What exactly is NED (no evidence of disease)?

NED is the term used that replaces “in remission” to better reflect what is going on. When a patient is recommended to take a certain number of cycles of chemo thought to achieve NED, that number is not from clinical studies but a consensus of oncologists whose opinion is that number of cycles is sufficient for most patients to achieve NED while keeping side effects tolerable. Peripheral neuropathy is one of those side effects of concern.

The oncologist looks to knock down the disease level so low that it is not detectable by current imaging instrumentation such as CT, MRI or PET. This means there is still likelihood of minimal residual disease (MRD). The hope is that one’s immune system is robust enough to withstand a challenge or not weaken to keep any micrometastatic disease or circulating tumor cells from progressing. There is now a more sensitive method to detect MRD called ctDNA. It has been in use for a number of years to monitor leukemia and lymphoma. In the past few years, CtDNA has been moving into the solid tumor realm and is now approved for colon cancer MRD surveillance/reoccurrence. It is under clinical studies for breast and pancreatic. I have been having my ctDNA measured since 2014 when I entered a clinical trial for maintenance monotherapy after treatment for stage IV disease.

My goal in chemotherapy was not to buy more time but longevity if not cure. And even though I was dealing with metastatic disease to my liver, I advocated for going well beyond 12 cycles of Folfirinox. I did not want to reach “NED” only to hear within the next several years the disease resurfaced and was now more aggressive and likely not survive the reoccurrence. This is why I advocated to go well beyond 12 cycles of Folfirinox. I did 24 cycles and 22 cycles of 5-FU/Leucovorin. They were alternated every six cycles to lessen the effects of peripheral neuropathy by oxaliplatin. A combined total of 46 cycles were administered and at the end point, it was likely all that remained of the tumors that could be visualized was scar tissue which over the years was cleared by immune system cells. ctDNA has been zero and I have since been designated cured.

So if one is able to handle additional rounds of chemo, you need to self-advocate and have a discussion with your oncologist on how to improve on going beyond NED to ensure there is no remaining MRD. My decision to push in getting the extra cycles has led to 11 years survival and the neuropathy resolving.

@stageivsurvivor
I am awaiting my ctDNA results. Told they could result in a false positive but I have decided I will request continued fulfurinox if it reads positive.
Do you remember when you dropped the “ox”? Thinking about the effectiveness of it vs the neuropathy. Also I tend to think it was behind losing so much hair Your thoughts?

You are a model of what can happen with the BRCA gene, but none of this would be possible with the ATM mutation, which I have. After only 6 months of GAC chemo with I believe only the abraxane reduced to 80%, my CA19-9 numbers are starting to slowly climb upwards every 2 weeks and my basic bloodwork (monocytes, lymphocytes, etc.) are starting to go haywire. I’m still on chemo, but hoping to get into a clinical trial now. From everything I’ve read, I don’t see any long-term success yet for those with ATM gene mutation (I also have KRAS12-D and TP53). It would be great if in profile we could put our mutations which would make our input more pertinent to others.

Hello Marie, I have KRAS G12D and TP53. A bit fearfully, I am starting s trial this week that targets KRAS G12D and another drug that is considered “pan KRAS”. My tumor marker was 136 at last check. The activity we know of is in my liver.

I will let you know how it goes once an assessment is done in 8 weeks. Maybe it will be of help to you!

Thank you, Maryanne. I wish you success! The little understanding I have of this disease, is that you have to attack it from several fronts. I believe immunotherapy is the key to success. My hunch is that masses in my abdominal area are no longer stable, the strong chemo seemed to attack those liver lesions well. My oncologist told me a few months ago that the abdominal masses would be the ones to worry about so that’s why I’m asking my drs to go into the CLD-18.2 trial that tries to attack gastric cancer but how long it can be effective is still in the works. A KRAS-12D trial would seem to be the next step (I don’t know of any trials for ATM mutations) after CLD18.2 so please let me know how it goes! God bless you in your fight.

Thank you, Maryanne. I wish you success! The little understanding I have of this disease, is that you have to attack it from several fronts. I believe immunotherapy is the key to success. My hunch is that masses in my abdominal area are no longer stable, the strong chemo seemed to attack those liver lesions well. My oncologist told me a few months ago that the abdominal masses would be the ones to worry about so that’s why I’m asking my drs to go into the CLD-18.2 trial that tries to attack gastric cancer but how long it can be effective is still in the works. A KRAS-12D trial would seem to be the next step (I don’t know of any trials for ATM mutations) after CLD18.2 so please let me know how it goes! God bless you in your fight.

Be aware that ATM mutations are being treated in trials by drugs called ATR-inhibitors (not ATM inhibitors). There have been a few.

berzosertib (formerly M6620, VX-970)
ART0380
Elimusertib (BAY-1895344)
Comonsertib
https://aacrjournals.org/cancerdiscovery/article/11/1/80/3075
https://news.vumc.org/2021/09/23/clinical-trial-tests-atr-inhibitor-in-difficult-to-treat-cancers/
Dr. Yap (in this article: https://www.mdanderson.org/newsroom/results-fgfr-inhibitors-parp-atr-inhibitor-combinations.h00-159617856.html ) is a clinical trial-generating machine, with focus on the DDR deficient mutations like ATM.

Thank you markymark. I will look into these trials and discuss with my dr on Tuesday. I hope you are doing well in your trial; please update us when possible. Also, have you heard of this drug: dostarlimab? My sister’s friend passed this on for me as something I could look into for pancreatic cancer tumors.

dostarlimab aka TSR-042

I'd never heard of it before your post, but it looks promising in tumors with certain properties.
https://newatlas.com/medical/colorectal-cancer-dostarlimab-gxly
I found over 50 hits for it on the government trials site.

This one explicitly mentioned pancreatic cancer as a condition being treated: https://clinicaltrials.gov/study/NCT04673448

Pancreatic cancer as long as it's not assoc w/ a BRCA mutation:
https://clinicaltrials.gov/study/NCT04983745
I might have missed a few.

In some cases, "pancreatic cancer" might not be listed in the search criteria, but the trial could still be open to patients with "solid tumors" so don't ignore those!

Also, some studies only list the treatment drug by its investigational name (TSR-042) rather than a commercialized name, so try to always include both in a search.