Genetic mutations

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Peregrine
Posts: 99
Joined: Tue Mar 01, 2022 1:18 am

Patient Navigator and "CRC Buddy" programs

Postby Peregrine » Tue May 10, 2022 10:14 pm

Lo-oc -

It seems to me that you might benefit from having contact with a Patient Navigator, or a Nurse Navigator.

Does your hospital have such a program? If not, you could try applying for a colorectal cancer "buddy" from one of the organizations that offer buddy programs:
.
  1. Colorectal Cancer Alliance, Patient Navigator Program

      "Call our free Helpline at (877) 422-2030 to speak with a Certified Patient & Family Support Navigator. We’re here to support and guide you through your screening and colorectal cancer journey.

      Our certified Patient & Family Support Navigators are here to connect you with a vetted Buddy who has been through a similar diagnosis to offer meaningful and useful advice that helped them get through colorectal cancer."

    CCA Buddy Program application
    https://ccalliance.tfaforms.net/77

      "... I actively participate in a buddy program with the Colon Cancer Alliance. The program allows me to share my story with newly-diagnosed patients and offer them hope. This is one of the most rewarding things I do..." Marty Andrews (Colon Club) - Reference: https://www.colonclub.com/our-stories/colon-cancer/marty-andrews
  2. The Colon Club's buddy program: The Colon Connection

    Link to apply for a Colon Connection "buTTy":
    https://www.colonclub.com/programs-support/colon-connection
    .

Lo-oc
Posts: 21
Joined: Sat Mar 26, 2022 4:40 pm

Re: Genetic mutations

Postby Lo-oc » Thu May 19, 2022 9:50 am

follow up on my liver enzymes situation - I had a consultation with the liver surgeon today. Although the rise in liver enzymes does not overly concern him, he is in agreement with the oncologist on not putting more strain on the liver right now. He was pleased with the shrinkage in the two mets, and is planning on operating in two weeks - he does not feel more chemo right now is the way to go, so I am assuming chemo treatment scheduled for next Tuesday will be canceled. The liver surgeon is planning on doing the surgery laparoscopically, completely resecting the larger met, and using ablation on the smaller one which is very close to a major vein. The met is under 1 cm, (.9) so he will use ablation on that, which he says is just as effective as resection of a smaller met. both of this mets are in the right lobe posterior.
After recovery from surgery, I will start radiation for 5 weeks (the cold-rectal surgeon said this will determine how he prcoeeds, the rectal tumor shrunk width wise after my initial chemo, but the radiation is the only think that may make it shrink from the AV.
Genetic testing was ordered on the original tumor, so waiting on those results.
Is there anything I should consider at this point (still wondering about a second opinion?) It's worrying not to have any more chemo at this point (I believe that is what the oncologist will choose to do with the liver surgeon on board) -chemo feels like a crutch to me, I worry about disease spread without, but you have to be off it to go through some of these procedures, and of course, there will be more chemo after, hopefully my liver will allow it !l Thanks........
2/22 - Dx with stage 4 rectal cancer 4cm on/1cm from AV - age 60
T4, poorly diff., EMVI + MSS
3/22 - CT/MRI 2 liver mets 2.1 cm and 1 smaller close to hepatic vein
3/22 Infusion - plan 6 treat. Folflox 6, liver res., chemoradiation, rectal surgery 6 more cycles Folfox
5/5 - CT/MRI, lung nodules no change, liver lesions red. to 1.1 and .9cm, rectal tumor/suspicious lymph node red..

Nor Cal
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Joined: Sun Dec 06, 2020 8:18 pm

Re: Genetic mutations

Postby Nor Cal » Thu May 19, 2022 11:37 am

I believe a 2nd opinion is a good decision for everyone. They'll likely confirm your current treatment plan, and if so, should give a little more confidence in the approach (at least worked that way for me). Plus I think it's good to be on people's radar in case you need to discuss your case further with them in the future.

