Concurrent temodar with hypofractionated GBM treatment?

[Mandelin Rain]

Thinking of original Roa dose of 4005 cGy in 15 fx in an elderly patient with a good PS, mainly out of social convenience. Med onc wants to give Temodar. Anyone doing concurrent with hypofractionated. My impression is, it's probably fine.

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[elementaryschooleconomics]

Thinking of original Roa dose of 4005 cGy in 15 fx in an elderly patient with a good PS, mainly out of social convenience. Med onc wants to give Temodar. Anyone doing concurrent with hypofractionated. My impression is, it's probably fine.

It's better than fine:

Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma​

 

[RadOncDoc21]

Doing it now as we speak. I’ll let you know how it goes. My patient doesn’t have a great performance status and is an at flight risk so my course may be even shorter. Getting to fraction 9 has been a miracle!

 

[Mandelin Rain]

It's better than fine:

Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma​

Dear God. How did I miss this one?

This is the content I come here for.

EDIT: and the memes. Always the memes.

 

[BobbyHeenan]

I do typically 45 in 15 to enchancing tumor/cavity, 40 in 15 to flair if good kps but old.

 

[MersiHadzi]

Definitely fine. This is a good Editorial piece after the Perry trial was published.

 

[FrostyHammer]

Although this is admittedly an idea aiming to reduce RT for GBM, here's what I would actually really love to know from a clinical perspective: in "fit" patients (possibly stratified by molecular markers) for whom 60/30+Temodar is indicated, is 40-45 in 15 + Temodar non-inferior?

 

[StIGMA]

We add TMZ to 40/15.

If not using TMZ but otherwise good enough performance status for RT consider 35/10 (our go-to hypofractionated if not receiving TMZ).

 

[seper]

I wonder how 60 Gy would look compared to 40/15 in a study of young patients

 

[Mandelin Rain]

I wonder how ketogenic diet vs chemoradiation would fair in GBM.

 

[elementaryschooleconomics]

I wonder how ketogenic diet vs chemoradiation would fair in GBM.

Oh man, I haven't had to have the "I'm going to avoid sugar because I heard that sugar feeds the cancer" argument this week, and it's already Thursday! Maybe those folks took this week off...

 

[Mandelin Rain]

I believe there is actually pre-clinical and scant prospective data of ketogenesis in GBM.

 

[evilbooyaa]

It's better than fine:

Short-Course Radiation plus Temozolomide in Elderly Patients with Glioblastoma​

It's the Best! Beat's the rest!

I wonder how 60 Gy would look compared to 40/15 in a study of young patients

As much as I hate to see trials lowering RT doses, having GBM patients waste 3 weeks instead of 6 on RT that works so rarely anyways.... I would not be against. Outcomes may be similar overall.

I frequently hear that patients aren't candidates for optune in TB if they get 40/15, which is another scenario I want Novocure to look into for an expansion of TTF.

I wonder how ketogenic diet vs chemoradiation would fair in GBM.

I describe GBM to patients as "the disease site where very few things actually help, and so trials have been done throwing everything but the kitchen sink at it" when explaining why in the world TTF/Optune is a strongly recommended portion of their treatment.

This is part of 'everything but the kitchen sink' I'm sure.

 

[medgator]

It's the Best! Beat's the rest!





As much as I hate to see trials lowering RT doses, having GBM patients waste 3 weeks instead of 6 on RT that works so rarely anyways.... I would not be against. Outcomes may be similar overall.

I frequently hear that patients aren't candidates for optune in TB if they get 40/15, which is another scenario I want Novocure to look into for an expansion of TTF.



I describe GBM to patients as "the disease site where very few things actually help, and so trials have been done throwing everything but the kitchen sink at it" when explaining why in the world TTF/Optune is a strongly recommended portion of their treatment.

This is part of 'everything but the kitchen sink' I'm sure.

Have never heard dosing of RT being an issue when getting optune. I'm a certified prescriber. Should be approved in any upfront or recurrent setting afaik

 

[evilbooyaa]

Have never heard dosing of RT being an issue when getting optune. I'm a certified prescriber. Should be approved in any upfront or recurrent setting afaik

I am as well and I don't know that insurance or novocure cares. I'm talking about referring docs who make patient expect 60/30 (when they're 75 for example) and I'm not senior enough (yet) to start pivoting people over to 40/15.

 

[seper]

Eyeballing the numbers, 60/30 studies look better than 40/15, but there is age difference

 

[Neuronix]

EB I think your posts sell radiotherapy short in GBM. RT improves overall survival in glioblastoma. Full stop. Quality of life during glioblastoma RT is not bad either and side effects are typically limited.

