Brain mets

[deleted4401]

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I still don't have a handle on when SRS is a better option than WBRT. The impression I have gotten is that is someone has 1-3 mets, controlled extrancranial disease, and a good performance status SRS+WBRT may be somewhat better than either modality alone. But, in that case, maybe they would be candidates for surgical resection + WBRT, so that gets a bit cloudy. If they have greater than 3 mets, WBRT seems to be a more prudent option, just based on the volume of dz needed to be treated. Otherwise, it is up in the air. And, if they have disease that is visualized by a solitary brain met, it seems logical they have microscopic disease all over their brain, so WBRT would seem to play some role.

What if someone has 1 met, progressive systemic disease, and poor performance status? I can buy that SRS is a shorter therapy than WBRT, but if it is the same outcome wise, is there any reason to choose one over the other? Is it cheaper to do 10 (or 5) EBRT treatments than 1 SRS treatment? Would it be worth doing SRS followed by WBRT in these patients? Is the toxicity of WBRT bad enough to consider SRS which is considered to be less morbid? I don't even really see the toxicity of WBRT since I'm on one service for a period of months and don't really see outcomes/toxicities. And is SRS really less morbid - I don't know, and nobody really seems to be able to tell me for sure. I do know we're treating a lot less normal tissue with SRS, so that may be better. Is it better for the patient to only have one long SRS treatment rather than 5 or 10 EBRT treatments? If a patient is in such poor shape to begin with, is any treatment even necessary? Or is it that my institution is so SRS-friendly (Pittsburgh), that we need to find indications to use it?

Well ... for something that is so 'basic' for a rad-onc resident, I'm not even sure where to look for the answers, and I feel like I get conflicting advice from my attendings. On top of that, some of the consulting med-onc attendings seem to be so pro-SRS for reasons I can't figure out.

What am I missing here and what framework do I need to assess what the right clinical decision is?

-S

 

[medgator]

http://www.ncbi.nlm.nih.gov/entrez/..._uids=16757720&query_hl=2&itool=pubmed_docsum

That study was published in JAMA randomizing SRS+WBRT vs SRS alone.... it didnt find a survival benefit to adding WBRT (SRS enthusiasts might argue that point).
It did however show significantly worse rates of intracranial relapse in pts who didnt get WBRT (kinda predictable---- similar in concept to the patchell study that demonstrated better in brain control after adding WBRT to a single surgical resection of a brain met).
I think from a healthcare resource utilization standpoint, it makes sense to add WBRT upfront--- to avoid further interventions down the road. The patchell study did show decreased rates of intracranial relapse as well as a decreased chance of death fron neurologic causes. Extrapolating that to SRS (no head to head comparisons, but surgery = radiosurgery in theory), I think it makes sense from a "preventing a death from neurologic cause" standpoint as well-- sounds bad to me to die from a "neurologic" cause like herniation/stroke/hemorrhage etc.

I guess the worrisome issue with being pro-WBRT is the long term cognitive outcome issue, which I really don't know a whole lot about. Is it really an issue in this population of patients with (generalizing here) a worse prognosis than most? Im sure Steph can probably weigh in on this.


Oh yeah, Here's the patchell study comparing surgical resection + WBRT to surgery alone: http://www.ncbi.nlm.nih.gov/entrez/...t_uids=9809728&query_hl=4&itool=pubmed_docsum

 

[radonc]

medgator-
very good response, i tend to agree with what you have said.

*per RTOG 9508 (Lancet 22: 1665-1672, 2004), the addition of SRS to WBRT had improved survival in patients with single metastases, RPA Class 1, and metastases > 2cm. There was also significant improvement in KPS and local control with WBRT+SRS. However, there was noo sig difference in neurologic death and no survival advantage in patients with multiple lesions.

*the omition of WBRT to either surgery or SRS for led to a 2x, 5x, and 8x increased need for salvage therapy (sneed 98, sneed 02, patchell 98)

 

[deleted4401]

There wasn't a WBRT alone arm, was there? That's what I'm trying to figure out - whether dual therapy is necessary. I've seen one abstract with WBRT alone vs SRS alone, didn't glean a whole lot from it, except OS wasn't different, which was expected.
-S

 

[medgator]

There wasn't a WBRT alone arm, was there? That's what I'm trying to figure out - whether dual therapy is necessary. I've seen one abstract with WBRT alone vs SRS alone, didn't glean a whole lot from it, except OS wasn't different, which was expected.
-S

There wasn't one in that JAMA study.

That WBRT alone vs SRS alone is interesting--- do you remember where that abstract was from? One of the original studies by Patchell looking at surgical resection of a single met versus biopsy with WBRT alone showed a survival benefit to surgery.

http://www.ncbi.nlm.nih.gov/entrez/...t_uids=9809728&query_hl=4&itool=pubmed_docsum

Assuming equivalence to surgery, I would have expected some kind of benefit with the SRS only arm (assuming we were talking about pts with a couple of mets at most with a good PS).

