Abstract 556: The detection of viable human circulating tumor cells (v-hCTCs) in resectable pancreatic cancer induced by neoadjuvant chemoradiotherapy (NACRT) using gemcitabine, S-1 and intensity-modulated radiotherapy (IMRT)
Authors: Tanemura Masahiro , Irei Toshimitsu , Inoue Masashi , Yamashita Shinya , Furukawa Kenta , Wakasugi Masaki , Kishi Kentaro , Nagano Hiroaki , Akamatsu Hiroki , Urata Yasuo , Hatanaka Nobuyoshi , Mori Masaki , Doki Yuichiro 
Published: August 2015

Abstract
Circulating tumor cells (CTCs) are thought to be “metastatic intermediates”. Recently, we reported encouraging survival rates following neoadjuvant therapy using gemcitabine (Gem) and S-1 concurrently with radiotherapy (NACRT) in patients (pts) with resectable pancreatic cancer (PC). However, NACRT may have disadvantages. We hypothesized that NACRT in PC may induce epithelial to mesenchymal transition (EMT), which is associated with metastasis followed by the increase of CTCs. To extend our assessment of EMT during NACRT, we investigate the results of the v-hCTC detection in the pts treated with NACRT. This study was a single institution trial, approved by the Kure Medical Center IRB. Pts with resectable cytologically or histologically proven ductal adenocarcinoma of the pancreas were enrolled. Treatment consisted of an intervenous infusion of Gem 800 mg/m2 on day 1, 8, 22, and 29; and S-1 80 mg/m2 orally on day 1-5, 8-12, 22-26, and 29-33 given concurrently with IMRT to 60 Gy (2 Gy/day, 5 times per week, 30 fractions). Surgical exploration was scheduled 4-7 weeks after the final radiation fraction. To detect v-hCTCs, we employed a telomerase-specific replication-selective adenovirous expressing GFP (TelomeScan F35). 7.5 ml of blood samples were obtained from the pts included in this clinical study before NACRT, after 1 month of NACRT, and after 2 months of surgical resection. To distinguish between leucocyte and cells with epithelial origin, cells were stained with anti-CD45 and anti-Cytokeratin Abs. To distinguish cells with mesenchymal origin, cells were labeled with anti-Vimentin Ab. GFP-positive and CD45-negative cells were counted as v-hCTC. 12 pts aged 44-77 years (2 males and 10 females) were enrolled. No treatment-related deaths occurred. CA19-9 was reduced to &lt;50% of baseline values in 7 of 9 measureable pts. 11 of 12 enrolled pts successfully underwent surgical resection. Only 4 out of 12 pts had one or two v-hCTCs detected before NACRT. After NACRT, 6 of 12 pts without tumor progression had v-hCTCs detected, which expressed Vimentin (1-56 CTCs). Among them, 3 pts had v-hCTCs detected at baseline. These 3 CTC-positive pts still had two or more Vimentin-positive CTCs detected (2-27 CTCs) after surgery, whereas remaining 9 pts had no detectable v-hCTCs. 1 of these 3 CTC-positive pts early developed liver metastasis and died, despite R0 resection. For the remaining 2 CTC-positive pts after surgery, one pt with postoperative therapy had no detectable CTCs at 1 year after surgery, however another pt without postoperative therapy still had 7 v-hCTCs detected (Vimentin[+]). We believe that our NACRT is feasible. However, we may consider “surgery first” for CTC-positive PC pts at baseline. In conclusion, v-hCTCs may become useful for prognosis assessment or stratification, especially when radiotherapy is considered.
Citation Format: Masahiro Tanemura, Toshimitsu Irei, Masashi Inoue, Shinya Yamashita, Kenta Furukawa, Masaki Wakasugi, Kentaro Kishi, Hiroaki Nagano, Hiroki Akamatsu, Yasuo Urata, Nobuyoshi Hatanaka, Masaki Mori, Yuichiro Doki. The detection of viable human circulating tumor cells (v-hCTCs) in resectable pancreatic cancer induced by neoadjuvant chemoradiotherapy (NACRT) using gemcitabine, S-1 and intensity-modulated radiotherapy (IMRT). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 556. doi:10.1158/1538-7445.AM2015-556