I've gotten opinions from 3 oncologists, 3 colorectal surgeons, 2 liver surgeons, 2 interventional radiologists, and have been referred to 2 hepatologists I've yet to meet with.
Dx June 2020, stage IV, w liver mets in both lobes. M, age 50. Right-sided colon tumor. BRAF mutation. CEA 120. TMB 5%
July 2020 - Present: 32 cycles chemo (All the various 5-FU regimens)
December 2020 - February 2021 Y90 Radioembolization, Chemoembolization x2

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Peregrine
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Joined: Tue Mar 01, 2022 1:18 am

Re: Genetic mutations

Postby Peregrine » Thu May 19, 2022 12:50 pm

Lo-oc wrote:... Anticipating a liver resection soon, do I need to ask to have the genetic testing done?

Lo-oc wrote: ... Is there anything I should consider at this point (still wondering about a second opinion?) ........

Lo-oc -
One thing you might do is to ask the liver surgeon if he is planning to send the large met out for any kind of genomic testing after it has been resected. Or perhaps your oncologist might have an opinion on this, too. It might be interesting to find out if the metastatic tissue in the liver has the same mutation profile as the tissue biopsied from the original primary tumor. Presumably they would have the same profile, but you never know... Sometimes strange things happen and then they take you by surprise.

Lo-oc
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Joined: Sat Mar 26, 2022 4:40 pm

Re: Genetic mutations

Postby Lo-oc » Thu May 19, 2022 1:30 pm

Thank you, I will definitely ask about this
2/22 - Dx with stage 4 rectal cancer 4cm on/1cm from AV - age 60
T4, poorly diff., EMVI + MSS
3/22 - CT/MRI 2 liver mets 2.1 cm and 1 smaller close to hepatic vein
3/22 Infusion - plan 6 treat. Folflox 6, liver res., chemoradiation, rectal surgery 6 more cycles Folfox
5/5 - CT/MRI, lung nodules no change, liver lesions red. to 1.1 and .9cm, rectal tumor/suspicious lymph node red..

Rock_Robster
Posts: 690
Joined: Thu Oct 25, 2018 5:27 am
Location: Brisbane, Australia

Re: Genetic mutations

Postby Rock_Robster » Thu May 19, 2022 7:28 pm

Hi Lo-oc, thanks for the update. It sounds like a very sensible plan to me. I’m glad the liver surgeon isn’t worried and is happy to proceed to resection now - that’s great news! I’m always happier if the person actually doing the surgery makes the call on how much chemo, as they know what they need in terms of margins etc. (and preserving enough liver function).

One question - do you know what type of ablation they’re proposing? Reason I ask is I understand that the more common thermal ablations (like RFA and cryoablation) tend to be less effective when performed close to major veins and arteries, due to the heat sink effect (where the blood flowing essentially carries the heat away from the tumour and can result in an under-treated margin). My surgeon was never comfortable ablating my tumour near my hepatic vein for this reason, and we went for a wedge resection instead. There are other techniques which may be less susceptible to this effect (eg IRE, MWA) that might be worth discussing as alternatives.

Good luck with it all,
Rob
40M Australia
2018 Dx RC, 12cm high
G2, EMVI, LVI. 4 liver mets
pT3N1aM1a Stage IVa. MSS NRAS G13R
CEA: Nov-18= 14; then <2. Jun-22: 5
11/18 FOLFOX x6
3/19 Liver resection
5/19 25x pelvic IMRT radiation
7/19 ULAR & ileo (reversed)
8/19 Liver lesion
8/19 FOLFOX, FOLFOXIRI, FOLFIRI x7
12/19 Liver resection
NED
11/21 Liver met & celiac node; 2-3 tiny lung things
12/21 PVE
3/22 Nodal spread & 3 liver mets. Lymphadenectomy
4/22 Liver SBRT
6/22 Liver looks good. Still some small lung things