I constantly deal with neuro oncs touting the amazing potential of immunotherapies that have already failed numerous clinical trials, vaccines that routinely fail clinical trials, and other drugs that are just repackaging of VEGF inhibition or other things already shown not to work. Oh I'm sorry RT in the recurrent setting didn't find you an overall survival benefit (RTOG 1205). What does have OS benefit in recurrent GBM? NOTHING. That doesn't stop everyone from giving chemo until the patient dies.

Radiotherapy improves overall survival in glioblastoma by ~4 months. Combine that with temozolomide another ~4 months. Combine that with Optune, another ~4 months. These are all ballpark numbers, but ta da you've prolonged someone's life a year. None of those three treatments are particularly bad for patients. When a drug improves OS by 4 months it generates a lot of buzz, becomes standard of care, and pharma gets paid big bucks. Radiotherapy is both effective and cost effective.

Dose finding studies from the early days found 60/30 to be the best dose. Dose escalation past that has not improved survival. Yes 40/15 is hypofractionated, but it's a dose de-escalation with BED calcs. Maybe we could back off on the dose with temozolomide, but I doubt it. I'm willing to bet there will be an underpowered non-inferiority study between 60/30 and 40/15 at some point, and I'm already rolling my eyes at it in advance.

I give 60/30 to everyone with a reasonable PS regardless of age. The study linked above states in the methods "Patients were deemed by their physicians not to be suitable to receive conventional radiotherapy (60 Gy in 30 fractions over a period of 6 weeks) in combination with temozolomide." Most of my high performance elderly patients are suitable to receive conventional radiotherapy and would not be eligible for that study.

Before you accuse me of giving too many fractions, several of the private practices in the area treat glioblastoma to 63 Gy in 1.8 Gy/fx.

 

[medgator]

). What does have OS benefit in recurrent GBM? NOTHING.

Original optune indication/approval was in that setting with the study showing an OS benefit

 

[Neuronix]

Original optune indication/approval was in that setting with the study showing an OS benefit

In recurrent? That was a negative trial comparing to physician's choice of chemotherapy with no survival benefit.

NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality - PubMed

This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to...

pubmed.ncbi.nlm.nih.gov

 

[evilbooyaa]

EB I think your posts sell radiotherapy short in GBM. RT improves overall survival in glioblastoma. Full stop. Quality of life during glioblastoma RT is not bad either and side effects are typically limited.

I constantly deal with neuro oncs touting the amazing potential of immunotherapies that have already failed numerous clinical trials, vaccines that routinely fail clinical trials, and other drugs that are just repackaging of VEGF inhibition or other things already shown not to work. Oh I'm sorry RT in the recurrent setting didn't find you an overall survival benefit (RTOG 1205). What does have OS benefit in recurrent GBM? NOTHING. That doesn't stop everyone from giving chemo until the patient dies.

Radiotherapy improves overall survival in glioblastoma by ~4 months. Combine that with temozolomide another ~4 months. Combine that with Optune, another ~4 months. These are all ballpark numbers, but ta da you've prolonged someone's life a year. None of those three treatments are particularly bad for patients. When a drug improves OS by 4 months it generates a lot of buzz, becomes standard of care, and pharma gets paid big bucks. Radiotherapy is both effective and cost effective.

Dose finding studies from the early days found 60/30 to be the best dose. Dose escalation past that has not improved survival. Yes 40/15 is hypofractionated, but it's a dose de-escalation with BED calcs. Maybe we could back off on the dose with temozolomide, but I doubt it. I'm willing to bet there will be an underpowered non-inferiority study between 60/30 and 40/15 at some point, and I'm already rolling my eyes at it in advance.

I give 60/30 to everyone with a reasonable PS regardless of age. The study linked above states in the methods "Patients were deemed by their physicians not to be suitable to receive conventional radiotherapy (60 Gy in 30 fractions over a period of 6 weeks) in combination with temozolomide." Most of my high performance elderly patients are suitable to receive conventional radiotherapy and would not be eligible for that study.

Before you accuse me of giving too many fractions, several of the private practices in the area treat glioblastoma to 63 Gy in 1.8 Gy/fx.

Perhaps, and I'll accept that as a bias of mine.

I knew that coming out of residency I could 'specialize' in anything when I was applying for academic positions, except for 3 things: Breast (so boring), Peds (don't have emotional capability to handle it) and CNS (f/u clinic of GBM and brain met patients would be depressing).

That being said, I think RT is good. I think all GBM patients should get RT, both at initial daignosis and should be evluated for it at recurrence. And yes, the Perry trial only enrolled those who were deemed unable to tolerate traditional 60/30, I just wish it hadn't. I just think that 40/15 + temodar + optune would have similar outcomes even in patients with good PS. Definitely in the elderly. Probably in the young.

