Worried -genetic results are in. KRAS MSS

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Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Worried -genetic results are in. KRAS MSS

Postby Nohogirl » Wed Oct 17, 2018 8:27 pm

Hi All,

I was wondering to know how many of us here are KRASS mutants with MSS.

My husband's tumor genetic tests came back and his tumor has KRASs mutation, MSS. Negative for BRAF or NRASS.
I am reading online and almost all studies mention poor prognoses with KRASS MSS mutation.


Anyone with the same mutations that beat the beast long term. Please please reply. I am freaking out and need some encouragement. Thank you all.
Last edited by Nohogirl on Wed Oct 17, 2018 9:27 pm, edited 1 time in total.
04/18 DH 49 Stage 2A T3N0M0 rectal cancer moderately differentiated.
05/18 chemorad. (Xeloda) 28 days
08/18 Surgery- 24 cm, including entire rectum out
Path -Stage II T2N0M0 moderate to poorly diff. adenocarcinoma
0 of 15 lymph nodes
No PNI
No LVI
Clear margins
10/18-02/19 8 cycles of Folfox
02/19 Normal Pet Scan

lpas
Posts: 1009
Joined: Wed Nov 19, 2014 11:11 pm

Re: Worried -genetic results are in.

Postby lpas » Wed Oct 17, 2018 8:37 pm

Do you know the specific variant of KRAS? From what I've read, not all KRAS types have the same prognosis. Keep in mind that most people don't have their tumor tested for specific mutations until and unless they're stage 4, so those who were KRAS mutants at a lower stage and survived are generally omitted from the sample. I am one of the exceptions to this rule and had my tumor tested as a stage III. Have been NED (so far) since my diagnosis in November 2014.
11/14 Dx sigmoid CC @ 45yo
12/14 Colectomy + hysterectomy
Stage IIIB, T3N1bM0, 2/20 nodes, MSS, G2, KRAS(A146T), TP53, SMAD4, ERBB2, CEA 1.0
2/15-7/15 XELOX & Celebrex
4/18 clean CT
2/19 clean scope
Ongoing Celebrex, Tagamet & other carefully-targeted supplements
Post-chemo CEA 3.0, 2.5, 2.3, 2.0, 1.6, 1.3, 1.8, 2.1, 1.8, 2.0, 1.8, 1.9, 1.7, 1.5, 1.6, 1.5, 1.4, 1.4, 1.3, 1.3, 1.6, 1.6, 1.3, 1.4, 1.6, 2.2, 2.4, 2.1 and ? For sanity's sake I've stopped looking.
Mom to a 5 & 7yo

Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Re: Worried -genetic results are in KRAS MSS

Postby Nohogirl » Wed Oct 17, 2018 8:59 pm

lpas wrote:Do you know the specific variant of KRAS? From what I've read, not all KRAS types have the same prognosis. Keep in mind that most people don't have their tumor tested for specific mutations until and unless they're stage 4, so those who were KRAS mutants at a lower stage and survived are generally omitted from the sample. I am one of the exceptions to this rule and had my tumor tested as a stage III. Have been NED (so far) since my diagnosis in November 2014.

Thank you lpas for the quick response. Was your tumor also KRAS, MSS?
My husband's KRAS mutation characteristics are protein alteration -p.Q61Ha, exon-5, and variant frequency 15%. Although i have no idea what each of these means. I also did not know there were different KRAS.
Last edited by Nohogirl on Wed Oct 17, 2018 9:26 pm, edited 1 time in total.
04/18 DH 49 Stage 2A T3N0M0 rectal cancer moderately differentiated.
05/18 chemorad. (Xeloda) 28 days
08/18 Surgery- 24 cm, including entire rectum out
Path -Stage II T2N0M0 moderate to poorly diff. adenocarcinoma
0 of 15 lymph nodes
No PNI
No LVI
Clear margins
10/18-02/19 8 cycles of Folfox
02/19 Normal Pet Scan

Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Re: Worried -genetic results are in.

