MSI negative what’s next?

[Daddysdaughter]

My fathers biopsy pathology came back MSI negative. I’m heartbroken because treatment options are slim. Just need to vent.

[Tonyland]

Oh no. Well what next steps did you all discuss?

[Tonyland in reply to Tonyland]

Wait, you all still have the immunotherapy option.

[Chiquis]

🙏💛

[FCoffey]

Get a second opinion! Always, but especially in cases involving newish technology like DNA sequencing.

The Johns Hopkins GAITWAY program has a good reputation. It stands for Genetic Alteration In Tumors With Actionable Yields. It is currently run by Dr, Josh Lauring

hopkinsmedicine.org/news/ar...

That article includes a story about a prostate cancer patient reported as MSI-negative. They ordered additional pathology tests and found the patient was actually MSI-positive.

The article includes a quote: "Others can do this, but not everyone does it well.”

These decisions are too important not to get second and sometimes even third opinions.

Good luck to you and your father.

[Daddysdaughter in reply to FCoffey]

Wow! Thank you for that information!!

[whatsinaname in reply to FCoffey]

I agree with your suggestion that one should ALWAYS get a second opinion. Especially with a "newer" technology.

Very good point. To be religiously followed.

Thanks and best regards.

[Daddysdaughter in reply to FCoffey]

This might be a silly question, but how do I go about calling John’s Hopkins and asking for them to just retest? Doesn’t he need to be a patient or on a trial?

[FCoffey in reply to Daddysdaughter]

The only silly questions are the ones that are never asked. It's a good question.

I don't have direct contact information. I would suggest calling Dr. Lauring's office and asking how to have your father's biopsy reviewed by the GAITWAY program. Or you could try browsing around the website in the article I linked and try to find contact info that way.

Believe me, you aren't the first patient who will have asked those questions. I don't know the procedure, but there certainly is a process. Hopefully they will be caring and helpful as they guide you through it.

[Nyquist5]

Please forgive my ignorance but does this mean he is exempt from certain forms of treatment due to being MSI negative? Sending prayers from one worried daughter to another!

[ctarleton in reply to Nyquist5]

See:

fda.gov/newsevents/newsroom...

Charles

[Daddysdaughter in reply to Nyquist5]

I’m learning as well. It’s my understanding and correct me if I’m wrong but most trials that are testing treatments specific to mutations need that to qualify for the trial. Not all but some. There are a handful + of trials available with medications that might help. At this point i don’t want to have my father try a medication if it already has low probability of being effective with his Cancer. I just want him to try the best option with a team of people that have seen this type of NEPC before.

[FCoffey in reply to Daddysdaughter]

On the bright side, a few years ago this type of screening was not available. Your father would have gotten "standard of care," which is medical speak for "same D#!n thing we do to everyone."

With this new information, it may be possible to steer your father away from treatments that are even more unlikely to benefit him than normal. The track record for many standard prostate cancer treatments is poor, with many standard approaches having less than 10% chance of adding an extra year of life after 10 years.

All of the treatments have life-altering side effects. Information that keeps your father away from treatments that are unlikely to help him is a benefit.

[Hidden]

City of Hope is LA. UCLA is doing a 177Lu/PSMA trial that is quite interesting.

I would say for sure call them on the phone.

clinicaltrials.gov/ct2/show...

[Daddysdaughter in reply to Hidden]

Interestingly COH is affiliated and my fathers MO is aware of this option but didn’t recommend it. He is going to meet with Dr. Posadas at Cedars and if he is unable to get into this trial then possibly dual immunotherapy..

[Hidden in reply to Daddysdaughter]

OK, if you have a good option, that's of course wonderful.

What trial is Dr Posadas at Cedars involved with?

ncbi.nlm.nih.gov/pmc/articl...

Here is what he is listed as running

clinicaltrials.gov/ct2/resu...

[Daddysdaughter in reply to Hidden]

clinicaltrials.gov/ct2/show...

[Daddysdaughter in reply to Hidden]

Sorry THIS is the study

clinicaltrials.gov/ct2/show...

[Hidden in reply to Daddysdaughter]

i never would have noticed this one. Thanks.

