Collagen gel droplet-embedded culture drug sensitivity test (CD-DST) predicts the effect of adjuvant chemotherapy on pancreatic cancer

  • Kyohei Ariake
  • Fuyuhiko MotoiEmail author
  • Masamichi Mizuma
  • Hideo Ohtsuka
  • Hiroki Hayashi
  • Kei Nakagawa
  • Tatsuo Hata
  • Katsutaka Mitachi
  • Takeshi Naitoh
  • Takashi Kamei
  • Michiaki Unno
Original Article



We evaluated the clinical effectiveness of collagen gel droplet-embedded culture drug sensitivity tests (CD-DSTs) in predicting the efficacy of adjuvant chemo-therapeutic treatments for pancreatic cancer (PC).


The clinicopathological characteristics and prognoses of 22 PC patients who underwent CD-DST after pancreatectomy at Tohoku University between 2012 and 2016 were analyzed retrospectively. Eligibility criteria were resectable or borderline resectable PC, successful evaluation for 5-fluorouracil sensitivity by CD-DST, treatment with S-1 adjuvant chemotherapy, and no preoperative chemotherapy.


The rate of successful evaluation by CD-DST was 52.3% in PC. The optimal T/C ratio, defined as the ratio of the number of cancer cells in the treatment group (T) to that in the control group (C), for 5-fluorouracil was 85% using receiver operating characteristic curve analysis. The sensitive group (T/C ratio < 85%; n = 11) had a better recurrence-free survival rate than the resistant group (T/C ratio ≥ 85%; n = 11; P = 0.029). A Cox proportional hazards regression model demonstrated that sensitivity to 5-fluorouracil was an independent predictor of recurrence on multivariate analysis (hazard ratio 3.28; 95.0% CI 1.20–9.84; P = 0.020).


CD-DSTs helped to predict PC recurrence after S-1 adjuvant chemotherapy.


Pancreatic cancer Chemosensitivity test CD-DST 



This work was supported in part by a Grant-in-Aid for Scientific Research (24592018) from the Japan Society for the Promotion of Science.

Compliance with ethical standards

Conflict of interest

We have no conflicts of interest to disclose and we did not receive any financial support in relation to this study.

Supplementary material

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Supplementary file1 (DOCX 18 kb)
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Supplementary file3 (DOCX 18 kb)
595_2019_1842_MOESM4_ESM.jpg (200 kb)
Receiver operating characteristic curve of the T/C ratios for predicting recurrence. At the intersection closest to the upper left corner (T/C ratio = 85%), the sensitivity and specificity were 61.1% and 100%, respectively. AUC, area under the curve (JPEG 200 kb)


