Rectal case from Hong Kong (UPDATE: Lung Met, NRAS MUTATED, FOLFOX+Avastin)

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NHMike
Posts: 2555
Joined: Fri Jul 21, 2017 3:43 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, KRAS MUTATED, PLZ HELP!)

Postby NHMike » Mon Sep 04, 2017 8:02 am

veckon wrote:It's good to have hope. Believe me, I want to be cured. But there is no evidence that it cures anything on its own. It just makes your immune system able to identify and kill cancer so long as it doesn't mutate and you still respond. There are a handful of examples of remission thanks to pembrolizumab and related drugs. Remission is not the same as cure. It's easy to forget the breakthrough trial for MSI-H and pembrolizumab was only conducted in 2015. Maybe we can make claims about a cure (in combination with surgery) after survival is studied over the next decade. When doing chemotherapy, do you assume a complete pathological response is the most likely outcome of such a treatment? Of course not, at least not if you are realistic and understand probability. Point in fact, more people have complete pathological responses with chemo/radiation alone (> 0) than with pembrolizumab alone (0).


Perhaps I should use the term remission. Though I do think that we will get to cures at some point. Right now we have better survival rates and the technology to make a lot of progress in determining how mechanisms work and, perhaps how to develop new drugs. There's far more to research, though, than there are researchers or money for those researchers. I toy around with the idea of learning this stuff a lot better than I know right now because I find it interesting and it's a real growth area for employment. But I'd have to essentially get an MS in the area and that's hard to do at my age. My son has textbooks where I could polish up on the basics of biology and genetics but it would be a lot of work for me and I'm already busy with my current job and dealing with cancer.

I don't take for granted that my course of treatment will work. I hope that it works and will find more in two or three weeks but I've read enough stories to know that things can take a turn for the worse. It may be that we need better protocols too - but affordability may be a big part of that problem.
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

veckon
Posts: 131
Joined: Thu Jul 27, 2017 7:44 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, KRAS MUTATED, PLZ HELP!)

Postby veckon » Mon Sep 04, 2017 8:11 am

NHMike wrote:
Perhaps I should use the term remission. Though I do think that we will get to cures at some point. Right now we have better survival rates and the technology to make a lot of progress in determining how mechanisms work and, perhaps how to develop new drugs. There's far more to research, though, than there are researchers or money for those researchers. I toy around with the idea of learning this stuff a lot better than I know right now because I find it interesting and it's a real growth area for employment. But I'd have to essentially get an MS in the area and that's hard to do at my age. My son has textbooks where I could polish up on the basics of biology and genetics but it would be a lot of work for me and I'm already busy with my current job and dealing with cancer.

I don't take for granted that my course of treatment will work. I hope that it works and will find more in two or three weeks but I've read enough stories to know that things can take a turn for the worse. It may be that we need better protocols too - but affordability may be a big part of that problem.


I agree with you about the long-term curative potential of immunotherapy when combined with surgery and targeted cancer vaccines. But we’re just not there yet, but the seeds of potential are there. I know that if I survive this I would love to use my experience (I have an academic and professional background in math, physics, and software) to tackle these problems.
27 yo male
Metastatic rectal cancer diagnosed 12/16
Liver metastases and peritoneal carcinomatosis
Lynch syndrome, MSI-H
Failed liver resection 3/17
FOLFOX6 12/16 - 05/17
Keytruda 5/17 - present
@Memorial Sloan Kettering

NHMike
Posts: 2555
Joined: Fri Jul 21, 2017 3:43 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, KRAS MUTATED, PLZ HELP!)

Postby NHMike » Mon Sep 04, 2017 8:17 am

I'd guess that you can see where biology is moving more and more to computational models and I think that we'll eventually get to the promises of computational chemistry but we're really early innings right now. Something like Next-Gen Sequencing is a huge step forward in being able to analyze tumors to look for patterns and percentages. I really don't know anything about drug development but I do think that the pathologists and researchers do work with the drug companies in identifying targets. And we have CRISPR-CAS9 as a tool for researchers to identify additional targets. So we have some pieces to make further progress and we're driving down the costs of making progress. But, from what I've seen, anything in biology is slow because there are so many discrete branches. We can come up with broad rules in physics, mathematics and computer science but bio is just so much harder.
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

Mercy110
Posts: 118
Joined: Wed Aug 16, 2017 12:13 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, KRAS MUTATED, PLZ HELP!)