Postby Nohogirl » Wed Oct 17, 2018 9:00 pm

Still hoping to hear from others :)
04/18 DH 49 Stage 2A T3N0M0 rectal cancer moderately differentiated.
05/18 chemorad. (Xeloda) 28 days
08/18 Surgery- 24 cm, including entire rectum out
Path -Stage II T2N0M0 moderate to poorly diff. adenocarcinoma
0 of 15 lymph nodes
No PNI
No LVI
Clear margins
10/18-02/19 8 cycles of Folfox
02/19 Normal Pet Scan

lpas
Posts: 1009
Joined: Wed Nov 19, 2014 11:11 pm

Re: Worried -genetic results are in KRAS MSS

Postby lpas » Wed Oct 17, 2018 10:14 pm

Nohogirl wrote:
lpas wrote:Do you know the specific variant of KRAS? From what I've read, not all KRAS types have the same prognosis. Keep in mind that most people don't have their tumor tested for specific mutations until and unless they're stage 4, so those who were KRAS mutants at a lower stage and survived are generally omitted from the sample. I am one of the exceptions to this rule and had my tumor tested as a stage III. Have been NED (so far) since my diagnosis in November 2014.

Thank you lpas for the quick response. Was your tumor also KRAS, MSS?
My husband's KRAS mutation characteristics are protein alteration -p.Q61Ha, exon-5, and variant frequency 15%. Although i have no idea what each of these means. I also did not know there were different KRAS.


Yes! My tumor tested MSS and I have the KRAS A146T mutation (see my signature below) which is one of the rarer variants. Your husband's Q61H is also somewhat less frequent. Codons 12 and 13 seem to be the most common. I've linked a few articles below that talk about different KRAS types and their association with prognosis. You'll see that neither one identifies Q61H as a particular variant that confers inferior outcomes.

Of course, the biggest drawback to having a KRAS mutation is the decreased number of chemo options (i.e. no erbitux or vectibix) if you reach the stage where that becomes important.

https://medicalresearch.com/genetic-research/only-some-kras-gene-mutations-linked-to-worse-prognosis-in-colon-cancer/14635/
https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-135
11/14 Dx sigmoid CC @ 45yo
12/14 Colectomy + hysterectomy
Stage IIIB, T3N1bM0, 2/20 nodes, MSS, G2, KRAS(A146T), TP53, SMAD4, ERBB2, CEA 1.0
2/15-7/15 XELOX & Celebrex
4/18 clean CT
2/19 clean scope
Ongoing Celebrex, Tagamet & other carefully-targeted supplements
Post-chemo CEA 3.0, 2.5, 2.3, 2.0, 1.6, 1.3, 1.8, 2.1, 1.8, 2.0, 1.8, 1.9, 1.7, 1.5, 1.6, 1.5, 1.4, 1.4, 1.3, 1.3, 1.6, 1.6, 1.3, 1.4, 1.6, 2.2, 2.4, 2.1 and ? For sanity's sake I've stopped looking.
Mom to a 5 & 7yo

rp1954
Posts: 1435
Joined: Mon Jun 13, 2011 1:13 am

Re: Worried -genetic results are in. KRAS MSS

Postby rp1954 » Thu Oct 18, 2018 12:39 am

Take a deep breath. I would look very hard now at CEA, LDH and CA199 (you probably need to order these your self for speed and convenience, at least a first time).

It may be that a choice could be made between normal Xeloda treatment, Xeloda+mild, generic adjuncts, and Folfox. The results from some papers suggest circumstances that oral 5FU + mild adjuncts might be superior to Folfox for recurrence, and a lot less debilitating. Also, to avoid chemos' worst side effects is a plus.
watchful, active researcher and caregiver for stage IVb/c CC since early 2010. surgeries 4/10 & 5/11; 8 yrs immuno-Chemo for mCRC; now mostly IV C & no chemo
most of 2010 Life Extension recommendations and possibilities + more, some (much) higher, peaking ~2011-12, taper to almost nothing mid 2018

