Recurrent brain met in left mid brain

[Gfunk6]

I'm treating an elderly patient between 70-80 with met HER2/neu amplified breast cancer. She has been NED since 2019 when I treated her with 15 Gy x 1 fx to a left mid brain metastasis prescribed to 75% of max dose. She remained NED for the next 4 years.

Her most recent MRI shows apparent reemergence of the same brain met in the same position. It is tiny (~ 3 mm) but has been slowly growing over the last few MRI studies (every three months). Her PET scans have been clear for years and she is off treatment and has no evidence of extracranial disease.

This region is too small for functional imaging (perfusion or spectroscopy). She is not symptomatic - any suggestion? Am considering observation vs. Avastin pulse x2c vs re-treatment.

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[Bequerel]

I’d do short interval imaging and retreat if enlarges. Might consider talking to med onc about role of Tukysa with brain met. I vaguely remember a drug rep (who brought a taco truck for lunch!) discussing its effectiveness with her 2 positive brain Mets..or at least I think it was tukysa…honestly I just enjoyed the street tacos

 

[Gfunk6]

It has already been growing. The MRIs below (left to right) are: current, 3 months ago, 18 months ago, 21 months ago

 

[Neuronix]

What was the original size?

 

[Bequerel]

Then I’d treat if systemic therapy not an option but I’d fractionate this time

 

[Gfunk6]

What was the original size?

3 mm. It was eliminated on imaging ~ 3 months after initial SRS but re-emerged recently

 

[Neuronix]

3 mm. It was eliminated on imaging ~ 3 months after initial SRS but re-emerged recently

I'd wait for it to get bigger than the original size because this could just be RT necrosis. Wouldn't try Avastin until it's bigger or symptomatic.

I would favor systemic therapy at this time with anti her2 agents if we think it's real. That versus another short interval MRI. If it responds that also answers the question of whether it was real. The new her2 agents have a lot of brain activity.

 

[evilbooyaa]

I'd probably re-discuss and monitor until larger than original size and compare FLAIR dynamics at that time.

15 x 1 to a small lesion unlikely to cause progressive necrosis.

Speaking of brain stem mets, what're people doing nowadays? 25/5? 24-27/3? I've never done < 18Gy SF either in training or as an attending so wouldn't be enthusiastic, although I know 2019 was a somewhat different time.

 

[thecarbonionangle]

My brainstem met dose is 30/5, usually try to keep a kiss to edge to 25, center can be hot. it has been four years so i’d be ok treating if above suggestions fail.

 

[Ray D. Ayshun]

As this thread ended on a relevant note, I'll post here and not start a new one. I'm seeing a lady with metastatic adneoid cystic carcinoma who had a 3 mm brainstem met treated 15 Gy x 1 19 months ago. I've been watching it slowly come back for the last 4 months, and on the most recent scan, it increased in size from 3 mm to 6 mm. Can't really find a standard treatment approach here beyond EQD2/BED stuff. Wondering if anyone like Neuronix has a go to for brainstem retreatment. She's otherwise doing well. I'm thinking 20-5/5 with avastin.

 

[Neuronix]

Go big or go home. I would have started at a higher dose 18-20 Gy SRS on GK. With a good linac setup you can probably just do the same thing without PTV margin.

Disease failures in the brainstem kill patients. I have caused some cranial neuropathies and mild sensory or motor issues in the body occasionally over the years, but knock on wood I haven't seriously damaged anyone with RT. So the benefits of an aggressive approach outweigh the risks in my opinion.

I started my career doing 15 Gy like that, but increased the dose after discussions with those I like to call the brain met illuminati (the ones who are on the cooperative group trials). They have written the 18-20 Gy dose in brainstem for small mets into some of the trial protocols as well if you want to cite something to make everyone feel better.

Ok well that ship has sailed in this case. What would I do in this situation? 30/5.

20 or 25/5 is spitting in the wind. Might as well not even treat.

 

[Ray D. Ayshun]

Go big or go home. I would have started at a higher dose 18-20 Gy SRS on GK. With a good linac setup you can probably just do the same thing without PTV margin.

Disease failures in the brainstem kill patients. I have caused some cranial neuropathies and mild sensory or motor issues in the body occasionally over the years, but knock on wood I haven't seriously damaged anyone with RT. So the benefits of an aggressive approach outweigh the risks in my opinion.

I started my career doing 15 Gy like that, but increased the dose after discussions with those I like to call the brain met illuminati (the ones who are on the cooperative group trials). They have written the 18-20 Gy dose in brainstem for small mets into some of the trial protocols as well if you want to cite something to make everyone feel better.

Ok well that ship has sailed in this case. What would I do in this situation? 30/5.

20 or 25/5 is spitting in the wind. Might as well not even treat.

Thanks. I generally recommend going smaller when talking on the internet. Do you use avastin with, and are there any papers out there on this specific issue?

 

[Neuronix]

Do you use avastin with, and are there any papers out there on this specific issue?