Postby Mercy110 » Mon Sep 04, 2017 9:46 am

Maia wrote:Hi, Mercy
In a rush here, so replying your PM in the open forum, in case it helps others

--My mum's genetic test shows KRAS mutation. Practically speaking, I know there are certain kinds of targeted drugs are not useful on her right now.

With a KRAS mutation, Erbitux and Vectibix can't be used. There are certain data that certain submutation of KRAS, G13D, might respond to them, anyway, but you need further testing. Having or not having the mutation adds one more line of therapy, that might last months, but doesn't affect the curable/non curable status.

--Does it mean that my mum cant be cured unless the mutation being cured? (Even Avastin is not curing the disease but just pushing the deadline? And I am wondering even though we remove tumors in her body through surgery, is it very likely to develop again as the mutation is still in place...Am I right?)

You are right on every point. Even if the chemo or the monoclonal antibody, Avastin, make her NED --not evidence of disease--, that lasts during a while. It might be months or one year, but the cancer reappears. The KRAS mutation is not important, regarding that --it is what happens with all the unresectable metastatic CRC. Those who are metastatic and had one/two spots in the liver, or one/two on the lungs and had a resection, have durable responses; they are ''cured'', some people say. Still, we see recurrences.

KRAS mutation is not relevant, at the present, for immunotherapy. What it is important is knowing if a patient is MSS --like 85 per cent of CRC-- or MSI-high --the rest. For those MSI-high, immunotherapy *monotherapy* (that is, on its own, like Keytruda, Opdivo, etc.) might mean ''durable'' response --as cautiously veckon said. For the rest, the MSS, being unresectable, the treatment that offers some chance of durable response is a *combination* immunotherapy trial (many times, an anti PD-1) PLUS ''something else''. That would be also the path for the MSI-high who doesn't respond to immunotherapy on its own, or progress on it.
In my signature, there is a link to a trial finder for MSS --most trials are for MSI-high, too-- that our fellow Tom Marsilje (DK37, in this forum) curates.
I already mentioned one trial that you have available in HK.
On the other hand, the best clinical data that we have of immunotherapy working for MSS is for a cohort where most were KRAS mutant. See literature in the thread from your HK colleague: viewtopic.php?f=1&t=58371

I hope I didn't make many mistakes... Hang in there!


Thanks for your reply and I am sorry to bother you again.
I understand that it is very difficult for stage4 patients to be completely cure. Even they are now, cancer may reappear. So what you mean is that KRAS mutation is not important becoz metastatic CRC can only be temporarily NED. Is that it? Still, I guess KRAS mutation is worse than wild type as it is more difficult to dual with?
Once the mutation is here than it is impossible to be cure, just buying time, even if it is not metastatic CRC, right?
I just wish her to be NED, but it seems almost impossible right now...
My Mum (age 56), NRAS-mutate Q61R (from HK)
2017-05: Surgery with stoma. T4N1M0. Stage3C. Xeloda Only. Increasing CEA. CT: Multiple lung nodules. Stage4.
2017-09: 85% FOLFOX + Avastin, stable CT
2018-03 to 05: Folfox Allergy, Folfiri (with Avastin since Oct)
2019: CEA:178, started Irinotecan+Zaltrip+TS-1, 25 times radio with xeloda
2020: CEA up, Stivarga for 6 months
2021: CEA up, 7L O2 and 24-hour morphine, on pc care
At peace 2021.4.14

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Maia
Posts: 2443
Joined: Fri Aug 24, 2012 8:00 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, KRAS MUTATED, PLZ HELP!)

Postby Maia » Mon Sep 04, 2017 10:02 am

The mutation is important to know because it has immediate clinical impact --treat with a certain drug or not. But it is not really a mutation that usually makes the cancer more aggressive. On the other hand, being KRAS practically exclude her from having other mutation that many times can be more aggressive --a certain type of BRAF mutation.
Tumours have usually several mutations. A wider panel, for most patients, find other mutations: P53, PICK3A, PTEN, ATM, APC, the mentioned BRAF and KRAS. A mutation is not ''cured'', fixed: a treatment can exploit that mutation, potentially. Think of it like a path that the cancer uses to escape; if you know about it, you can target it, or at least try.
For immunotherapy, experimental, we can't exactly say what KRAS mutation does mean, in terms of response, but there are data saying that KRAS mutation might respond better to a combination of anti PD-1 plus a MEK inhibitor --like cobimetinib, trametinib, etc. Those are not approved for CRC, and the combinations are in clinical trials.
Also, there is known now that in even in MSS patients, when there are many, many mutations, there are higher chances to response to immunotherapy as if the patient were MSI-high.
So, what at some point in time seems like a worst, might be exactly what makes the cancer more treatable.

