Pancreatic Cancer Recurrence after Whipple

My story is a little different but worth telling here. I had a Whipple procedure in 2012 and was staged as III, locally advanced, borderline resectable. Surgical margins were clear. There was portal vein resection required and pathology showed invasion into the vascular wall. Eleven of 22 lymph nodes were positive. One week after surgery a CT was done and the radiologist noted suspicion of metastatic disease to the liver. It was not large enough to be seen two weeks earlier at the time of the initial CT scan. So this was how I ended up having a Whipple and being stage IV…..it had not been detected prior to surgery that was done a couple of days after the initial diagnosis. No cure was to be achieved for me by having the Whipple.

My first thoughts on treatment were to find a clinical trial. To make the search easier, molecular profiling was done and a liquid biopsy revealed a germline (inherited) mutation. So now I knew the type of trials to focus my search on. A trial matching my criteria would take 14 months so in the meantime, standard of care chemo was required. Standard of care is just what it means….and it was not going to give me the longevity in survival I was looking for. I knew I would require better than SoC and strongly advocated for more aggressive chemo.

The “gold standard” of chemotherapy regimens in 2012 as it is today is Folfirinox. Administering 12 cycles is the number selected that is felt to achieve No Evidence of Disease (NED) and yet be tolerable by the majority of patients as adverse events, side effects and peripheral neuropathy are concerns. Few oncologists explain what NED means, especially in how it is determined. The goal of the oncologist is to knock the disease down low enough that it is not detectable by current sensitivity by imaging such as CT, MRI or PET. It is hoped that at this level, one’s immune system can keep any minimal residual disease (MRD) in check. As long as one continues to have a robust immune status, the MRD is held in check. But is the immune system comes under challenge and gets compromised, MRD can come back and usually in a more aggressive form.

Knowing this is why I advocated for more aggressive treatment with Folfirinox. Rather than stopping at 12 cycles, I indicated my desire and committed to doing as much as my body would tolerate. Thankfully my oncologist honored my request. Because neuropathy would likely be experienced and could become permanent, he decided to treat with six cycles of Folfirinox (FFX) followed by six resting cycles of just 5-FU with Leucovorin. After those six cycles, it was back to full-dose FFX for another six cycles. This alternating dosing regimen went for 24 months resulting in a total of 46 cycles of 24 FFX and 22 of 5-FU. At that point, a clinical trial opened that I met the criteria for and enrolled after a two week washout period. After the final 5-FU treatment, all liver metastasis had shrunk 80% and it was believed only scar tissue was being observed on imaging.

The clinical trial was designed to target a gene mutation for maintenance monotherapy. Many oncologists feel it was the excessive FFX that destroyed any MRD and the clinical trial drug has helped in preventing any new primary tumor from forming in the residual pancreas as I have a lifetime risk from that gene mutation.

Anyone can say to their oncologist they want to survive and be cured. Saying and doing are two very different things. I was 55 years old and strong physically from having done 100-200 mile bike rides per week. I was also strong emotionally and mentally. I set realistic expectations that setbacks might be encountered. I found ways to tolerate the treatment, deal with a setback and then move forward. I stayed focused on my goal and had the determination and very strong will to survive. In 2016 at the conclusion of the trial I was declared NED. It was likely I was already NED at the conclusion of the FFX treatments. In 2022 I was informed by a number of pancreatic cancer oncologists that they consider me cured. In a few months I will be celebrating 11 years of survival of having had stage IV disease.

My story is a little different but worth telling here. I had a Whipple procedure in 2012 and was staged as III, locally advanced, borderline resectable. Surgical margins were clear. There was portal vein resection required and pathology showed invasion into the vascular wall. Eleven of 22 lymph nodes were positive. One week after surgery a CT was done and the radiologist noted suspicion of metastatic disease to the liver. It was not large enough to be seen two weeks earlier at the time of the initial CT scan. So this was how I ended up having a Whipple and being stage IV…..it had not been detected prior to surgery that was done a couple of days after the initial diagnosis. No cure was to be achieved for me by having the Whipple.

My first thoughts on treatment were to find a clinical trial. To make the search easier, molecular profiling was done and a liquid biopsy revealed a germline (inherited) mutation. So now I knew the type of trials to focus my search on. A trial matching my criteria would take 14 months so in the meantime, standard of care chemo was required. Standard of care is just what it means….and it was not going to give me the longevity in survival I was looking for. I knew I would require better than SoC and strongly advocated for more aggressive chemo.

The “gold standard” of chemotherapy regimens in 2012 as it is today is Folfirinox. Administering 12 cycles is the number selected that is felt to achieve No Evidence of Disease (NED) and yet be tolerable by the majority of patients as adverse events, side effects and peripheral neuropathy are concerns. Few oncologists explain what NED means, especially in how it is determined. The goal of the oncologist is to knock the disease down low enough that it is not detectable by current sensitivity by imaging such as CT, MRI or PET. It is hoped that at this level, one’s immune system can keep any minimal residual disease (MRD) in check. As long as one continues to have a robust immune status, the MRD is held in check. But is the immune system comes under challenge and gets compromised, MRD can come back and usually in a more aggressive form.