  1. 1.
    Groot VP, Rezaee N, Wu W, Cameron JL, Fishman EK, Hruban RH, et al. Patterns, timing, and predictors of recurrence following pancreatectomy for pancreatic ductal adenocarcinoma. Ann Surg. 2018;267:936–45.CrossRefGoogle Scholar
  2. 2.
    National Comprehensive Cancer Network. NCCN guidelines version.018 pancreatic adenocarcinoma.
  3. 3.
    Michalski CW, Erkan M, Sauliunaite D, Giese T, Stratmann R, Sartori C, et al. Ex vivo chemosensitivity testing and gene expression profiling predict response towards adjuvant gemcitabine treatment in pancreatic cancer. Br J Cancer. 2008;99:760–7.CrossRefGoogle Scholar
  4. 4.
    Tanigawa N, Yamaue H, Ohyama S, Sakuramoto S, Inada T, Kodera Y, et al. Exploratory phase ii trial in a multicenter setting to evaluate the clinical value of a chemosensitivity test in patients with gastric cancer (JACCRO-GC 04, Kubota memorial trial). Gastric Cancer. 2016;19:350–60.CrossRefGoogle Scholar
  5. 5.
    Mekata E, Sonoda H, Shimizu T, Tatsuta T, Yamaguchi T, Endo Y, et al. Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of adjuvant chemotherapy in patients with stages II–III colorectal cancer. Mol Clin Oncol. 2013;1:763–7.CrossRefGoogle Scholar
  6. 6.
    Kobayashi H, Tanisaka K, Doi O, Kodama K, Higashiyama M, Nakagawa H, et al. An in vitro chemosensitivity test for solid human tumors using collagen gel droplet embedded cultures. Int J Oncol. 1997;11:449–55.Google Scholar
  7. 7.
    Yasuda H, Takada T, Wada K, Amano H, Isaka T, Yoshida M, et al. A new in-vitro drug sensitivity test (collagen-gel droplet embedded-culture drug sensitivity test) in carcinomas of pancreas and biliary tract: possible clinical utility. J Hepatobiliary Pancreat Surg. 1998;5:261–8.CrossRefGoogle Scholar
  8. 8.
    Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501:346–54.CrossRefGoogle Scholar
  9. 9.
    Maejima K, Tokunaga A, Kiyama T, Kanno H, Bou H, Watanabe M, et al. Chemosensitivity test for 5-fluorouracil and 5-chloro-2,4-dihydroxypyridine predicts outcome of gastric cancer patients receiving s-1 postoperatively. Gastric Cancer. 2010;13:231–7.CrossRefGoogle Scholar
  10. 10.
    Naitoh H, Yamamoto H, Murata S, Kobayashi H, Inoue K, Tani T. Stratified phase II trial to establish the usefulness of the collagen gel droplet embedded culture-drug sensitivity test (CD-DST) for advanced gastric cancer. Gastric Cancer. 2014;17:630–7.CrossRefGoogle Scholar
  11. 11.
    Higashiyama M, Oda K, Okami J, Maeda J, Kodama K, Imamura F, et al. Prediction of chemotherapeutic effect on postoperative recurrence by in vitro anticancer drug sensitivity testing in non-small cell lung cancer patients. Lung Cancer. 2010;68:472–7.CrossRefGoogle Scholar
  12. 12.
    Kawamura M, Gika M, Abiko T, Inoue Y, Oyama T, Izumi Y, et al. Clinical evaluation of chemosensitivity testing for patients with unresectable non-small cell lung cancer (NSCLC) using collagen gel droplet embedded culture drug sensitivity test (CD-DST). Cancer Chemother Pharmacol. 2007;59:507–13.CrossRefGoogle Scholar
  13. 13.
    Ochiai T, Nishimura K, Watanabe T, Kitajima M, Nakatani A, Nagayasu K, et al. Impact of the individualization of the first-line chemotherapy for advanced colorectal cancer based on collagen gel droplet-embedded drug sensitivity test. Oncol Lett. 2017;14:6045–52.Google Scholar
  14. 14.
    Uesaka K, Boku N, Fukutomi A, Okamura Y, Konishi M, Matsumoto I, et al. Adjuvant chemotherapy of s-1 versus gemcitabine for resected pancreatic cancer: a phase 3, open-label, randomised, non-inferiority trial (JASPAC 01). Lancet. 2016;388:248–57.CrossRefGoogle Scholar
  15. 15.
    Japan Pancreas Society. Classification of pancreatic carcinoma, 4th English ed. Tokyo: Kanehara & Co., Ltd.; 2017.Google Scholar
  16. 16.
    Motoi F, Satoi S, Honda G, Wada K, Shinchi H, Matsumoto I, et al. A single-arm, phase ii trial of neoadjuvant gemcitabine and s1 in patients with resectable and borderline resectable pancreatic adenocarcinoma: Prep-01 study. J Gastroenterol. 2019;54:194–203.CrossRefGoogle Scholar
  17. 17.
    Satoi S, Yamaue H, Kato K, Takahashi S, Hirono S, Takeda S, et al. Role of adjuvant surgery for patients with initially unresectable pancreatic cancer with a long-term favorable response to non-surgical anti-cancer treatments: results of a project study for pancreatic surgery by the Japanese Society of Hepato-biliary-Pancreatic Surgery. J Hepatobiliary Pancreat Sci. 2013;20:590–600.CrossRefGoogle Scholar
  18. 18.
    Ariake K, Motoi F, Mizuma M, Murakami K, Takadate T, Ohtsuka H, et al. Locally advanced pancreatic cancer successfully treated by distal pancreatectomy with celiac axis resection (DP-CAR) after s-1 with radiation therapy followed by gemcitabine/nab-paclitaxel therapy: a case report. Surg Case Rep. 2017;3:15.CrossRefGoogle Scholar
  19. 19.
    Bai J, Sata N, Nagai H. Gene expression analysis for predicting gemcitabine sensitivity in pancreatic cancer patients. HPB (Oxford). 2007;9:150–5.CrossRefGoogle Scholar

Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Kyohei Ariake
    • 1
  • Fuyuhiko Motoi
    • 1
    Email author
  • Masamichi Mizuma
    • 1
  • Hideo Ohtsuka
    • 1
  • Hiroki Hayashi
    • 1
  • Kei Nakagawa
    • 1
  • Tatsuo Hata
    • 1
  • Katsutaka Mitachi
    • 1
  • Takeshi Naitoh
    • 1
  • Takashi Kamei
    • 1
  • Michiaki Unno
    • 1
  1. 1.Department of SurgeryTohoku University Graduate School of MedicineSendaiJapan

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