Abstract 1539: Live circulating tumor cells as a predictive biomarker of response to neoadjuvant chemoradiotherapy for resectable pancreatic cancer
Authors: Tanemura Masahiro , Furukawa Kenta , Wakasugi Masaki , Kishi Kentaro , Urata Yasuo , Taniyama Kiyomi , Akamatsu Hiroki 
Published: July 2016

The detection of increase in the number of circulating tumor cells (CTCs) during a patient's clinical course may be a harbinger of forthcoming overt metastasis. To detect live CTCs (l-CTCs) in blood samples of cancer patients (pts), we employed a new genetically modified telomerase-specific replication-selective adenovirous, expressing GFP (TelomeScanF35), containing both type 35 fiber that induce broad infectivity and miR-142-3p target sequence that can prevent a false positive toward blood cells. Recently, we indicated that preoperative chemoradiation therapy comprising gemcitabine and S-1 administration concurrent with full-dose radiation (NACRT) lead to encouraging survival rate in pts with resectable pancreatic cancer. But, NACRT may have disadvantages. NACRT requires several months, potentially delaying surgical resection, and can be waste of time and may result in the pts missing the chance for surgery. We assessed the l-CTCs burden in pts treated with NACRT. This study was approved by the Osaka Police Hospital 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. Surgical exploration was scheduled 4-7 weeks after the final radiation fraction. 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 l-CTC. 16 pts aged 44-78 years (5 males and 11 females) were enrolled. No treatment-related deaths occurred. CA19-9 was reduced to &lt;50% of baseline values in 10 of 12 measureable pts. 13 of 16 enrolled pts successfully underwent surgical resection. 5 of 16 enrolled pts had l-CTCs (1∼4CTCs,Vimentin[+]) detected before NACRT. An increase in CTCs was seen in 4 of 5 pts after NACRT, but no detectable l-CTCs were observed in only 1 pt after NACRT. These 4 CTC-positive pts continuously had CTCs detected after surgery. 2 of 4 CTC-positive pts early developed liver metastasis and died, despite R0 resection. On the contrary, small increase (1∼2CTCs) of CTCs was seen after NACRT in 4 of 11pts, who had no CTCs detected before NACRT. But, no l-CTCs were detected in these 11 pts after surgery and they survived without recurrence. CTC-positive pts before NACRT presented a higher rate of liver metastasis after surgery than CTC-negative pts (50% vs. o%). We may consider surgery first for the CTC-positive pts before NACRT. The capture of l-CTCs may be useful biomarker for prognosis assessment or stratification.

Citation Format: Masahiro Tanemura, Kenta Furukawa, Masaki Wakasugi, Kentaro Kishi, Yasuo Urata, Kiyomi Taniyama, Hiroki Akamatsu. Live circulating tumor cells as a predictive biomarker of response to neoadjuvant chemoradiotherapy for resectable pancreatic cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1539.