Sneak Peek - Major MSI Education Project

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DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

Sneak Peek - Major MSI Education Project

Postby DK37 » Sun Oct 11, 2015 9:20 am

Sneak peek! As many of you know, one of the first questions I usually ask people when they ask about trials is "What is your MSI status". This is largely because it has a HUGE impact on immunotherapy trial strategy. Explaining the background science and reason why it's important isn't best served by SOLELY writing a Colon Talk Message Thread (but this IS a very important COMPONENT which is why I did it already a month ago or so!! :) ) --- so I've been working to help develop a major education initiative to try to educate ALL CRC PATIENTS, on the importance of knowing their MSI-status whether actively considering trials or not. This info is of utmost importance for potential trial participants i.e. all non-surgically cured Stage IV patients and even very important for earlier stage patients to have in the back of their minds due to chance of recurrence to Stage IV! Indirectly it also screens for the possibility of Lynch which impacts many treatment strategies. I'm sure we will have followup discussions here which I am looking forward to! Stay tuned, expect a post from me coming very soon........

-DK
Last edited by DK37 on Sun Oct 11, 2015 9:42 am, edited 1 time in total.
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

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Nik Colon
Posts: 5210
Joined: Thu Jan 08, 2015 3:35 pm
Location: MN

Re: Sneak Peek - Major MSI Education Project

Postby Nik Colon » Sun Oct 11, 2015 9:31 am

Thanks hon ♡
KRAS-mut G12V,MSS
Stage IVa Sig CC 2 lvr mets 1/12 Ln
(3, =<3 lng spots at dx til 5/16)
=T3N1aM1a 4cmX4mm (lng not included)
dx 12/2014 at age 39
CEA 1/15-4.9, 12/16-4.9 again
neoadj FOLFOX 1/15-3/15 (4tx, 3w/1wo oxi)
Col/Lvr surg 4/23/15 NED
adj FOLFIRI start 6/15-9/15 (8tx, 5w/3wo iri)
1 sml lvr spot/cyst
12/6/16 multi lung spots/mets?
No longer NED :(
My tx ongoing-start 1/20/15
Adding your SIGNATURE, etc

Ceebo
Posts: 132
Joined: Sat Feb 14, 2015 9:15 am
Location: Southwest Michigan

Re: Sneak Peek - Major MSI Education Project

Postby Ceebo » Sun Oct 11, 2015 9:45 am

Thanks DK!! We appreciate all the education you can send our way!!
DH 64 Stage 4 on 4/14 ; cecal tumor; 5+ nodes ; mets to liver; colon resection
5/14 FOLFOX
9/14 - Liver surgery aborted; peri mets
10/14 CT mult.1-2 mm lung mets; FOLFIRI & Avastin
1/15 CT -liver & lung mets shrinking
3/15 PET - ? New met. site colon; CEA rising
7/15 Chemo has failed; looking for clinical trial
9/29/15 started TAS-102 trial
KRAS mutant; MSS

ieowi
Posts: 202
Joined: Mon Jul 27, 2015 1:27 am

Re: Sneak Peek - Major MSI Education Project

Postby ieowi » Sun Oct 11, 2015 11:54 am

Thank youuuuu very much,,, :D
Father 58 yo , Colon cancer IV + 4 Lymph. 7/2015
K-ras Mutant,GNAS,FBXW7,PIK3CA, MSI-low
4 cycles irinotecan+FU5
developed abdominal met + lung met...Failed
4 cycle Oxaliplatin+folfox. peri met growing...Failed
unofficial trial !!!

daughterseekinginfo
Posts: 40
Joined: Mon Mar 31, 2014 7:10 pm

Re: Sneak Peek - Major MSI Education Project

Postby daughterseekinginfo » Thu Feb 04, 2016 9:08 pm

Hi DK,

When my father's original CR tumor was resected, I asked about microsatellite instability testing and was told this by surgical oncologist:

"We look at it routinely at mismatch repair genes. If these are intact, we do not test further for microsatellite instability unless we have a high suspicion for Lynch syndrome. He has intact mismatch repair proteins, and I’m not suspicious for Lynch."

