confusion re fractionalized "stereotactic brain radiosurgery"

[leapyrtwins]

Hold the popcorn, Phyl.

Kate says there is nothing to debate.

Jan

[ppearl214]

Philip,

In follow up to your response to Mark, can you all please elaborate on the protocols offering "fractionated" treatments. Ie: Trilogy, Cyberknife and yes, there are sites doing fractionated GK (one in TX and since Dr. Gorj Noren is noted on your site, pls check with him as, from my understanding, he has also been pursuing it. He's a terrific reference, as we know....)

thanks for the consideration.
Phyl


Jan, the popcorn is done popping and I've got the bowl... thanks!

[leapyrtwins]

Jan, the popcorn is done popping and I've got the bowl... thanks!

Wait, I didn't mean literally hold the popcorn - I meant hold it (as in stop making it) 

Apparently we aren't debating.

Jan

[ppearl214]

Haven't stopped popping the popcorn... just the bowl in my lap... got butter on it too, if anyone cares to have any.

[leapyrtwins]

Any martinis tonight 

[ppearl214]

Had a bloody mary at the brunch today... 1's my limit for the day  

[Philip]

Phyl,

... can you all please elaborate on the protocols offering "fractionated" treatments. Ie: Trilogy, Cyberknife and yes, there are sites doing fractionated GK (one in TX and since Dr. Gorj Noren is noted on your site, pls check with him as, from my understanding, he has also been pursuing it. He's a terrific reference, as we know....)

There are exceptions everywhere. GK is usually single-session and modern Linac protocols are usually fractionated. But as you note Dr Noren does fractionated GK (I hadn't heard about the Texas one), and conversely there are probably many cases of single-session Linac. In fact the Dutch center quoted by Mark does both single-session and multi-session Linac, depending on whether or not the patient has teeth to secure the face mask! 

I think CK at Stanford is always fractionated, but I'm not sure.  There are probably others who do single-session CK.  There is also proton beam.  Again I'm not sure but I think that is single-session.

Do we get popcorn only when we disagree?

Philip

[sgerrard]

In fact the Dutch center quoted by Mark does both single-session and multi-session Linac, depending on whether or not the patient has teeth to secure the face mask! 

Aha! Now the separation of patients into the dentate and edentate groups makes sense; if you have no teeth, you can't hold the mouth-guard mask, so you get it all in one shot. No connection to armadillos after all...
- - - -

Perhaps some of the issue is about terminology. I consider FSR to mean 20 or more sessions, on a machine other than a GK or CK machine. If you use that acronym  to refer to GK or CK, you are just confusing people. The technical definition of fractionation is not the main thing (unless you are making margaritas).

The choices most people face are GK with 1 shot; CK with 3-5 shots; or Trilogy-style machines, with 20 + shots (aka FSR). Using GK or Trilogy to do 3-5 shots is possible, but you might as well use CK for that.

Hm, margaritas, chips, salsa...

Steve

[Philip]

Hello Steve,

some of the issue is about terminology.

How right you are.  On the ANworld mailing list, FSR is always understood to mean what Johns Hopkins and Lederman do: 4-5 sessions, low dose.  The 20-30 session protocols are hardly ever mentioned and nor is Trilogy.  Other machines/systems exist such as the Novalis or Tomotherapy. It might be a good idea to update the equipment information on the ANworld site or even provide a list. 

I wonder if it isn't unnecessarily confusing though.  There are so many factors which count at least as much as the machine: the experience of the medical team, the targeting software... Patients can't hope to understand all the variables. It's best to look at the published outcome statistics, hope you can trust them, and choose the treatment center with the best results.

Just one example to illustrate.  Last year a hospital in Toulouse (France) made a mistake when they set up their new Novalis machine.  As a result over 100 patients, including AN patients, received considerably higher doses than were intended.  Many are suffering as a result, a few have died though not necessarily from the over-dose.  One lady on the ANworld Francophone mailing list was a victim and now has facial paralysis which is almost unheard of with radiation. 

Philip

[ppearl214]

Terminology is key and has been discussed on this site before.  We have noted to folks to clearly elaborate on which machine when referencing "FSR" as "FSR" is the fact of fractionating a treatment, not necessarily due to one machine. On this discussion forum, many have referenced "FSR" in discussions when referencing a machine, such as Novalis, and usually note it as 25-30 day protocol, not approx 4-5. 

A clear elaboration of which machine is necessary when noting "FSR" to help AN patients understand the "fractionation" of a radio-treatment, where GK is usally a single-dose (non-fractionated) but as noted, fractionation of GK is also coming into play.

Popcorn is for those sitting on the sofa watching a spirited discussion.  Better than watching a movie on cable tv..... as we never know what direction a conversation will go.  Trail mix and virtual drinks that many cannot have in life are also offered to enhance the viewing pleasure.

Phyl

[jb]

Thanks for saving drinks and snacks!  Thought I might have missed out over the weekend.

