ACE in the hole.

Top Line: Margin-negative resections remain the elusive goal in any curative treatment of pancreatic cancer.
The Study: In the past year, we’ve learned either neoadjuvant radiation or adjuvant FOLFIRINOX can really move the goalposts for achieving ideal surgical outcomes. It took a group of Harvard men—well, to be more precise, the group is actually largely comprised of women—to combine the two in bringing the total neoadjuvant therapy approach to locally-advanced pancreatic cancer. In this phase 2 trial 49 patients with unresectable disease received FOLFIRINOX x 8 with daily losartan followed by chemoradiation in an attempt to convert to surgical candidacy. Ok that all makes sense, except...what? Did we say losartan? Apparently, pre-clinical studies indicate the angiotensin receptor blocker (ARB) harbors anti-proliferative effects among many others. When it came to the chemoradiation, capecitabine was given with short-course radiation (5 Gy x 5 via protons or 3 Gy x 10 via photons) if post-chemo re-staging CT demonstrated conversion to resectable disease (n=7) or with long-course radiation (1.8 Gy with SIB of 2.1 Gy to vessel-tumor margin all x 28 via photons ) if there was persistent post-chemo vascular involvement (n=38). After all this, 42 (86%) proceeded with surgery and a remarkable 34 (69%) achieved the elusive margin-negative resection of what was once deemed straight-up unresectable.
Bottom Line: For the first-time ever, unresectable pancreatic cancer has a decent chance to become resectable. | Murphy, JAMA Oncol 2019


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