Abstract 3486: Efficacy of neoadjuvant chemotherapy in combination with fluorescence-guided surgery on a pancreatic cancer patient-derived orthotopic xenograft (PDOX)
Authors: Hiroshima Yukihiko , Maawy Ali , Zhang Yong , Sato Sho , Murakami Takashi , Yamamoto Mako , Uehara Fuminari , Miwa Shinji , Yano Shuya , Momiyama Masashi , Chishima Takashi , Tanaka Kuniya , Bouvet Michael , Endo Itaru , Hoffman Robert M. 
Published: May 2015

The aim of this study is to determine the efficacy of neoadjuvant chemotherapy (NAC) in combination with fluorescence-guided surgery (FGS) on pancreatic cancer patient derived orthotopic xenograft (PDOX). We established the PDOX from the patient suffering from metastatic CA19-9-positive pancreatic cancer. Forty nude mice were implanted with tumor using surgical orthotopic implantation (SOI) on the nude mouse pancreas. Four weeks after implantation, the mice with tumor were randomized into 4 treatment groups: (1) bright-light surgery (BLS) only; (2) FGS; (3) NAC-BLS; (4) NAC-FGS. Gemcitabine (80 mg/kg, ip, weekly, 3 weeks) was used for NAC. Seven weeks after implantation, BLS was performed on all tumor-bearing mice. A monoclonal anti-human CA19-9 antibody conjugated with Dylight 650 was delivered to tumor-bearing mice in the FGS groups as a single intravenous dose 24 hours before BLS. Postoperatively, the surgical resection bed of FGS mice were imaged with the OV100 fluorescence imaging system to detect fluorescent residual tumors. The fluorescent residual tumors of FGS groups were then resected under fluorescence navigation. The average resected tumor weight of each group was as follows: (1) BLS, 188.5 ± 50.0 mg; (2) FGS, 278.0 ± 111.4 mg; (3) NAC-BLS, 84.5 ± 48.7 mg; (4) NAC-FGS, 141.8 ± 48.9 mg. The average resected tumor weight of NAC groups was significantly less than the non-NAC groups (113.1 ± 57.0 mg and 235.6 ± 94.3 mg, respectively; p&gt;0.001). The average resected tumor weight of the FGS groups was significantly larger than the BLS groups (213.4 ± 107.1 mg and 136.5 ± 73.8 mg, respectively; p=0.016). Eight weeks after resection, we performed laparotomy to examine recurrence. The recurrence rate of each group was as follows: (1) BLS, 9 / 9 (100%); (2) FGS, 4 / 8 (50%); (3) NAC-BLS, 6 / 9 (66.7%); (4) NAC-FGS, 2 / 8 (25%). The recurrence rate of FGS groups was significantly lower than BLS groups (6 /16; 37.5% and 15 / 18; 83.3%, respectively; p=0.012), whereas there was no significant difference between FGS and NAC-FGS groups (p=0.608). There was no significant difference in the total recurrence rate between NAC and non-NAC groups (p=0.157). However NAC significantly reduced peritoneal recurrence (29.4 % and 0%, respectively; p=0.044). The results indicate that NAC in combination with FGS might reduce or even eliminate the peritoneal recurrence of pancreatic cancer.

Citation Format: Yukihiko Hiroshima, Ali Maawy, Yong Zhang, Sho Sato, Takashi Murakami, Mako Yamamoto, Fuminari Uehara, Shinji Miwa, Shuya Yano, Masashi Momiyama, Takashi Chishima, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M. Hoffman. Efficacy of neoadjuvant chemotherapy in combination with fluorescence-guided surgery on a pancreatic cancer patient-derived orthotopic xenograft (PDOX). [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3486. doi:10.1158/1538-7445.AM2014-3486