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Re: Max/hemangio...he's gone [Re: JeanKBBMMMAAN] #214651
02/22/12 09:56 PM
02/22/12 09:56 PM
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New Milford, CT
Woodreb Offline
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I did a little research after reading through the last couple of pages. From what is out there in the literature, the TK certainly appears to be a valid marker for tumors. Unfortunately, I think that VDI, for whatever reason, may have their threshold set too high. Maybe they are trying to refine the model and just don't have enough data - or they didn't read the paper I linked to below.

Lisa - if you're interested take a look at this publication . It sets a cut off of 6 U/l as a threshold above which there is cause for concern. I don't know if the results you got for Max were in these units, but if they are, 18.5 is significantly different than 6 in my view.

In any event grouphug


Johanna

Caleb (aka Caleb-Moose)
Ciara(aka Ciara Belle, Black Devil)

RIP Aodhán, Rica, Max, Kelly - gone but never forgotten - forever in my heart
Re: Max/hemangio...he's gone [Re: Woodreb] #214979
02/24/12 01:35 AM
02/24/12 01:35 AM
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Northern CA
MaxaLisa Offline OP

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Checking in...thanks so much for the information! I want to read carefully, but flat out exhausted right now, been slammed at work on top of everything else and I am not seeing straight.

So glad tomorrow is friday! It will be a long friday, but still good to have the week over...


MaxaL (aka LisaT)

Jazmine, mini-mix, 10/18/2011
Max-n-Indy
Max, 5/2001-2/2012, RIP my partner, my Regal Boy
Indy, 5/1997-10/2010, RIP my friend, my teacher

Health Index
K9 TBD info and Tick List Links
http://www.rabieschallengefund.org/
Re: Max/hemangio...he's gone [Re: MaxaLisa] #215001
02/24/12 06:04 AM
02/24/12 06:04 AM
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Central Florida
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hugging


Gayle
Faith, Ledgie & Scooby
My Bridge Kids: Andy, Abbey, Tasha, Tex, Echo, Yukon, JR, Too, Niki, Bo, Ringer, Kelly, Honey, Mac, Slider & Bruiser
Re: Max/hemangio...he's gone [Re: Woodreb] #215427
02/26/12 05:27 AM
02/26/12 05:27 AM
Joined: Jan 2010
Posts: 19,487
Northern CA
MaxaLisa Offline OP

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MaxaLisa  Offline OP

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Originally Posted By: Woodreb
I did a little research after reading through the last couple of pages. From what is out there in the literature, the TK certainly appears to be a valid marker for tumors. Unfortunately, I think that VDI, for whatever reason, may have their threshold set too high. Maybe they are trying to refine the model and just don't have enough data - or they didn't read the paper I linked to below.

Lisa - if you're interested take a look at this publication . It sets a cut off of 6 U/l as a threshold above which there is cause for concern. I don't know if the results you got for Max were in these units, but if they are, 18.5 is significantly different than 6 in my view.

In any event grouphug


You know, the paperwork sets the top of the normal range at 6.0. The sheet that was given with the initial results in Nov, says that 9.0 is highly indicative of cancer. I don't understand why a result of 18.5 would come with a note that says to not be overly concerned and retest in 60 days. These seem to me to be contradictory messages.

I need to ask about this, not really that it makes a difference for me in the grand scheme of things, but it just doesn't make sense.

In the podcast that I just listened to, he said that it was highly specific for fast growing cells, and in one case picked up an anal tumor. More questions than answers, again.


MaxaL (aka LisaT)

Jazmine, mini-mix, 10/18/2011
Max-n-Indy
Max, 5/2001-2/2012, RIP my partner, my Regal Boy
Indy, 5/1997-10/2010, RIP my friend, my teacher

Health Index
K9 TBD info and Tick List Links
http://www.rabieschallengefund.org/
Re: Max/hemangio...he's gone [Re: MaxaLisa] #215441
02/26/12 11:59 AM
02/26/12 11:59 AM
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Victoria, Australia
Qyn Offline
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hugging