He's now a very advanced stage IV and I'm wondering if there's anything else I should be asking/looking at. They are doing a liver biopsy to confirm spread is CRC as he had stage 2 bladder cancer removed within 6 months of CRC diagnosis.

Thanks for any insight you can provide.
daughter of a 68-y-o male
10/13: T4N0MO CC (sig colon resection, part bladder resection)
04/14: radical resection remaining bladder--both recurrent CC in bladder & stage 2 bladder cancer (high grade).
10/14: questionable pelvic lymph nodes; biopsy of one clear
02/15: Clear CT scan & X-rays; small bowel fistula put off re-connection
02/16: Advanced cancer found on CT scan; determined to be aggressive bladder cancer; in lungs/liver/abdomen/hip bone.
03/27/16: My dear father died at home on hospice.

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Nik Colon
Posts: 5210
Joined: Thu Jan 08, 2015 3:35 pm
Location: MN

Re: Sneak Peek - Major MSI Education Project

Postby Nik Colon » Thu Feb 04, 2016 10:26 pm

daughterseekinginfo wrote:Hi DK,

When my father's original CR tumor was resected, I asked about microsatellite instability testing and was told this by surgical oncologist:

"We look at it routinely at mismatch repair genes. If these are intact, we do not test further for microsatellite instability unless we have a high suspicion for Lynch syndrome. He has intact mismatch repair proteins, and I’m not suspicious for Lynch."

He's now a very advanced stage IV and I'm wondering if there's anything else I should be asking/looking at. They are doing a liver biopsy to confirm spread is CRC as he had stage 2 bladder cancer removed within 6 months of CRC diagnosis.

Thanks for any insight you can provide.

Since you said they are intact, I believe that means MSS, but I will let DK answer as I am not positive.
KRAS-mut G12V,MSS
Stage IVa Sig CC 2 lvr mets 1/12 Ln
(3, =<3 lng spots at dx til 5/16)
=T3N1aM1a 4cmX4mm (lng not included)
dx 12/2014 at age 39
CEA 1/15-4.9, 12/16-4.9 again
neoadj FOLFOX 1/15-3/15 (4tx, 3w/1wo oxi)
Col/Lvr surg 4/23/15 NED
adj FOLFIRI start 6/15-9/15 (8tx, 5w/3wo iri)
1 sml lvr spot/cyst
12/6/16 multi lung spots/mets?
No longer NED :(
My tx ongoing-start 1/20/15
Adding your SIGNATURE, etc

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O Stoma Mia
Posts: 1364
Joined: Sat Jun 22, 2013 6:29 am
Location: Traveling abroad

MSI testing questions

Postby O Stoma Mia » Fri Feb 05, 2016 4:36 am

DK37 wrote:Sneak peek! As many of you know, one of the first questions I usually ask people when they ask about trials is "What is your MSI status". This is largely because it has a HUGE impact on immunotherapy trial strategy. Explaining the background science and reason why it's important isn't best served by SOLELY writing a Colon Talk Message Thread (but this IS a very important COMPONENT which is why I did it already a month ago or so!! :) ) --- so I've been working to help develop a major education initiative to try to educate ALL CRC PATIENTS, on the importance of knowing their MSI-status whether actively considering trials or not. This info is of utmost importance for potential trial participants i.e. all non-surgically cured Stage IV patients and even very important for earlier stage patients to have in the back of their minds due to chance of recurrence to Stage IV! Indirectly it also screens for the possibility of Lynch which impacts many treatment strategies. I'm sure we will have followup discussions here which I am looking forward to! Stay tuned, expect a post from me coming very soon........
-DK

DK – Thank you for offering to make MSI testing intelligible to those of us who are non-scientists. Since I have never had any training in molecular biology, I have lots of questions in this area. The whole area is very confusing to me. Any clarification or simplification that you could provide in your upcoming overview would be much appreciated. Thank you for your efforts in this area.

