My Blood Biopsy Story (From Voxx66's News from Dr appt post)

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DK37
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My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby DK37 » Sat Jun 27, 2015 8:19 am

Hi Everyone,

I noticed a discussion on Blood Biopsies as a part of Voxx66's recent post "News from Dr appt" (thank you Phoung for drawing my attention to it!). Since this might be a topic of general interest & since that post covered a number of different topics, I figured I would respond with a new post instead of hidden in a pretty long the comments thread.

Here is my personal experience and opinion on them: Although they are still working through some issues e.g. in terms of the best use (as highlighted in a recent MIT Tech Review article), I believe this technology will transform cancer diagnostics within the <5 years. In particular in monitoring (as a first pass) for new cases as well as recurrence since it is so non-invasive and non dangerous (it is just a simple blood draw). There are also potential uses to guide treatment choice (like a standard biopsy does e.g. KRAS). There are also certain specialized cases (I was one) where the test could answer a diagnostic question much easier/safer than a current method.

In broad terms the way they detect cancer is that cancer cells shed their DNA and it floats in the blood stream. The tests look for clinically validated tumor genetic markers that are not present in normal cellular DNA. Previously it was a needle in the haystack problem - but current technology is so sensitive it can pick up these small signals and computationally remove them from the pile of noise of normal DNA. Currently I think it is approx. $5000 per test but there are more & more clinically certified companies coming on board, so between competition & volume increases, prices per test should come down.

My personal experience:
In my case, it appeared that I had recurrence in two places: lymph nodes along my spinal cord (too dangerous to biopsy) and lung mets which were not easy to reach (without safety risk) with a needle biopsy (e.g. one is directly next to my heart). We were pretty sure they were CRC but there was a question mark. My CRC does not shed CEA, so the CEA test is useless for me.

Then things got interesting... I was also diagnosed with melanoma last January. At that point two things happened: 1.) I became much more genetically interesting and 2.) There became a question mark whether the lung spots were CRC or melanoma (which is important since they have different treatments).

Thankfully I had access to a n=1 personal clinical trial where I could be extensively genetically profiled, without costing anything (to me).

What they did (so far - multiple new more in depth experiments are still on going):
1.) I had standard genetic marker tests already for my primary CRC tumor (prior to FOLFOX & FOLFIRI chemo when I was Stage 3) to serve as benchmark for the liquid biopsy
2.) I got standard genetic marker tested on my melanoma primary tumor to serve as benchmark for liquid biopsy
3.) I then got the liquid biopsy done.
Results:
1.) There were ZERO signs of the melanoma markers. So the lung spots are not melanoma and at least to the point of test detection limits, it indicated I had been surgically cured of melanoma
2.) There were the EXACT same tumor markers as seen in my primary CRC tumor. Except for one. A had a new mutation (SMAD4) show up. This mutation correlates with tumor resistance to 5-FU therapies.

Overall:
The test made perfect sense for me. We were then almost 100% sure the lung spots were CRC. The only major (known) new mutation made sense too - since my stage IV recurrence by definition had to come from Stage 3 tumor cells resistant to my Stage 3 FOLFOX and FOLFIRI chemotherapy - indicated by the blood biopsy to be based upon a SMAD4-resistance mechanism. So in my case, I believe the technology worked perfectly.

Current next steps:
1.) I had a lung RFA done this week. During it, they extracted biopsy material. This biopsy material will be used to verify the liquid biopsy results.
2.) They have already performed Whole Exome sequencing of my primary CRC and Melanoma tumors (https://en.wikipedia.org/wiki/Exome_sequencing) to see if they are interrelated at all at the genetic level. With this week's fresh biopsy tissue, they are going to do whole exome sequencing of my lung mets to compare at that level the genetic changes since the original 2012 CRC primary tumor.
3.) They'll be performing Whole genome sequencing and RNA-sequencing on my lung mets to potentially set me up for a personalized immunotherapy trial. I can't go through standard clinical trial routes since most of them exclude patients with more than one type of cancer within 3-5 years.

A final use I am planning to use blood biopsies for (JUST PUBLISHED: Siravegba, G. et al. Nature Medicine (2015): http://www.nature.com/nm/journal/vaop/n ... bal=remove
I am currently responding to cetuximab. But like all targetted agents, I know that via natural selection/evolution - I will become resistant. A recent paper highlighted how you can use serial blood biopsies to monitor in real time for the appearance of resistant mutations upon cetuximab treatment (e.g. KRAS). The same paper kept monitoring patients after cetuximab resistance occurred and in a number of them, resistance disappeared after the evolutionary pressure of cetuximab treatment ended - at which point they were restarted on cetuximab and the tumors once again responded. Depending on the resistance mutation identified, e.g. this type of treatment paradigm may indicate the use of a EGFR & MET-inhibitor co-therapy cocktail.

