12 Gy. Would I have expected that? No. A perfectly normal case of metastatic NSCLC, nothing "fancy" about the histology. There are factors in the molecular level that we do not yet understand, it may have to do with repopulation or damage repair mechanisms.
Molecular insights will hopefully one day allow us to guide treatment. Perhaps some of these "tough" cases require a certain fractionation schedule or dose per day or combination with systemic agents or even other forms of radiotherapy (perhaps heavy ions, who knows?).
I have high hopes in both these diagnostics and potentially new agents that will modulate the effect of radiotherapy.
One example for one of these new agents is Xevinapant, tested in H&N cancer.

xevinapant

www.debiopharm.com

It’s not magic.

We… the soi disant radiation experts… are just very ignorant about how much photon irradiation it takes to render a PARTICULAR cancer cell (inside the patient we are treating, amongst the billions of cancer cells in the patient) mitotically neutered.

Weirdly, not many people in rad onc seem keen to get unignorant about this. They’d rather let med onc and/or immunotherapy make our ignorance a moot point.

 

[madchemist89]

The argument that there are no radioresistant histologies stems from the fact that we are talking about 1.5x to 2x dose needed to achieve similar cell kill. In comparison to chemotherapy resistance, we are talking about orders of magnitude. There really aren't many ways for a cell to escape the effects of ionizing radiation. With chemo, they can develop pumps to remove the drug from the cell, upregulate alternate pathways, etc.

 

[ramsesthenice]

The argument that there are no radioresistant histologies stems from the fact that we are talking about 1.5x to 2x dose needed to achieve similar cell kill. In comparison to chemotherapy resistance, we are talking about orders of magnitude. There really aren't many ways for a cell to escape the effects of ionizing radiation. With chemo, they can develop pumps to remove the drug from the cell, upregulate alternate pathways, etc.

But it treats the whole body. It has to be better right? Right???

 

[communitydoc13]

Weirdly, not many people in rad onc seem keen to get unignorant about this. They’d rather let med onc and/or immunotherapy make our ignorance a moot point.

I think the advent of combined modality (chemorads) therapy and more recently immunotherapy, markedly reduced the appetite for high quality and deep research on radiation alone.

I remember learning about radbio as a medstud. I read the Steel basic clinical radbio book (loved it, I was stoked) and gave my rotation presentation on alternative fractionation schemes. This went over great and folks at my med school were very impressed.

Of course, I gave a version of this presentation on my away rotation at a bigger name place. They were like. "meh, we do combined modality for head and neck and lung now, I think the value of alternative fractionation is probably very limited in this space".

This was mid/late 2000s.

The shear clinical space provided by new systemic agents just distracts radiation researchers. I have seen 10+ years now of XRT plus ipi plus nivo or some sort or similar experiment in both in-vitro and clinical settings dominating our literature.

Maybe this is RWs putative "lack of imagination" at work.

 

[Palex80]

Maybe this is RWs putative "lack of imagination" at work.

Of, you mean like low dose radiotherapy for Covid?

 

[communitydoc13]

Of, you mean like low dose radiotherapy for Covid?

Don't get me wrong.... Stuff should be tried. Lord knows I'm not running any experiments.

 

[evilbooyaa]

The discussion is interesting to me because of all the hoops we have to jump through for SBRT authorization. I was just talking about this recently. Would be nice to be able to use a "classically radioresistant histology" as an indication for SBRT even in the clearly palliative setting.

There's already data that SBRT for non-spine metastases does better than conventional EBRT (Nguyen MDACC trial, SC.24) regardless of histology. But EviCore still doesn't consider SBRT an option. Because it's more expensive. And it costs them more money to allow us to treat with something more effective.

In an ideal world, all patients would get 1-5 Fx SBRT for every bony metastasis, that could be planned as fast as 3D, in every scenario where it was deemed safe to do so.

 

[TheWallnerus]

There's already data that SBRT for non-spine metastases does better than conventional EBRT (Nguyen MDACC trial, SC.24) regardless of histology. But EviCore still doesn't consider SBRT an option. Because it's more expensive. And it costs them more money to allow us to treat with something more effective.

In an ideal world, all patients would get 1-5 Fx SBRT for every bony metastasis, that could be planned as fast as 3D, in every scenario where it was deemed safe to do so.

You can do that for every straight Medicare patient

You could do it for every Medicare advantage patient, and it will get denied almost 100% of the time; but if you have the patient do their own appeal of the denial, the denial will get overturned 100% of the time

‘Merica

 

[evilbooyaa]

You can do that for every straight Medicare patient

You could do it for every Medicare advantage patient, and it will get denied almost 100% of the time; but if you have the patient do their own appeal of the denial, the denial will get overturned 100% of the time

‘Merica

Eh, but if it's palliation for metastatic disease, can we really wait for the lengthy appeals process? And is it really 100%?

I'm sure MSKCC is doing it on every Medicare patient already at minimum.... Right now my institutional inertia would be the time necessary to create a SBRT plan, QA, treatment time, etc for inpatients. Slapping on some fields would be easier. We're not at the point yet of SBRTing every medicare patient.... because then isn't that bias in care? If you do one thing more so for another patient based on what insurance they have?

 

[TheWallnerus]

Eh, but if it's palliation for metastatic disease, can we really wait for the lengthy appeals process? And is it really 100%?

I'm sure MSKCC is doing it on every Medicare patient already at minimum.... Right now my institutional inertia would be the time necessary to create a SBRT plan, QA, treatment time, etc for inpatients. Slapping on some fields would be easier. We're not at the point yet of SBRTing every medicare patient.... because then isn't that bias in care? If you do one thing more so for another patient based on what insurance they have?

The appeals process can be set for a hard 72h if the patient knows the right appeal to make

Usually will happen within 48h in fact

I wanna be specific: I’m talking Part C only… it’s very unique

 

[evilbooyaa]

The appeals process can be set for a hard 72h if the patient knows the right appeal to make

Usually will happen within 48h in fact

I wanna be specific: I’m talking Part C only… it’s very unique

May be worth a post in the business forum of the voodoo that you've learned...