Lo-oc
Posts: 21
Joined: Sat Mar 26, 2022 4:40 pm

Re: Genetic mutations

Postby Lo-oc » Thu May 19, 2022 7:49 pm

I do not know what type of ablation he will be doing. I did not realize there were different methods. Great question I will direct to him, thank you for that.
2/22 - Dx with stage 4 rectal cancer 4cm on/1cm from AV - age 60
T4, poorly diff., EMVI + MSS
3/22 - CT/MRI 2 liver mets 2.1 cm and 1 smaller close to hepatic vein
3/22 Infusion - plan 6 treat. Folflox 6, liver res., chemoradiation, rectal surgery 6 more cycles Folfox
5/5 - CT/MRI, lung nodules no change, liver lesions red. to 1.1 and .9cm, rectal tumor/suspicious lymph node red..

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Peregrine
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Joined: Tue Mar 01, 2022 1:18 am

Re: Genetic mutations

Postby Peregrine » Fri May 20, 2022 1:31 am

Lo-oc -

Another couple thoughts ...

  • For a second opinion you could try to find a good Naturopathic Doctor (ND) near you who could give you some alternative ideas on how to tackle your liver problem and how to change your lifestyle and diet to reduce systemic inflammation in your liver, since systemic inflammation is one of the things that promotes rapid growth of micro-metastases. See this post for more details. I think there are probably some good ND's near your location. It's worth it trying to find a good ND near you who can explain things to you and give you good tips on how to reduce systemic inflammation. Also, he can give information on biomarkers of systemic inflammation, like hsCRP, and others, that you might want to monitor on a regular basis.

    How to Find a Naturopathic Doctor Near You
    https://naturopathic.org/?
    .
  • I think you should also re-read Rock_Robster's list of red flags, because you really need to get a good understanding of what all your options will be in the future, especially if the post-op chemo fails and you need to advance to 2nd-line or 3rd-line treatment options. You need to have your team explain to you the range of options available to you. And this might even include eventual participation in an MSS clinical trial if one is available for your type of tumor mutation status.

    Late Stage MSS Colorectal Cancer Clinical Trials Finder
    https://fightcolorectalcancer.org/resources/late-stage-mss-crc-trial-finder/
Last edited by Peregrine on Sat May 21, 2022 10:25 am, edited 1 time in total.

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Peregrine
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Re: Genetic mutations

Postby Peregrine » Sat May 21, 2022 12:01 am

Lo-oc wrote:... Is there anything I should consider at this point (still wondering about a second opinion?) ........

Lo-oc -

As others have already said, getting a second opinion is very important, especially for patients initially staged as Stage IV "inoperable, incurable". Even if you have to get 2 or 3 additional second opinions it may be worthwhile making the effort and enduring the extra expense. Actually, it could be a bit risky to "put all of your eggs in one basket" and depend on only one doctor's opinion, because this single opinion might turn out to be narrow, biased or uninformed.

You can read the story of one such Stage IV liver met patient here. I encourage you to take the time to read the article.

Lo-oc
Posts: 21
Joined: Sat Mar 26, 2022 4:40 pm

Re: Genetic mutations

Postby Lo-oc » Sat May 21, 2022 6:14 am

Thanks Peregrine. I totally agree with what you’re saying regarding being proactive re 2nd opinion. Right now I am an “early” stage IV if there is such a thing, two Mets to the liver that were initially operable, the liver surgeon wanted to get them smaller with chemo, which has happened. The oncologist has gone with what seems to be standard treatment 6 cycles Folflox, liver resection, radiation, rectal resection, possible reversal and 6 more cycles of Folflox. Given the good response to 3 cycles of folflox I will have the liver resection in two weeks. The liver surgeon told me that 1 in 4 will have no more liver Mets, so I know that reoccurrence will probably happen From everyone’s advice here on this really helpful forum, this is what I need to find out - what’s the plan if a..b.. or c occurs going forward.
I will be paying out of network going to the major cancer hospitals in Boston or NY, if that’s what I have to do I will, have a large deductible right now….
I’m waiting on the genetic profiling of the tumor. Having some issues with the oxi pushing up the liver enzymes, so this is why I am questioning the oncologist, the liver surgeon seems in agreement with the oncologist to resect now and not stress out the liver anymore. I am going to inquire about the ablation as the one met is close to a major vein. There’s a lot to take in with this, lots of information and overwhelming . I am benefiting from everyone’s experiences on here. Thank you
2/22 - Dx with stage 4 rectal cancer 4cm on/1cm from AV - age 60
T4, poorly diff., EMVI + MSS
3/22 - CT/MRI 2 liver mets 2.1 cm and 1 smaller close to hepatic vein
3/22 Infusion - plan 6 treat. Folflox 6, liver res., chemoradiation, rectal surgery 6 more cycles Folfox
5/5 - CT/MRI, lung nodules no change, liver lesions red. to 1.1 and .9cm, rectal tumor/suspicious lymph node red..

