LG Glioma. But maybe a little high grade.

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Damn_Daniel

Damn_Daniel

Third Rate Physician at Third Rate Academic Center
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60 yo man presents with seizure. Work up includes MRI, and he has a right paramedian frontal tumor, 3.5 x 3.5cm, "likely a glioma", mild mass effect. Metastatic work up did not reveal a primary, so went to crani. The path comes back as low grade oligodendroglioma, 1p/19q co-deletion. However, "Ki67 is low in grade II areas, but other cellular areas are high. Focal grade III oligodendroglioma can not be ruled out." Post op MRI showed a bit of residual disease. His dad died of GBM.

Medical oncologist is leaning on me heavy to radiate (like when Kimmy Gibler forced DJ to hitchhike to Berkeley), and then give PCV after. Not entirely unreasonable, since STR. But, with that possible focal grade III, anyone want to consider Vitamin T? It's an option on NCCN for both grade II and III, but category 2B.
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I would send to your local academic center for a second opinion on Grade III. For Grade II our local practice is XRT --> PCV. For Grade III would do concurrent XRT + Temodar.

If he is truly Grade II his OS is probably 15 years + with 1p/19q co-deletion so would cause one to be more prudent with post-op treatment.
 
Damn_Daniel said:
60 yo man presents with seizure. Work up includes MRI, and he has a right paramedian frontal tumor, 3.5 x 3.5cm, "likely a glioma", mild mass effect. Metastatic work up did not reveal a primary, so went to crani. The path comes back as low grade oligodendroglioma, 1p/19q co-deletion. However, "Ki67 is low in grade II areas, but other cellular areas are high. Focal grade III oligodendroglioma can not be ruled out." Post op MRI showed a bit of residual disease. His dad died of GBM.

Medical oncologist is leaning on me heavy to radiate (like when Kimmy Gibler forced DJ to hitchhike to Berkeley), and then give PCV after. Not entirely unreasonable, since STR. But, with that possible focal grade III, anyone want to consider Vitamin T? It's an option on NCCN for both grade II and III, but category 2B.
Click to expand...

Most of the country would give Temodar for this even though the studies used PCV. I'd say PCV for the oral boards but do Temodar in practice. By any chance are you at UTMB?
 
That path read was from a First Rate Academic Center. Basically some of the tumor cells had more atypia, but not enough to upgrade.

P53 testing is a good idea. I'll grovel with med onc for some T.

UTMB? Gosh I'd kill to be in a major metro like Galveston, "The Paris of East Texas".
 
It's a tough case to say no to the patient. Any contrast enhancement on initial MRI? If not, would observe.
 
I'm very surprised your med onc prefers PCV. I never seen anything other than Temozolomide for gliomas (even in low grades). Maybe Bev for recurrences.
 
There are widely varying patterns of care across the US. It simply isn't true that "no one uses PCV" though. Some don't use it at all and say its too toxic, some used modified versions of it, and some swear by it. There is extremely compelling data behind PCV that currently trumps some of the TMZ data by a landslide, although there are some current trials that may clarify this. If I was a patient, knowing what I know, I would absolutely want to be considered for PCV in certain scenarios.
 
My med onc colleagues don't believe in data.
 
No contrast enhancement.

Spoke to First Rate med onc, and she explained to me that in this era, the 1p/19q co-deletion trumps pathologic findings, that the molecular signature is what should guide the treatment. Patients with anaplastic tumors with 1p/19q co-deletion and treated with RT/PCV have a several year improvement in PFS compared to RT alone (RTOG 9402 - 14 years vs 7 year median survival, EORTC 26951 - PFS 157 months vs 50 months, median survival - not reached vs 112 months). And, RTOG 9802 (grade 2) had a 5.5 year survival benefit with RT/PCV vs RT alone, though they have not completed the 1p/19q group analysis (low numbers, not stratified). So, that would be the evidence-based approach.

No comparative data for Temodar, there is phase II data that shows pretty good outcomes, but that's not randomized. Randomized trial - NOA4 - outcome still pending. So, Temodar is an option, because of ease of administration and less toxicity, but she would go with PCV.

