European Radiology

, Volume 28, Issue 10, pp 4265–4273 | Cite as

Surgery after FOLFIRINOX treatment for locally advanced and borderline resectable pancreatic cancer: increase in tumour attenuation on CT correlates with R0 resection

  • Giovanni Marchegiani
  • Valentina Todaro
  • Enrico Boninsegna
  • Riccardo Negrelli
  • Binit Sureka
  • Debora Bonamini
  • Roberto Salvia
  • Riccardo Manfredi
  • Roberto Pozzi Mucelli
  • Claudio BassiEmail author



To assess factors associated with radical resection (R0) of pancreatic ductal adenocarcinoma (PDAC) after induction treatment with FOLFIRINOX.


Patients with either locally advanced (LA) and borderline resectable (BR) PDAC undergoing surgical exploration after FOLFIRINOX were retrospectively enrolled. Two pancreatic radiologists reviewed the CT blinded to the final outcome and assessed chemotherapy response and resectability. Patients were then divided into R0 resected (group A) and not resected/R1 resected (group B), which were compared.


Of 59 patients included, 19 were defined as unresectable (32%), 33 borderline resectable (56%) and 7 resectable (12%) during the blind radiological evaluation after FOLFIRINOX. Once in a surgical setting, 27% were non-resectable, whereas 73% received surgical resection with a 70% R0 rate. Consequent sensitivity and specificity were 86% and 29%. At imaging review, significant decreases in longest tumour dimension were observed in both groups: from 32 mm (95% CI 15–55) to 21 (10–44) in group A and from 34 (18–70) to 26 (7–60) in group B, p < 0.05. However, a significant increase in tumour attenuation in all phases was only observed for R0 resected, from 52 HU (26–75) to 65 (35–92) in arterial phase (p < 0.001) and from 62 (36–96) to 78 (40–120) in the venous (p = 0.001).


After neoadjuvant FOLFIRINOX, CT predicted resectability with acceptable sensitivity but low specificity. The observation of increased tumour attenuation at CT scan after FOLFIRINOX treatment might represent a reliable predictor of R0 resection.

Key Points

• CT drives the assessment of PDAC resectability after FOLFIRINOX

• CT predicts resectability with acceptable sensitivity but low specificity

• Significant increase in tumour attenuation was only observed for R0 resected PDAC

• Tumour attenuation after FOLFIRINOX represents a reliable predictor of R0 resection


Pancreas ductal carcinoma Multidetector computed tomography Neoplasm staging Induction chemotherapy Pancreatectomy 



Americas Hepato-Pancreato-Biliary Association


American Joint Committee on Cancer


Borderline resectable


Computed tomography


Diffusion-weighted imaging


Locally advanced


Magnetic resonance


Pancreatic ductal adenocarcinoma


Response Evaluation Criteria In Solid Tumours



The authors state that this work has not received any funding.

Compliance with ethical standards


The scientific guarantor of this publication is Claudio Bassi, MD.

Conflict of interest

The authors of this manuscript declare no relationships with any companies whose products or services may be related to the subject matter of the article.

Statistics and biometry

One of the authors has significant statistical expertise.

No complex statistical methods were necessary for this paper.

Informed consent

Written informed consent was obtained from all subjects (patients) in this study.

Ethical approval

Institutional review board approval was obtained.