Here are some of the types of questions that I have:

    MSI status – is it a property of patient or a property of a tumor? Some of the writings on the topic of MSI testing refer to “MSI patients” while other passages refer to “ MSI tumors”. So, is MSI status something that a patient has always had (like blood type), and if so can this be assessed at anytime during lifetime – for example could MSI status be assessed for a fetus by doing amniocentesis in the same way that Down’s Syndrome is assessed before childbirth, etc,?
    MSI status for tumors – Does MSI testing require a tumor? If so, does it make any difference whether it is the primary tumor or a metastatic tumor?
    MSI status for tumors – within-tumor variability - If MSI testing is done on tumors, then can the specimen from one part of the tumor turn out to be MSI-High while a specimen from a different part of the same tumor turns out to be MSI-Low?
    MSI status for tumors – tumor location - If MSI testing is done on metastatic tumors, and if the patient has several such tumors (eg., one in liver and one in lungs) then can one of these tumors test as MSI-High while the other tumor tests as MSI-Low? Can MSI testing on a primary tumor yield different results from MSI testing on a metastatic tumor?
    MSI status test-retest reliability - If MSI status is determined as MSI-Low on one testing, what is the likelihood that it will turn out to be MSI-High when a second test is done on the same sample? What if different labs give different results when they are doing tests on the same tumor?
    MSI testing sample requirements - What is minimally needed in order to do MSI testing? Can this be done on a blood sample or on a urine samle, or does it have to be done on a sample from a tumor? If it requires a tumor, then does it have to be a primary tumor, or a metastatic tumor, or does it make any difference? Can an MSI test be done on a pre-cancerous polyp, for example?
    MSI testing – specimen preservation requirements. If MSI testing requires a specimen taken from a tumor, does it make any difference how the specmen was preserved? What if it was not preserved in a paraffin block, but was preserved in a bottle of formaldehyde or in some non-standard manner? In other words, are there industry-wide standards on specimen preservation that must be met before MSI testing can take place? Prior to surgery, does the surgeon need to be informed that MSI testing will be needed so that he/she will be sure to preserve the specimen in the proper manner to allow subsequent MSI testing?
    MSI testing when tumor specimen is not available - What if the requirement is for a tumor sample, but the patient has been NED for 5 or 10 years, does not have any visible tumors any more, and the original resected/biopsied tumor is no longer available? Can MSI testing still be done, for example, by testing the Circulating Cancer Cells in the blood instead, or by using some other method?
    MSI testing for family members. If a patient has received his/her MSI testing results and now wants to have family members tested for MSI status, is this at all possible if the family members have never been diagnosed with cancer?
    MSI status stability - If a patient is tested for MSI now, in 2016, will these results still be valid 5 or 10 years from now, or could the patient’s current MSI status change after being subjected to 4 or 5 years of continuous chemo regimens of one type or another?

Last edited by O Stoma Mia on Thu Jun 01, 2017 10:38 am, edited 1 time in total.

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DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

Re: Sneak Peek - Major MSI Education Project

Postby DK37 » Fri Feb 05, 2016 8:43 am

O Stoma Mia wrote:
Here are some of the types of questions that I have:

    MSI status – is it a property of patient or a property of a tumor? Some of the writings on the topic of MSI testing refer to “MSI patients” while other passages refer to “ MSI tumors”. So, is MSI status something that a patient has always had (like blood type), and if so can this be assessed at anytime during lifetime – for example could MSI status be assessed for a fetus by doing amniocentesis in the same way that Down’s Syndrome is assessed before childbirth, etc,?
    MSI status for tumors – Does MSI testing require a tumor? If so, does it make any difference whether it is the primary tumor or a metastatic tumor?
    MSI status for tumors – within-tumor variability - If MSI testing is done on tumors, then can the specimen from one part of the tumor turn out to be MSI-High while a specimen from a different part of the same tumor turns out to be MSI-Low?
    MSI status for tumors – tumor location - If MSI testing is done on metastatic tumors, and if the patient has several such tumors (eg., one in liver and one in lungs) then can one of these tumors test as MSI-High while the other tumor tests as MSI-Low? Can MSI testing on a primary tumor yield different results from MSI testing on a metastatic tumor?
    MSI status test-retest reliability - If MSI status is determined as MSI-Low on one testing, what is the likelihood that it will turn out to be MSI-High when a second test is done on the same sample? What if different labs give different results when they are doing tests on the same tumor?
    MSI testing sample requirements - What is minimally needed in order to do MSI testing? Can this be done on a blood sample or on a urine samle, or does it have to be done on a sample from a tumor? If it requires a tumor, then does it have to be a primary tumor, or a metastatic tumor, or does it make any difference? Can an MSI test be done on a pre-cancerous polyp, for example?
    MSI testing – specimen preservation requirements. If MSI testing requires a specimen taken from a tumor, does it make any difference how the specmen was preserved? What if it was not preserved in a paraffin block, but was preserved in a bottle of formaldehyde or in some non-standard manner? In other words, are there industry-wide standards on specimen preservation that must be met before MSI testing can take place? Prior to surgery, does the surgeon need to be informed that MSI testing will be needed so that he/she will be sure to preserve the specimen in the proper manner to allow subsequent MSI testing?
    MSI testing when tumor specimen is not available - What if the requirement is for a tumor sample, but the patient has been NED for 5 or 10 years, does not have any visible tumors any more, and the original resected/biopsied tumor is no longer available? Can MSI testing still be done, for example, by testing the Circulating Cancer Cells in the blood instead, or by using some other method?
    MSI testing for family members. If a patient has received his/her MSI testing results and now wants to have family members tested for MSI status, is this at all possible if the family members have never been diagnosed with cancer?
    MSI status stability - If a patient is tested for MSI now, in 2016, will these results still be valid 5 or 10 years from now, or could the patient’s current MSI status change after being subjected to 4 or 5 years of continuous chemo regimens of one type or another?



Absolutely fantastic questions O Stoma Mia! You are much better than some formally trained molecular biologists!! I'll try to gather answers for them

Cheers,
-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

Wonderfullymade
Posts: 122
Joined: Tue Jan 12, 2016 4:33 pm

Re: Sneak Peek - Major MSI Education Project

Postby Wonderfullymade » Fri Feb 05, 2016 3:20 pm

I too am waiting for the answer to those questions! I think it was my tumor that tested MSI-H (no staining on MLH1 and PMS2) and because my blood that was negative ( so far...Dr said they just might not know which gene (?) is in control) I have only had 1 scan since I have been on the Prembro but that results so far have been more favorable than the foxfire and Folfox and Vectibix.
And....I could be completely off because this is the part of myself that I am still trying to understand! A big thank you to all the scientists out there who are working hard on this immnotheray because it has really changed my options! And a a lot of prayers for my fellows club members that a breakthrough for MSS
DX 3/2015 53
Stage IVa CC w/liver met
BRAF/KRAS wild type MSI-High Lynch?
Folfox 3 cycles
5/2015 ER for subtotal colectomomy due to perforated colon, ovary removed
Folfuri/Pantiumumab 5 cycles
8/2015 liver resection, gallbladder removed and new LN
10/2015 CT scan new nodes
10/2015 Pembro started CEA 2.2
5/2017 stable lung things, coltis, lymph nodes stable cea 1/2017 1.1

User avatar
DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

Re: Sneak Peek - Major MSI Education Project

Postby DK37 » Fri Feb 05, 2016 6:09 pm

daughterseekinginfo wrote:Hi DK,

When my father's original CR tumor was resected, I asked about microsatellite instability testing and was told this by surgical oncologist:

"We look at it routinely at mismatch repair genes. If these are intact, we do not test further for microsatellite instability unless we have a high suspicion for Lynch syndrome. He has intact mismatch repair proteins, and I’m not suspicious for Lynch."

