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Resection of Locally Advanced Pancreatic Cancer without Regression of Arterial Encasement After Modern-Era Neoadjuvant Therapy

  • 2017 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery

Abstract

Introduction

Modern-era systemic therapy for locally advanced pancreatic adenocarcinoma (LAPC) offers improved survival relative to historical regimens but not necessarily improved radiographic downstaging to allow more patients to undergo resection. The aim of this study was to evaluate the survival, progression, and pathologic outcomes after resection of LAPC that did not regress from > 180 degrees arterial encasement after neoadjuvant therapy.

Methods

Sixty-one LAPC patients were brought to the operating room after neoadjuvant therapy for NCCN-defined unresectable pancreatic cancer between 2012 and 2017. Pts were explored with intent of pancreatectomy and irreversible electroporation for margin extension; 5 (8%) had metastatic lesions on exploratory laparoscopy and were excluded from analyses. Imaging was re-examined to confirm LAPC prior to surgery. Data were analyzed from a prospective pancreatic cancer database.

Results

Patients had arterial involvement of the celiac axis (37.5%) and/or superior mesenteric artery (42.9%) and/or an extended length of the common hepatic (n = 44.6%) artery. Twenty-nine males and 27 females, median 65 years of age, received neoadjuvant gemcitabine-based (58.9%) or FOLFIRINOX (35.7%) chemotherapy and stereotactic body (42.9%) or intensity-modulated (51.8%) radiation therapy. Median months from initiation of neoadjuvant therapy to surgery was 7.5. Sixty-one percent underwent Whipple, 21% distal, and 18% modified Appleby procedures; 57% patients underwent venous reconstruction. Ninety-day mortality was 2%. An R0 margin was achieved in 80%, and 53% were N0. Median overall and progression-free survival was 18.5 (95%CI 12.27–32.33) and 8.5 months (95%CI 6.0–15.0), respectively. One- and 3-year survival from surgery was 68.5% (95%CI 53.0–79.7) and 39.0% (95%CI 23.7–53.8), respectively.

Conclusion

With modern-era neoadjuvant therapy, R0 resections can be achieved in a majority of non-metastatic patients with locally advanced, unresectable disease based on cross-sectional imaging.

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Abbreviations

IRE:

Irreversible electroporation

LAPC:

Locally advanced pancreatic cancer

References

  1. McDowell BD, Chapman CG, Smith BJ, Button AM, Chrischilles EA, Mezhir JJ. Pancreatectomy Predicts Improved Survival for Pancreatic Adenocarcinoma Results of an Instrumental Variable Analysis. Ann Surg. 2015;261:740–745.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, Bassi C, Dervenis C, Fernandez-Cruz L, Lacaine F, Buckels J, Deakin M, Adab FA, Sutton R, Imrie C, Ihse I, Tihanyi T, Olah A, Pedrazzoli S, Spooner D, Kerr DJ, Friess H, Büchler MW; European Study Group for Pancreatic Cancer. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234(6):758–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Konstantinidis IT, Warshaw AL, Allen JN, Blaszkowsky LS, Castillo CF, Deshpande V, Hong TS, Kwak EL, Lauwers GY, Ryan DP, Wargo JA, Lillemoe KD, Ferrone CR. Pancreatic ductal adenocarcinoma: is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg. 2013;257(4):731–6.

    Article  PubMed  Google Scholar 

  4. Strobel O, Berens V, Hinz U, Hartwig W, Hackert T, Bergmann F, Debus J, Jäger D, Büchler MW, Werner J. Resection after neoadjuvant therapy for locally advanced, “unresectable” pancreatic cancer. Surgery. 2012;152(3 Suppl 1):S33–42.

    Article  PubMed  Google Scholar 

  5. Sherman WH, Chu K, Chabot J, et al. Neoadjuvant gemcitabine, docetaxel, and capecitabine followed by gemcitabine and capecitabine/radiation therapy and surgery in locally advanced, unresectable pancreatic adenocarcinoma. Cancer. 2015;121(5):673–80.