That I believe is the wave of the future...I am glad & very thankful to currently be a mouse for these genetic studies to help figure out best uses for future standard clinical practice - as well as therapeutic paths forward for me! ;)

SO that is my story & my take on blood biopsies - turned into a longer post than I planned, hope you made it this far! :)

-DK
Last edited by DK37 on Sat Jun 27, 2015 10:52 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

ilivebyfaith
Posts: 116
Joined: Mon Oct 27, 2014 8:18 am

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby ilivebyfaith » Sat Jun 27, 2015 8:35 am

Thank you for this post. Very useful. I am just thankful that detection and medication on CRC are gaining medical advances.
Carer to DH 42, DX MCRC IV mets liver,lungs 9/9/14;Wild type, KRAS/NRAS nonmutant; Folfox 3x Folfox+Vectibix 3x CTscan, liver mets gone, colon tumor 12 to 15cm, lung mets inc (31-R, 19-L); Change: FOLFIRI + erbitux 6x, colon and liver clear, progress in lungs. Change: folfirinox + Avastin 12x, lung metastasectomy, molecular profiling, folfiri + erbitux, progression, will be switched to stivarga PRAISE GOD FOR HIS FAITHFULNESS!

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Annemiek
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Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby Annemiek » Sat Jun 27, 2015 8:53 am

i'm so taking this story to my oncologist!!
Thank you for posting,

Annemiek

43 yr mum of a girl aged 7
10/2014 coloncancer stage IIIc
11/2014 HIPEC, tumor removed + 12 positive out of 60 ln
hysterectomy, abdominal lining partly removed
Peridonitus, stoma fitted, 6 abcesses drained in abdomen
MSS, kras
3/2015 Folfox, someones playing kill Bill inside me
9/2015 finished 12 rounds,
First scan results: NED!!!!!!!!!
4/2016 ct scan: NED!!!
7/2016 ultrasound: NED
10/2016 cr scan: NED
5/2017 ultrasound: NED 2,5 yrs!
CEA 8/2017 1.8 stable.
CT scan 11/2017 NED! 3 yrs
CEA 1.9

Cancerwithcancer
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Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby Cancerwithcancer » Sat Jun 27, 2015 9:24 am

Thank you for all the details! I am going to revisit the testing of tumor ( pre-tx) and bring up the blood DNA. I was "talked" out of sending off the tumor for testing related to the fact that the treatment pathways stay the same. ( unless KRAS). I did mention that knowing which chemotherapy works best toward the tumor provides one with a mental fortitude to keep going through Chemo. Your resistance to 5FU proves my point. I am learning a lot. Thanks for helping me advocate for myself and the treatment of CRC.
46yo Mom of 2 (13 & 16)
DX: 12/22/14 CEA .6
CT/MRI 8cm rectal mass with lymph node involvement
RAD/Xeloda 6wks : 2/20/15
PET: 3/23/15
APR (colostomy for life) 4/23/15
5 of 20 lymph nodes positive
CT of chest-5/21/15
Wound VAC/hyperbaric tx 6/1/15
FOLFOX started 6/13/15

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DK37
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Location: San Diego

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby DK37 » Sat Jun 27, 2015 9:32 am

Cancerwithcancer wrote: Your resistance to 5FU proves my point. I am learning a lot. Thanks for helping me advocate for myself and the treatment of CRC.


I should point out that my blood biopsy suggests that I may be resistant to 5-FU via a SMAD4 mutation but this is a statistical correlation which makes "logical sense" in my data's particular case - but it has not been proven conclusively...

Just wanted to add that disclaimer. It doesn't change my viewpoint of this exciting technology though!
-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

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

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby Ceebo » Sat Jun 27, 2015 10:43 am

Such interesting and valuable information. Thanks so much for sharing! You are a pioneer!!!
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

Val*pal
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Location: Metro Detroit, Michigan

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby Val*pal » Sat Jun 27, 2015 11:30 am

Wow! I am impressed!

Thanks for sharing this information. As you said, I bet in the not too distant future these blood draws will be able to inform at levels we didn't dream possible. It's very encouraging.

