Ablative ultra-hypofractionated radiotherapy with surgical GI exclusion as a “functional spacer” for pancreatic cancer: a phase I safety and feasibility study

OBJECTIVES: The therapeutic window for radiotherapy in locally advanced pancreatic cancer (LAPC) is severely constrained by the anatomical proximity of the duodenum. We hypothesized that radiation-induced gastrointestinal (GI) injury is exacerbated by physiological digestion, and that surgically bypassing the irradiated duodenum would provide a biological "functional spacer." We aimed to evaluate the safety and clinical feasibility of ablative ultra-hypofractionated radiotherapy (UHRT) followed directly by elective GI exclusion surgery. METHODS: In this prospective Phase I protocol, 10 patients with LAPC received ablative UHRT using Helical Tomotherapy at a prescribed dose of 40-60 Gy in 5 fractions. A prophylactic GI exclusion surgery (gastric truncation and GI bypass) was strictly scheduled within 7 days post-radiotherapy to place the high-dose irradiated duodenal segment into physiological quiescence. The primary endpoint was treatment safety assessed via CTCAE v4.02 and technical feasibility. RESULTS: All participants provided written informed consent and successfully completed the combined radiotherapeutic and surgical protocol. After a median follow-up of 12 months, no Grade 4-5 toxicities, bleeding, or gastrointestinal perforations were recorded. Only one patient (10%) experienced Grade 3 GI toxicity (abdominal pain). The Objective Response Rate (ORR) was 50%, with a 1-year overall survival rate of 60%. Furthermore, 70% of symptomatic patients achieved significant cancer-related pain relief. CONCLUSIONS: Preliminary results suggest that the integration of ablative UHRT with an immediate prophylactic surgical GI bypass is a feasible and safe protocol. This "functional spacer" concept potentially mitigates the duodenal dose-limiting bottleneck, allowing the practical delivery of biologically ablative radiation doses in LAPC without catastrophic GI consequences. However, larger multi-center trials are warranted for further validation. TRIAL REGISTRATION: Not prospectively registered. At the time of study initiation in 2015, this investigator-initiated, single-center exploratory Phase I safety and technical feasibility study was reviewed and approved by the Institutional Ethics Committee of Air Force Medical Center, PLA, and public trial registration was not requested by the committee. The study was not designed as a randomized comparative efficacy trial, but rather as a pilot evaluation of the safety and feasibility of an individualized combined radiotherapy-surgical strategy. The protocol was approved by the Institutional Ethics Committee of Air Force Medical Center, PLA (Approval No. 2015-118-S01) on 12 March 2015.