heiders33
Posts: 336
Joined: Sat Nov 04, 2017 11:08 am

Re: Worried -genetic results are in. KRAS MSS

Postby heiders33 » Thu Oct 18, 2018 6:05 am

I didn't find out my genetic mutation until I switched to MSK. Why my previous oncologist never told me I was KRAS I'll never know. I just looked up my surgical pathology report again and I'm KRAS G12A. Yes, I did end up with a pesky liver met that escaped the initial treatment. But I've had it removed and I'm currently NED and (fingers crossed) plan to stay that way. My KRAS mutation was one of my motivations for pursuing aggressive follow-up chemo -- FOLFIRI plus FUDR through the Medtronic HAI pump, which I'm starting soon. The biggest disadvantage as lpas said is that KRAS mutants aren't candidates for EGFR inhibitors like Vectibix and Erbitux. That's why I'm doing everything I can to keep it from coming back.
36 year-old female
May 2017: Dx rectal cancer T3N2M0
MSS, KRAS G12D
6/17: 28 days chemorad
9/17: LAR/loop ileostomy
10/17 - 2/18: XELOX six rounds
3/18: reversal
5/18: CT liver spot, blood counts normal
8/18: Abnormal PET, CEA 2.4
9/18: liver resection/HAI pump
10/18: Clear CT/sigmoidoscopy
10/18 - 4/19: 6MO FUDR/5FU

Brearmstrong
Posts: 74
Joined: Sun Mar 26, 2017 3:24 pm
Location: CT

Re: Worried -genetic results are in. KRAS MSS

Postby Brearmstrong » Thu Oct 18, 2018 8:23 am

I too am KRAS and MSS. Have had folfiri and folfox so future lines of chemo or treatments are unlikely. BUTT, here's to hoping I stay NED forever.

-Brenda
45 F Jan 17 Mom 2 boys
tumor appendix/colon
Muc Adeno 4cm
mod diff G2 T4aN2
nodes 8/50
CEA 4.6 after surgery <.05
KRAS G12D MSS
FOLFOX Apr-sep 17
Clean CT scan Jul 2017 lung nodule 4mm, clean CT oct 17, CEA 3.4, nov 17 CEA 8.1. May 18 2.3 Jul 18 1.0 oct 18 1.3 Jan 19 1.3
Oct 2017 clean CT
Nov 17 PET para aortic nodes uptake Stage IV
Folfori w/avastin Dec 17 CEA 7.1
May 18- surgery to remove nodes- 5 positive xeloda 2000mg/day indefinitely
Aug 18-CT NED! Nov 18 CT clear, Feb 19 CT clear

Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Re: Worried -genetic results are in KRAS MSS

Postby Nohogirl » Thu Oct 18, 2018 11:35 am

lpas wrote:
Nohogirl wrote:
lpas wrote:Do you know the specific variant of KRAS? From what I've read, not all KRAS types have the same prognosis. Keep in mind that most people don't have their tumor tested for specific mutations until and unless they're stage 4, so those who were KRAS mutants at a lower stage and survived are generally omitted from the sample. I am one of the exceptions to this rule and had my tumor tested as a stage III. Have been NED (so far) since my diagnosis in November 2014.

Thank you lpas for the quick response. Was your tumor also KRAS, MSS?
My husband's KRAS mutation characteristics are protein alteration -p.Q61Ha, exon-5, and variant frequency 15%. Although i have no idea what each of these means. I also did not know there were different KRAS.


Yes! My tumor tested MSS and I have the KRAS A146T mutation (see my signature below) which is one of the rarer variants. Your husband's Q61H is also somewhat less frequent. Codons 12 and 13 seem to be the most common. I've linked a few articles below that talk about different KRAS types and their association with prognosis. You'll see that neither one identifies Q61H as a particular variant that confers inferior outcomes.

