Can/should you add Tmz to short course RT for GBM in the elderly? Yes.

[scarbrtj]

In elderly patients with glioblastoma, the addition of temozolomide to short-course radiotherapy resulted in longer survival than short-course radiotherapy alone.

An interesting discussion: not adding Tmz for uMGMT older patients based on this data (a point they seem intentionally not to make in the abstract). I'm not sure what the reticence is to make Tmz treatment recommendations based on MGMT status. Just the general crappiness of the GBM diagnosis itself (i.e., what's it gonna hurt)? Who knows. It's a weird affectation to me at this point.

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[Cooluser123]

What's it gonna hurt? Cost, toxicity. You need to draw labs and monitor. Primarily hematologic toxicity, but nausea can be impactful as well. I've seen a couple serious bleeds from thrombocytopenia while on Tmz. I despise when the neuro-oncs give this med without drawing periodic labs.

 

[Palex80]

It is certainly worth doing, as you said, if MGMT is methylated and the patient seems fit enough to tolerate combined treatment.

Another alternative is to give TMZ alone and use radiotherapy upon progression (we seldom do that), but there is data showing this approach is also valid (Nordic trial and the German trial).

 

[medgator]

What's it gonna hurt? Cost, toxicity. You need to draw labs and monitor. Primarily hematologic toxicity, but nausea can be impactful as well. I've seen a couple serious bleeds from thrombocytopenia while on Tmz. I despise when the neuro-oncs give this med without drawing periodic labs.

Yup. I've seen icu admissions with platelet counts under 50K for several days in the elderly where the med onc wasn't keeping an eye weekly with CBCs.

Tmz is chemo and should be treated as such

 

[seper]

Cost, also. For Medicaid patients on East Coast it takes us forever to find a MedOnc willing to see the patient. Then it takes forever to get TMZ approved and dispensed. Literally, this process can take 2-3 months.

 

[evilbooyaa]

An interesting discussion: not adding Tmz for uMGMT older patients based on this data (a point they seem intentionally not to make in the abstract). I'm not sure what the reticence is to make Tmz treatment recommendations based on MGMT status. Just the general crappiness of the GBM diagnosis itself (i.e., what's it gonna hurt)? Who knows. It's a weird affectation to me at this point.

If you read the paper, for non-MGMT, TMZ+RT had 10.0 months vs 7.9 for RT alone, p =0.055. I wouldn't use this paper to definitively conclude that MGMT negative patients should NOT get TMZ.

 

[scarbrtj]

If you read the paper, for non-MGMT, TMZ+RT had 10.0 months vs 7.9 for RT alone, p =0.055. I wouldn't use this paper to definitively conclude that MGMT negative patients should NOT get TMZ.

This reminds me of that classic scene from Shrek the Third...

Prince Charming: You. You can't lie. So tell me, puppet, where is Shrek?
Pinocchio: Uh, hmm, well, uh, I don't know where he's not.
Prince Charming: You're telling me you don't know where Shrek is?
Pinocchio: It wouldn’t be inaccurate to assume that I couldn’t exactly not say that it is or isn’t almost partially incorrect.
Prince Charming:- So you do know where he is?
Pinocchio: Oh, on the contrary. I'm possibly more or less not definitely rejecting the idea that in no way with any amount of uncertainty that I undeniably...
Prince Charming: Stop it!
Pinocchio: ...do or do not know where he shouldn’t probably be, if that indeed wasn’t where he isn’t. Even if he wasn’t at where I knew he was, that’d mean I’d really have to know where he wasn't.

So tell me, has TMZ+XRT vs XRT alone ever shown a statistically significant benefit in uMGMT patients?

EDIT: I do note that now the most updated NCCN guidelines allow for omission of adjuvant Tmz along with the XRT in uMGMT patients.

 

[evilbooyaa]

So tell me, has TMZ+XRT vs XRT alone ever shown a statistically significant benefit in uMGMT patients?

EDIT: I do note that now the most updated NCCN guidelines allow for omission of adjuvant Tmz along with the XRT in uMGMT patients.

Not that I'm aware of, but as a specialty I do believe we've made recommendations (or at least had a discussion of patient about a study regarding risks/benefits) for treatment based off p-values that weren't exactly significant. It's rare, but we've justified treating patients per the POET trial in certain scenarios, for example.

It's certainly still an option as per NCCN guidelines, and I'm not saying that you're at all incorrect for proceeding without TMZ (given that what you're recommending is the Category 1 recommendation from NCCN), but I don't think that this "closes the book" about the value of TMZ in the uMGMT elderly population with GBM. Small population and, at the end of the day, if it were my elderly patient with uMGMT GBM, I certainly wouldn't push for TMZ.

 

[Palex80]

TMZ probably only works in methylated GBMs.

Why do we still give it to unmethylated GBM-patients? Cause it's GBM. At the end of the day, "more" treatment is often given with minimal to no effect on OS, if the disease is deadly enough. The deadlier the disease, the more non-evident treatment the patient will get. And GBM is not the sole cancer this is happening to.
Look at pancreas:
1. Erlotinib given to thousands of patients with metastatic for an OS benefit of a couple of weeks.
2. Millions of patients have gone down the path of Whipple-surgery for (very) advanced disease. Almost all of them relapsed, less than 5% were alive 5 years later, all of them suffered the toxicity and morbidity of major pancreas surgery. Yet we still do it. Every single day.
Make a randomized trial for pancreas: Include T3 or N+ resectable patients and randomize them to surgery + chemo vs. upfront palliative chemo with the option for chemo-RT. Even if you put 2000 patients on that trial you will still not find a statistical significant difference in favor of one approach in terms of OS. I bet though you will find a statistical difference in favor of the non-surgical arm in the first 3 months in terms of QoL.

 

[scarbrtj]

TMZ probably only works in methylated GBMs.

Why do we still give it to unmethylated GBM-patients? Cause it's GBM. At the end of the day, "more" treatment is often given with minimal to no effect on OS, if the disease is deadly enough. The deadlier the disease, the more non-evident treatment the patient will get.

That perfectly returns to my original point