What exactly is NED (no evidence of disease)
I hear it a lot, even with stage 4. Is NED when the cancer is inactive or when the tumor is completely gone, like after surgery. My tumor itself is undefined but it is still wrapped around several veins and arteries. The very last lymph node on my left side by my neck reacted to chemo so they diagnosed me at stage 4. I’m in “chemical remission” but does that mean I am NED or just maintaining? It’s quite confusing to be honest!
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I am termed NED just now. After chemo, Y90, and two surgeries, tumors are not evident in scans and all margins were clear per the pathology reports. CA19-9 is dropping close to normal range.
No evidence of cancer. Of course we will continue doing blood work and scans to see if there is a cowboy trying to set up show somewhere else!
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.
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?
Which ctDNA tests is everyone using?
FWIW the Grail/Galleri cfDNA (cell-free DNA) blood test claims to detect 50+ types of cancer at a microscopic level, before imaging can typically detect anything. The Signatera ctDNA test is customized to look for "Microscopic Residual Disease" (ctDNA) specifically from tumor tissue you had removed.
I had open Whipple in June 2022 after 6 months of FOLFIRINOX. All intra-op and post-op pathology clean, MRI clean, CA19-9 good, Galleri and Signatera all negative in the first 4 months after surgery. About 3 weeks after the Galleri and Signatera tests, MRI spotted a 2 cm tumor recurrence at the original surgical site.
Long-story short: The ctDNA and cfDNA tests are not gold standards by any stretch of the imagination. It was the slowly rising CA19-9 level that we should have reacted to as the first hint! You can get repeat CA19-9 testing done at some walk-in labs or Rx-only labs with a "serial testing" prescription from many doctors for about $25 per test, if your onco is not testing super-often. (See mdsave.com for one option.)
My onco team had no comment about the Galleri test, but told me Signatera was not exceptionally good for pancreatic tumors. "If Signatera > 0, you definitely have cancer. If Signatera = 0.00, you might still have cancer."
In my case, the Signatera ctDNA test finally went up to 0.14 around the same time imaging detected multiple mets in my abdomen, with CA19-9 around 600. Last Signatera (2 months ago) was back down to 0.00, and my CA19-9 has come down to 158 after 6th round of chemo (Gemcitabine + Abraxane + Cisplatin). But we know from imaging all my tumors are still there.
So, I'm thrilled to hear @stageivsurvivor is doing well, and I am now in your camp of agreeing with the need to beat this monster into total submission. (I read long ago about a patient who had undergone around 37 rounds of FOLFIRINOX. Ouch!)
On top of that, don't underestimate the value of cheap, easily available CA19-9 testing. Stay vigilant!
P.S. Of my 12 FOLFIRONOX treatments, the hair loss wasn't bad at all (60 y/o male here), but we cut the oxaliplatin by 20% for the last 4 treatments to address the peripheral neuropathy, which persisted for about 6 months after the last treatment.
On my new treatment, the cisplatin was said to cause a little less than neuropathy than oxaliplatin, but the Abraxane is worse than both (for me) neuropathy-wise, and it has also claimed almost every hair on my body, but the overall cocktail seems to be more effective for me (in terms of CA19-9 response) than the FOLFIRONOX was. FWIW, I have the ATM mutation that allegedly responds well to platinum.
I have taken the Grail test twice, November 2021 and 2022, with negative findings for any cancer. I was particularly interested in pancreatic and bile duct cancers. According to a 2021 study published in the Annals of Oncology (https://www.annalsofoncology.org/article/S0923-7534(21)02046-9/fulltext), Grail sensitivity for detecting PC in stages I, II, III, and IV was 61.9%, 60%, 85.7% and 94.9%, respectively. For liver and bile duct cancers, 100% for stage I! (page 1174). There are no statistics for specificity (that is, the percentage of true negatives) in the study.
Grail is currently being tested by the National Health Service. Results from that study will be significant since it involves a great many people.
As to the “slowly rising CA 19-9 level,” what do you mean? Are you referring to slowly rising within the normal range or above the normal range.?
The patient that underwent the 37 rounds of Folfirinox is Camille Moses. She is an 11 year survivor but still has neuropathy. When I advocated for the aggressive chemo with Folfirinox, my oncologist did the first six cycles with Folfirinox. It was the original formulation used between 2011-2018 that was 20% stronger in its components. Camille had the same. But with me, the next six removed the oxaliplatin and irinotecan and were considered resting cycles. My tumors were still shrinking significantly on just the 5-FU with Leucovorin. After the six resting cycles, it was back to full dose Folfirinox. This alternating dosing was continued until 46 cycles in total were administered-24 of Folfirinox and 22 of 5-FU/Leucovorin. It is likely the “resting cycles” were the reason why my neuropathy resolved over several years.