Of course, the biggest drawback to having a KRAS mutation is the decreased number of chemo options (i.e. no erbitux or vectibix) if you reach the stage where that becomes important.

https://medicalresearch.com/genetic-research/only-some-kras-gene-mutations-linked-to-worse-prognosis-in-colon-cancer/14635/
https://molecular-cancer.biomedcentral.com/articles/10.1186/1476-4598-13-135

Thank you so much Lpas for the links. Its also very encouraging to see people with KRAS MSS doing well. So which of the KRAS characteristics is the codone? I am lost in this terminology.
04/18 DH 49 Stage 2A T3N0M0 rectal cancer moderately differentiated.
05/18 chemorad. (Xeloda) 28 days
08/18 Surgery- 24 cm, including entire rectum out
Path -Stage II T2N0M0 moderate to poorly diff. adenocarcinoma
0 of 15 lymph nodes
No PNI
No LVI
Clear margins
10/18-02/19 8 cycles of Folfox
02/19 Normal Pet Scan

Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Re: Worried -genetic results are in. KRAS MSS

Postby Nohogirl » Thu Oct 18, 2018 11:38 am

Brearmstrong wrote:I too am KRAS and MSS. Have had folfiri and folfox so future lines of chemo or treatments are unlikely. BUTT, here's to hoping I stay NED forever.

-Brenda

Wow. You're doing so good Brearmstrong. Keep it up! I wish you a long lasting NED.
04/18 DH 49 Stage 2A T3N0M0 rectal cancer moderately differentiated.
05/18 chemorad. (Xeloda) 28 days
08/18 Surgery- 24 cm, including entire rectum out
Path -Stage II T2N0M0 moderate to poorly diff. adenocarcinoma
0 of 15 lymph nodes
No PNI
No LVI
Clear margins
10/18-02/19 8 cycles of Folfox
02/19 Normal Pet Scan

Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Re: Worried -genetic results are in. KRAS MSS

Postby Nohogirl » Thu Oct 18, 2018 11:47 am

rp1954 wrote:Take a deep breath. I would look very hard now at CEA, LDH and CA199 (you probably need to order these your self for speed and convenience, at least a first time).

It may be that a choice could be made between normal Xeloda treatment, Xeloda+mild, generic adjuncts, and Folfox. The results from some papers suggest circumstances that oral 5FU + mild adjuncts might be superior to Folfox for recurrence, and a lot less debilitating. Also, to avoid chemos' worst side effects is a plus.

Thank you rp1954. My husbands CEA and ca199 was checked only after his recent CT and MRI early this month. His CEA was <0.5 and CA199 was 8. According to his oncologist these are as good as they can get.
I still can't get over his iliac lymph node issue.
I am not sure if i should really trust this cEA thing, since i have seen many people with low markers while having recurrence and vice versa high markers but no recurrence.
04/18 DH 49 Stage 2A T3N0M0 rectal cancer moderately differentiated.
05/18 chemorad. (Xeloda) 28 days
08/18 Surgery- 24 cm, including entire rectum out
Path -Stage II T2N0M0 moderate to poorly diff. adenocarcinoma
0 of 15 lymph nodes
No PNI
No LVI
Clear margins
10/18-02/19 8 cycles of Folfox
02/19 Normal Pet Scan

User avatar
GrouseMan
Posts: 796
Joined: Mon Aug 12, 2013 12:30 pm
Location: SE Michigan USA

Re: Worried -genetic results are in. KRAS MSS

Postby GrouseMan » Thu Oct 18, 2018 7:22 pm

There is evidence accumulating I believe that the KRAS G13D mutant is actually sensitive to treatment with EGFr Inhibitors like Erbitux. See the following two links, they are both pretty new:

https://www.omicsonline.org/open-access ... ?aid=88407
https://www.biorxiv.org/content/biorxiv ... 6.full.pdf

Most Kras mutations turn the Kras pathway on. It cannot be inhibited by its natural substrate so it remains activated and this often results in downstream activation of other growth factors of which EGF is one.

Here are some other publications that are older but talk about Kras Mutations. Most of these are in Lung Cancer but the idea still applies to Colon Cancer as well.