Philip, thanks for the link to the Japanese paper with the follow-up MRI's following GK.  I hadn't seen that one before.  I actually see some of the same (new) hyperintensity on my own follow-up MRI as one of the GK patients had.  My doc said it should be temporary, so it's reassuring to see that it was temporary for the GK patient.

....It does not even mention CK, just GK and FSR which are to be understood as meaning single-session and fractionated.  Since that seems to be causing confusion, I'll change the wording to make it plain that we are saying that fractionation might be preferable to single-session for larger tumors.

Philip

I have to say I'm still stuck on the claim that a fractionated treatment may be preferable for large tumors.  Does this assume fractionation results in less swelling and is therefore safer?  Most of the information I've read suggests that tumor necrosis, if it occurs, is a pretty unpredictable process and can produce a lot of swelling no matter what kind of radiation scheme was used.  Seems like only about 5-10% of patients experience significant swelling, but it can be life-threatening to those with a large tumor to begin with.  However, I did notice that one of the patients in the Japanese paper had a very large tumor and apparently had no problem with GK.

I also took a look at Dr. Lederman's slides from the January '08 presentation.  I noticed that he quoted a total of 4 failures from 372 treated tumors; 465 were actually treated, but apparently about 100 were lost to follow-up (http://anworld.com/radiation/lederman-Paris-Jan-2008/img52.html).  In comparison, the "Radiation Failures Study" on the ANWorld website (http://www.anworld.com/radiation/failures/) reports 11 failures among just 40 Lederman/SIUH-Cabrini patients back in 2005.  The definition of failure for the study was a "tumor re-growth or life-threatening tumor swelling", so maybe Dr. Lederman is counting only tumor regrowth as a failure.  Still, he also states that no further treatment is required for 99% of patients, but I would have to think that further treatment would be needed for "life-threatening tumor swelling."  Any thoughts on the discrepancy?

Thanks,
JB

[Philip]

Hello JB,

Does this assume fractionation results in less swelling and is therefore safer? 

Yes.  I have always understood that the purpose of fractionation is to allow non-tumor surrounding tissue to recover between sessions.  Otherwise what would be the rationale for fractionation? It does seem logical that swelling would be minimized as a result.

Can it be proved?  I doubt it.  Individual response to radiation varies as you point out.  There is a good discussion of the pro's and con's of fractionation by Dr Mitchell K Schwaber in an excellent eMedecine article: http://www.emedicine.com/ent/topic668.htm. He says: "The main advantage of fractionation is that it allows higher doses to be delivered to the tumor because of increased tolerance of the surrounding healthy tissues to these smaller fractionated doses."  Dr Lederman claims that he gets good hearing preservation because he insists on a full day or two of rest between sessions.

As to your second question, I can't talk for Dr Lederman, but I do think he, and other radiosurgeons, define "failure" as inability to control growth in the long term.  Patients have a different viewpoint.  We might consider a procedure to have failed if the results don't match our expectations. 

Surgeons are just as bad.  If the patient has chronic headaches or facial paralysis or a regrowth, that, in surgeon speak, is a complication, not a failure.    Even if the patient dies I think the doctor might consider the operation a success!

Donna's report on FSR failures was from the patients' viewpoint.  And her sample was necessarily skewed because patients who are happy with their results usually don't stick around on mailing lists to tell us about it as much as unhappy patients do.

Philip

[sgerrard]

On the ANworld mailing list, FSR is always understood to mean what Johns Hopkins and Lederman do: 4-5 sessions, low dose.

That explains a lot. I don't think that is generally understood to be the meaning of FSR, however. I would suggest not using the acronym, and being more explicit about what sort of treatment protocol you mean. "Low dose" is really a function of how many doses; it isn't linear, but there is a formula, such that the total effective dose is roughly the same. So I would assume that a 3-5 session protocol would use a dose smaller than a single GK shot, and larger than a 25 day FSR protocol. Just saying "3-5 fractions" is enough, and would be a lot clearer.

- - - - - -

For jd as well, on the swelling subject:

It seems to me that there are two kinds of swelling that occur. The first is swelling of surrounding normal tissue, along with the tumor, in an immediate response to the radiation. This kind of swelling can be reduced by fractionation, and also by taking a steroid during and just after treatment.

The second kind occurs later, perhaps 2-3 months, when the tumor begins to die off, and is undergoing necrosis. This swelling is a result of having had radiation damage to the tumor, and the treatment protocol doesn't really make any difference. Once you have received your full allotment of radiation, and the tumor begins to die from the damage it has sustained, it is a dying tumor, regardless of how it got that way.

The purpose of fractionation is to reduce the first kind of swelling, where healthy neighboring tissue can suffer, including the hearing nerve and cochlea. None of the treatments can do anything about the second kind. Tumor death is the goal, and the edema and swelling that often accompany it must simply be accepted, and treated with steroids when necessary. That is the reason that tumors over 3 cm are not good candidates for any kind of radiation - they can swell up too much when they start dying 3 months later.

That's the way I see it, anyway.

