Skip to main content

Advertisement

SpringerLink
Log in

Outcomes of a Clinical Pathway for Borderline Resectable Pancreatic Cancer

  • Pancreatic Tumors
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Without prospective data establishing a consensus multimodality approach to borderline resectable pancreatic adenocarcinoma, institutional treatment regimens vary. This study investigated the outcomes of the clinical pathway at the author’s institution, which consists of neoadjuvant gemcitabine, docetaxel, capecitabine, and stereotactic radiotherapy followed by surgery.

Methods

The study reviewed all cases that met the National Comprehensive Cancer Network (NCCN) diagnostic criteria for borderline resectable pancreatic adenocarcinoma from 1 January 2006, to 31 December 2013. Pancreatectomy rates, margin status, pathologic response, disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS) were retrospectively examined. Standard statistical methods and Kaplan–Meier survival analysis were used for statistical comparisons.

Results

Of 121 patients who met criteria, 101 entered the clinical pathway, and 94 (93.1 %) completed neoadjuvant chemotherapy and radiation therapy. Of the 101 patients, 55 (54.5 %) underwent pancreatectomy, with 53 patients (96.4 %) having microscopically negative margins (R0) and 2 patients (3.6 %) having microscopically positive margins (R1). Vascular resection was required for 22 patients (40 %), with rates of 95.5 % for R0 (n = 21) and 4.5 % for R1 (n = 1). A pathologic response to treatment was demonstrated by 45 patients (81.8 %) and a complete response by 10 patients (14.5 %). Pancreatectomy resulted in a median DFS of 23 months (95 % conflidence interval [CI] 14.5–31.5), a median DSS of 43 months (95 % CI, 25.7–60.3), and a median OS of 33 months (95 % CI, 25.0–41.0) versus a median DSS and OS of 14 months (95 % CI, 10.9–17.1) for patients without pancreatectomy (DSS: P = 3.5 × 10−13; OS: P = 4.7 × 10−10).

Conclusions

The study demonstrated high rates for neoajduvant therapy completion (93.1 %) and pancreatectomy (54.5 %). After pancreatectomy, DSS was significantly improved (43 months), with a pathologic response demonstrated by 81.8 % and a complete response by 14.5 % of the patients. The results support further study of this borderline resectable pancreatic adenocarcinoma clinical pathway.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel R, DeSantis C, Virgo K, et al. Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin. 2012;62:220–41.

    Article  PubMed  Google Scholar 

  2. American Cancer Society. Cancer Facts and Figures 2014. Retrieved 21 May 2014 at http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2014.

  3. Howlander N, Noone AM, Krapcho M, et al. SEER Cancer Statistics Review, 1975–2011. Bethesda, MD: National Cancer Institute; 2011.

    Google Scholar 

  4. Yeo CJ, Abrams RA, Grochow LB, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival: a prospective, single-institution experience. Ann Surg. 1997;225:621–33; discussion 633–626.

  5. Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma: an outcomes trial. Cancer. 2000;89:314–27.

    Article  CAS  PubMed  Google Scholar 

  6. Stokes JB, Nolan NJ, Stelow EB, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol. 2011;18:619–27.

    Article  PubMed  Google Scholar 

  7. Zakharova OP, Karmazanovsky GG, Egorov VI. Pancreatic adenocarcinoma: outstanding problems. World J Gastrointest Surg. 2012;4:104–13.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Evans DB, Farnell MB, Lillemoe KD, Vollmer C Jr, Strasberg SM, Schulick RD. Surgical treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1736–44.

    Article  PubMed  Google Scholar 

  9. Forrest JF, Longmire WP Jr. Carcinoma of the pancreas and periampullary region. Ann Surg. 1979;189:129–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Neoptolemos JP, Stocken DD, Dunn JA, et al. 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;234:758–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas—616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.

    Article  CAS  PubMed  Google Scholar 

  12. 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;16:1727–33.

    Article  PubMed  Google Scholar 

  13. Talamonti M. Borderline resectable pancreatic cancer: a new classification for an old challenge. Ann Surg Oncol. 2006;13:1019–20.

    Article  PubMed  Google Scholar 

  14. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13:1035–46.

    Article  PubMed  Google Scholar 

  15. Varadhachary GR, Tamm EP, Crane C, Evans DB, Wolff RA. Borderline resectable pancreatic cancer. Curr Treat Options Gastroenterol. 2005;8:377–84.

    Article  PubMed  Google Scholar 

  16. Evans DB, Erickson BA, Ritch P. Borderline resectable pancreatic cancer: definitions and the importance of multimodality therapy. Ann Surg Oncol. 2010;17:2803–5.