    Article  CAS  PubMed  Google Scholar 

  6. Heinemann V, Haas M, Boeck S. Neoadjuvant treatment of borderline resectable and non-resectable pancreatic cancer. Annals of Oncology 2013;24(10):2484–92.

    Article  CAS  PubMed  Google Scholar 

  7. Gurusamy KS, Kumar S, Davidson BR, Fusai G. Resection versus other treatments for locally advanced pancreatic cancer. Cochrane Database of Systematic Reviews 2014, Issue 2. Art. No.: CD010244.

  8. Bockhorn M, Uzunoglu FG, Adham M, Imrie C, Milicevic M, Sandberg AA, et al. Borderline resectable pancreatic cancer: a consensus statement by the International Study Group of Pancreatic Surgery (ISGPS). Surgery. 2014;155(6):977–88.

    Article  PubMed  Google Scholar 

  9. Suker M, Beumer BR, Sadot E, Marthey L, Faris JE, Mellon EA, El-Rayes BF, Wang-Gillam A, Lacy J, Hosein PJ, Moorcraft SY, Conroy T, Hohla F, Allen P, Taieb J, Hong TS, Shridhar R, Chau I, van Eijck CH, Groot Koerkamp B. FOLFIRINOX for locally advanced pancreatic cancer: a systematic review and patient-level meta-analysis. Lancet Oncol. 2016;17(6):801–10

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Conroy T, Desseigne F, Ychou M, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. New Engl J Med. 2011;364:1817–1825.

    Article  CAS  PubMed  Google Scholar 

  11. Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, Seay T, Tjulandin SA, Ma WW, Saleh MN, Harris M, Reni M, Dowden S, Laheru D, Bahary N, Ramanathan RK, Tabernero J, Hidalgo M, Goldstein D, Van Cutsem E, Wei X, Iglesias J, Renschler MF. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703

    Article  Google Scholar 

  12. Martin RC 2nd, Kwon D, Chalikonda S, Sellers M, Kotz E, Scoggins C, McMasters KM, Watkins K. Treatment of 200 locally advanced (stage III) pancreatic adenocarcinoma patients with irreversible electroporation: safety and efficacy. Ann Surg. 2015;262(3):486–94

    Article  PubMed  Google Scholar 

  13. Kluger MD, Epelboym I, Schrope BA, Mahendraraj K, Hecht EM, Susman J, Weintraub JL, Chabot JA. Single-Institution Experience with Irreversible Electroporation for T4 Pancreatic Cancer: First 50 Patients. Ann Surg Oncol. 2016;23(5):1736–43

    Article  PubMed  Google Scholar 

  14. Callery MP, Chang KJ, Fishman EK, Talamonti MS, William Traverso L, Linehan DC. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–1733

    Article  PubMed  Google Scholar 

  15. Pancreatic Ductal Adenocarcinoma Radiology Reporting Template: Consensus Statement of the Society of Abdominal Radiology and the American Pancreatic Association. Radiology 2014;270(1); 248–260.

  16. Verbeke CS, Leitch D, Menon KV, et al. Redefining the R1 resection in pancreatic cancer. Br J Surg. 2006;93:1232–1237.

    Article  CAS  PubMed  Google Scholar 

  17. Esposito I, Kleeff J, Bergmann F, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–1660.

    Article  PubMed  Google Scholar 

  18. Menon KV, Gomez D, Smith AM, et al. Impact of margin status on survival following pancreatoduodenectomy for cancer: the Leeds Pathology Protocol (LEEPP). HPB. 2009;11:18–24.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Morgan DE, Waggoner CN, Canon CL, et al. Resectability of pancreatic adenocarcinoma in patients with locally advanced disease downstaged by preoperative therapy: a challenge for MDCT. AJR Am J Roentgenol 2010;194(3):615–622.

