Hello All - First Post Please Share Your Thoughts

[DeeMeee]

Hello All,

Reading for days, first post now. Your wealth of experience is like a waterfall of information. Thank you all, for sharing your moments.

My brother had a few weeks of stomach issues, primary sent him for CT Scan, two days later he is in surgery. My signature hopefully gives the key information.

Signet ring cell adenocarcinoma
Stage 3c pT4bpN2b

MSI High

Tell me if Immunotherapy, as first line is what you think.

Please share your thoughts with me.

Thanks
Take Care
Dee

[Green Tea]

...Please share your thoughts with me...

Hi DeeMeee, and welcome to the forum.

Yes, I have some thoughts, but before I post anything I need some information. You said in your signature:

4/21 next CT/PET surgeon consult, start of decided treatment.

What I need to know is

• When will the surgeon consult take place?
• When is the decision on treatment due to be made and who will make it?
• Will your brother have any say in what treatment will be chosen?

Please post a message as soon as possible so that we can know how much time is left before the decision must be made.

This is important because there are not many days left in April, and if you say that the start of the decided treatment will be sometime in 4/2021 then we need to know right away whether there is any point in making suggestions about type of treatment.

Thank you.

[DeeMeee]

Hi Green Tea,

CT PET scan is Wed 4/28
Surgeon consult is Thu 4/29

Fulfox was to begin On Mon 5/3

The plan was, surgeon was to see if he felt my brother was ready ASAP for debunking surgery and EPIC, if not scan 2 months in from fulfox start, with reevaluate to see if it got him to surgical point or continue with 2 month scans and reevaluates.

His surgeon from initial hospital, called last Saturday (was scheduled for Mediport that Monday 7:30am)to say he received Foundation One results and was cautiously optimistic with hope seeing he is MSI H. He advised to contact oncologist immediately with that result, and speak before Mediport placement, because with immunotherapy he would not need the port at this time.
There was no reaching med oncologist directly for guidance, my brother decided to postpone.

We were very surprised to hear from the nurse, that after reviewing the FOne report I sent over, oncologist was still leaning towards FULFOX, and wanted the Mediport rescheduled. Decision would depend on if surgeon said he was ready now for surgery,then it would Immunotherapy, or would need time to see if chemo got him to where surgery was an option. My brother did not like that response, he felt the opportunity for Immunotherapy was positive news. I asked why it wouldn’t be first line, and the reason his oncologist felt that way. Our research all pointed to, best results as first line before chemo, and go to chemo if results are not effective.

My brother is now scheduled to meet his oncologist first thing Mon 5/3, with all available results address his concerns and make an educated decision on his plan. I questioned how long will this delay start of treatment. He is now scheduled tentatively for Immunotherapy for Mon 5/3 after the treatment plan meeting.

I appreciate and eagerly await your thoughts.

Thanks
Take Care
Dee

[Green Tea]

Hello again,

I'm having trouble deciphering some parts of your signature. Would you be able to help clarify a few things? Your current signature is:

SIGNATURE
sister to 57yo m
3/21 2 wks sto issues CT sb blockage highly susp of ileal adenocarcinona mass w nodal mets & perit carcinomatosis
3/21 lap R hemi innum mes nod perit nod 9.5 cm ileocecal mass. Remvd mass, apnx,12i sm int 6i l int nodules CEA 7.8
3/21 Path:Stage 3c pt4b pn2b signet ring cell carcinoma prly diff close mrg 18/28 nodes
4/21 CEA 3.9 FOne MSI H TMB 13mb KRAS G13D NRAS wt
4/21 Enc Rules out UGI prmy: bpy:mild peptic duodenitis
4/21 next CT/PET surgeon consult, start of decided treatment.

Please post another message soon clarifying what you mean by innum mes nod perit nod .

Thank you.

PS: I think you may eventually need to create an expanded signature (in a separate NewTopic post) to explain all of the components of the diagnosis/staging. Your brother has a rather complicated diagnosis that needs to be set in the proper context. Your current signature is almost up to the maximum 512 character limit, but it has a lot of abbreviations that need to be expanded and clarified.

[catstaff]

Probably "innumerable mesenteric nodules and peritoneal nodules," correct?