UpToDate says PCV, but then "winks" and says to give Temodar, even though not strong data

Low grade glioma is an f'in mess! Thanks for your help!
 
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The above does not apply to LGG. Just sayin )
 
seper said:
The above does not apply to LGG. Just sayin )
Click to expand...

I said in the first sentence that pathological grading is being trumped by the molecular sig store.. That grade 2/3 has significant inter-observer variability amongst pathologists. Using the molecular signature to make treatment decisions is becoming en vogue, and the distinction between LGG/HGG via looking at a microscope doesn't matter. Ya dig?
 
Show me the data that 1p/19q trumps pathologic grading, or fall silent!
Pathologic grading of glioma is something that even RadOnc residents are expected to master )
 
PCV+RT applies to high risk LGG (>40 OR STR, this patient meets both) AND anaplastic tumors with oligo component and 1p/19q codeletion and is the ONLY category 1 recommendation in both situations.
 
*Anticipated* changes in WHO grading will incorporate molecular / genetic factors over light microscopy. So indeed glioma grading is a mess and comparing new to old will be tough.


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Hahahahahahahahaha!
1993 wants their way of practicing medicine back!!! And they want their light microscope back, too!
 
Damn_Daniel said:
Hahahahahahahahaha!
1993 wants their way of practicing medicine back!!! And they want their light microscope back, too!
Click to expand...

Yea, ASTRO refresher stated that molecular profiling trumps histology now.
 
radmonckey said:
PCV+RT applies to high risk LGG (>40 OR STR, this patient meets both) AND anaplastic tumors with oligo component and 1p/19q codeletion and is the ONLY category 1 recommendation in both situations.
Click to expand...
Whole brain xrt is the only category 1 recommendation after craniotomy and resection of a brain met.

Yet it seems almost everyone these days does srs or fsrt to the cavity plus a margin
 
The problem with whole brain RT after resection of brain mets is that's it all based on one trial and we are all aware of the detrimental effect of wbrt on neurocognition. Plus it's palliative treatment.

Treating grade III oligos with prognostic favorable features is not palliative treatment, these patients often survive more than 10 years.

On a side note: Patchell gave 50.4/1.8 wbrt. I have yet to see someone do that... :)
 
Those guidelines need to be updated. There is a trial showing WBRT kills after focal treatment. Category 1 means no disagreement, and clearly the members of that team either forgot to read my boy Chang's trial or they were in a really bad lunch situation and had to come to agreement or just starve. We all would have done the same thing, as would have Belushi. That dude did not miss lunch.
 
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You're telling me you would offer WBRT after focal treatment, despite the results of that trial???

Hahahahahaha.

Please tell me this isn't consensus thinking?

Explain the refresher I need. Adding a costly treatment (WBRT) to a dying patient may give them worse QOL and side effects, possibly may kill them (undetermined, but possible) is something you consider to be evidence based medicine?

This field is almost as bad as obstetrics.
 
There have been many randomized trials comparing WBRT to SRS. All, save one, have established no difference in survival. The one that demonstrated a difference in survival did not have OS as a primary endpoint and the PI of the trial is on the record that it should not be interpreted as such.

As much as one may be biased towards SRS (I certainly am!) we have to accept that WBRT in this setting (in conjunction with Namenda or hippocampal sparing) is a category I intervention.


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DD has GOT to learn the data
 
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So, the trial showed a detrimental effect of WBRT, for whatever reason, there is no trial that shows that WBRT benefits survival, one major trial that used 50 Gy and showed a huge local control benefit but no survival benefit, most people no longer give WBRT after local treatment, and ASTRO says via Choosing Wisely not to give WBRT routinely, and I'm the one who doesn't know the data? Huh? Sounds like people arguing just to argue. "Yeah, ur a dummy and don't know datas, but we also wouldn't give it!! So there!"

And this notion that it wasn't a primary endpoint ... Does that really mean you ignore it?
 
I think you are misquoting ASTRO:

"Don’t routinely add adjuvant whole brain radiation therapy to stereotactic radiosurgery for limited brain metastases."

Regarding Eric Chang's trial, yes you ignore it. When you have multiple Phase III trials showing no OS of SRS > WBRT, you don't cherry pick the secondary endpoint of another trial to justify what you are trying to do.

