The standard of care for PDAC and PACC forms of pancreatic cancer is 12 cycles of (m)Folfirinox when used for curative intent. That number was selected by a working committee of oncologists convened by either the National Clinical Comprehensive Cancer Network (NCCN) or the American Society of Clinical Oncology (ASCO) in response to the question as to how much of it was felt adequate to achieve no evidence of disease (N.E.D) while also being tolerable by the average patient receiving it.

The definition of N.E.D. no observable or detectable disease using current imaging techniques such as CT, MRI or PET. at the time treatment is completed. What is important to realize is that each of those imaging systems has a limit as to its lower threshold of sensitivity in detecting a cluster of cancer cells. What can not be detected should it be present after treatment finishes is termed Minimal Residual Disease (M.R.D.). It is the hope of the oncologist that this low level of potentially remaining disease is kept in check by one’s immune system. If the immune system gets challenged and weakens, M.R.D. Can become active and come back more aggressively. If resistance to the initial treatment did not occur, the same regimen can be tried again.

The statistics show that there is recidivism at a rate as high as 80% within 24 months of surgery and treatment. This is due to M.R.D. where remaining cells had become quiescent/dormant and not killed. Chemo works on actively growing/dividing cells but not cells that became quiescent and stayed in a G0 (zero) phase of the DNA cycle. This is why so many patients have recurrence of their cancer. There are no studies showing doing more cycles of the initial treatment improves the prognosis, so the risks of permanent neuropathy and other sequela related to the cytotoxic chemotherapy drugs outweigh the risk.

There are cases of patients who were stage IV doing well beyond 12 cycles that became long-term survivors. I did 24 cycles of Folfirinox of the original formulation that was 20% higher than what is used today. I have the germline BRCA2 mutation and entered a maintenance monotherapy trial of a PARP inhibitor medication after completing the 46th chemo cycle which was a resting cycle of 5-FU/Leucovorin. These were used as part of alternating groups of six between groups of six of Folfirinox to lessen the chance of developing permanent chemo induced peripheral neuropathy (CIPN. This alternate method of dosing was successful in preventing CIPN. I will reach 13 years survival, declared cured and one that is considered an “exceptional responder” being studied by a research lab at the NCI as to what factors contributed to achieving cure. Despite being a long-term survivor and declared cured, I remain vigilant and continue having an MRI/MRCP every 6 months as having a (g)BRCA2 mutation slightly increases my risk of developing a new primary pancreatic cancer as well as prostate and male breast cancer.

Another patient also stage IV did 37 cycles of the same formulation but the concentration was gradually decreased during treatment and has permanent neuropathy in her feet. A third patient I speak to frequently did 9 cycles and was then moved into a PARP inhibitor trial targeting her somatic BRCA mutation. She has surpassed 7 years and is N.E.D.