Phase 2 single-arm trial (NCT03523312) at Memorial Sloan Kettering evaluated hypofractionated ablative radiation therapy (A-RT: 67.5 Gy/15 fractions or 75 Gy/25 fractions) with capecitabine, followed by surgical evaluation, in 48 patients with LAPC remaining unresectable after ≥3 months of induction chemotherapy (94% mFOLFIRINOX).
27% of patients (13/48) achieved resection; 2-year overall survival was 38% for the full cohort, 54% (95% CI, 33%–89%) in resected patients vs. 31% (95% CI, 19%–51%) in unresected patients. Two-year local progression rates were low (11–15%), though 2-year distant metastasis reached 73%. No 90-day postoperative deaths occurred; grade III+ late RT toxicity affected 26.1% of participants.
Single-arm, non-randomized design at a single high-volume center limits generalizability and precludes causal inference. Small sample size (n=48) reduces statistical precision. High distant metastasis rate (73% at 2 years) suggests systemic disease remains the dominant failure mode regardless of local control.
For LAPC patients with extensive vascular encasement after induction chemotherapy, hypofractionated A-RT can convert ~27% to resectability without increasing surgical morbidity and provides durable local control even in unresected patients. Clinicians should weigh this approach against the high distant metastasis risk and refer patients to high-volume centers experienced with ablative dose regimens.
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