3DCRT for PostOp Brain Mets...

[Neuronix]

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The pathology from the re-op showed active disease, right?

In these situations I wait for the disease to regrow a second time with serial scans and treat GTV of whatever regrows. I don't like to make large fields again after doses that high.

 

[evilbooyaa]

The pathology from the re-op showed active disease, right?

In these situations I wait for the disease to regrow a second time with serial scans and treat GTV of whatever regrows. I don't like to make large fields again after doses that high.

Agree with this. Despite that most of that has probably been resected, I'd be wary of causing necrosis treating a big field. I'd be wary of going at 2.5Gy in colorectal cancer. It already shrugged off 30/5, I'm not sure how useful additional palliative doses at 2.5 or 3.0Gy will be.

 

[scarbrtj]

So I am seeing a young guy who had a solitary cerebellar met from colorectal cancer. Was subtotally resected initially and had a 3x 3 cm type cavity. I treated the cavity + 3mm to 30Gy in 5 fx. No progression for about 1.5 years, then had slow radiographic progression over serial scans with stable clinical picture. All the typical systemic stuff was tried, but it continued to progress slowly. I had the surgeon look at him and he did a repeat crani with perhaps a more aggressive surgery. He's had several post op complications requiring a graft revision and VP shunt etc... But that has all healed and now he comes back in walking and talking normally, no symptoms, and only slight CN XI and XII asymmetry on exam. Cavity is large on MRI, about 5 cm with peripheral enhancement 8 weeks out from surgery.

Overall, he is >2 years out from previous XRT. Still only site of disease.

Any suggestions? I'm thinking a larger, partial brain volume covering the cerebellar hemisphere and dura in maybe 15 fractions. 2.5Gy fractions to cover edema and dose paint the enhancement a bit. Does that sound reasonable?

1) Colorectal cancer in the young: not on anyone's radar (great video)
2) You know I like to take clinical situations and reverse engineer them to math...

a) In Hall in chapter 3 there's this cell surv curve graph, and then DNA electrophoresis of irradiated cell lines. The "laddering" of the DNA electrophoresis indicates radiosensitivity. There were prostate, ovarian, lymphoma, and colon cancer cell lines. The lymphoma cell line showed extreme laddering (lots of radiosensitivity). Ovarian and prostate showed some laddering. The colon cancer lines showed ZERO laddering, indicating, surprisingly, radioresistance.​

b) One mark of radioresistance in a tumor is a high D0.* The "average" tumor D0 is ~3 Gy. A radioresistant tumor's D0 might be 5 Gy.​

c) The amount of cell kill of 30/5 for D0 = 5 Gy is (e^-(6/5))^5 = 0.002. This is not much cell kill. Postop tumor cell number might be as high as 100,000.​

0.002 * 100,000 = ~200​

Thus 30/5 postop would leave behind about ~200 cancer cells after surgery.​

d) If you decided to do 60/30 postop in this situation, and D0 = 5 Gy, and assume 100,000 cells left behind postop, the cell kill would be:​

(e^-(2/5))^30 = 0.000006​

And 0.000006 x 100,000 = 0.6, or ~60% chance for LC.​

​

I show #2 as an example that 1) in certain situations, hypofractionation is not the panacea we tend to rely on, and 2) depending on a tumor's radioresistance, pure dose escalation trumps hypofractionation. Hypothetical but provocative.​

​

(However, 60/30 would have more late effects than 30/5. Yet there seems something appealing about using standard fractionation in this re-irradiation situation... if you re-irradiate. My take.)​

​

* D0 equals dose that achieves 1/e cell kill​

​

 

[Palex80]

One (provocative) question for your patient, Mandelin Rain, is what exactly the target should be.

Would you treat the entire resection cavity up to the same dose or would you consider restricting yourself to the part where the recurrence popped up.

I had a patient like this quote a long time ago.
She had a solitary breast cancer metastasis, resected. I treated WBRT (that was back in 2012 when we were still giving all the patients post surgery WBRT) with 36/2 then boosted the cavity to 50/2. Please don't ask me why I boosted. And certainly don't ask me why I chose 50/2, I presume it had to do with Patchell...

Anyways...

2 years passed then she recurred within the cavity. Surgeon offered re-operation. She got complete resection and I declined RT, fearing complication after 50/2. She was on systemic treatment by that time due to lymph node progression as well.

Another 2 years passed and she re-recurred at exactly the same spot she recurred the first time. Surgeon (great guy!) re-resected. I treated her with 30/5 but chose to limit the volume only to the site of the recurrence with a CTV-margin of 3mm along the cavity walls and another 3mm PTV-margin.
I did not treat the entire cavity.

It's been 3 years now and she remains recurrence- (and necrosis-) free. Extracerebral disease is controlled as well.

N=1, that's all I can offer...

 

[scarbrtj]

One (provocative) question for your patient, Mandelin Rain, is what exactly the target should be.

Would you treat the entire resection cavity up to the same dose or would you consider restricting yourself to the part where the recurrence popped up.

I had a patient like this quote a long time ago.
She had a solitary breast cancer metastasis, resected. I treated WBRT (that was back in 2012 when we were still giving all the patients post surgery WBRT) with 36/2 then boosted the cavity to 50/2. Please don't ask me why I boosted. And certainly don't ask me why I chose 50/2, I presume it had to do with Patchell...

Anyways...

2 years passed then she recurred within the cavity. Surgeon offered re-operation. She got complete resection and I declined RT, fearing complication after 50/2. She was on systemic treatment by that time due to lymph node progression as well.

