Why you really need to know your tumor genetics

[boxhill]

https://www.onclive.com/web-exclusives/ ... p7sGQX0dU8

[AmyG]

I found out today that I'm wild for everything. KRAS BRAF and two others, as well as low probability for MSI-H.

I'm trying to educate myself and see my oncologist again before starting any treatment. I'm assuming that's what I wanted? No mutations?

In other news, CEA is up to 71. Was 24 in December.

[rp1954]

You need to get as much lab data as possible on Day 1, including genetic, to avoid losses, present and future. Medicine often does a poor job of this on an asset basis e.g. if they were managing a multimillion dollar technical asset to avoid larger loss, or to maximize yield. The rationing aspects of "standard" are in direct conflict with asset management on a technical basis. Especially as prices decline, the liquid biopsy option should be available on the first day of diagnosis, despite a potential for marketing abuses.

We have encountered a lot of data losses in medicine. Any patient receiving neoadjuvant treatment is likely to lose important data if maximum Day 1 testing is not done. Chemo, radiation, even immune treatments destroy or alter recoverable tissue, so liquid biopsy may be the only chance for early genetic data. Likewise, inoperable patients frequently don't have large tissue sample recoveries and likely will be delayed in follow ups.

Also, extra blood and tissue panels are pregnant with partial information that can be very useful, or life saving. Most doctors seem oblivious to these uses and possibilities, beyond standard tests or their offered treatment options. Almost everywhere we go, providers, both as institutions and individuals try to control, or at least strongly influence, our decisions and information. A lot of this has social and economic dimensions. I often wonder how many will people die years sooner because some SOB interfered with $100-$200 worth of initial data (at Medicare type prices).

[hopie]

This is a great article, boxhill, thanks for sharing it!

I found out today that I'm wild for everything. KRAS BRAF and two others, as well as low probability for MSI-H.

I'm trying to educate myself and see my oncologist again before starting any treatment. I'm assuming that's what I wanted? No mutations?

In other news, CEA is up to 71. Was 24 in December.

And AmyG, sorry about your CEA but, yes, you want them to be not-mutated! Kras wild type (aka no mutation) means you have more options in terms of targeted therapy (EGFR inhibitors, in particular). Unlikelihood for MSI-H means immunotherapy is probably not an option.

[AmyG]

Hey thanks! Not overly upset about my CEA rising. I mean, I have a pretty large liver met, so it makes plenty of sense that it's going up. I know being pregnant can also impact it as well. Same for my liver function values. Those were raised, but well within the normal limits of someone in their third trimester.

I'll see my oncologist again 4/3. I should be getting a better plan of action then. Everything is still up in the air with exactly what is happening when, but should tentatively get a port, chest, abdomen and pelvic CT as well as another MRI of my liver before any chemo starts. Folfox and Avastin for 4 cycles, then 2 cycles without Avastin, rescan, liver resection, then 6 more cycles. Maintenance chemo after all that, I think she said for 6 months?

I'm ready to get this show on the road so I can be cancer free.

[NHMike]

I found out today that I'm wild for everything. KRAS BRAF and two others, as well as low probability for MSI-H.

I'm trying to educate myself and see my oncologist again before starting any treatment. I'm assuming that's what I wanted? No mutations?

In other news, CEA is up to 71. Was 24 in December.

NGS tests for all of the mutations in one run. Doing point mutation tests seems inefficient unless the cost of doing point tests is really far below testing for everything.

[boxhill]

I got the KRAS, BRAF, and dMMR results with my initial pathology report.

Full genetic testing was done later.

[ginabeewell]

Hey thanks! Not overly upset about my CEA rising. I mean, I have a pretty large liver met, so it makes plenty of sense that it's going up. I know being pregnant can also impact it as well. Same for my liver function values. Those were raised, but well within the normal limits of someone in their third trimester.

I'll see my oncologist again 4/3. I should be getting a better plan of action then. Everything is still up in the air with exactly what is happening when, but should tentatively get a port, chest, abdomen and pelvic CT as well as another MRI of my liver before any chemo starts. Folfox and Avastin for 4 cycles, then 2 cycles without Avastin, rescan, liver resection, then 6 more cycles. Maintenance chemo after all that, I think she said for 6 months?