Lo-oc
Posts: 21
Joined: Sat Mar 26, 2022 4:40 pm

Re: Genetic mutations

Postby Lo-oc » Wed May 25, 2022 4:05 pm

I'm assuming bad news - my tumor profile came back. I have a RAD51D mutation. I've been told by the radiation oncologist this is very rare. I do not find it on this forum in a search. It is both in the rectal tumor and my blood. They are sending me for genetic counseling, there is a propensity for ovarian and breast cancer with this mutation.

It was explained to my that everyone has two copies of this RAD51D - one of my mine is mutated. They think that because of that, my liver enzymes shot up so quickly because my body was more vulnerable to the toxicity of the chemo . they also think that my rectal tumor and liver mets were more responsive to the oxi in the Folflox because I only have one functioning copy. I have not had a chance to go over with oncologist yet as this came in yesterday afternoon. I do not know what this means for me getting treatment, I think because of my mutation the tumors will be responsive to platinum based chemo, but I do not know if I can tolerate the chemo. Does not sound promising.

Laparoscopic liver resection set for June 6th, and radiation to start right after, so no chemo until after that's wrapped up. I do not know if that is the way to go or not. This is so overwhelming....
2/22 - Dx with stage 4 rectal cancer 4cm on/1cm from AV - age 60
T4, poorly diff., EMVI + MSS
3/22 - CT/MRI 2 liver mets 2.1 cm and 1 smaller close to hepatic vein
3/22 Infusion - plan 6 treat. Folflox 6, liver res., chemoradiation, rectal surgery 6 more cycles Folfox
5/5 - CT/MRI, lung nodules no change, liver lesions red. to 1.1 and .9cm, rectal tumor/suspicious lymph node red..

MadMed
Posts: 146
Joined: Sun May 02, 2021 5:52 pm
Location: Massachusetts

Re: Genetic mutations

Postby MadMed » Wed May 25, 2022 6:53 pm

Sorry you have this weirdness, but from what I’m reading, it’s not a worse prognosis. It just seems that you are more susceptible for a cancer: https://www.mskcc.org/cancer-care/patient-education/about-mutations-rad51d-gene

You may have treatment options that work well https://www.facingourrisk.org/info/hereditary-cancer-and-genetic-testing/hereditary-cancer-genes-and-risk/genes-by-name/rad51d/cancer-treatment

It seems that you are getting the right guidance in terms of the genetic counseling. They should tailor your treatment accordingly instead of the hammer that most get like FOLFOX etc..

It’s not only rare but also a new thing, so there may be good outcome here. MSI for example didn’t respond well to chemo and now they have immunotherapy. Hopefully this also is true for you.
52M DX: RC lower rectum, guessing now 2cm from AV 4/27/2021
T3N0M0 adenocarcinoma with signet ring cell features
Tumor size 30mm
Tumor grade: G3
Baseline CEA 1.0
MSI status: MSS pMMR
Started Folfox 5/12/2021
Switched to FOLFIRINOX from session 2. 8 rounds total.
CT+MRI tumor contained shrunk 80%, no spread to other organs.
CRT started xeloda + 28 days Radiation 9/27-11/04
NED as of 4/06 CT/MRI/sigmoidoscopy
On W&W 04/06/2022

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Peregrine
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Re: Genetic mutations

Postby Peregrine » Thu May 26, 2022 8:47 pm

Lo-oc -

There are several things I find puzzling about your case. I can't say that any of these things are wrong or questionable, but only that they seem to me to be out-of-the-ordinary, or unconventional. That's all. Here is one of the things I find puzzling. I hope you don't mind the detail. I'm just trying to make sense out of your case and put the facts together in a meaningful context.