The following talks about Mutations and testing:
https://biochemmack.ru/upload/iblock/42 ... 9ab5ba.pdf

This one is about he new third generation EGFr Inhibitors and why they may work with KRAS mutant Lung Cancers. Again This is lung Cancer but I suspect this will also be true for colon cancer as well. The drug they discuss in this paper is neratinib which is similar to a drug I worked on recently approved as Vizimpro (dacomitinib). Take note of a statement made in the third paragraph of the introduction!

http://stm.sciencemag.org/content/10/44 ... citransmed

I suspect that when all is said and done and proper clinical trials are run some of the new Pan Erbb inhibitors will start to make their way into colon cancer treatment regardless of KAS status.

Good luck

GrouseMan
DW 53 dx Jun 2013
CT mets Liver Spleen lung. IVb CEA~110
Jul 2013 Sig Resct
8/13 FolFox,Avastin 12Tx mild sfx, Ongoing 5-FU Avastin every 3 wks.
CEA: good marker
7/7/14 CT Can't see the spleen Mets.
8/16/15 CEA Up, CT new abdominal mets. Iri, 5-FU, Avastin every 2 wks.
1/16 Iri, Erbitux and likely Avastin (Trial) CEA going >.
1/17 CEA up again dropped from Trial, Mets growth 4-6 mm in abdomen
5/2/17 Failed second trial, Hospitalized 15 days 5/11. Home Hospice 5/26, at peace 6/4/2017

Nohogirl
Posts: 111
Joined: Sun Oct 14, 2018 12:15 am

Re: Worried -genetic results are in. KRAS MSS

Postby Nohogirl » Sun Oct 21, 2018 12:21 am

GrouseMan wrote:There is evidence accumulating I believe that the KRAS G13D mutant is actually sensitive to treatment with EGFr Inhibitors like Erbitux. See the following two links, they are both pretty new:

https://www.omicsonline.org/open-access ... ?aid=88407
https://www.biorxiv.org/content/biorxiv ... 6.full.pdf

Most Kras mutations turn the Kras pathway on. It cannot be inhibited by its natural substrate so it remains activated and this often results in downstream activation of other growth factors of which EGF is one.

Here are some other publications that are older but talk about Kras Mutations. Most of these are in Lung Cancer but the idea still applies to Colon Cancer as well.

The following talks about Mutations and testing:
https://biochemmack.ru/upload/iblock/42 ... 9ab5ba.pdf

This one is about he new third generation EGFr Inhibitors and why they may work with KRAS mutant Lung Cancers. Again This is lung Cancer but I suspect this will also be true for colon cancer as well. The drug they discuss in this paper is neratinib which is similar to a drug I worked on recently approved as Vizimpro (dacomitinib). Take note of a statement made in the third paragraph of the introduction!

http://stm.sciencemag.org/content/10/44 ... citransmed

I suspect that when all is said and done and proper clinical trials are run some of the new Pan Erbb inhibitors will start to make their way into colon cancer treatment regardless of KAS status.

Good luck

GrouseMan

Thank you GrouseMan. Very helpful information.

NHMike
Posts: 1907
Joined: Fri Jul 21, 2017 3:43 am

Re: Worried -genetic results are in. KRAS MSS

Postby NHMike » Mon Oct 22, 2018 7:52 pm

KRAS is a gene that provides the code for making a protein, KRAS, which is involved primarily in controlling cell division. This protein is part of the MAP kinase signaling cascade (RAS/RAF/MEK/ERK) that relays chemical signals from outside the cell to the cell's nucleus and is primarily involved in controlling cell division. KRAS is an enzyme (a GTPase) that converts a molecule called GTP into GDP. When KRAS is attached (bound) to GDP, it's in its "off" position and can't send signals to the nucleus. But when a GTP molecule arrives and binds to KRAS, KRAS is activated and sends its signal, and then it converts the GTP into GDP and returns to the "off" position.

When mutated, KRAS can act as an oncogene, causing normal cells to become cancerous. The mutations can shift the KRAS protein into the "on" position all the time. KRAS mutations are common in pancreatic, lung and colorectal cancers. These KRAS mutations are said to be somatic, because instead of coming from a parent and being present in every cell (hereditary), they are acquired during the course of a person's life and are found only in cells that become cancerous.


http://targetedcancercare.massgeneral.o ... -(c-183A-T).aspx

KRAS mutations are by far the most common mutations in CRC, and, today, survival rates for CRC, up to stage 3, are quite good.