This is very reminiscent of what my mother had years ago, though hers was carcinomatosis of unknown primary (appendix/cecal would have been a good suspect, though). Fortunately the treatment options are much better now. (My mother died of a stroke, probably from throwing a clot due to the cancer's effect on clotting.)

[Green Tea]

Thanks to catstaff for the insights and to DeeMeee for the timeline clarification.

I will work on collecting my thoughts over the next day or so with the goal of posting a reply that addreses your concerns. In my reply I will explain what I think is missing, incorrect, or unexplained in the signature, and I will then give my thoughts about the immunotherapy issue.

Until tomorrow ... Hasta mañana ...

[DeeMeee]

Please post another message soon clarifying what you mean by innum mes nod perit nod .

Hi Green Tea,

Yes, it was difficult trying to fit as much as I could, so I tried abbreviating in some spots, I’m sorry it was a poor job.
That line was : innumerable mesenteric nodules and peritoneal nodules
LVI

I appreciate your continued deciphering, and your thoughts.

Thanks
Take Care
Dee

[DeeMeee]

Probably "innumerable mesenteric nodules and peritoneal nodules," correct?

This is very reminiscent of what my mother had years ago, though hers was carcinomatosis of unknown primary (appendix/cecal would have been a good suspect, though). Fortunately the treatment options are much better now. (My mother died of a stroke, probably from throwing a clot due to the cancer's effect on clotting.)

Hi Catstaff,

I am very sorry for your loss of your mom. I lost my mom to duodenal cancer in 2007. It does feel more promising to see the different options these days, yet the chemo plan that is being presented is the same as my mom’s was, FULFOX, so a mix of tried and true with new and innovative, isn’t it.

Your clarification is exactly correct, thank you for stepping in with it. My brother is technically unknown origin, leaning towards colon with the appendix a close second. The hope is they will be better certain after this week.

I just want the first step to be the right step forward.

Thanks
Take Care
Dee

[Green Tea]

Hi Dee,

Here is my version of your brother's expanded signature and timeline. You can make changes and corrections as you see fit and then use the draft as a point of departure in your discussions with doctors next week.

The NCCN recommendations for 1st line therapy for Stage IV metastatic cases having mets amenable to surgery are given in the last section below. The last three regimens in the list are immunotherapies. The rest are either standard , traditional cyto-toxic chemo regimens or targeted therapy combo regimens.

The regimens are listed generally in the order in which the FDA approved them for use in colorectal cancer. That's why FOLFOX is at the top of the list and all of the immunotherapies are at the bottom of the list.

Good luck with your consultations with the doctors next week!

EXPANDED SIGNATURE (DRAFT) - Subject to additions/corrections

• March 2021 - Symptoms: 2 weeks of stomach issues,
• March 2021 - CT scan (pre-surgery): small bowel blockage, highly suspicious of ileal adenocarcinona, mass with nodal mets & peritoneal carcinomatosis.
• March 2021 - CEA: 7.8 ng/ml (pre-surgery)
• March 2021 - Type of Surgery: Laparoscopic right hemicolectomy + appendectomy + partial ileoectomy
  
  (innumerable mesenteric nodules & peritoneal nodules, 9.5 cm ileocecal mass)
  Removed mass, removed appendix, removed 12 inches of small intestine, removed 6 inches of large intestine; removed 28 lymph nodules.
• March 2021 - Post-surgery pathology: pT4b pN2b pMX
  
  • Tumor type: Signet ring cell carcinoma
  • Location of primary: Undetermined; possibly ileo-cecum; possibly colon; possibly appendix.
  • Size of tumor: 9 cm.
  • Grade: G3: poorly differentiated
  • Margins: Close surgical margins
  • Lymphovascular Invasion (LVI) - present
  • Perineural Invasion (PNI) - not mentioned
  • LN (Lymph Node Involvement): 18/28 nodes positive
• March 2021 - Final Staging
  • TNM Code: T4bN2bM1c
  • Stage: Stage IV-C, with mets to the peritoneum
• April 2021 - CEA 3.9 ng/ml (post surgery)
• April 2021 - Foundation One testing:
  
  • MSI Status: MSI-H
    
  • KRAS Status: KRAS G13D mutant
    
  • NRAS Status: NRAS wild type (normal; no mutations)
    