    Article  PubMed  Google Scholar 

  17. Tempero MA, Arnoletti JP, Behrman SW, et al. Pancreatic adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines. J Natl Compr Cancer Netw. 2012;10:703–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Vauthey JN, Dixon E. AHPBA/SSO/SSAT Consensus Conference on Resectable and Borderline Resectable Pancreatic Cancer: rationale and overview of the conference. Ann Surg Oncol. 2009;16:1725–6. Epub April 2009, 1724.

  19. Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46; discussion 846–838.

  20. Wolff RA. Neoadjuvant therapy for resectable and borderline resectable adenocarcinoma of the pancreas. Curr Drug Targets. 2012;13:781–8.

    Article  CAS  PubMed  Google Scholar 

  21. Andriulli A, Festa V, Botteri E, et al. Neoadjuvant/preoperative gemcitabine for patients with localized pancreatic cancer: a meta-analysis of prospective studies. Ann Surg Oncol. 2012;19:1644–62.

    Article  PubMed  Google Scholar 

  22. Gillen S, Schuster T, Meyer Zum Buschenfelde C, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Morganti AG, Massaccesi M, La Torre G, et al. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 2010;17:194–205.

    Article  PubMed  Google Scholar 

  24. Zhou Y, Zhang Z, Liu Y, Li B, Xu D. Pancreatectomy combined with superior mesenteric vein–portal vein resection for pancreatic cancer: a meta-analysis. World J Surg. 2012;36:884–91.

    Article  PubMed  Google Scholar 

  25. Brunner TB, Geiger M, Grabenbauer GG, et al. Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer. J Clin Oncol. 2008;26:2699–706.

    Article  CAS  PubMed  Google Scholar 

  26. Hosein PJ, Macintyre J, Kawamura C, et al. A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma. BMC Cancer. 2012;12:199.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Lee JL, Kim SC, Kim JH, et al. Prospective efficacy and safety study of neoadjuvant gemcitabine with capecitabine combination chemotherapy for borderline-resectable or unresectable locally advanced pancreatic adenocarcinoma. Surgery. 2012;152:851–62.

    Article  PubMed  Google Scholar 

  28. Patel M, Hoffe S, Malafa M, et al. Neoadjuvant GTX chemotherapy and IMRT-based chemoradiation for borderline resectable pancreatic cancer. J Surg Oncol. 2011;104:155–61.

  29. Rose JB, Rocha FG, Alseidi A, et al. Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival. Ann Surg Oncol. 2014;21:1530–7.

    Article  PubMed  Google Scholar 

  30. Landry J, Catalano PJ, Staley C, et al. 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. 2010;101:587–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Rashid OM, Mullinax J, Pimiento JM. Robotic whipple in the management of pancreatic cancer: description of a clinical pathway and systemic review of prior experience. Cancer Control. 2015;22:340–51.

  32. Neoptolemos JP, Stocken DD, Bassi C, 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 

  33. Regine WF, Winter KA, Abrams RA, et al. Fluorouracil vs gemcitabine chemotherapy before and after fluorouracil-based chemoradiation following resection of pancreatic adenocarcinoma: a randomized controlled trial. JAMA. 2008;299:1019–26.

    Article  CAS  PubMed  Google Scholar 

  34. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Washington MK, Berlin J, Branton PA, et al. Protocol for the examination of specimens from patients with carcinoma of the distal extrahepatic bile ducts. Arch Pathol Lab Med. 2010;134:e8–e13.

    PubMed  Google Scholar 

  36. Chun YS, Milestone BN, Watson JC, et al. Defining venous involvement in borderline resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2832–8.

    Article  PubMed  Google Scholar 

  37. Walters DM, Lapar DJ, de Lange EE, et al. Pancreas-protocol imaging at a high-volume center leads to improved preoperative staging of pancreatic ductal adenocarcinoma. Ann Surg Oncol. 2011;18:2764–71.

  38. McClaine RJ, Lowy AM, Sussman JJ, Schmulewitz N, Grisell DL, Ahmad SA. Neoadjuvant therapy may lead to successful surgical resection and improved survival in patients with borderline resectable pancreatic cancer. HPB Oxford. 2010;12:73–9.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Parsons CM, Sutcliffe JL, Bold RJ. Preoperative evaluation of pancreatic adenocarcinoma. J Hepatobiliary Pancreat Surg. 2008;15:429–35.

    Article  Google Scholar 

  40. Satoi S, Yanagimoto H, Toyokawa H, et al. Pre-operative patient selection of pancreatic cancer patients by multi-detector row CT. Hepatogastroenterology. 2009;56:529–34.

