Impact of neoadjuvant intensity-modulated radiation therapy on borderline resectable pancreatic cancer with arterial abutment; a prospective, open-label, phase II study in a single institution

Toshihiko Masui, Kazuyuki Nagai, Takayuki Anazawa, Asahi Sato, Yuichiro Uchida, Kenzo Nakano, Akitada Yogo, Akihiro Kaneda, Naoto Nakamura, Michio Yoshimura, Takashi Mizowaki, Norimitsu Uza, Akihisa Fukuda, Shigemi Matsumoto, Masashi Kanai, Hiroyoshi Isoda, Masaki Mizumoto, Satoru Seo, Koichiro Hata, Kojiro Taura, Yoshiya Kawaguchi, Kyoichi Takaori, Shinji Uemoto, Etsuro Hatano

Borderline resectable pancreatic cancer (BRPC) is a category of pancreatic cancer that is anatomically widely spread, and curative resection is uncommon with upfront surgery. Intensity-modulated radiation therapy (IMRT) is a form of radiation therapy that delivers precise radiation to a tumor while minimizing the dose to surrounding normal tissues. Here, we conducted a phase 2 study to estimate the curability and efficacy of neoadjuvant chemoradiotherapy using IMRT (NACIMRT) for patients with BRPC with arterial abutment (BRPC-A). A total of 49 BRPC-A patients were enrolled in this study and were treated at our hospital according to the study protocol between June 2013 and March 2021. The primary endpoint was microscopically margin-negative resection (R0) rates and we subsequently analyzed safety, histological effect of the treatment as well as survivals among patients with NACIMRT. Twenty-nine patients (59.2%) received pancreatectomy after NACIMRT. The R0 rate in resection patients was 93.1% and that in the whole cohort was 55.1%. No mortality was encountered. Local therapeutic effects as assessed by Evans classification showed good therapeutic effect (Grade 1, 3.4%; Grade 2a, 31.0%; Grade 2b, 48.3%; Grade 3, 3.4%; Grade 4, 3.4%). Median disease-free survival was 15.5 months. Median overall survival in the whole cohort was 35.1 months. The only independent prognostic pre-NACIMRT factor identified was serum carbohydrate antigen 19-9 (CA19-9) > 400 U/ml before NACIMRT. NACIMRT showed preferable outcome without significant operative morbidity for BRPC-A patients. NACIMRT contributes to good local tumor control, but a high initial serum CA19-9 implies poor prognosis even after neoadjuvant treatment. UMIN-CTR Clinical Trial: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000011776 Registration number: UMIN000010113. Date of first registration: 01/03/2013.