Another 2 years passed and she re-recurred at exactly the same spot she recurred the first time. Surgeon (great guy!) re-resected. I treated her with 30/5 but chose to limit the volume only to the site of the recurrence with a CTV-margin of 3mm along the cavity walls and another 3mm PTV-margin.
I did not treat the entire cavity.

It's been 3 years now and she remains recurrence- (and necrosis-) free. Extracerebral disease is controlled as well.

N=1, that's all I can offer...

Now if I get this correct, part of her brain saw: 36 Gy/18 fx, plus 50 Gy/25 fx, plus 30 Gy/5 fx? Approximately 116 Gy in 48 fx? (Plus two crani's.)
Perhaps you should submit this to Guinness 🙂

 

[Neuronix]

Now if I get this correct, part of her brain saw: 36 Gy/18 fx, plus 50 Gy/25 fx, plus 30 Gy/5 fx? Approximately 116 Gy in 48 fx? (Plus two crani's.)
Perhaps you should submit this to Guinness 🙂

I saw a kid with multiply recurrent ependymoma once who had full dose RT 3 times to the same place with protons. No RT necrosis either. I was amazed.

 

[scarbrtj]

I saw a kid with multiply recurrent ependymoma once who had full dose RT 3 times to the same place with protons. No RT necrosis either. I was amazed.

All this says to me: we don't really know squat. We think we see necrosis after 30/5, or 18/1. (And we probably do.) And not after ~100+ Gy fractionated. There was a time at my training institution, at the inner city hospital, where--long story short--a quite large number (about 20) of patients got ~60 Gy to a few cm's of cord during their H&N treatments (discovered 1+ years after their treatments). Never saw a single case of myelitis in them in f/u. And then in our own practices we will see cases of radiation toxicity at much lower doses. Again, clearly, there's a lot we don't know about radiation's interactions with an individual's body. I think another key point: the CNS seems to forgive a lot of previously delivered dose; ain't no monkey business (a classic).

 

[taserlaser]

Merchant has a series on retreatment for paediatric ependymoma, full dose. Off the top of my head something like 10% brain stem necrosis rate.

 

[medgator]

All this says to me: we don't really know squat. We think we see necrosis after 30/5, or 18/1. (And we probably do.) And not after ~100+ Gy fractionated. There was a time at my training institution, at the inner city hospital, where--long story short--a quite large number (about 20) of patients got ~60 Gy to a few cm's of cord during their H&N treatments (discovered 1+ years after their treatments). Never saw a single case of myelitis in them in f/u. And then in our own practices we will see cases of radiation toxicity at much lower doses. Again, clearly, there's a lot we don't know about radiation's interactions with an individual's body. I think another key point: the CNS seems to forgive a lot of previously delivered dose; ain't no monkey business (a classic).

Cervical cord =/= thoracic cord.

 

[radiation]

Now if I get this correct, part of her brain saw: 36 Gy/18 fx, plus 50 Gy/25 fx, plus 30 Gy/5 fx? Approximately 116 Gy in 48 fx? (Plus two crani's.)
Perhaps you should submit this to Guinness 🙂

St Jude outcomes for kids getting >100 gy to brainstem after re-irradiation are actually pretty reasonable

Outcomes After Reirradiation for Recurrent Pediatric Intracranial Ependymoma - PubMed

Reirradiation for relapsed pediatric ependymoma was well tolerated by most patients and resulted in long-term survival in a subset of patients. The best results were observed in patients who experienced distant-only failure after RT1 and were treated with CSI as part of RT2, without anaplasia at...

www.ncbi.nlm.nih.gov

 

[nkmiami]

wisconsin also had large series of patients who got 100 + Gy to large volumes

Reirradiation of large-volume recurrent glioma with pulsed reduced-dose-rate radiotherapy - PubMed

PRDR allowed for safe retreatment of larger volumes to high doses with palliative benefit.

www.ncbi.nlm.nih.gov

 

[Palex80]

Now if I get this correct, part of her brain saw: 36 Gy/18 fx, plus 50 Gy/25 fx, plus 30 Gy/5 fx? Approximately 116 Gy in 48 fx? (Plus two crani's.)
Perhaps you should submit this to Guinness 🙂

Actually not quite. She got WBRT 36/2 + a boost to the cavity up to 50/2 cumulative dose (I didn't phrase that quite correct) and then she received 30/5.
Plus 3 resections.

I don't think its awfully alot, because we do treat GBM often with something like 35/3.5 or 39.9/2.66 after 60/2.
However one could make the point GBM-patients probably don't live long enough (especially after the second course of RT) for us to make clear statements on long term toxicity.

 

[medgator]

Actually not quite. She got WBRT 36/2 + a boost to the cavity up to 50/2 cumulative dose (I didn't phrase that quite correct) and then she received 30/5.
Plus 3 resections.

I don't think its awfully alot, because we do treat GBM often with something like 35/3.5 or 39.9/2.66 after 60/2.
However one could make the point GBM-patients probably don't live long enough (especially after the second course of RT) for us to make clear statements on long term toxicity.

Recent Rtog protocols in GBM allow for point doses of 60 to the brainstem IIRC.... Not sure I would use that type of tolerance for a meningioma or pituitary tumor

 

[Brim]

Laser Interstitial Thermal Therapy

I hope everyone in the group laughed like an evil henchman after the CNS tumor conference suggested this.

 

[Mandelin Rain]

In these situations I wait for the disease to regrow a second time with serial scans and treat GTV of whatever regrows. I don't like to make large fields again after doses that high.

Thanks for all the input. I'm going with this as my plan.