After Whipple surgery, Pathology showed Positive Lymph Nodes

I had a Whipple in 2012 with 11 of 22 lymph nodes positive, portal vein resection and clear margins. I was staged III, locally advanced and borderline resectable. The cellular pathology was poorly differentiated and high grade. A week after the Whipple which was two weeks after the initial CT scan, a radiologist noted multiple suspicious areas in the liver resembling metastatic disease and it needed to be surveilled going forward.

Prognosis- I never asked my exact diagnosis and thankfully it was never volunteered in being divulged. I was also never told about the suspicion of metastatic disease. So in my mind, things were better than actual. The tumor board met and decided to treat me with Gemzar instead of Folfirinox. Abraxane was not available until 2013. I indicated I was willing to take Folfirinox and as much as my body could handle and go for curative intent. The tumor board was of the mindset no one is cured with metastatic disease and the reason why palliative care was chosen despite my willingness for more aggressive chemotherapy.

A CT was done after completing three months of Gemzar. The result- 6 sizable tumors in the liver. Now I got the chemo I asked to be administered on day 1. The first CT on Folfirinox showed 54% reduction on all tumors. The next six cycles were 5-FU+Leucovorin as resting cycles to lessen neuropathy from Oxaliplatin. Continued shrinkage was observed. When those six cycles were completed, it was back on Folfirinox. And so it went until 46 cycles in total were administered (24 of Folfirinox and 22 of 5-FU).

After the fist 6 cycles of Folfirinox, a liquid biopsy was done detecting a germline genetic mutation. That information allowed me to focus on finding a clinical trial. It took 14 months of searching until an ideally suited trial was available. After treatment cycle 46, my tumors shrank about 80%. The efficacy of 5-FU was slowing. I started the trial and had a complete response in 18 months and was declared NED in April 2016. Overall survival is 10 years 3 months.

I would not give up, was willing to possibly have to live with permanent neuropathy and willing to take as much of an aggressive treatment my body could tolerate.I was 55 when diagnosed, no other co-morbidities, had been bike riding as much as 200 miles/week up until I was diagnosed. I continued to push myself hard all through chemo exercising and living as normal a life as I could. I got my chemo where I worked at a large medical center in NYC. So every day I got up at 5:00 am whether for work or chemo and did a 4’20” round trip commute. I never missed a day of work or took a break from chemo in 3.5 years. I was determined to survive and prepared myself physically, mentally and emotionally to deal with the adversity and challenges.

On the subject of neuropathy, I felt it better to be alive with neuropathy than dead. It was uncomfortable but I was willing to accept it and learned how to deal with it. Gabapentin gave me relief and after 2.5 years of finishing Folfirinox, I began to notice slow but steady improvement. Several years after improvement, the neuropathy has almost resolved. I have a small amount remaining in the large toes and it does not impact my activities. I chose to get MRI surveillance twice a year despite being told I could go down to once a year. I also have ctDNA measured several times a year which affords earlier detection of reoccurrence. ctDNA measurements were experimental for following solid tumors in 2014. An offshoot of the clinical trial was in donating blood for a very vaguely described study. I was to later learn it was for ctDNA which has become a paradigm shift in monitoring for reoccurrence over CA19-9 and CT or MRI which have detection limitations.

That is a very good question and one where not having an effective chemo regimen for late stage pancreatic cancer until the FDA approval of Folfirinox in 2011 reinforced the idea it was not possible to achieve cure in this cohort. It then required many more years to accumulate case histories documenting long-term survivors. While there are increasing reports of long-term survivors and exceptional responders that are considered cured, in nearly all cases it required going beyond standard of care treatments or adding targeted therapy as part of the treatment plan.

Folfirinox and (m)Folfirinox which is a lower concentration regimen approved in 2018 and has been used since, has a treatment plan of 12 cycles. That number was picked in response to a question posed to pancreatic cancer oncologists as to how many cycles did they feel a patient could tolerate with respect to side effects/adverse events and achieve No Evidence of Disease. It was by working committee consensus, probably convened by the American Society of Clinical Oncology, that the number twelve was selected. This does not in any way guarantee eradication of minimal residual disease (MRD) which is the cause in the vast majority of recalcitrance-as much as 80% within 24 months following treatment. The hope of the oncologist is his/her patient achieves N.E.D. and their immune system remains robust to keep MRD under control. If one’s immune system is challenged and weakens, all bets are off.

Oncologists will not push or suggest going beyond 12 cycles. The reason is the chemo is very toxic and causes short, long and permanent damage to tissues and organs. No oncologist wants to put themselves in the position of criticism by patient or caregivers that they were the cause of the impact chemo had on quality of life. This impacts quality of life and older patients and those exhibiting frailty often have to stop or have Folfirinox modified by reducing concentrations or eliminating one or more components. It requires self-advocacy of a patient to confront their oncologist and clearly convey one’s objective and willingness to go beyond standard of care for more aggressive treatment or consider treatment methods not standard of care yet for pancreatic cancer but are used for other solid tumor types with a degree of success.

When I was diagnosed in 2012 with stage IV disease to the liver, it was obvious to me that standard of care was only going to give standard results and that was not acceptable to me. I was physically, emotionally and mentally strong and made it clear to my oncologist I had the fortitude, persistence and ability to persevere. I’m certain no member of my team ever expected me to survive more than one year. They never had a patient like me that pushed myself very hard and expressed my willingness to withstand considerable discomfort and rise above the adversity that comes with the diagnosis. I made the point that I had nothing to lose, my affairs were in order and understood the ramifications of short, long and permanent effects I could experience. I made it clear those were acceptable risks and would deal with them if they occurred. And with that, my oncologist and care team members worked together in getting me through the challenges resulting in first achieving N.E.D and years later pronounced cured. So to go beyond standard of care, it requires the patient to self-advocate.

Hello! I too wish to be a StageIV survivor. Would you be willing to say what your course of treatment was please?

I was treated at an NCI Center of Excellence with an a high volume pancreas program and oncologists experienced in treating cancers of the pancreas. Original version of Folfirinox that was 20% higher in concentration of its components than today’s (m) Folfirinox was used. It was administered at full dose every 15th day for 24 months with no pause, delay or break in treatment. In the two times WBC count dropped, Neulasta was used to boost the count and prevent a delay in the next treatment cycle.

Because the technique of cold therapy was not known back in 2012 and there was concern in developing permanent chemo induced peripheral neuropathy, alternate dosing was used where the first six cycles were Folfirinox and the next six were considered resting cycles of just 5-FU/Leucovorin. This was to give the peripheral nerves a break and was hoped the 5-FU alone would be sufficient to keep the tumors stable until the next six doses of Folfirinox were administered. To everyone’s surprise, my tumors continued to have a significant shrinkage on just the 5-FU. This alternate dosing continued until 46 cycles when it was felt I had obtained as much benefit and what remained was scar tissue from what had been the two largest tumors.

I maintained moderate exercise throughout chemo of walking a minimum of 150 minutes per week, riding a stationary bike or walking multiple flights of stairs at work several times a day. I was strong physically, emotionally and mentally and committed to persevering.