He's now a very advanced stage IV and I'm wondering if there's anything else I should be asking/looking at. They are doing a liver biopsy to confirm spread is CRC as he had stage 2 bladder cancer removed within 6 months of CRC diagnosis.

Thanks for any insight you can provide.


My basic understanding (but I am a drug discovery scientist & not a geneticist) matches your surgeons's comment. If the Mismatch repair (MMR) proteins are intact, based upon the clinical trial data I think it is unlikely he would respond to PD-1 monotherapy... sorry- but if you have any question marks, it is very good to double-check with your MD medical oncologist as well.

-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

User avatar
DK37
Posts: 510
Joined: Tue Sep 17, 2013 8:31 am
Location: San Diego

Re: Sneak Peek - Major MSI Education Project

Postby DK37 » Sun Feb 07, 2016 1:11 am

O Stoma Mia wrote:Here are some of the types of questions that I have:



I'm not ready to talk about it but something happened in my personal life - I may need to be a less active participant here for a little while - sorry it is hitting me answering your questions, I hope you understand... Don't worry, no medical emergencies for me or anyone in my family. I'll be back...

-DK
6/4/2012 Dx Stage 3C CRC @ 40 yo. MSS, KRAS-WT, BRAF-WT, p53-mut
7/12 FOLFOX/FOLFIRI
2/13 NED!
8/13 Enlarged lymphs - Stable
10/14 Stage IV. Lung & Lymph mets. 5-FU+bev
3/15 Cetuximab
11/15 FOLFIRI + bev
11/16 Signs of FOLFIRI resistance (Lymph mets)
1/17 Palliative radiation for resistant mets
2/17 FOLFIRI + bev + Maraviroc (off-label)
3/17 FOLFIRI + Erbitux + Maraviroc (off-label)
MSS-CRC Clinical Trial Finder: http://trialfinder.fightcrc.org/
2016 Colondar 2.0 Model
DK37 Science Posts List

User avatar
Nik Colon
Posts: 5210
Joined: Thu Jan 08, 2015 3:35 pm
Location: MN

Re: Sneak Peek - Major MSI Education Project

Postby Nik Colon » Sun Feb 07, 2016 1:42 am

DK37 wrote:
O Stoma Mia wrote:Here are some of the types of questions that I have:



I'm not ready to talk about it but something happened in my personal life - I may need to be a less active participant here for a little while - sorry it is hitting me answering your questions, I hope you understand... Don't worry, no medical emergencies for me or anyone in my family. I'll be back...

-DK

Take care of you and your family.
KRAS-mut G12V,MSS
Stage IVa Sig CC 2 lvr mets 1/12 Ln
(3, =<3 lng spots at dx til 5/16)
=T3N1aM1a 4cmX4mm (lng not included)
dx 12/2014 at age 39
CEA 1/15-4.9, 12/16-4.9 again
neoadj FOLFOX 1/15-3/15 (4tx, 3w/1wo oxi)
Col/Lvr surg 4/23/15 NED
adj FOLFIRI start 6/15-9/15 (8tx, 5w/3wo iri)
1 sml lvr spot/cyst
12/6/16 multi lung spots/mets?
No longer NED :(
My tx ongoing-start 1/20/15
Adding your SIGNATURE, etc

daughterseekinginfo
Posts: 40
Joined: Mon Mar 31, 2014 7:10 pm

Re: Sneak Peek - Major MSI Education Project

Postby daughterseekinginfo » Wed Feb 17, 2016 11:56 am

Thank you for your help, DK. I hope all is well with you and yours.
daughter of a 68-y-o male
10/13: T4N0MO CC (sig colon resection, part bladder resection)
04/14: radical resection remaining bladder--both recurrent CC in bladder & stage 2 bladder cancer (high grade).
10/14: questionable pelvic lymph nodes; biopsy of one clear
02/15: Clear CT scan & X-rays; small bowel fistula put off re-connection
02/16: Advanced cancer found on CT scan; determined to be aggressive bladder cancer; in lungs/liver/abdomen/hip bone.
03/27/16: My dear father died at home on hospice.


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