Maximal ablative RT (67.5Gy/15fx or 75Gy/25fx) + capecitabine enables 27% resection and 38% 2-year OS in vascular-encased LAPC

Hypofractionated ablative radiation therapy (A-RT)—dose-escalated external-beam RT (67.5Gy in 15 fractions or 75Gy in 25 fractions) with concurrent capecitabine—was tested in a single-arm Phase 2 MSK trial (NCT03523312) in locally advanced pancreatic adenocarcinoma still deemed unresectable after ≥3 months induction chemotherapy (n=48; 94% received mFOLFIRINOX; 98% had arterial + venous involvement). After A-RT, 34% had staging laparoscopy and 27% ultimately underwent resection; 2-year OS from A-RT was 38% overall (31% unresected; 54% resected) with low 2-year local progression (11% unresected; 15% resected) but high 2-year distant metastasis (73%)—local control looks better than many SBRT/chemo series where 2-year local control is often ~60–70%, while survival is broadly in the range reported for induction chemo approaches (median OS ≈24 months with FOLFIRINOX meta-analyses) and prior ablative-RT experiences reporting ~38% 2-year OS from irradiation. Grade ≥3 RT-related AEs occurred in 12.5% acute and 26.1% late (late ascites 15.2%); among surgical patients there were no 90-day deaths and 4 Clavien-Dindo grade III events (11 AEs in 12 evaluable).