    PubMed  Google Scholar 

  41. Dewitt J, Devereaux BM, Lehman GA, Sherman S, Imperiale TF. Comparison of endoscopic ultrasound and computed tomography for the preoperative evaluation of pancreatic cancer: a systematic review. Clin Gastroenterol Hepatol. 2006;4:717–25; quiz 664.

  42. Tempero MA, Arnoletti JP, Behrman S, et al. Pancreatic adenocarcinoma. J Natl Compr Cancer Netw. 2010;8:972–1017.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Buchs NC, Chilcott M, Poletti PA, Buhler LH, Morel P. Vascular invasion in pancreatic cancer: Imaging modalities, preoperative diagnosis and surgical management. World J Gastroenterol. 2010;16:818–31.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Majumder S, Chubineh S, Birk J. Pancreatic cancer: an endoscopic perspective. Expert Rev Gastroenterol Hepatol. 2012;6:95–103; quiz 104.

  45. Greer SE, Pipas JM, Sutton JE, et al. Effect of neoadjuvant therapy on local recurrence after resection of pancreatic adenocarcinoma. J Am Coll Surg. 2008;206:451–7.

    Article  PubMed  Google Scholar 

  46. Kelly KJ, Winslow E, Kooby D, et al. Vein involvement during pancreaticoduodenectomy: is there a need for redefinition of “borderline resectable disease”? J Gastrointest Surg. 2013;17:1209–17; discussion 1217.

  47. Reddy SS, Hoffman JP. “Vein involvement during pancreaticoduodenectomy: is there a need for redefinition of borderline resectable disease”: a commentary on the article published by Kelly et al. in the J Gastrointest Surg 2013;17:1209. J Gastrointest Surg. 2014;18:1719.

    Article  PubMed  Google Scholar 

  48. Varadhachary GR. Preoperative therapies for resectable and borderline resectable pancreatic cancer. J Gastrointest Oncol. 2011;2:136–42.

    PubMed  PubMed Central  Google Scholar 

  49. Wang F, Kumar P. The role of radiotherapy in management of pancreatic cancer. J Gastrointest Oncol. 2011;2:157–67.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgment

We thank Rasa Hamilton (Moffitt Cancer Center) for editorial assistance. This work was supported in part by the Moffitt’s Total Cancer Care Initiative and Collaborative Data Services Core at the H. Lee Moffitt Cancer Center & Research Institute, an NCI-designated Comprehensive Cancer Center, under grant number P30-CA076292. This study was supported in part by the National Institutes of Health Grants 1R01 CA-129227-01A1, 5RO1 CA-098473-05, and DAVOS 69-15099-99-01 (to MP Malafa).

Conflict of interest

There are no conflicts of interest.

Author information

Author notes

    Authors and Affiliations

    1. Department of Gastrointestinal Oncology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

      Omar M. Rashid MD, JD, Jose M. Pimiento MD, Andrew W. Gamenthaler MD, Phuong Nguyen BS, Tin T. Ha BSc, Tai Hutchinson RN, Gregory Springett MD, Sarah Hoffe MD, Ravi Shridhar MD, Pamela J. Hodul MD, Barbara A. Centeno MD & Mokenge P. Malafa MD

    2. University of South Florida, Tampa, FL, USA

      Brad L. Johnson MD, Karl Illig MD & Paul A. Armstrong MD

    3. Department of Biostatistics, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, USA

      William J. Fulp MS & Dung-Tsa Chen PhD

    Authors
    1. Omar M. Rashid MD, JD
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Jose M. Pimiento MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Andrew W. Gamenthaler MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Phuong Nguyen BS
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Tin T. Ha BSc
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Tai Hutchinson RN
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Gregory Springett MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Sarah Hoffe MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Ravi Shridhar MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Pamela J. Hodul MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    11. Brad L. Johnson MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    12. Karl Illig MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    13. Paul A. Armstrong MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    14. Barbara A. Centeno MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    15. William J. Fulp MS
      View author publications

      You can also search for this author in PubMed Google Scholar

    16. Dung-Tsa Chen PhD
      View author publications

      You can also search for this author in PubMed Google Scholar

    17. Mokenge P. Malafa MD
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Mokenge P. Malafa MD.

    Additional information

    O. M. Rashid and J. M. Pimiento contributed equally to this work

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Rashid, O.M., Pimiento, J.M., Gamenthaler, A.W. et al. Outcomes of a Clinical Pathway for Borderline Resectable Pancreatic Cancer. Ann Surg Oncol 23, 1371–1379 (2016). https://doi.org/10.1245/s10434-015-5006-1

    Download citation

    • Received:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1245/s10434-015-5006-1

    Keywords

    Search

    Navigation