 

[stephew]

this study has to be interpreted within the context of its comparison to other data out there.
a few points


1) these patients had FAR MORE intracranial and systemic diease and aren't comparable to the outcomes of the patchell patients

2) there was interesting effect of the wbrt in local control given they pulled back on srs dose by 30% in that arm

3) there is sitll no data that analyzes neuro deficit of iether disease or wbrt well. Chang et al has a nice review of the mets topic in hemeatology and oncology this month worth your time. Mehta and Bill Regine have a nice diaglogue in a CME out now tyhat addresses this.

4) we dont have enough numbers to test the survival benefit of wbrt and distant lapse on people with minimal burdens of disease (ie the curative population, which doest exist).

From a boards answer its straightfoward. For real life, Ive learned how complex it is (as is most management. its funny how that happens); just an example: we tend to want to withhold wbrt in the young..these are the people who have the least long term side effects. and they often are the ones with the lowest burden of disease..should they be the ones who benefit from wbrt in a survival sence but we cant tell due to pt numbers? we simply do not know. most long term cognitive deficit occurs in people with significant small vessle related issues (DM, age etc) and in folks with persisant disease in the brain. NOT with those with intracranial control.

In so-called radioresistant tumors the role of wbrt is different that for radiosensitive tumors maybe..but how? Small cell, sure very sensitive. but it always comes back. renal cell? resistant! but...can often be VERy well controled and even keep shrinking more than 5 years out from wbrt. i just saw something this week who had complete resolution after wbrt alone. ive seen it a lot. (think of MFH sarcoma..we can cure that. we dont cure sensitive small cell. so we lie to patients abotu how great it is to ahve a sensitive tumor.)

I highly recommend that students/residents look at a good review paper. its not considered as sexy as reading peer reviewed papers, but unless you want to delve into the literature so you can compare the studies and thus see the lmitations in interpreting the outcomes of a single trial (even a multi-institutional prospective trial etc), check out a review from good folks. The recent Mehta Regine cme is good and this months hematology and oncology has a nice Chang, Mehta article that goes trhough the context of the papers out there. worth you 1/2 hour. also a Senator Obama article off topic. I PM'd simul some comments that i think about, he can repost them here if he wishes

http://www.ncbi.nlm.nih.gov/entrez/..._uids=16757720&query_hl=2&itool=pubmed_docsum

That study was published in JAMA randomizing SRS+WBRT vs SRS alone.... it didnt find a survival benefit to adding WBRT (SRS enthusiasts might argue that point).
It did however show significantly worse rates of intracranial relapse in pts who didnt get WBRT (kinda predictable---- similar in concept to the patchell study that demonstrated better in brain control after adding WBRT to a single surgical resection of a brain met).
I think from a healthcare resource utilization standpoint, it makes sense to add WBRT upfront--- to avoid further interventions down the road. The patchell study did show decreased rates of intracranial relapse as well as a decreased chance of death fron neurologic causes. Extrapolating that to SRS (no head to head comparisons, but surgery = radiosurgery in theory), I think it makes sense from a "preventing a death from neurologic cause" standpoint as well-- sounds bad to me to die from a "neurologic" cause like herniation/stroke/hemorrhage etc.

I guess the worrisome issue with being pro-WBRT is the long term cognitive outcome issue, which I really don't know a whole lot about. Is it really an issue in this population of patients with (generalizing here) a worse prognosis than most? Im sure Steph can probably weigh in on this.


Oh yeah, Here's the patchell study comparing surgical resection + WBRT to surgery alone: http://www.ncbi.nlm.nih.gov/entrez/...t_uids=9809728&query_hl=4&itool=pubmed_docsum

 

[stephew]

however do you know which was ad hoc analysis and not included upfront?

medgator-
very good response, i tend to agree with what you have said.

*per RTOG 9508 (Lancet 22: 1665-1672, 2004), the addition of SRS to WBRT had improved survival in patients with single metastases, RPA Class 1, and metastases > 2cm. There was also significant improvement in KPS and local control with WBRT+SRS. However, there was noo sig difference in neurologic death and no survival advantage in patients with multiple lesions.

*the omition of WBRT to either surgery or SRS for led to a 2x, 5x, and 8x increased need for salvage therapy (sneed 98, sneed 02, patchell 98)

 

[stephew]

i should add this: non radoncs who are pro-srs are NOT radonc doctors. Do NOT get bullied into something that the medoncs have set up. the classic is a strong opinion to the pt by a non- radiation oncologist. your job is to discuss the issues. and remind the pts if you have to that just as you can give an overview talk of chemo but you know youre not the expert in the area, so too the medoncs re NOT the experts in radonc. that another service is very pro-anything is not a clue to you as to what teh right thing to do is. A good doc knows their limitations and works WITH the other teams in a multidisciplinary way. They don't dictate what folks who've spent years training in a speciality think is best.