I have KRAS G12D. Most people with CRC don't know their mutations because genomic tumor testing is not part of the standard of care. Genomic tumor testing can cost from $1,000 to $5,000 and many patients will balk at paying for this out-of-pocket. I believe that there is a trial in Canada to see if it would be worthwhile doing this testing for patients in general. I asked my oncologist to do the testing but he blew me off. Then my son's manager offered to do it for me so I had the sample sent over and he did it for me and my mutation was KRAS G12D - I think that this is the most common CRC mutation. But, at the time, I didn't know that it would help knowing this information. I think that it's more useful to know if you have something more aggressive like BRAF V600E. I later found out that some people with KRAS G12D can be cured with a revolutionary treatment from NCI - but they were only taking Stage 4 patients.

I'm technically NED after the tumor was removed in October 2017 and on surveillance now.

There are other cancers that have quite good treatments but Colorectal Cancer is still treated using approaches that are relatively mature ("old"). Chemo, radiation, surgery. I asked my son why there has been great progress in some other cancers but we're still using old technology for treating Colorectal Cancer. His answer was that the cancer was inside the cell and that drugs have no way of telling whether a cell was a good cell or a cancerous cell - so our drugs attack them all. Targeted drugs can detect whether or not a cell is cancerous and target them for destruction.

Here's a paper describing why RAS mutations are so tough to treat: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355017/

It says that KRAS mutations account for 44.7% of Colorectal Cancers. But it's a good paper on the prevalence of RAS and the history of approaches in tackling it.
6/17: ER rectal bleeding; Colonoscopy
7/17: 3B rectal. T3N1bM0. 5.2 4.5 4.3 cm. Lymphs: 6 x 4 mm, 8 x 6, 5 x 5
7/17-9/17: Xeloda radiation
7/5: CEA 2.7; 8/16: 1.9; 11/30: 0.6; 12/20 1.4; 1/10 1.8; 1/31 2.2; 2/28 2.6; 4/10 2.8; 5/1 2.8; 5/29 3.2; 7/13 4.5; 8/9 2.8, 2/12 1.2
MSS, KRAS G12D
10/17: 2.7 2.2 1.6 cm (-90%). Lymphs: 3 x 3 mm (-62.5%), 4 x 3 (-75%), 5 x 3 (-40%). 5.1 CM from AV
10/17: LAR, Temp Ileostomy, Path Complete Response
CapeOx (8) 12/17-6/18
7/18: Reversal, Port Removal
2/19: Clean CT

CrossfitChick1980
Posts: 46
Joined: Wed Nov 25, 2015 9:40 pm

Re: Worried -genetic results are in. KRAS MSS

Postby CrossfitChick1980 » Thu Nov 08, 2018 10:07 am

My husband is KRAS, MSS with condone 12/13 mutation. He is still alive and kicking but going through a rough spot right now. He has been on almost every chemo with the greatest success on Folfiri+Avastin. He stayed on maintenance 5fu and Avastin for over 2 years before a pesky spot showed up in his liver again. He is currently being treated with theraspheres to the liver and lonsurf. Currently trying to nurse him back to health!
Caregiver to DH dx with Adenocarcinoma of Small Intestine
Mar14- Small Bowel Resection (dx @31)
May14-Oct14: Folfox
Apr15- Liver mets
Jun15- Xeloda/Oxalyplatin
Oct15- Folfiri/Avastin
Dec15- Liver Mets, lymph nodes shrinking.
Apr16- Liver mets gone! lymph nodes stable
Jun16- Avastin/Xeloda (MSS, KRAS)
Jul16- Maintenance Chemo
Jun18- Cancer is back in liver
Sep18- Lonsurf
Oct18- Therasphere txment (failed)
Dec18- Folfiri/Avastin
Dec 22 2018- He is no longer suffering- My Love is sleeping in Peace


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