    Article  PubMed  Google Scholar 

  20. Ferrone CR, Marchegiani G, Hong TS, Ryan DP, Deshpande V, McDonnell EI, Sabbatino F, Santos DD, Allen JN, Blaszkowsky LS, Clark JW, Faris JE, Goyal L, Kwak EL, Murphy JE, Ting DT, Wo JY, Zhu AX, Warshaw AL, Lillemoe KD, Fernández-del Castillo C. Radiological and surgical implications of neoadjuvant treatment with FOLFIRINOX for locally advanced and borderline resectable pancreatic cancer. Ann Surg. 2015;261(1):12–7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Vogel JA, van Veldhuisen E, Agnass P, Crezee J, Dijk F, Verheij J, van Gulik TM, Meijerink MR, Vroomen LG, van Lienden KP, Besselink MG. Time-Dependent Impact of Irreversible Electroporation on Pancreas, Liver, Blood Vessels and Nerves: A Systematic Review of Experimental Studies. PLoS One. 2016;11(11):e0166987.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Vroomen LGPH, Scheffer HJ, Melenhorst MCAM, de Jong MC, van den Bergh JE, van Kuijk C, van Delft F, Kazemier G, Meijerink MR. MR and CT imaging characteristics and ablation zone volumetry of locally advanced pancreatic cancer treated with irreversible electroporation. Eur Radiol. 2017;27(6):2521–2531.

    Article  PubMed  Google Scholar 

  23. Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, et al. Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. JAMA. 2016;315(17):1844–53.

    Article  CAS  PubMed  Google Scholar 

  24. Katz MHG, Shi Q, Ahmad SA, et al. Preoperative Modified FOLFIRINOX Treatment Followed by Capecitabine-Based Chemoradiation for Borderline Resectable Pancreatic Cancer: Alliance for Clinical Trials in Oncology Trial A021101. JAMA surgery. 2016;151(8):e161137.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004;350:1200–10.

    Article  CAS  PubMed  Google Scholar 

  26. Neoptolemos JP, Stocken DD, Bassi C, Ghaneh P, Cunningham D, Goldstein D, et al. Adjuvant chemotherapy with fluorouracil plus folinic acid vs gemcitabine following pancreatic cancer resection: a randomized controlled trial. JAMA 2010;304:1073–81.

    Article  CAS  PubMed  Google Scholar 

  27. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007;297:267–77.

    Article  CAS  PubMed  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Surgery, Division of Gastrointestinal and Endocrine Surgery, Columbia University, College of Physicians and Surgeons, New York, NY, USA

    Michael D. Kluger, M. Farzan Rashid, Vilma L. Rosario, Beth A. Schrope & John A. Chabot

  2. Department of Radiology, Columbia University, College of Physicians and Surgeons, New York, NY, USA

    Jonathan A. Steinman & Elizabeth M. Hecht

  3. Division of GI & Endocrine Surgery, Columbia College of Physicians and Surgeons, New York-Presbyterian Hospital, 161 Fort Washington Ave—8th Floor, New York, NY, 10032, USA

    John A. Chabot

Authors
  1. Michael D. Kluger
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  2. M. Farzan Rashid
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  3. Vilma L. Rosario
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  4. Beth A. Schrope
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Contributions

All the authors contributed to the conception or design of the project; assisted with the acquisition, analysis, or interpretation of data; drafted and/or revised the manuscript; and had final approval of the version to be published. All the authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity may be resolved.

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Correspondence to John A. Chabot.

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The authors declare that they have no conflicts of interest.

Additional information

Presented: Digestive Disease Week 2017. Chicago, IL; May 2017

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Kluger, M.D., Rashid, M.F., Rosario, V.L. et al. Resection of Locally Advanced Pancreatic Cancer without Regression of Arterial Encasement After Modern-Era Neoadjuvant Therapy. J Gastrointest Surg 22, 235–241 (2018). https://doi.org/10.1007/s11605-017-3556-1

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  • DOI: https://doi.org/10.1007/s11605-017-3556-1

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