Safety and pathological impact of resection after high-dose PBT for locally advanced pancreatic cancer.

Background: A multidisciplinary approach is essential for treating lethal pancreatic cancer. Proton beam therapy (PBT), with its potential for dose escalation, shows promising effect for the local tumor, but the safety of subsequent resection and its pathological impact remain uncertain.

Methods: A retrospective single-center analysis was conducted on patients with locally advanced pancreatic cancer who underwent multidisciplinary treatment, including PBT, chemotherapy and hyperthermia (January 2014 to December 2022). PBT target dose was 67.5 Gy concurrently gemcitabine infusion and local hyperthermia was applied 1 h after gemcitabine infusion. The standard chemo regimens (such as gemcitabine with nab-paclitaxel or FOLFIRINOX) followed triple-modal treatment. Surgical complications, pathological assessment and survival were analyzed in resected cases.

Results: Among 133 patients treated with PBT, 110 underwent triple-modal treatment combining PBT, hyperthermia, and chemotherapy. Ultimately, 11 patients underwent tumor resection after a median preoperative treatment duration of 210 days. Surgical procedures included five pancreaticoduodenectomies and six distal pancreatectomies. Three patients experienced complications of Clavien-Dindo grade 3 or higher (2; delayed gastric empty, 1; pancreatic fistula), but no mortality occurred. Histological evaluations revealed three cases of Grade 4 (27%, pathological complete response), four of Grade 3, three of Grade 2, and one of Grade 1. R0 resection was achieved in 10 cases.

Conclusions: Surgical resection following high-dose PBT can be safely performed under strict selection criteria and demonstrates strong pathological disease control of the primary tumor. This multidisciplinary approach may offer improved outcomes for locally advanced pancreatic cancer.