  1. You have had genetic testing done for hereditary cancers, but how did this all come about? As far as I know, genetic testing for hereditary mutations is not ordinarily done unless there is evidence for cancers in your family line.  So, my first question is this: Did they ever have you provide information on the history of cancer in your family? Did they have you fill out a form like the one below? 

    http://www.cancer.net/sites/cancer.net/ ... nnaire.pdf

    If they didn't ask for this information, then what justification did they have for doing the expensive panel of genetic tests that discovered the RAD51D mutation, both in your blood and in your tumor tissue? And what reason did they give your Insurance Company that such a panel was needed?

    One of the tests that covers KRAS, NRAS, BRAF as well as the  RAD51D mutation is the expensive160-gene panel:


    This panel also tests the 6 genes that underlie MSI/MSS testing, so this is what could have confirmed your MSS test result.

    Why did they not just do the much simpler, quicker, and much cheaper test for the most common colorectal cancer mutations, e.g, KRAS/NRAS/BRAF/mutations plus MSI testing? And why did they not do this testing before starting you on a chemo regimen? This smaller subset of genomic tests is what is mentioned in the NCCN guidelines as the main prerequisite for treatment planning in Stage IV metastatic colorectal cancer.  The guidelines also mention the need to test CEA level before the start of any treatment.The NCCN guidelines don't seem to mention anything at all about the RAD51D mutation in the colorectal cancer context.  The RAD51D mutation is mainly linked to ovarian cancer, as I understand it, and there is hardly any research at all on RAD51D in the colorectal cancer context, so I would say that knowing that you have this mutation is not of much help in planning CRC treatment because of lack of applicable research findings on relative efficacy of various available treatments for colorectal cancer.

    If they did find a RAD51D mutation, then it must have been because they were searching specifically for any hereditary mutations related to cancer.  Do you know why they were looking for hereditary mutations?

    -----
    For your information, RAD51D is one of several genes in the group of genes called ' Homologous Recombination Repair (HRR)'  genes.  There are drugs already approved for treating some cancers having HRR gene mutations. Specifically, there is the drug Lynparza (olaparib) for breast cancer, and Rubraca (rucaparib) for ovarian cancer, but apparently these drugs are not approved for treating colorectal cancers or colorectal metastases. But there may come a day when some researchers, thinking "out of the box", may want to use drugs like this off-label in the colorectal cancer context. In fact, there are some clinical trial studies at Dana Farber Cancer Center in Boston right now that are testing drugs like this in other types of cancers.

    If you are going to ever get a second opinion on your case you might want to give Dana Farber serious consideration because they have some high-level expertise there in HRR mutations like RAD51D.

    Also, when you are meeting with your oncologist you might want to ask him what he knows about about PARP inhibitor drugs (i.e., "Poly (ADP-ribose) polymerase" inhibitors. PARP inhibitors, like Rubraca (rucaparib), are only approved now for ovarian cancer, prostate cancer, peritoneal cancer, fallopian tube cancer, peritoneal cancers, etc., but not for colorectal cancer, as far as I can tell.

    .

Lo-oc
Posts: 21
Joined: Sat Mar 26, 2022 4:40 pm

Re: Genetic mutations

Postby Lo-oc » Fri May 27, 2022 6:30 am

Thank you for the links Mad Med, most of the information I'm finding are in relation to this mutation as it pertains to ovarian and breast cancer treatment, and not how it might be impacting my treatment as a CRC patient.