I've always wondered if my husband's thyroid cancer, which was discovered shortly after his colon cancer, was related in some way to the colon cancer or vice versa. His oncologists always just shrugged and said they didn't know, but one onc did indicate she wondered the same thing. I know that a few studies have indicated there may be some sort of connection, but there is no definite link. Maybe Danny was just incredibly unlucky and had two separate types of cancer.
DH dx'ed May '11, age 62
Jul '11: resection Stage IV
10/11: 6 mo Folfox
8/12:thyr canc, surg/tx
2/13: peri mets
2/13: Firi/Avas
6/13: Ok
8/13: break
10/13: Lung, peri, mets
10/13: Firi/Erb
1/14: Erb Fail; spread
5/14: Tx stopped
6/20/14: At rest

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bitchslapped
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Location: PNW/USA

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby bitchslapped » Sat Jun 27, 2015 1:53 pm

From what I'm reading, one company is researching a finger prick form of liquid biopsy, another through urine analysis. Maybe one day it will be a matter of finger pricks & urine sticks. That would certainly bring the costs down. All the better for early detection & staying on top of mutations for patients in treatment. Articles suggest there are a lot of companies jumping on the biobank bandwagon.

DK37 wrote:3.) They'll be performing Whole genome sequencing and RNA-sequencing on my lung mets to potentially set me up for a personalized immunotherapy trial. I can't go through standard clinical trial routes since most of them exclude patients with more than one type of cancer within 3-5 years.


Everybody's story matters in educating the rest of us. Thanks for sharing yours. Hope that potential for personalized immunotherapy trial becomes your reality. Look forward to updates HERE :) .


Best Wishes

BS
DSS,35YO,unresect mCRC DX 7/'14,lvr,LN,peri,rib
FOLFOX+Avstn 4 Rnds d/c 10/'14
Stent 9/'14
FOLFIRI+Avstn 10/'14
Gone From My Sight 2/20/15
Me:garden variety polyps + precancerous polyp
Carergver x2 DH,DM dbl occupancy,'03-'10
DH dx 47YO mCRC,'04-'07 fried x HAI
DM dx CC 85YO,CC,CHF,stroke,dementia,aphasia

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DK37
Posts: 510
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Location: San Diego

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby DK37 » Sat Jun 27, 2015 2:04 pm

bitchslapped wrote:
DK37 wrote:3.) They'll be performing Whole genome sequencing and RNA-sequencing on my lung mets to potentially set me up for a personalized immunotherapy trial. I can't go through standard clinical trial routes since most of them exclude patients with more than one type of cancer within 3-5 years.


Everybody's story matters in educating the rest of us. Thanks for sharing yours. Hope that potential for personalized immunotherapy trial becomes your reality. Look forward to updates HERE :) .


Best Wishes

BS


Hi BS- Right now my immunotherapy plans are still at the brainstorming, dreaming & crossing-fingers stage. I PROMISE, this group will be very much kept in the loop if anything ever starts approaching reality!! As I said, I'm forced to be "creative" for the next 2.5 years due to that stoopid melanoma excluding me from most clinical trials... But who knows, necessity is the mother of all invention ;)

-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

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Voxx66
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Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby Voxx66 » Sat Jun 27, 2015 2:07 pm

Thanks very much for the great info. I'll post what they find once my results are in. Also - I think the reason the companies are waiving the fee in my case is that Siteman is a big cancer center and they are trying to show the ways these tests can be useful.
DX and resect 10/2012 age 46
Stage IIa CRC
liver mets both lobes 8/2013
CEA 28
FOLFOX + Avastin 8/26/13 3 rounds
Folfox only 3 rds + rd 8
platelets low round 7,9,10 5FU only
1/14 CEA 1.0 y90
5fu
10/14 mets lung and peri
1/15 Folfiri

JDinNC
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Location: Murphy, N.C.

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby JDinNC » Sun Jun 28, 2015 1:33 am

I guess this is why the nurse said I Couldn't be part of a melanoma trial because I had colon cancer. Still waiting for my test result regarding my melanoma that a company was doing for free.
61 y/o female @ DX...........
T3N0M1
6/13 DX- stage 4
Sigmoid colon cancer.
One met to lung
7/13 colon resection
8/13 lung resection
FOLFOX with avastin
7/17 four years....NED

MELANOMA
63 y/o @ DX
6/15 stage 2a
7/15 surgery on arm
7/15 NED
4/16 recurrance
5/16 remove metastasis from back
5/16. Started immunotherapy
8/16 discontinue treatment

JENNJ
Posts: 115
Joined: Tue Feb 17, 2015 8:00 pm

Re: My Blood Biopsy Story (From Voxx66's News from Dr appt post)

Postby JENNJ » Sun Jun 28, 2015 5:20 pm

Thank you so much for all the valuable information! My Dads just had a liquid biopsy done at MSKCC and I'm really intrigued by all this science.
Thank you again!!
Katy


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