  • BRAF Status: (not mentioned)
    
  • TMB (Tumor Mutation Burden) = 13 mutations/mb, i.e., a medium-to-high TMB
• April 2021 - Endoscopy rules out upper gastrointestinal primary: Biopsy: mild peptic duodenitis
• April 28, 2021 - Next CT/PET
• April 29, 2021 - Surgeon consult
• May 3, 2021 - Oncologist consult
  
  
  Review of NCCN's 1st-line treatment options for metastatic Stage IV-C colorectal cancer. Reference:
  NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Colon Cancer
  VERSION 2.2021 Dated January 21 2021. 198 pp. 1,029 references, page 32:
  
  
  1. FOLFOX ± bevacizumab, OR
     
  2. CAPEOX ± bevacizumab, OR
  3. FOLFOX + (cetuximab or panitumumab) -->(for KRAS/NRAS/BRAF WT and left-sided tumors only), OR
  4. FOLFIRI ± bevacizumab, OR
  5. FOLFIRI + (cetuximab or panitumumab) -->(for KRAS/NRAS/BRAF WT and left-sided tumors only), OR
  6. FOLFOXIRI ± bevacizumab, OR
  7. nivolumab(Opdivo) ± ipilimumab(Yervoy), OR
  8. pembrolizumab(Keytruda) [preferred]* --> (for dMMR/MSI-H only)
• May 3, 2021 - Start of decided treatment

[DeeMeee]

Thank You Green Tea,

Yes, I researched the chemotherapy treatment combinations available. My brother had that discussion plan with his medical oncologists, first and second opinion, at his initial appointments.

Immunotherapy was presented as a strong “IF“ option, pending results of next generation sequencing assessment for actionable mutations. That was forefront with both oncologists I thought, but perhaps more so with first oncologist in retrospect?

Yes, mutations seemed low to me for my brother to be designated MSI H. However Foundation One, did add in not remembering exact without referencing the report in hand, but approximately 23 additional mutations. They were noted as: “variants of unknown scientific significance at this time, that may become clinically meaningful in the future”, so perhaps that weighed in on the analysis.

I believe the signet ring cell identification, and the aggressive nature, is possibly what his medical oncologist is focused on, and could that be the weighing factor in leaning towards FULFOX first line instead of Immunotherapy. I haven’t found much where signet ring cell and immunotherapy is specifically measured with results. Seemingly because most I find, controlling the progression is not promising, when it is the driving force of the cancer. This is my fear.

Thank you again, Green Tea, I will look to revising the signature information. I placed as much as I could for this moment, with the intention to truncate it to minimal, as most signatures are, at a later date.

Anyone who has been presented with first line immunotherapy possibility, at a similar disease and progression point as my brother, please share your experience.


Wishing A Healthiest & Positive Week Ahead To All !
Dee

[boxhill]

Here's my unvarnished opinion, based on my own experience of being diagnosed with Stage IV MSI-H cancer with KRAS mutation. I am not a doctor.

Cases that are MSI-H with a KRAS mutation, like your brother and me, are LESS LIKELY to respond to FOLFOX; however, they are MORE LIKELY to respond to immunotherapy. Of the immunotherapy options I would prefer Keytruda, because Yervoy has nasty side effects that can persist. (Which is one reason why O+Y only includes 4 infusions of Y) My oncologist now prefers to use Keytruda if possible for this reason.

Being MSI-H is akin to winning the CRC Stage IV lottery. When I was diagnosed, a mere three years ago, immunotherapy was not approved as first line therapy, and unavailable as such outside of trials, for which I did not qualify. (No detectable masses after surgery.) Only after enduring 12 rounds of useless folfox and experiencing progression in the hepatic lymph nodes, detected by MRI, was I allowed to start Keytruda. I was NED by my first scan 4 months later, and remain so.

If I were your brother, I would **demand** to be put on Keytruda or O+Y, and I would find another oncologist if this one refused. This, unless the oncologist could offer absolutely convincing scientific evidence that your brother's case doesn't warrant it. And at that I would require a second opinion from a major cancer center, which could be obtained by sending your records and pathological samples.