• retrospective

• diagnostic or prognostic study

• performed at one institution


  1. 1.
    American Cancer Society (2017) Key statistics for pancreatic cancer. Accessed 8 Sept 2017
  2. 2.
    Hidalgo M (2010) Pancreatic Cancer. N Eng J Med 362:1605–1617CrossRefGoogle Scholar
  3. 3.
    Konstantinidis IT, Wharshaw AL, Allen JN et al (2013) Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg 257:731–736CrossRefGoogle Scholar
  4. 4.
    Suker M, Beumer BR, Sadot E et al (2016) FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol 17:801–810CrossRefGoogle Scholar
  5. 5.
    Conroy T, Desseigne F, Ychou M et al (2011) FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Eng J Med 364:1817–1825CrossRefGoogle Scholar
  6. 6.
    White RR, Hurwitz HI, Morse MA et al (2001) Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol 8:758–765CrossRefGoogle Scholar
  7. 7.
    Landry J, Catalano PJ, Staley C et al (2010) Randomized phase II study of gemcitabine plus radiotherapy versus gemcitabine, 5-fluorouracil, and cisplatin followed by radiotherapy and 5-fluorouracil for patients with locally advanced, potentially resectable pancreatic adenocarcinoma. J Surg Oncol 101:587–592CrossRefGoogle Scholar
  8. 8.
    Cai S, Hong TS, Goldberg SI et al (2013) Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. Cancer 119:4196–4204CrossRefGoogle Scholar
  9. 9.
    Nitsche U, Wenzel P, Siveke JT et al (2015) Resectability after first line folfirinox in initially unresectable locally advanced pancreatic cancer: a single center experience. Ann Surg Oncol 22:s1212–s1220CrossRefGoogle Scholar
  10. 10.
    Gillen S, Schuster T, Meyer Zum Büschenfelde C, Friess H, Kleeff J (2010) Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 7:e1000267CrossRefGoogle Scholar
  11. 11.
    Strobel O, Hank T, Hinz U et al (2017) Pancreatic cancer surgery: the new R-status counts. Ann Surg 265:565–573CrossRefGoogle Scholar
  12. 12.
    Katz MH, Pisters PW, Evans DB et al (2008) Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg 206:833–846 discussion 46-8CrossRefGoogle Scholar
  13. 13.
    Katz MH, Marsh R, Herman JM et al (2013) Borderline resectable pancreatic cancer: need for standardization and methods for optimal clinical trial design. Ann Surg Oncol 20:2787–2795CrossRefGoogle Scholar
  14. 14.
    Tempero MA, Arnoletti JP, Behrman SW et al (2012) Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Canc Netw 10:703–713CrossRefGoogle Scholar
  15. 15.
    Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC (2009) Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 16:1727–1733CrossRefGoogle Scholar
  16. 16.
    Balachandran A, Bhosale PR, Charnsangavej C, Tamm EP (2014) Imaging of pancreatic neoplasms. Surg Oncol Clin N Am 23:751–788CrossRefGoogle Scholar
  17. 17.
    Brennan DDD, Zamboni GA, Raptopoulos VD, Kruskal JB (2007) Comprehensive preoperative assessment of pancreatic adenocarcinoma with 64-section volumetric CT. Radiographics 27:1653–1666CrossRefGoogle Scholar
  18. 18.
    Lee ES, Lee JM (2014) Imaging diagnosis of pancreatic cancer: a state-of-the-art review. World J Gastroenterol 20:7864–7877CrossRefGoogle Scholar
  19. 19.
    Lu DSK, Reber HA, Krasny RM, Kadell BM, Sayre J (1997) Local staging of pancreatic cancer: criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT. AJR Am J Roentgenol 168:1439–1443CrossRefGoogle Scholar
  20. 20.
    Chang J, Schomer D, Dragovich T (2015) Anatomical, physiological, and molecular imaging for pancreatic cancer: Current clinical use and future implications. Biomed Res Int 2015:269641PubMedPubMedCentralGoogle Scholar
  21. 21.
    Cassinotto C, Cortade J, Belleannée G et al (2013) An evaluation of the accuracy of CT when determining resectability of pancreatic head adenocarcinoma after neoadjuvant treatment. Eur J Radiol 82:589–593CrossRefGoogle Scholar
  22. 22.
    Kim YE, Park MS, Hong HS et al (2009) Effects of neoadjuvant combined chemotherapy and radiation therapy on the CT evaluation of resectability and staging in patients with pancreatic head cancer. Radiology 250:758–765CrossRefGoogle Scholar
