Safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiotherapy for resectable pancreatic cancer: A prospective, open-label, phase II study

Toshihiko Masui; Kazuyuki Nagai; Takayuki Anazawa; Yosuke Kasai; Akitada Yogo; Michio Yoshimura; Takashi Mizowaki; Norimitsu Uza; Akihisa Fukuda; Shigemi Matsumoto; Masashi Kanai; Hiroyoshi Isoda; Yoshiya Kawaguchi; Shinji Uemoto; Etsuro Hatano

doi:10.1002/cam4.6470

Safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiotherapy for resectable pancreatic cancer: A prospective, open-label, phase II study

Cancer Med. 2023 Sep;12(18):18611-18621. doi: 10.1002/cam4.6470. Epub 2023 Aug 30.

Authors

Affiliations

¹ Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
² Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
³ Department of Gastroenterology and Hepatology, Kyoto University, Kyoto, Japan.
⁴ Department of Real World Data Research and Development, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
⁵ Department of Clinical Oncology, Kyoto University, Kyoto, Japan.
⁶ Department of Diagnostic Imaging and Nuclear Medicine, Kyoto University, Kyoto, Japan.

Abstract

Background: Resectable pancreatic cancer (RPC) is potentially resectable on admission, and the impact of neoadjuvant therapy on these tumors is controversial. Moreover, the safety and efficacy of neoadjuvant chemoradiotherapy with moderately hypofractionated intensity-modulated radiation therapy (NACIMRT) for RPC have not been studied. Here, we conducted a phase II study to evaluate the safety and efficacy of hypofractionated NACIMRT for RPC.

Methods: A total of 54 RPC patients were enrolled and treated according to the study protocol. We used moderately hypofractionated (45 Gy in 15 fractions) IMRT with gemcitabine to shorten the duration of radiotherapy and reduce gastrointestinal toxicity. The primary endpoint was overall survival (OS), and we subsequently analyzed the microscopically margin-negative resection (R0) rate, disease-free survival (DFS), and histologic effects and safety of NACIMRT.

Results: Median OS for the cohort was 40.0 months. Forty-two patients (77.8%) underwent pancreatectomy after NACIMRT. Median DFS was 20.3 months. The R0 resection rate was 95.2% (40/42) per protocol and 85.2% (46/54) for the cohort. There were no intervention-related deaths during the study period. Local treatment response, as assessed by the CAP classification, showed no residual tumor in 4.8% of patients. Overall, 23.9% of patients experienced CTCAE grade 3 or 4 during NACIMRT. Adjuvant therapy was initiated in 88% of patients undergoing resection. Postoperative complications grade ≥3b on the Clavien-Dindo scale occurred in 4.8% of patients. CA19-9 level at enrollment was an independent prognostic factor for OS and DFS.

Conclusions: This is the first prospective study of hypofractionated IMRT as neoadjuvant therapy for RPC. Hypofractionated NACIMRT for RPC could be safely introduced with a high induction rate of adjuvant chemotherapy, with an overall survival of 40.0 months.

Keywords: IMRT; chemoradiotherapy; intensity-modulated radiotherapy; neoadjuvant therapy; pancreatic cancer; surgery.

Grants and funding

21K08732/Japan Society for the Promotion of Science