Knowing this is why I advocated for more aggressive treatment with Folfirinox. Rather than stopping at 12 cycles, I indicated my desire and committed to doing as much as my body would tolerate. Thankfully my oncologist honored my request. Because neuropathy would likely be experienced and could become permanent, he decided to treat with six cycles of Folfirinox (FFX) followed by six resting cycles of just 5-FU with Leucovorin. After those six cycles, it was back to full-dose FFX for another six cycles. This alternating dosing regimen went for 24 months resulting in a total of 46 cycles of 24 FFX and 22 of 5-FU. At that point, a clinical trial opened that I met the criteria for and enrolled after a two week washout period. After the final 5-FU treatment, all liver metastasis had shrunk 80% and it was believed only scar tissue was being observed on imaging.

The clinical trial was designed to target a gene mutation for maintenance monotherapy. Many oncologists feel it was the excessive FFX that destroyed any MRD and the clinical trial drug has helped in preventing any new primary tumor from forming in the residual pancreas as I have a lifetime risk from that gene mutation.

Anyone can say to their oncologist they want to survive and be cured. Saying and doing are two very different things. I was 55 years old and strong physically from having done 100-200 mile bike rides per week. I was also strong emotionally and mentally. I set realistic expectations that setbacks might be encountered. I found ways to tolerate the treatment, deal with a setback and then move forward. I stayed focused on my goal and had the determination and very strong will to survive. In 2016 at the conclusion of the trial I was declared NED. It was likely I was already NED at the conclusion of the FFX treatments. In 2022 I was informed by a number of pancreatic cancer oncologists that they consider me cured. In a few months I will be celebrating 11 years of survival of having had stage IV disease.

The clinical targeted drug I received and still take is Rubraca (Rucaparib). It is a biosimilar drug to Lynparza (Olaparib).

You are amazing. I will keep your persistence in mind as I make my way along this journey. I will be getting my 6th treatment. I carry the BRCA1 gene and have had a previous breast and ovarian cancer. What was your clinical trial drug?

Hello Bethf, while I know it is tough to find out that the tumor marker tests are going up, it is great news that you are feeling well and the scans are stable so far. In regards to your two options, my understanding is that most clinical trials do require "measurable disease" in order to qualify. Specifically, they need to see at least one centimeter of tumor somewhere in the body that is confirmed either with a biopsy or PET scan showing that it is in fact cancer. You mention in your post that your scans do not show evidence of cancer right now. Please double check the requirements to get on the immunotherapy trial to be sure there is no requirement for measurable disease. If there is such a requirement (which is common), your choices at the moment would only be chemo or waiting until measurable disease appears on the scan. It's difficult to say what is the best option, as you do not want to interrupt the good quality of life you are having now. I would talk to your oncologist and see what he/she recommends. One medium option I can think of is to perhaps try chemotherapy for a month or two and see if your tumor marker numbers go down. If they do, you know it is working and you can continue for some time if you feel your quality of life is still ok while on chemo. If not, you can then attempt to get on the trial. Generally, clinical trials that are not specifically geared to a specific mutation/fusion that your tumor has are used after the standard chemo options are no longer working or tolerable. The great thing right now for you is that you are feeling great and have some time to make a very well researched and planned out treatment decision. This is a huge blessing.

I have been replying to others but I want to post a question of my own here:
After 10 months of NED/remission, (I was diagnosed April 2021, Whipple May 2021, chemo Aug 2021 to January 2022, short course SBRT radiation in April 2022, excellent health and good followups- since April 2022)

Since 4 weeks ago, I found out that I am having an aggressive recurrence which I just found out about within the past few weeks. I am considering what my options are and whether further treatment and what type of treatment has the greatest likelihood of success. My basic choices are chemo (probably Gemzar as I am not willing to do Abraxane with it) or an immunotherapy trial (ELI 002, Phase 1B) that I am almost certain to qualify for that is here at UC Health Anschutz in Denver. Or wait and see.
Right now tumor markers are going up rapidly, no evidence of a tumor or met on scan but have converted from ctDNA (testing for tumor circulating in the bloodstream) from negative on past two ctDNA tests to positive on the test 3 weeks ago.
My oncologist in Denver says that there are only 2 reasons to do chemo: to live longer or to feel better. I feel excellent now and have for the past 10 months, so chemo would not make me feel better but very likely make me feel worse. Or to increase longevity, which most research indicates has a very small chance of giving you a much longer life when started early than when given with delayed treatment that would be given only for clearly defined metastatis or for symptoms that may arise. I have no symptoms and no tumor to treat at this point.
My questions are: Have any of you known others (or been through yourself) treatment that felt truly worthwhile to you after Whipple and first line chemo (mine was Folfirinox) that you think either made you or your friend or family member live longer or feel better?
If faced with a recurrence and chemo (proven not to be effective for very long in most cases) or an immunotherapy or targeted therapy trial option, what do you think you would choose?
I would appreciate having your input based on your own experiences and even just your opinions. I am obviously also getting professional input and consultation about this as well. Thank you, Beth