Peregrine - thank you again for so many helpful resources. After my inquiry to the onc. about tumor profiling he ordered two different testings. There was original testing after colonoscopy showing showed no loss staining for DNA mismatch repair proteins (MLH-1, PMS-2, MSH-2, MSH-6 ), unlikely MSI.
The GI ordered a C-Reactive protein blood test prior to colonoscopy which is not the CEA, that CRP test came back normal. I'm not sure if the onc, was assuming CEA might not be a tumor marker for me, but it should have been ordered.

Additional Testing for PD-L1 = <1% staining at any intensity HER-2 = 2+ FISH was negative for HER-2 in tissue sampled.

Other testing:Variant Allelic Fraction (Tumor) Allelic Fraction (Normal)
RAD51D R206Ter 48% 50%
Somatic variants detected in the tumor:

Variant Allelic Fraction
TP53 R175H 25%
KRAS G12V 17%
I'm well aware the variant's in this testing are not good - the KRAS G12V was probably the worst KRAS to have. I'm not sure why he ordered the extensive testing, my insurance paid for it - I was adopted so had no familial history going into this, maybe that's why? I will get the genetic counseling, more for how this could affect my daughters ( don't think it will affect my son) for ovarian and breast cancer. I've had a hysterectomy in late 2020 (ovarian cyst - benign, ovarian fibrothecoma which is a benign rare ovarian tumor )(surprised they didn't see this rectal tumor on MRI then, even though they weren't looking for that ),
The radiation oncologist brought up the RAD51 as a possible explanation for both the responsive tumor shrinkage after my scans and also the quick response to toxicity to my liver, I am concerned that 1, it limits the chemo that will work for me, and 2. will I be able to tolerate it, 3. does my oncologist have any experience treating people with CRC with this mutation if it affects how I react to the Folflox.
I don't get much feedback from the onc., I just don't think he is telling me things that I shouldn't worry about NOW, but I look at everything pretty negatively, and I look to have all the possible scenarios laid out, good, bad, and ugly.
I'm not sure if the genetic components of my disease will be the driving factor for reoccurrence and short survival, or if it's the amount of disease currently in my body, (which for now is resectable ) but it seems every time there is something new being thrown at me that doesn't sound good, I feel going through treatment is pointless and very discouraged. I was looking at MSK in NYC as a place to seek out a second opinion, Dana Farber is doable to. There are so many good cancer hospitals in NYC and Boston which I can get to both. It's not an affordable situation with insurance so....I think getting a consultation anyway is necessary.
2/22 - Dx with stage 4 rectal cancer 4cm on/1cm from AV - age 60
T4, poorly diff., EMVI + MSS
3/22 - CT/MRI 2 liver mets 2.1 cm and 1 smaller close to hepatic vein
3/22 Infusion - plan 6 treat. Folflox 6, liver res., chemoradiation, rectal surgery 6 more cycles Folfox
5/5 - CT/MRI, lung nodules no change, liver lesions red. to 1.1 and .9cm, rectal tumor/suspicious lymph node red..

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Peregrine
Posts: 99
Joined: Tue Mar 01, 2022 1:18 am

Re: Genetic mutations

Postby Peregrine » Fri May 27, 2022 8:47 am

Lo-oc wrote:... I don't get much feedback from the onc., I just don't think he is telling me things that I shouldn't worry about NOW, but I look at everything pretty negatively, and I look to have all the possible scenarios laid out, good, bad, and ugly...

Lo-oc -

Thank you for posting the detailed reply. This gives me a better idea of what you are dealing with.

I follow the philosophy, "Plan for the worst, but hope for the best", so I, too, like to have as much data available as possible, both good and bad, so that I can lay out all possible scenarios ahead of time. Since you say that you are having difficulty getting complete information from your oncologist, I think this is a good reason to look elsewhere for second opinions so that you can have a more complete account of your health situation.

On another topic, I still think it would be a good idea to ask your liver surgeon if he could send samples of your resected metastasis out for testing, just to see if the met has the same mutation profile as the primary tumor.

That's about all for now ...


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