[Daddysdaughter in reply to Hidden]

It’s for Rova-T primarily used for small cell lung cancer, and neuroendocrine cancers. My father has NEPC. I was reading some of the side effects from patients that were in the trial for lung Ca and they sound pretty bad.. i want to ask in this community if anyone has tried it..

[Hidden in reply to Daddysdaughter]

Oh! I didnt realize it it was NEC.

Europe started this maybe a decade ago (for NEC, not necessarily for NEPC). 177Lu radioactive warhead but a different guidance system. Instead of targeting PSMA, they target the somatostatin (receptor).

Did I say this already? Sorry if I am repeating myself.

clinicaltrials.gov/ct2/resu...

(These recruiting trials seem to be using Yttrium. Like 177Lu, also a beta emitter. I am curious about the 225Actinium, an alpha emitter. I assume they tried to use 223Radium, but could not get it to stick to the hormone ligand (the somatostatin mimetic)). mimetic=look-alike The guidance system.

[Daddysdaughter in reply to Hidden]

So this means my father would need to be tested for Somatostatin. Tall -Allen also recommended this. But how do i know if this option, immunotherapy, Rova-T or Lu 177 is the correct choice? I’m sure they all have pluses and minuses but how do I/We narrow it down to the BEST? My fathers not a spring chicken 🐓 ya know lol!! He’s 78, but still i don’t want to take him through all of these with minimal chance of QOL..

[Daddysdaughter in reply to Hidden]

What do you know or think about the Rova-T?

[Hidden in reply to Daddysdaughter]

The {177Lu}+[somatastatinLigand] for NEC (or NEPC) is farther along by far than the {177Lu}+[PSMA] for standard proste cancer. Both seem farther along than Rova-T, based in part on reading the trials. I have not heard of Rova-T before today. Possibly it is a NEC drug. I don't know those.

Dont be so sure that each has some plusses and many minuses. Many trials (most) fail completely.

I assume that they would do a scan with something like

{positron-emitter}+[somatastainLigand] and do a PET scan to see if the

{positron-emitter} accumulates in the area where they believe the cancer is; that is, they check that the guidance system works. If so, then they attach

the drug warhead to the [somatostainLigand] and inject that.

I'd say look at the trials, and see what you can make out of it. And then ask more people, certainly. See how many people have had the treatment that you are considering.

How do you know? It takes work.

[Daddysdaughter in reply to Hidden]

There’s only been 1 Prostate Cancer patient that has actually documented 1st treatment but no results. Study’s says 4.4 months PFS .. seems so little?

[Hidden in reply to Daddysdaughter]

Yes, but many drugs get have gotten approved for a 4 month overall survival benefit.

Here is a report of FDA approval for the use of 177Lu in another setting. It is relevant in that you can see a probable maximum benefit might be, and a probably maximum risk might be. unlikely that you would have better benefit than reported in this article, or worse side effects than here. The average benefit of 177Lu+dotatate was not reported because not enough people got sicker yet. ["median PFS was not reached "]

fda.gov/Drugs/InformationOn...

It's not clear if any trials are open using 177Lu, but there may be, and I would think that other radio-neucleotides would have about the same effect even though they would have their own levels of energy released upon fission.

audio/video raredr.com/news/lutathera-fda

[Tall_Allen]

Although disappointing, it's not surprising. MSI-Hi/dMMR is a rarity in prostate cancer. Much more likely for colon cancer.

[Daddysdaughter in reply to Tall_Allen]

His mother had colon cancer and ended up passing because of it. This was in he early 80s when there wasn’t many options for testing or treatment. I also read that one of the genetic mutations on his liquid biopsy came back 0.8 for PDGFRA which can be related to colon cancer.

[Tall_Allen in reply to Daddysdaughter]

I'm not sure what your point is. I would think that his risk of colon cancer is a very remote concern now. Or perhaps you don't understand that somatic (tumor) genomics is completely different from germline (inherited) genomics.

[Daddysdaughter in reply to Tall_Allen]

I don’t understand, in process of learning. Thank you for explaining Now i understand the difference.