At the moment, ctDNA is only recommended for monitoring colon cancer in the solid tumor realm. The American Society of Clinical Oncologists has working committees that review clinical studies and the technical issues were overcome so that it achieved the reliability the working committee felt was sufficient. There are working groups looking at other solid tumor cancers to monitor with ctDNA and one of those is pancreatic cancer. I am on my way to Chicago tomorrow for the semi-annual meeting of ECOG-ACRIN and one of the meetings I will be participating in is the GI Cancers Committee of which I am a research patient advocate on.
In the past meeting, an update was given on where things stand with improving the sensitivity of the ctDNA assay. I will inquire during the committee meeting of the pancreatic cancer oncologists who are on the committee if there has been an update from the ASCO. That professional organization will also be meeting in Chicago the first week of June when an update may be presented. I’ll post if I hear anything new.
@stageivsurvivor Thank you for such a thorough explanation. I just finished cycle 26 of chemo. We stopped the Oxaliplatin after 12 cycles to minimize the neuropathy and I have since been on FOLFIRI. CA19-9s are ~16 now and have been since Nov. We intend to continue this regime until it quits working.
Thank you to all who have commented on ctDNA tests. In summary, I think I am hearing to trust but verify.
My first Signatera has returned 0.00. I am awaiting my current CA19-9.
If it has dropped further from 50 to normal range, and next scan shows nothing-would you wait until next round of tests to request maintenance chemo?
@gamaryanne , congrats on that progress. I would be far out of my lane if I were to advise skipping anything. "Trust but verify" sounds like a good plan. Anything out of the ordinary is a good reason to react *very* quickly.
As a side note, I've found it takes a really long time to see a new specialist in any field. With oncology, it's especially difficult to get into a good one, ideally at a center where clinical trials are offered. Part of my plan (lesson learned) is that if I can already be an established patient from at least one visit at another center, it speeds my possibility of jumping to the new clinical trial if current therapy fails. Out of 4 cancer centers I've consulted with, none could offer me any trial recommendations that weren't being done at their own center, so the burden of shopping and doing the homework seems to be on the patient.
@patientone, my CA19-9 was 166 a week before the Whipple, with a ~2.2 cm tumor at head of pancreas. It was down to 12 four weeks after Whipple, along with all the clean pathology reports and MRI 4 weeks post-op.
It was up to 33 three months after Whipple, high end of normal, but from a different lab. It raised my eyebrows, but not alarms yet, since I got the negative Signatera and Grail tests within 2 weeks of that.
Six weeks after that, CA19-9 hits 77 (at main/original lab), and MRI shows 2 cm mass/lesion at the original surgical site (remnant pancreas anastomosis w/ jejunum). Tissue sample from endoscopic ultrasound a few days later is negative for cancer. Endoscopist suspects inflammation from chronic pancreatitis or other post-op inflammation. Zero symptoms or discomfort. Tumor board recommended new Signatera and follow-up MRI in 6 weeks.
At follow-up, CA19-9 = 279 with MRI showing a possible met in the abdomen. 🙁 CT at another center a month later reveals more mets, with CA19 at 623 on their lab. A month after that, CA19 peaked at 677 (main lab again) before my first chemo started to kick in (now down to 158 after 7 cycles).
So, I viewed all the negative MRIs, post-op path reports, DNA tests, and CA19 of 33 as "NED," but if I had jumped into an MRI the day of that CA19=33 result, it would probably have spotted the recurrent tumor.
CA19=33 (after rise from 12) should have accelerated my 3-month follow-up MRI.
CA19=77 should have been the red flag to resume treatment, but two negative DNA tests misled me.
Negative EUS biopsy, due to difficult post-Whipple anatomy, caused 6-7 weeks of delay. (I'm wondering if percutaneous or laparoscopic biopsy could have gotten cancer-positive tissue at that point.)
When CA19 hit 279 and MRI confirmed a met, the 5-week delay before starting chemo was totally on me, because 1) I didn't want to be sick over the Christmas holidays with my kids in town, and 2) I wasn't excited with my oncologist's response or plan, and I didn't want starting his plan to disqualify me from clinical trials, so… I took that time to gather expert opinions from two other centers, who both concluded that, due to the mets, delay getting into appropriate trials, and complications of traveling to participate in them, I should really start the systemic chemo ASAP at my hometown oncologist, which is what I'm doing now.
Paranoia now rules my thought process. This recurrence probably could have been avoided by better intra-operative pathology or a total pancreatectomy. The rapid growth of the recurrence probably could have been slowed by adjuvant chemo (mine was total neoadjuvant, i.e., before surgery). And the metastasis probably could have been avoided by faster response to the "slowly rising" CA19 of 12 –> 33 in 3 months before it jumped from 33 –> 77 in 6 weeks. "Faster response" being a near-immediate expert second opinion, followed by chemo or resection.
@stageivsurvivor, thanks for digging up Camille's name; that's the one I had read about. Thanks also, in advance, for any info you can share here from the conference.
Blessings and best wishes to all, along with thanks for all for sharing your stories.
Thank you for this. Patient advocacy and self-help are very important.