 

[radiation]

Interesting to hear different takes on the data. Here's some reasons I've convinced myself to make hypofrac my default for all pts >60
- there is no compelling data for dose-response in high or low grade gliomas and the preponderance of randomized data suggests no difference amongst all comers. BN001, Believers, Intergroup, Roa, IAEA, etc all show no difference in OS no matter the fractionation schedule. Concurrent chemo unlikely to change this
- In the Nordic study, in pts greater than 70, there was survival benefit for short course vs. long course
- Hypofractionated courses typically are associated with less fatigue and lymphopenia
- In certain subgroups like MGMT methylated tumors, getting to the higher dose chemo part 3 weeks earlier may be beneficial
- In pts that want Optune, there is less scalp irritation with hypofrac (anecdotal)

 

[FrostyHammer]

What does have OS benefit in recurrent GBM? NOTHING. That doesn't stop everyone from giving chemo until the patient dies.

This is so on point. Oncology is such a hypocritical discipline... Chemo is OK to give indefinitely but when anyone talks about RT they start to scoff. I hate this double standard.

Someone smart should do a trial of chemo alone vs RT alone for recurrent GBM and look not only at OS/PFS but also QOL. No way that outcomes will be any different, but we will win the QOL battle.

This idea is analogous to elderly early-stage breast cases. If doing RT is just as comparably good as 5 years of hormones, you better believe I'll do RT any day of the week. But it's always been a question of RT vs no RT, not systemic therapy vs no systemic therapy. Eff those double standards.

 

[medgator]

In recurrent? That was a negative trial comparing to physician's choice of chemotherapy with no survival benefit.

NovoTTF-100A versus physician's choice chemotherapy in recurrent glioblastoma: a randomised phase III trial of a novel treatment modality - PubMed

This is the first controlled trial evaluating an entirely novel cancer treatment modality delivering electric fields rather than chemotherapy. No improvement in overall survival was demonstrated, however efficacy and activity with this chemotherapy-free treatment device appears comparable to...

pubmed.ncbi.nlm.nih.gov

I thought it was a positive study which is how it got the approval there first... Guess not.

 

[elementaryschooleconomics]

This is so on point. Oncology is such a hypocritical discipline... Chemo is OK to give indefinitely but when anyone talks about RT they start to scoff. I hate this double standard.

Someone smart should do a trial of chemo alone vs RT alone for recurrent GBM and look not only at OS/PFS but also QOL. No way that outcomes will be any different, but we will win the QOL battle.

This idea is analogous to elderly early-stage breast cases. If doing RT is just as comparably good as 5 years of hormones, you better believe I'll do RT any day of the week. But it's always been a question of RT vs no RT, not systemic therapy vs no systemic therapy. Eff those double standards.

I think this is basically NOA-08, although that was for new GBM not recurrent. The results were meh.

I totally agree about the chemo/hormones though, especially for breast - give me the shorter upfront XRT instead of dragging it on with drugs.

Although if I were diagnosed with GBM, I'd probably disappear to Ibiza to die in that club that fills up with bubbles.

 

[Neuronix]

- there is no compelling data for dose-response in high or low grade gliomas and the preponderance of randomized data suggests no difference amongst all comers.

An analysis of dose-effect relationship in the radiotherapy of malignant gliomas

The relationship between increasing survival and increasing doses of radiotherapy has been examined in 621 patients who were entered into three succes…

www.sciencedirect.com

 

[radiation]

An analysis of dose-effect relationship in the radiotherapy of malignant gliomas

The relationship between increasing survival and increasing doses of radiotherapy has been examined in 621 patients who were entered into three succes…

www.sciencedirect.com

Lol I knew someone would hit me with the walker trial. I get it, thats the teaching. But honestly not sure what to make of 1970s data using whole brain radiation, cobalt, and no MRI. Keep in mind it was prescribed to midplane, so who knows what the actual dose to tumor was

 

[StIGMA]

Anyone work with neuro-oncs routinely using the NOA-09 regimen (+lomustine)?

 

[FrostyHammer]

I think this is basically NOA-08, although that was for new GBM not recurrent. The results were meh.

I totally agree about the chemo/hormones though, especially for breast - give me the shorter upfront XRT instead of dragging it on with drugs.

Although if I were diagnosed with GBM, I'd probably disappear to Ibiza to die in that club that fills up with bubbles.

The conclusion of Noa 08 was so BS and implies that very same double standard...why give RT when you can give chemo because it's noninferior (SMH). Didn't look at QOL which is why I don't give one bit of crap about that trial.

 

[Palex80]

I have been giving 20 x 2.66 Gy to quite a few younger patients since COVID started.
15 x 2.66 Gy is clearly less dose than 30 x 2 Gy.