Background
Phase II prospective trial. 48 patients with borderline resectable (n=33) or locally advanced (n=15) pancreatic cancer treated with total neoadjuvant therapy: gemcitabine/nab-paclitaxel × 4 cycles followed by stereotactic body radiotherapy (SBRT) 33–40 Gy in 5 fractions, then surgical evaluation.
Interventions and follow up
Arm A: Gemcitabine 1,000 mg/m² + nab-paclitaxel 125 mg/m² days 1, 8, 15 every 4 weeks × 4 cycles → SBRT 33–40 Gy in 5 fractions → restaging and surgical resection if appropriate
Primary endpoint: R0 resection rate
mFollow up: 18 month
Primary endpoint: R0 resection rate
mFollow up: 18 month
Results
Resection rate (BRPC): 66% (22/33)
R0 resection (of resected BRPC): 78%
mOS (BRPC): 33.4 months
mOS (LAPC): 18.4 months
Grade ≥3 toxicity during chemotherapy: 27%
R0 resection (of resected BRPC): 78%
mOS (BRPC): 33.4 months
mOS (LAPC): 18.4 months
Grade ≥3 toxicity during chemotherapy: 27%
Adverse events
Main adverse events: Grade ≥3 AEs: 27% during gemcitabine/nab-paclitaxel. SBRT well tolerated — grade ≥3 radiation toxicity <5%. No treatment-related deaths.
Conclusions
Total neoadjuvant gemcitabine/nab-paclitaxel followed by SBRT for borderline resectable pancreatic cancer is feasible and achieves promising R0 resection rates (78% of resected) and mOS of 33 months in BRPC. SBRT appears to be a tolerable, effective approach for local consolidation after systemic induction.
Key Limitations
Key Limitations: Single-arm phase 2 trial — no comparator group. Small sample size (n=48). Gemcitabine/nab-paclitaxel has been largely superseded by mFOLFIRINOX for fit patients. Only 66% of BRPC patients proceeded to resection. Heterogeneity between BRPC and LAPC subgroups. Patient selection at academic center with multidisciplinary expertise limits generalizability.
Clinical Context
This trial supports the "total neoadjuvant therapy" paradigm combining systemic chemotherapy and SBRT before resection. The results informed Alliance A021501 (comparing SBRT vs ablative RT after mFOLFIRINOX in BRPC). SBRT as local consolidation has an increasing role in pancreatic cancer management.
References
References: Murphy JE et al, JAMA Oncol 2018