Steve

[Mark]

Even though I have a glass of wine and not a martini, I'll add a couple thoughts here:

Does this assume fractionation results in less swelling and is therefore safer?

Yes.  I have always understood that the purpose of fractionation is to allow non-tumor surrounding tissue to recover between sessions.  Otherwise what would be the rationale for fractionation? It does seem logical that swelling would be minimized as a result.

Can it be proved?  I doubt it.  Individual response to radiation varies as you point out.  There is a good discussion of the pro's and con's of fractionation by Dr Mitchell K Schwaber in an excellent eMedecine article: http://www.emedicine.com/ent/topic668.htm. He says: "The main advantage of fractionation is that it allows higher doses to be delivered to the tumor because of increased tolerance of the surrounding healthy tissues to these smaller fractionated doses."

Based on my conversations with neurosurgeons and radiation docs, my understanding is a little different and I think one has to separate the issues of cranial nerve preservation and swelling. As pointed out in the quote by Dr. Schwaber , I would agree that the primary value in fractionating the treatment is to allow the Healthy tissue with normal DNA to recover between treatments which the abnormal DNA of the tumor is unable to do. This is primarily to the benefit of hearing nerve which is far more sensitive with it's thousands of hairlike elements used in the transmission of sound to the brain. Studies suggest this improves hearing by 10-15% over one dose protocols. There is some value also to the facial nerve results  but it is more tolerant than than hearing so studies don't show that much of an improvement. Swelling in the treated area on the other hand is a function of how the tumor reacts to the lethal cumulative dose of radiation as well as how much surrounding healthy tissue is impacted which is why I personally do believe machine accuracy is a factor to be considered. Biologically the tumor is killed because of either immediate cell death or the DNA damage to the surviving cells makes further replication impossible. Blood and other fluids will also expand within the tumor in reaction to being zapped. Swelling can also be impacted by the machines ability to provide isocentric treatment to irregular shaped tumors thus avoiding hot and cold spots in the treatment. Not all machines have equal ability in this area. So even in a fractionated treatment the level of swelling  can be influenced by these factors as well. Also keep in mind that while a one dose GK is about 12 GY and a 3 dose with CK is about 18GY, a 25-30 day protocol is closer to 45-50 GY and all are calculated to those numbers based on what will provide a biological lethal dose to the AN. I can very quickly get beyond my knowledge base in this area but that is what the physicists and radiation folks are paid to know and figure out 

Dr Lederman claims that he gets good hearing preservation because he insists on a full day or two of rest between sessions.

I'll probably get the popcorn popping on this one , but I posted Dr. lederman's 48 hour protocol over on the CPSG site and got this response from Dr. Medbery who I have a lot of respect for:

There are considerable reasons for thinking that using the sort of fractionation scheme he is proposing is going to result in significantly higher failure rates. Those may not become evident for a few years, but are going to cause a lot of grief for the patients whose tumors grow.

His words, not mine. I'm not sure how much better Lederman's hearing preservation rates are than other fractionated protocols, but it would be quite meaningless to the patient if his failure rates increase substanially. I guess time will tell on that one.

As to your second question, I can't talk for Dr Lederman, but I do think he, and other radiosurgeons, define "failure" as inability to control growth in the long term.  Patients have a different viewpoint.  We might consider a procedure to have failed if the results don't match our expectations.

Surgeons are just as bad.  If the patient has chronic headaches or facial paralysis or a regrowth, that, in surgeon speak, is a complication, not a failure.  Sad  Even if the patient dies I think the doctor might consider the operation a success!


I think Philip's comments here are very fair and accurate as a general statement. I do think there are pockets of physicians that do assess the outcome based on the patients outcome and not whether the surgery was technically correct or the tumor was killed. I was fortunate that was the philosophy expressed by the doctors I had at Stanford ( Chang, Schuer  and Gibbs). I did not ask that question , they each expressed it in separate conversations which impressed me tremendously.

Donna's report on FSR failures was from the patients' viewpoint.  And her sample was necessarily skewed because patients who are happy with their results usually don't stick around on mailing lists to tell us about it as much as unhappy patients do.

Agree 100%, it's really the human nature aspect and applies to both surgery and radiosurgery patients. It's very easy to look in the mirror and say you've survived a bump in life's road and simply move on. In hindsight , that was one of the drawbacks to the Cyberknife patient group and why we felt there was no point to continuing it. We simply couldn't keep people involved, they got treated , had no issues , and went back to their daily lives. That is the reason I personally applaud and appreciate everyone who's a "postie" and stays involved on this forum to give back and support either the newly diagnosed or those who are having issues. It takes a commitment to others and a gift each of you give 

Mark

[ppearl214]

That is the reason I personally applaud and appreciate everyone who's a "postie" and stays involved on this forum to give back and support either the newly diagnosed or those who are having issues. It takes a commitment to others and a gift each of you give 

... as do I, as I stated in the ANA March Newsletter.... kudo's to all that do.

*pours martini, shaken/not stirred, slightly dirty, straight up, extra olives.... and pulls bowl of popcorn back into lap*