I still don't have a handle on when SRS is a better option than WBRT. The impression I have gotten is that is someone has 1-3 mets, controlled extrancranial disease, and a good performance status SRS+WBRT may be somewhat better than either modality alone. But, in that case, maybe they would be candidates for surgical resection + WBRT, so that gets a bit cloudy. If they have greater than 3 mets, WBRT seems to be a more prudent option, just based on the volume of dz needed to be treated. Otherwise, it is up in the air. And, if they have disease that is visualized by a solitary brain met, it seems logical they have microscopic disease all over their brain, so WBRT would seem to play some role.

What if someone has 1 met, progressive systemic disease, and poor performance status? I can buy that SRS is a shorter therapy than WBRT, but if it is the same outcome wise, is there any reason to choose one over the other? Is it cheaper to do 10 (or 5) EBRT treatments than 1 SRS treatment? Would it be worth doing SRS followed by WBRT in these patients? Is the toxicity of WBRT bad enough to consider SRS which is considered to be less morbid? I don't even really see the toxicity of WBRT since I'm on one service for a period of months and don't really see outcomes/toxicities. And is SRS really less morbid - I don't know, and nobody really seems to be able to tell me for sure. I do know we're treating a lot less normal tissue with SRS, so that may be better. Is it better for the patient to only have one long SRS treatment rather than 5 or 10 EBRT treatments? If a patient is in such poor shape to begin with, is any treatment even necessary? Or is it that my institution is so SRS-friendly (Pittsburgh), that we need to find indications to use it?

Well ... for something that is so 'basic' for a rad-onc resident, I'm not even sure where to look for the answers, and I feel like I get conflicting advice from my attendings. On top of that, some of the consulting med-onc attendings seem to be so pro-SRS for reasons I can't figure out.

What am I missing here and what framework do I need to assess what the right clinical decision is?

-S

 

[radonc]

however do you know which was ad hoc analysis and not included upfront?

yes, but it raises some interesting issues...basically what kinds of pts will benefit from wbrt & upfront srs.

this is a great topic, and it shows that even the 'simplest' of topics has a great deal of controversy and impact in our field. fractionation schemes& QOL, local recurrence rates, and coming up with a treatment algorithm are all aspect of WBRT that have yet to be defined.

 

[Brim]

That WBRT alone vs SRS alone is interesting--- do you remember where that abstract was from?

The abstract of WBRT alone vs SRS alone is a study by P.B. Chougule out of Rhode Island Hospital / Brown University, published as abstract #7 in the Red Journal 2000, vol 48 (3 Suppl), page 114. (Coincidentally, RTOG 95-08 was published that same year in abstract form as #6.)
I don't believe this has ever been published in manuscript form. <-- WHY?

The trial randomized pts with 1-3 mets to Gamma Knife alone, WBRT alone, or GK + WBRT. There was no difference in survival among the 3 arms. Local control was superior in the GK and GK+WBRT arms. Appearance of new brain lesions, however, was high for the WBRT only arm. Somewhat muddying the water was the fact that 51 of 109 pts underwent surgical resection for large, symptomatic mets. This was prior to randomization, so those pts undergoing resection should theoretically be distributed evenly among the 3 arms, but the abstract didn't say if that was stratified for.

My take on this is that the results support what other published studies have shown. RTOG 95-08 showed that adding SRS to WBRT didn't improve survival (except for pts with 1 met) but there was an improvement in local control, KPS, and decreased need for steroids at 6 months. The Japanese trial of SRS +/- WBRT (the JAMA one alluded to by medgator) showed that adding WBRT to SRS did not improve overall survival but decreased overall brain failure rates. If you adopt the belief that radiosurgery is equivalent to resection, then RTOG 95-08 is Patchell's first study and the Japanese trial is Patchell's second study. From an effect on overall survival, the results are the same -- in Patchell #1, for one met surgery resulted in improved overall survival as well as local control and functional independence; in Patchell #2, whereas WBRT did not improve survival, it decreased failure in the brain.



Is it just me or does this symbol in the yellow triangle look like a ... I'll shut up now.

 

[stephew]

that paper really doesnt add much to the literature.

 

[stephew]

no i dont agree that the ad hoc analysis i was refering to really tells you who will and wont benefit; the issue is in what way and sure it raises intersting questions but the trouble is answering them of course.

i agree however, the topic in practice is not simple at all. its always very interesting to watch how much harder things get for people the day they leave residency; as much as you learn (and you learn a ton) you realize there are nuiasnces you never thought of that persent in so many cases.

yes, but it raises some interesting issues...basically what kinds of pts will benefit from wbrt & upfront srs.

this is a great topic, and it shows that even the 'simplest' of topics has a great deal of controversy and impact in our field. fractionation schemes& QOL, local recurrence rates, and coming up with a treatment algorithm are all aspect of WBRT that have yet to be defined.