I'm ready to get this show on the road so I can be cancer free.

If you are wild type, why are they choosing to use Avastin versus an EGFR inhibitor like Vectibix which shows better results for patients like you? Vectibix is no picnic for side effects but it has really been effective in my case so curious whether you've discussed.

[NHMike]

I got the KRAS, BRAF, and dMMR results with my initial pathology report.

Full genetic testing was done later.

It looks like the approach is to look for the dangerous ones and if it's not one of those, then to run the full test.

One of these days, the price of full testing will come down to the cost of an individual test.

[AmyG]

If you are wild type, why are they choosing to use Avastin versus an EGFR inhibitor like Vectibix which shows better results for patients like you? Vectibix is no picnic for side effects but it has really been effective in my case so curious whether you've discussed.

I honestly have no idea, that's just what was discussed Wednesday. When I see her next month, I will be asking her a laundry list of questions! Vectibix is the one that usually causes the rash, right?

[ginabeewell]

I honestly have no idea, that's just what was discussed Wednesday. When I see her next month, I will be asking her a laundry list of questions! Vectibix is the one that usually causes the rash, right?

Yes, unfortunately. But best practice is to start meds to address prophylactically 2 weeks ahead of time, something I didn't do originally, but which seemed to help after my seven week chemo break. Once you get it, very tough to get rid of it. I think oncologists like to see that reaction because conventional wisdom is "the rash means it's working" but my onc has said that is not necessarily true. So if you discuss and go down this path, ask for docycycline and steroid cream well BEFORE you start chemo!

My onc has explained that EGFR inhibitors do not work on non-wild-type, but that they tend to perform better than Avastin for wild type.

[Pyro]

I’m Kras wild, I used both Avastin and Vectibux (and erbitux but had an allergic reaction to it) with much success. Good luck!

[Pyro70]

My onc has explained that EGFR inhibitors do not work on non-wild-type, but that they tend to perform better than Avastin for wild type.

Amy sorry to butt in here. Centuximab (EGFR) is now only recommended in first line if you have a left sided tumor. Your signature didn’t say the location of your tumor but that may be why they will start with VEGF (Avastin). Even for left sided, in the US it’s not uncommon to use Avastin first and save centuximab for second line. In EU there is a strong preference for centuximab first. I think either way is fine.

My bigger question based off your signature would be why are they not jumping straight to liver resection? Is it inoperable? If it is currently inoperable i would think to use FOLFOXFIRI to try and downstage the tumor and hopefully make it resectable.

[Pyro70]

A few more thoughts:
With a 4.7cm tumor they are likely afraid that there may be some occult metastases that should be controlled with chemo before surgery. Using FOLFOX perioperatively (3 months or less before and again after surgery) is likely a good idea. However, I would question if you should use Avastin before surgery. I believe the up-to-date guidelines say don’t use avastin prior to hepa metasectomy due to the potential liver toxicity. I would suggest reading up-to-date’s article on managing hepametastases in Colon cancer and questioning the oncologists if they veer from those reccomendations.

[AmyG]

Amy sorry to butt in here. Centuximab (EGFR) is now only recommended in first line if you have a left sided tumor. Your signature didn’t say the location of your tumor but that may be why they will start with VEGF (Avastin). Even for left sided, in the US it’s not uncommon to use Avastin first and save centuximab for second line. In EU there is a strong preference for centuximab first. I think either way is fine.

My bigger question based off your signature would be why are they not jumping straight to liver resection? Is it inoperable? If it is currently inoperable i would think to use FOLFOXFIRI to try and downstage the tumor and hopefully make it resectable.

Hey Pyro!

My tumor was left sided, sigmoid colon was damn near totally obstructed. As for why not starting with liver resection, I was under the impression they wanted it smaller to be sure they can obtain clear margins. I believe my met is in segment 6 or 7. Due to being pregnant, no one has really wanted to deal with me much.

As soon as I'm given the all clear from OB, oncology will basically start over with me. CT of chest, abdomen and pelvis, MRI of the liver, restaging and presumably changing any plans based on what they find.

I want to be sure they are treating me appropriately, so if there's a list of questions I should be asking at my next appointment let me know!!