[boxhill]

BTW, from what I recall, my genetic report from Dana-Farber looked a lot like your brother's, with most mutations classified as of undetermined effect. Yet it also reported it as being more mutated than 95% of the samples examined by them.

I never had Foundation One testing, although I did have testing primarily to determine if I had Lynch Syndrome, which thankfully I do not. It did find ATM, a mutation which significantly increases the likelihood of breast cancer.

[DeeMeee]

Here's my unvarnished opinion, based on my own experience of being diagnosed with Stage IV MSI-H cancer with KRAS mutation. I am not a doctor.

Cases that are MSI-H with a KRAS mutation, like your brother and me, are LESS LIKELY to respond to FOLFOX; however, they are MORE LIKELY to respond to immunotherapy. Of the immunotherapy options I would prefer Keytruda.

Being MSI-H is akin to winning the CRC Stage IV lottery.

If I were your brother, I would **demand** to be put on Keytruda or O+Y, and I would find another oncologist if this one refused. This, unless the oncologist could offer absolutely convincing scientific evidence that your brother's case doesn't warrant it. And at that I would require a second opinion from a major cancer center, which could be obtained by sending your records and pathological samples.

Hello Boxhill,

Truth be told, when I searched Keytruda here, your posts stood out to me. I read as many of your posts, as my eyes allowed that night. Your success with Immunotherapy gave me more confidence, in my feeling that my brother’s best hope for good results, is with Keytruda, and as a first line, not after FULFOX, as my reading has indicated it’s success diminishes greatly as
second or third line treatment.

I am so thankful you saw my post, and took the time to respond. Sharing your experience, is helping so many, your decision to do so is appreciated. I cheer on and send good wishes and prayers, for your continued slaying of this beast.

I want to put my advocating for my brother’s best care, in perspective, and not only push for what I feel is his best path in treatment. If I’m missing an important piece, that I’m not realizing is more significant than my non medical eye can see, I’m willing to understand it.

There is also an EPIC over HIPEC surgical plan, if he is now or can become in short time a candidate for surgery.

That’s what my brother and I have discussed, he wants his best treatment plan, and needs to be strongly convinced why Immunotherapy is not it.

He is at a top 5 cancer center in the country, he wants their expertise and total package. He also wants to be part of the decision in his plan, which is where his little sister speaks loudest so he is heard.

Thanks
Take Care
Dee

[Green Tea]

... If I’m missing an important piece ... I’m willing to understand it...
There is also an EPIC over HIPEC surgical plan, if he is now or can become in short time a candidate for surgery.

Hi Dee,
It looks like your brother has already done comprehensive research in preparation for his surgeon consult and has a tentative plan in place. He's probably "up to his ears" in reading material right now, though, and can't assimilate much more, but If he does need more thoughts or references in the EPIC / HIPEC area you could always post a new message on this board requesting the kind of information he is still looking for.

There is at least one person on this forum who has had HIPEC and who has logged in here just in the past week or so. Maybe if you post a special request in this topic area you could get a reply from someone here with past HIPEC experience.

Chemotherapy for intraperitoneal use: a review of hyperthermic intraperitoneal chemotherapy (HIPEC) and early post-operative intraperitoneal chemotherapy (EPIC)
https://jgo.amegroups.com/article/view/5503/5760

American Society for Peritoneal Surface Malignancies
https://aspsm-members.blogspot.com/

Some HIPEC topics on Colon Talk (2008 - 2016)
https://coloncancersupport.colonclub.com/viewtopic.php?f=1&t=53554&p=424674#p424674

HIPEC references in PubMed
https://pubmed.ncbi.nlm.nih.gov/?term=hipec

Intraperitoneal immunotherapy: historical perspectives and modern therapy (2016)
https://www.nature.com/articles/cgt201649

Peritoneal Surface Disease Severity Score as a predictor of resectability in the treatment of peritoneal surface malignancies (2014)
https://www.americanjournalofsurgery.com/article/S0002-9610(13)00738-1/fulltext

[catstaff]

My mother died before even irinotecan was approved in the US; oxaliplatin was a few years later. She got only 5FU. They determined the origin was colon though I'm not sure how they did that a quarter century ago. Maybe they were able to do the protein assays then.

This sounds like a complicated case with little clinical data for the specific combination he has. My guess is they are aiming for surgery. Good luck!