  23. 23.
    Wagner M, Antunes C, Pietrasz D et al (2017) CT evaluation after neoadjuvant FOLFIRINOX chemotherapy for borderline and locally advanced pancreatic adenocarcinoma. Eur Radiol 27:3104–3116CrossRefGoogle Scholar
  24. 24.
    Katz MH, Fleming JB, Bhosale P et al (2012) Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer 118:5749–5756CrossRefGoogle Scholar
  25. 25.
    Cassinotto C, Mouries A, Lafourcade JP et al (2014) Locally advanced pancreatic adenocarcinoma: reassessment of response with CT after neoadjuvant chemotherapy and radiation therapy. Radiology 273:108–116CrossRefGoogle Scholar
  26. 26.
    Morgan DE, Waggoner CN, Canon CL et al (2010) Resectability of pancreatic adenocarcinoma in patients with locally advanced disease downstaged by preoperative therapy: a challenge for MDCT. AJR Am J Roentgenol 194:615–622CrossRefGoogle Scholar
  27. 27.
    Compton CC, Henson DE (1997) Protocol for the examination of specimens removed from patients with carcinoma of the exocrine pancreas: a basis for checklists. Cancer Committee, College of American Pathologists. Arch Pathol Lab Med 121:1129–1136PubMedGoogle Scholar
  28. 28.
    Tempero MA, Malafa MP, Behrman SW et al (2014) Pancreatic adenocarcinoma, version 2.2014: featured updates to the NCCN guidelines. J Natl Compr Canc Netw 12:1083–1093CrossRefGoogle Scholar
  29. 29.
    Eisenhauer EA, Therasse P, Bogaerts J et al (2009) New response evaluation criteria in solid tumor: Revised RECIST guideline (version 1.1). Eur J Cancer 45:228–247CrossRefGoogle Scholar
  30. 30.
    National Comprehensive Cancer Network (NCCN). NCCN updates pancreatic adenocarcinoma guidelines, 2008Google Scholar
  31. 31.
    Varadhachary GR, Tamm EP, Abbruzzese JL et al (2006) Borderline resectable pancreatic cancer: definitions, management and role of preoperative therapy. Ann Surg Oncol 13:1035–1046CrossRefGoogle Scholar
  32. 32.
    Ferrone C, Marchegiani G, Hong TS et al (2015) Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg 261:12–17CrossRefGoogle Scholar
  33. 33.
    Lee SS, Byun JH, Park BJ et al (2008) Quantitative analysis of diffusion-weighted magnetic resonance imaging of the pancreas: usefulness in characterizing solid pancreatic masses. J Magn Reson Imaging 28:928–936CrossRefGoogle Scholar
  34. 34.
    Kartalis N, Manikis GC, Loizou L et al (2016) Diffusion-weighted MR imaging of pancreatic cancer: A comparison of monoexponential, bi-exponential and non-Gaussian kurtosis models. Eur J Radiol Open 3:79–85CrossRefGoogle Scholar
  35. 35.
    Braithwaite AC, Dale BM, Boll DT, Merkle EM (2009) Short and midterm reproducibility of apparent diffusion coefficient measurements at 3.0-T diffusion-weighted imaging of the abdomen. Radiology 250:459–465CrossRefGoogle Scholar
  36. 36.
    Niwa T, Ueno M, Ohkawa S et al (2009) Advanced pancreatic cancer: the use of the apparent diffusion coefficient to predict response to chemotherapy. Br J Radiol 82:28–34CrossRefGoogle Scholar
  37. 37.
    Cuneo KC, Chenevert TL, Ben-Josef E et al (2014) A pilot study of diffusion-weighted MRI in patients undergoing neoadjuvant chemoradiation for pancreatic cancer. Transl Oncol 7:644–649CrossRefGoogle Scholar
  38. 38.
    Barral M, Taouli B, Guiu B et al (2015) Diffusion-weighted MR imaging of the pancreas: current status and recommendations. Radiology 274:45–63CrossRefGoogle Scholar

Copyright information

© European Society of Radiology 2018

Authors and Affiliations

  • Giovanni Marchegiani
    • 1
  • Valentina Todaro
    • 1
  • Enrico Boninsegna
    • 2
  • Riccardo Negrelli
    • 2
  • Binit Sureka
    • 3
  • Debora Bonamini
    • 1
  • Roberto Salvia
    • 1
  • Riccardo Manfredi
    • 4
  • Roberto Pozzi Mucelli
    • 2
  • Claudio Bassi
    • 1
    Email author
  1. 1.Department of General SurgeryVerona University HospitalVeronaItaly
  2. 2.Department of RadiologyVerona University HospitalVeronaItaly
  3. 3.Institute of Liver and Biliary Sciences of New DelhiNew DelhiIndia
  4. 4.Department of Radiology of the Policlinico GemelliCatholic University of RomeRomeItaly

Personalised recommendations