I'm convinced that there's a retrospective review for everything. I don't know if there's any data for this, but it probably exists.

The biggest benefit of Avastin to the physician is that any recurrent disease will kill the patient before the MRI shows much change.

Does it prevent RT necrosis or improve RT safety in high-risk settings? Maybe. That data is weak to my knowledge.

Edit: I forgot to answer your question -- I would only use Avastin if the patient becomes symptomatic. Avastin has a lot of its own issues and side effects that lead me to favor not using it prophylactically--except maybe in recurrent GBM which is a different discussion.

 

[OTN]

I've also been upping my brainstem doses over the years- I haven't gotten as high as 20 Gy, but I'm glad to know there's data suggesting we can try. I'll have to give it a shot.

I agree that 20 or 25 in 5 isn't enough. I would also go to 30 in 5.

Avastin would treat the MRI well, but whether or not there's a patient benefit isn't clear in my experience.

 

[communitydoc13]

Avastin would treat the MRI well, but whether or not there's a patient benefit isn't clear in my experience.

My consideration of avastin would be to mitigate risks of necrosis, not for any meaningful prevention of disease progression.

A preclinical study.

https://www.sciencedirect.com/science/article/abs/pii/S1878875018310477

Anyone doing 27 Gy in 3 fractions in the brain stem up front?

 

[evilbooyaa]

My consideration of avastin would be to mitigate risks of necrosis, not for any meaningful prevention of disease progression.

A preclinical study.

https://www.sciencedirect.com/science/article/abs/pii/S1878875018310477

Anyone doing 27 Gy in 3 fractions in the brain stem up front?

I personally favor 30 to GTV, 25 to PTV, both in 5 fractions for upfront brainstem mets, even if small. Fractionation has its own benefits. Recommended point dose to brainstem is < 31Gy in 5 fractions on TG-101 so GTV dosing to 30Gy is doable. If I had to do a 3Fx regimen I'd probably do 27Gy to GTV, 24Gy to PTV but even that is technically 'above' TG-101 constraints similar to 1Fx, with caveats that a number of people have published going higher than TG-101 without badness happening.

For @Ray D. Ayshun 's case, I agree with Neuronix to having done 18Gy x 1 up front. I am not routinely doing 20Gy x 1 for brainstem mets, but I think if you can meet V12 < 5cc (as should be easily doable for a 3mm met) I think 20Gy would've been very reasonable. We know 15Gy x 1 is inferior control than lower doses SF, now, and less effective than fractionated SRS regimens.

That being said, as presented, a recurrent case after 15Gy x 1, I'd probably take the good (but not as good as 30/5) control seen in 25Gy in 5 fractions to GTV and PTV and call it a day.

Would not give Avastin unless patient became symptomatic from necrosis. Avastin is not 'free' and unless studied (like for recurrent GBM) would not add it on concurrently or whatever.

 

[Brim]

I vaguely remember a drug rep (who brought a taco truck for lunch!)

That's ****ing awesome.

even better if they drove the taco truck!

 

[StIGMA]

As this thread ended on a relevant note, I'll post here and not start a new one. I'm seeing a lady with metastatic adneoid cystic carcinoma who had a 3 mm brainstem met treated 15 Gy x 1 19 months ago. I've been watching it slowly come back for the last 4 months, and on the most recent scan, it increased in size from 3 mm to 6 mm. Can't really find a standard treatment approach here beyond EQD2/BED stuff. Wondering if anyone like Neuronix has a go to for brainstem retreatment. She's otherwise doing well. I'm thinking 20-5/5 with avastin.

Ok to fractionate (such as 54-60Gy in 2s or 45/3s) to small volume if want something durable and disease is otherwise well controlled and expect a longer prognosis. Im aware that’s not what most on here would do but it works.

 

[RSAOaky]

I personally favor 30 to GTV, 25 to PTV, both in 5 fractions for upfront brainstem mets, even if small.

This is what I do as well. I think best compromise in terms of dose delivered, safety, and time.

 

[SneakyBooger]

I personally favor 30 to GTV, 25 to PTV, both in 5 fractions for upfront brainstem mets, even if small.

I agree here.

 

[JustAdocInBox]

Resurrecting this thread, I have a 39 yo with triple negative breast cancer and a 5 mm met to the medulla. Have done multiple rounds of SRS over the past 2 years, no systemic disease. No prior brainstem metastases and no prior whole brain. I know medulla constraints are more conservative than pons/midbrain. I am doing Linac based, am able to dose the GTV to 27.5 Gy in 5 fraction and meet TG101 constraints for medulla, would anyone push beyond to 30 Gy?

Here are TG101 5 fx constraints for Cord and Medulla



Max 30 Gy
22 - 23 Gy (0.35 cc)
14.5 - 15.6 Gy (1.2 cc)

 

[Gfunk6]

Resurrecting this thread, I have a 39 yo with triple negative breast cancer and a 5 mm met to the medulla. Have done multiple rounds of SRS over the past 2 years, no systemic disease. No prior brainstem metastases and no prior whole brain. I know medulla constraints are more conservative than pons/midbrain. I am doing Linac based, am able to dose the GTV to 27.5 Gy in 5 fraction and meet TG101 constraints for medulla, would anyone push beyond to 30 Gy?