For a metastatic CRC, unresectable, keeping low tumour burden during as much as time as possible, with good quality of life, might be more important than being NED, IMHO.

Mercy110
Posts: 118
Joined: Wed Aug 16, 2017 12:13 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, KRAS MUTATED, PLZ HELP!)

Postby Mercy110 » Tue Sep 05, 2017 7:45 am

Maia wrote:The mutation is important to know because it has immediate clinical impact --treat with a certain drug or not. But it is not really a mutation that usually makes the cancer more aggressive. On the other hand, being KRAS practically exclude her from having other mutation that many times can be more aggressive --a certain type of BRAF mutation.
Tumours have usually several mutations. A wider panel, for most patients, find other mutations: P53, PICK3A, PTEN, ATM, APC, the mentioned BRAF and KRAS. A mutation is not ''cured'', fixed: a treatment can exploit that mutation, potentially. Think of it like a path that the cancer uses to escape; if you know about it, you can target it, or at least try.
For immunotherapy, experimental, we can't exactly say what KRAS mutation does mean, in terms of response, but there are data saying that KRAS mutation might respond better to a combination of anti PD-1 plus a MEK inhibitor --like cobimetinib, trametinib, etc. Those are not approved for CRC, and the combinations are in clinical trials.
Also, there is known now that in even in MSS patients, when there are many, many mutations, there are higher chances to response to immunotherapy as if the patient were MSI-high.
So, what at some point in time seems like a worst, might be exactly what makes the cancer more treatable.

For a metastatic CRC, unresectable, keeping low tumour burden during as much as time as possible, with good quality of life, might be more important than being NED, IMHO.


Thank you. I understood now. My mum has met onco today and she suggested us to use chemo and Avastin. So we temporarily choose Avastin with Folfox. This is the first time we use Oxa and 5FU coz we have just used xeloda before. Not sure what the side effects rely are but I have seen lots of people here using Folfox so it is properly ok...
My Mum (age 56), NRAS-mutate Q61R (from HK)
2017-05: Surgery with stoma. T4N1M0. Stage3C. Xeloda Only. Increasing CEA. CT: Multiple lung nodules. Stage4.
2017-09: 85% FOLFOX + Avastin, stable CT
2018-03 to 05: Folfox Allergy, Folfiri (with Avastin since Oct)
2019: CEA:178, started Irinotecan+Zaltrip+TS-1, 25 times radio with xeloda
2020: CEA up, Stivarga for 6 months
2021: CEA up, 7L O2 and 24-hour morphine, on pc care
At peace 2021.4.14

Mercy110
Posts: 118
Joined: Wed Aug 16, 2017 12:13 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, NRAS MUTATED, FOLFOX+Avastin)

Postby Mercy110 » Thu Sep 07, 2017 5:02 am

UPDATE

Today I have receive the lab report from the onco, and it saids my mum has NRAS mutation instead of KRAS. I know basically it represents the drugs still cannot be used on her, but I am just hoping if there are any differences between KRAS and NRAS that makes NRAS mutation "better". She is going to receive a new form of chemo on coming Sat, which is Folfox plus Avastin. As she is going to be admitted in hospital for 2 nights and we are unable to be with her whole day according to the rules of public hospital, we are just wondering is there anything we can do to make her feel better from the side effects...
God bless!
My Mum (age 56), NRAS-mutate Q61R (from HK)
2017-05: Surgery with stoma. T4N1M0. Stage3C. Xeloda Only. Increasing CEA. CT: Multiple lung nodules. Stage4.
2017-09: 85% FOLFOX + Avastin, stable CT
2018-03 to 05: Folfox Allergy, Folfiri (with Avastin since Oct)
2019: CEA:178, started Irinotecan+Zaltrip+TS-1, 25 times radio with xeloda
2020: CEA up, Stivarga for 6 months
2021: CEA up, 7L O2 and 24-hour morphine, on pc care
At peace 2021.4.14

NHMike
Posts: 2555
Joined: Fri Jul 21, 2017 3:43 am

Re: Rectal case from Hong Kong (UPDATE: Lung Met, NRAS MUTATED, FOLFOX+Avastin)

Postby NHMike » Thu Sep 07, 2017 5:41 am

If you can't be there, then maybe just be available via phone if she needs or wants to call.
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


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