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I would also lean towards SRS as WBRT treats a lot of normal brain.
 
Not misquoting.

Saying that exactly - Astro says don't add WBRT routinely. That's what the Chang study showed. Dr Gator originally made the comment about the category 1 recommendation of WBRT after surgery or SRS. Not sure where the confusion is. Isn't WBRT after surgery or SRS considered adjuvant?

Sorry for the sharp words, though. It does sound like there is a sharp divide. I'd never add WBRT after SRS or surgery. That trial scares me. But, seems like many people are ignoring it and would give WBRT after local treatment. It's fine. It's category 1. It's just that when there is certainly no survival benefit, why do it, routinely? Costs more, more side effects, Inconvenient. Look, I'd love to be swayed to offer a treatment that gets me more cheese. I'm broke after the third wife. As an overweight, acne ridden man who is generally surly, even though I probably won't get a fourth, I still wouldn't mind some more money.
 
I think everyone should calm down here. There's no reason to carry out the debate in this way.

Daniel has a point, when he says that WBRT should not be routinely used after focal therapy of brain mets. It is true that toxicity is high and Chang's trial clearly showed that WBRT can be detrimental both to neurocognition and possibly to OS.
We do have the old EORTC trial looking into dose escalation for PCI in SCLC which also demonstrated a decline in OS with 36 Gy WBRT. Surely, totally different scenario, since it was PCI but it's another hint that aggressive therapy to the whole brain, can also lead to less favorable outcomes, that one wouls suggest or hope. Patchell did 50/1.8 WBRT, which is going to cause a lot of toxicity, clearly more than 30/3.

Another nice anecdote is the level of "evidence" we sometimes base our recommendations on. Patchell included all kinds of histologies in his trial. I am certain than thousands of patients with singular resected brain mets from melanoma have received postoperative WBRT in the past decades. Do you know how many melanoma patients were in Patchell's trial? 1. :)
So, strictly speaking, we have been giving WBRT for postoperative melanoma brain mets, based on data of 1 patients, which was treated like that in the trial? Great.

On the other hand, focal radiation of resection cavities has also very little if not poor evidence. We don't even know, if it will enhance survival. since we don't have any trials at all looking into that. We do have clear signs that local control after surgery is worse with surgery without RT than with sole radiosurgery. The EORTC trial clearly showed that. On the other hand, there was a paper last month in the Red Journal demonstrating quite high rates of leptomeningeal spread in brain met patients undergoing sole resection compared to radiosurgery. Can focal postoperative irradiation prevent leptomeningeal spread? I don't think so.

This is a highly controversial topic, one in which we have invested way too little in terms of trials.
WBRT is not always the best option in many brain met patients. A british trial shows preliminary data, that it's actuall not worth it at all in patients with more than a few mets.
On the other hand some patients may even be cured with postoperative WBRT after resection of singular metastasis, I have 2 patients with follow-up >3 years in this situation.
 
It sounds like at least one person reads more than abstracts. Palex is making radiation oncology great again.
 
Palex80 said:
WBRT is not always the best option in many brain met patients. A british trial shows preliminary data, that it's actuall not worth it at all in patients with more than a few mets.
Click to expand...

What are you supposed to do in that case, just send them to hospice?

Hard to do with someone with a good ps with no other option
 
medgator said:
What are you supposed to do in that case, just send them to hospice?

Hard to do with someone with a good ps with no other option
Click to expand...

The QUARTZ trial in the UK suggests doung so, won't mecessary decrease survival. We only have preliminar results, but it looks as if 20/4 are not better than steroids only for patients with limited options (not candidates for SRS).
http://www.ncbi.nlm.nih.gov/pubmed/23211715

We should await full results and yes, I'd still offer treatment to patients with good PS.

However, how often have you seen people dying within 2 months after WBRT.
I have, often enough.
 
Palex80 said:
The QUARTZ trial in the UK suggests doung so, won't mecessary decrease survival. We only have preliminar results, but it looks as if 20/4 are not better than steroids only for patients with limited options (not candidates for SRS).
http://www.ncbi.nlm.nih.gov/pubmed/23211715

We should await full results and yes, I'd still offer treatment to patients with good PS.