Here are TG101 5 fx constraints for Cord and Medulla



Max 30 Gy
22 - 23 Gy (0.35 cc)
14.5 - 15.6 Gy (1.2 cc)

I would use brainstem max constraints on TG101. That is 31 Gy point dose so V31 <= 0.03 cc. Edit: Also, to the extent possible I try to make these plans centrally hot and cooler in the periphery where you have the tumor/brainstem interface.

I find the intermediate dose contraints to be comically useless. Why would you be concerned if 1.2 cc of brainstem got 15 Gy in 5 fractions when we routinely treat whole brain to 30 Gy in 10??

 

[deleted1180461]

Cones or MLC?

A local failure in the brainstem would be catastrophic. 27.5 Gy in 5 fractions is not a definitive dose for TNBC.

(https://journals.sagepub.com/doi/10.1177/1533033818799355 suggests BED10 between 85-100 Gy). No, I wouldn't prescribe 40 Gy in 5 fractions to the PTV, but I would consider 30 in 5 to the margin and cover with 75% isodose line = 40 Gy hotspot.

 

[JustAdocInBox]

Cones or MLC?

A local failure in the brainstem would be catastrophic. 27.5 Gy in 5 fractions is not a definitive dose for TNBC.

(https://journals.sagepub.com/doi/10.1177/1533033818799355 suggests BED10 between 85-100 Gy). No, I wouldn't prescribe 40 Gy in 5 fractions to the PTV, but I would consider 30 in 5 to the margin and cover with 75% isodose line = 40 Gy hotspot.

True beam edge with 2.5 mm MLC.

 

[StIGMA]

0mm gtv->ptv

 

[evilbooyaa]

Resurrecting this thread, I have a 39 yo with triple negative breast cancer and a 5 mm met to the medulla. Have done multiple rounds of SRS over the past 2 years, no systemic disease. No prior brainstem metastases and no prior whole brain. I know medulla constraints are more conservative than pons/midbrain. I am doing Linac based, am able to dose the GTV to 27.5 Gy in 5 fraction and meet TG101 constraints for medulla, would anyone push beyond to 30 Gy?

Here are TG101 5 fx constraints for Cord and Medulla



Max 30 Gy
22 - 23 Gy (0.35 cc)
14.5 - 15.6 Gy (1.2 cc)

Would do 30 to GTV, 27.5 to PTV.

Cones or MLC?

A local failure in the brainstem would be catastrophic. 27.5 Gy in 5 fractions is not a definitive dose for TNBC.

(https://journals.sagepub.com/doi/10.1177/1533033818799355 suggests BED10 between 85-100 Gy). No, I wouldn't prescribe 40 Gy in 5 fractions to the PTV, but I would consider 30 in 5 to the margin and cover with 75% isodose line = 40 Gy hotspot.

No SRS dose for brain mets (inside or outside of the brainstem) is 'definitive'. It's better than 30/10, but studies have shown 40/5 to GTV is excessively toxic.

 

[deleted1180461]

Would do 30 to GTV, 27.5 to PTV.



No SRS dose for brain mets (inside or outside of the brainstem) is 'definitive'. It's better than 30/10, but studies have shown 40/5 to GTV is excessively toxic.

Pardon my misuse of the language. I guess ablative is the correct term. Although I know that's also controversial. What is the correct word for blasted DNA to bits and never coming back ever?

Edit: I guess what I meant, if you wanted to cure a TNBC primary with radiation alone, 27.5/5 is not going to do it, see the Japanese paper I linked for their estimates of "curative" BED.

2nd edit: also to clarify I was not saying give 40/5 to GTV. I was saying 30/5 to PTV (GTV + 1mm) with max 40 Gy central hotspot.

 

[evilbooyaa]

Pardon my misuse of the language. I guess ablative is the correct term. Although I know that's also controversial. What is the correct word for blasted DNA to bits and never coming back ever?

Also not ablative. BED 80-100 is not safely achievable in the brain, hence why we don't do it....

Definitive/ablative are mostly synonyms IMO. Definitive is also in the eye of the beholder and limited generally by OAR doses/toxicity concerns.

 

[deleted1180461]

Also not ablative. BED 80-100 is not safely achievable in the brain, hence why we don't do it....

I never said it was. 🙂

I said "27.5 Gy in 5 fractions is not a definitive dose for TNBC."

And that a local failure would be catastrophic.

The goal is to maximize cell kill. Therefore go as high as safely possible. I don't think you'd be crazy to do 27/3 to the PTV either. I personally would not. Plenty would also do 18/1. For me, single fraction is 20 or nothing.

I'm not sure I want to wade into the swamp of what the correct alpha/beta for TNBC cancer is...