Alison
~~~~~~~~~~
Nix (derivative of Phoenix) Black GSD born 6 June 2011 (Gotcha day 9 Dec 2013)

Quynne gsdhalo - Black Female GSD - Sept 29, 2004 - 11 Nov 2013 Deeply missed

If you don't agree with me ... you are just not listening well enough. smile
Re: Max/hemangio...he's gone [Re: Qyn] #215472
02/26/12 03:55 PM
02/26/12 03:55 PM
Joined: Feb 2010
Posts: 5,452
New Milford, CT
Woodreb Offline
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Just listened to the podcast you linked to in the other thread.

I'd love to see their validation data, but that's probably not going to be available to the public, unless they published a paper somewhere - and even that may not contain all of the data.

I can't imagine why there is such a disconnect between the paperwork information - 6 U/l as a threshold and 9 U/l as highly indicative of cancer and 18.5 U/l "not to be overly concerned". I think it's worth asking the question. I know it doesn't make a difference for you but if the letter you got was in error, it could make a difference for other dogs.

And if I remember correctly, the study was intended to refine a model for more early warning rather than just when the cancer is full blown active. They can't achieve that goal without feedback that gives them the whole story.

They're marketing this product as a tool to help indentify cancers and possibly as an early warning - they need to have a decent model and they need to be sure they're not sending out false negatives as well as "false positives".

I note in the podcast, they talk about the minimal chance of false positives, but don't address the question of a false negative - which is almost what your letter sounds like to me.

On a separate note - it's interesting that they are also looking at markers that may indicative of HD as well.

Last edited by Woodreb; 02/26/12 03:59 PM.

Johanna

Caleb (aka Caleb-Moose)
Ciara(aka Ciara Belle, Black Devil)

RIP Aodhán, Rica, Max, Kelly - gone but never forgotten - forever in my heart
Re: Max/hemangio...he's gone [Re: Woodreb] #215484
02/26/12 04:59 PM
02/26/12 04:59 PM
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Mary Jane Offline
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For what it's worth, the cut-offs in a recent article are not far off. Max's reading was just higher than the mean for affected dogs, in this study. It all makes me feel bad.

Vet Comp Oncol. 2011 Oct 20

Elevated serum thymidine kinase activity in canine splenic hemangiosarcoma(*).

Thamm DH, Kamstock DA, Sharp CR, Johnson SI, Mazzaferro E, Herold LV, Barnes SM, Winkler K, Selting KA.


Abstract

Thymidine kinase 1 (TK1) is a soluble biomarker associated with DNA synthesis. This prospective study evaluated serum TK1 activity in dogs presenting with hemoabdomen and a splenic mass. An ELISA using azidothymidine as a substrate was used to evaluate TK1 activity. Sixty-two dogs with hemoabdomen and 15 normal controls were studied. Serum TK1 activity was significantly higher in dogs with hemangiosarcoma (HSA) than in normal dogs (mean ± SEM = 17.0 ± 5.0 and 2.01 ± 0.6, respectively), but not dogs with benign disease (mean ± SEM = 10.0 ± 3.3). Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93, positive predictive value of 0.94 and negative predictive value of 0.48 for distinguishing HSA versus normal. When interval thresholds of <1.55 and >7.95 U/L were used together, diagnostic utility was increased. Serum TK1 evaluation may help to discriminate between benign disease and HSA in dogs with hemoabdomen and a splenic mass.

Mary Jane

Re: Max/hemangio...he's gone [Re: Mary Jane] #215518
02/26/12 08:42 PM
02/26/12 08:42 PM
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Posts: 19,487
Northern CA
MaxaLisa Offline OP

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Yeah, this all kinda makes me want to throw up frown

In my first email back, he mentioned that the number seems to represent aggressiveness and/or speed of growth, rather than than tumor size. I was thinking with all that cancer, it should have been higher. But I think we had it slowed, until I greatly decreased his doxy frown , and then it just took off. It was probably still growing on the doxy, but more slowly.

Interesting about those numbers MJ. A few questions for you science types:

Serum TK1 activity was significantly higher in dogs with hemangiosarcoma (HSA) than in normal dogs (mean ± SEM = 17.0 ± 5.0 and 2.01 ± 0.6, respectively), but not dogs with benign disease (mean ± SEM = 10.0 ± 3.3).