However, how often have you seen people dying within 2 months after WBRT.
I have, often enough.
Click to expand...
I have as well, but it is nihilistic to offer good PS patients with innumerable mets hospice IMO.

It sounds like that trial had pts with a KPS of 60 of less and closed early secondary to poor accrual. I usually don't offer 20/5 to WBRT patients unless they are an ECOG 3+ and can understand/cooperate with Tx.
 
38% of the trial patients had a KI < 70.
Having a KI < 70 is not hard. One metastatic site in an area which can prevent you from moving your leg or significant edema and you are stuck in the wheelchair, thus KI < 70.
62% of the patients had better performance status.

The trial was completed in the end, I found an update:
http://meetinglibrary.asco.org/content/149588-156

No difference in OS.
 
you guys are drifting away... For LG oligodendroglioma, which has good overall prognosis after partial resection alone, what is the role of 1p/19q codeletion? Does it make prognosis even better??
 
Yes. It makes it even better.

This is a nice paper that shows the prognostic significance and also IDH1, MGMT in the higher grade tumors.
 
Damn_Daniel said:
Yes. It makes it even better.

This is a nice paper that shows the prognostic significance and also IDH1, MGMT in the higher grade tumors.
Click to expand...

Prognostic and most probably predictive (at least for 1p19q and MGMT) too.
 
That's exactly what I mean - why radiate at diagnosis a low grade glioma patient, whose survival is 8 years (Figure 1 from Daniel's paper). A few cases I've seen were observed and recommended clinical trial of chemo alone at the time of progression.

Are you going to use GBM doses and margins?
 
Good question. Med onc ended up proceeding with original plan - adjuvant PCV after RT.
I ended up doing residual disease + 1cm for CTV, and then editing out of bone/air. Then 0.3cm 3D expansion for PTV. Then, 3D plan, so 0.7-0.8 block margin. So, equivalent to old school ~2cm block margin. 50.4 Gy/28 fx, halfway between the 45 to 54 that is recommended. I think reasonable to go to GBM dose. Maybe add a few fractions to a smaller volume and take it to 59.4?
 
seper said:
That's exactly what I mean - why radiate at diagnosis a low grade glioma patient, whose survival is 8 years (Figure 1 from Daniel's paper). A few cases I've seen were observed and recommended clinical trial of chemo alone at the time of progression.

Are you going to use GBM doses and margins?
Click to expand...

I was under the impression, that Daniel's patient was high grade. It certainly didn't seem to be an innocent grade II astrocytoma.
 
I'd do 50 Gy with small margin, if I'm forced to treat a patient like that.
 
I thought that for those patients that were >40 and had STR, that RT was indicated, regardless of if it is grade 2/3? Those are the highest risk patients, right? And the trials that have shown a benefit of PCV was in the setting of sequential RT (RTOG 9802). NCCN doesn't even list omitting RT as an option. I'd be hesitant about omitting RT in this scenario. Would anyone else omit? I was just wondering about the systemic therapy. Anyway, went with 50.4 Gy and tight.

It's match week! Hopefully those of you in academics picked some real stars (yeah, right)...

upload_2016-3-16_12-3-50.png
 
You right, I see that it does say that.
The only way to interpret this is that anybody > 40 y/o is getting upfront XRT for low risk glioma, regardless of extent of surgery?? That has to be inconsistent with standard practice in the US.
 
At our institution, a number of patients are chemo alone (TMZ) after an STR, in particular those with 1p19q codeletion. Per NCCN, anyone >40 OR with STR should get adjuvant RT (i.e. RTOG 9802 criteria). To me, it seems a little crazy to radiate a 42 year old with a 1p19q codeleted oligodendroglioma status post a GTR on the basis of age alone.
 
Arguably the RTOG study was generous with their eligibility criteria with respect to who was considered high risk. So it remains unclear in the chemo era who >40 yo can be observed. Single institution data suggests benefit to earlier treatment but I think it remains unknown. Unplanned subset analyses of RTOG patients using genetic / molecular markers may give more insight into who most benefits chemo but still won't answer who to observe. A trial might answer this but with several years of cooperative group politics, CTEP hurdles and then 10 years of patient follow up we'll never really know.


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