Okay, Max's was 18.5, yes, right above the average.

Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93
This is a measurement that says it's actually measuring what we think it is, and not something else (like B-12 deficiency, for example?), right?

positive predictive value of 0.94
Is this the measurement that describes the "false positive"? That once you get a positive, the chances that it is false is very low?

negative predictive value of 0.48 for distinguishing HSA versus normal.
Is this the measurement that describes the "false negative"? That once you get a negative, the chances that there is cancer might still be high?

Johanna, yes, I will email him back, and ask those questions regarding the test results versus the letter. There are (were frown , two have now passed) easily 10 dogs from both forums that are/were in this study, and this certainly might be relevant for a few of them, and certainly down the road for others.

Last edited by MaxaLisa; 02/26/12 08:46 PM.

MaxaL (aka LisaT)

Jazmine, mini-mix, 10/18/2011
Max-n-Indy
Max, 5/2001-2/2012, RIP my partner, my Regal Boy
Indy, 5/1997-10/2010, RIP my friend, my teacher

Health Index
K9 TBD info and Tick List Links
http://www.rabieschallengefund.org/
Re: Max/hemangio...he's gone [Re: MaxaLisa] #215520
02/26/12 08:56 PM
02/26/12 08:56 PM
Joined: Jan 2010
Posts: 19,487
Northern CA
MaxaLisa Offline OP

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MaxaLisa  Offline OP

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Originally Posted By: MaxaLisa

Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93
This is a measurement that says it's actually measuring what we think it is, and not something else (like B-12 deficiency, for example?), right?


Oops, didn't see both measurements on my little phone window.

So, the specificity is the thing that tells us it's measuring what we think it is?

The sensitivity is how likely it is to pick that thing up?


MaxaL (aka LisaT)

Jazmine, mini-mix, 10/18/2011
Max-n-Indy
Max, 5/2001-2/2012, RIP my partner, my Regal Boy
Indy, 5/1997-10/2010, RIP my friend, my teacher

Health Index
K9 TBD info and Tick List Links
http://www.rabieschallengefund.org/
Re: Max/hemangio...he's gone [Re: MaxaLisa] #215530
02/26/12 10:16 PM
02/26/12 10:16 PM
Joined: Feb 2010
Posts: 5,452
New Milford, CT
Woodreb Offline
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Woodreb  Offline
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Originally Posted By: MaxaLisa
Yeah, this all kinda makes me want to throw up frown Deep breath - It takes time and effort to come up with good models. Understanderably frustrating from your end, but they're not deliberately trying to cause hurt to anyone. And they do hope to be able to help.

In my first email back, he mentioned that the number seems to represent aggressiveness and/or speed of growth, rather than than tumor size. I was thinking with all that cancer, it should have been higher. But I think we had it slowed, until I greatly decreased his doxy frown , and then it just took off. It was probably still growing on the doxy, but more slowly.

Interesting about those numbers MJ. A few questions for you science types:

Serum TK1 activity was significantly higher in dogs with hemangiosarcoma (HSA) than in normal dogs (mean ± SEM = 17.0 ± 5.0 and 2.01 ± 0.6, respectively), but not dogs with benign disease (mean ± SEM = 10.0 ± 3.3).
Okay, Max's was 18.5, yes, right above the average. And based on this value, if I were looking at the result, I'd say there is something to worry about, unless they've got other data that isn't apparent that says different.

Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93
This is a measurement that says it's actually measuring what we think it is, and not something else (like B-12 deficiency, for example?), right? It's specific but not a sensitive as you might want it to be. At least that's what it sounds like to me. From some of the things I've been reading, this TK level is pretty low. I wish they used a real unit of measure like ppm or µg/ml, U/l doesn't really mean that much to me in terms of how low the level is that they are trying to measure.

positive predictive value of 0.94
Is this the measurement that describes the "false positive"? That once you get a positive, the chances that it is false is very low? That's how I would interpret this statement.

negative predictive value of 0.48 for distinguishing HSA versus normal.
Is this the measurement that describes the "false negative"? That once you get a negative, the chances that there is cancer might still be high? And a need for more data to further refine the model. Of course, we also have to remember that we can never really answer anything with absolute certainty, much as we as inidividuals want that to be so - Heisenburg Uncertainty Principle.

Johanna, yes, I will email him back, and ask those questions regarding the test results versus the letter. There are (were frown , two have now passed) easily 10 dogs from both forums that are/were in this study, and this certainly might be relevant for a few of them, and certainly down the road for others.


hugging Hang in there.

PS - In my work, I don't really deal with biologics, so I'm not sure how different, if at all, validation data for biologics is compared to chemical entities.

Last edited by Woodreb; 02/26/12 10:19 PM.

Johanna

Caleb (aka Caleb-Moose)
Ciara(aka Ciara Belle, Black Devil)

RIP Aodhán, Rica, Max, Kelly - gone but never forgotten - forever in my heart
Re: Max/hemangio...he's gone [Re: Woodreb] #215543
02/26/12 11:23 PM
02/26/12 11:23 PM
Joined: Jan 2010
Posts: 19,487
Northern CA
MaxaLisa Offline OP

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Thanks Johanna, I wanted to make sure that I was understanding.

I've sent another email off to Steve at VDI. Not very well-worded, but I'm hoping he'll respond with some more info.


MaxaL (aka LisaT)

Jazmine, mini-mix, 10/18/2011
Max-n-Indy
Max, 5/2001-2/2012, RIP my partner, my Regal Boy
Indy, 5/1997-10/2010, RIP my friend, my teacher

Health Index
K9 TBD info and Tick List Links
http://www.rabieschallengefund.org/
Re: Max/hemangio...he's gone [Re: Woodreb] #215584
02/27/12 02:01 AM
02/27/12 02:01 AM
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Mary Jane Offline
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Lisa,

I read the terminology like you do, but I'll read more. I don't know what'sensitivity' means or 'specificity'. Positive and negative predictive values are like they sound, I think, but I don't know how bad it can be before you discount it.

Mostly, the test is supposed to tell us something about our dog's health or illness and it's just not so clear.

awful,
MJ

Re: Max/hemangio...he's gone [Re: Mary Jane] #215853
02/28/12 07:01 AM
02/28/12 07:01 AM
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Posts: 19,487
Northern CA
MaxaLisa Offline OP

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Originally Posted By: Mary Jane
Mostly, the test is supposed to tell us something about our dog's health or illness and it's just not so clear.

awful,
MJ


Absolutely.

...I was walking to lunch on campus today and ran into an old student. He said that he had heard about Max and offered his condolences.

The day before I ran into two students that had long graduated and were back visiting. Of course they asked me how Indy was doing.

It brings comfort to me that they are so warmly remembered.


MaxaL (aka LisaT)

Jazmine, mini-mix, 10/18/2011
Max-n-Indy
Max, 5/2001-2/2012, RIP my partner, my Regal Boy
Indy, 5/1997-10/2010, RIP my friend, my teacher

Health Index
K9 TBD info and Tick List Links
http://www.rabieschallengefund.org/
Re: Max/hemangio...he's gone [Re: MaxaLisa] #215854
02/28/12 08:34 AM
02/28/12 08:34 AM
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Queensland. Australia
bianca Offline
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Molly Moo (aka The Piranha, 4 legged mouth) GSD (31/10/09)
Cooper GSD (The Gremlin) 19/10/11
Texas - Tabby cat (Feb 1996-2013) Run free sweet Teppie
Paris - Tabby cat (Feb 1996-2013) Run free my beautiful girl.
Re: Max/hemangio...he's gone [Re: bianca] #215931
02/28/12 04:26 PM
02/28/12 04:26 PM
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Mary Jane Offline
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I hate statistics. Sensitivity is the fraction of true positives called positive in the test, specificity is the fraction of true negatives called negative. They are calculated differently than positive and negative predictive value-and I don't know how any of it is calculated.

This is a figure from the paper I cited showing that a ton of dogs who actually had hemangiosarcoma had TK values similar to unaffected dogs; particularly dogs with benign splenic masses for some reason.

OK, we're all nauseated now. An essay in the NY Times today by a physician questions the value of a lot of disease prevention by screening.

I just don't know.

Mary Jane

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