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Neoadjuvant Therapy is Associated with a Reduced Lymph Node Ratio in Patients with Potentially Resectable Pancreatic Cancer

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Abstract

Background

The use of neoadjuvant therapy (NAC) for the treatment of potentially resectable pancreatic cancer remains controversial. In this study, we sought to evaluate cancer-specific endpoints in patients undergoing a NAC versus a surgery-first (SF) approach with specific emphasis on lymph node metastases.

Methods

A total of 222 patients who underwent NAC and 85 patients who underwent SF were identified from 1990 to 2008 and compared for cancer-related endpoints. Peripancreatic lymph nodes from 135 neoadjuvant therapy patients were evaluated for histologic tumor regression.

Results

Patients who underwent NAC followed by surgery had improved overall survival and time to local recurrence compared with the SF approach. NAC patients were less likely to have lymph node metastases (p = 0.001), lymphovascular invasion (LVI), and had smaller tumors. On multivariate analysis, lymph node positivity was associated with SF, tumor size, and the presence of LVI. NAC patients with N0 disease had equivalent outcomes to patients with a low-LNR (0.01–0.15), whereas patients with a LNR >0.15 had reduced survival, and time to local and distant recurrence. Ten of 135 (7.4 %) NAC patients had evidence of tumor regression in at least one lymph node.

Conclusions

Patients with potentially resectable PDAC selected to undergo NAC had improved survival and longer time to recurrence. Although some of these differences may be related to improvements in multimodality therapy completion rates, tumor regression in lymph node metastases exists and may demonstrate a biologic benefit of NAC compared with a SF approach.

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References

  1. Tzeng CW, Tran Cao HS, Lee JE, et al. Treatment sequencing for resectable pancreatic cancer: influence of early metastases and surgical complications on multimodality therapy completion and survival. J Gastrointest Surg. 2014;18(1):16-24; discussion 24-5.

    Article  PubMed  Google Scholar 

  2. Varadhachary GR, Wolff RA, Crane CH, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3487-95.

    Article  CAS  PubMed  Google Scholar 

  3. Bilimoria KY, Bentrem DJ, Ko CY, et al. Multimodality therapy for pancreatic cancer in the U.S.: utilization, outcomes, and the effect of hospital volume. Cancer. 2007;110(6):1227-34.

    Article  PubMed  Google Scholar 

  4. Colbert LE, Hall WA, Nickleach D, et al. Chemoradiation therapy sequencing for resected pancreatic adenocarcinoma in the National Cancer Data Base. Cancer. 2014;120(4):499-506.

    Article  PubMed  Google Scholar 

  5. Evans DB, Varadhachary GR, Crane CH, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26(21):3496-502.

    Article  CAS  PubMed  Google Scholar 

  6. Embuscado EE, Laheru D, Ricci F, et al. Immortalizing the complexity of cancer metastasis: genetic features of lethal metastatic pancreatic cancer obtained from rapid autopsy. Cancer Biol Ther. 2005;4(5):548-54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Dholakia AS, Kumar R, Raman SP, et al. Mapping patterns of local recurrence after pancreaticoduodenectomy for pancreatic adenocarcinoma: a new approach to adjuvant radiation field design. Int J Radiat Oncol Biol Phys. 2013;87(5):1007-15.

    Article  PubMed Central  PubMed  Google Scholar 

  8. Pancreatic adenocarcinoma Version 2.2102. NCCN Clinical Practice Guideline in Oncology (NCCN Guidelines). New York: National Comprehensive Cancer Network (NCCN), 2012.

  9. Winter JM, Brennan MF, Tang LH, et al. Survival after resection of pancreatic adenocarcinoma: results from a single institution over three decades. Ann Surg Oncol. 2012;19(1):169-75.

    Article  PubMed  Google Scholar 

  10. Simons JP, Ng SC, McDade TP, Zhou Z, Earle CC, Tseng JF. Progress for resectable pancreatic cancer: a population-based assessment of US practices. Cancer. 2010;116(7):1681-90.

    Article  PubMed  Google Scholar 

  11. Bhatti I, Peacock O, Awan AK, Semeraro D, Larvin M, Hall RI. Lymph node ratio versus number of affected lymph nodes as predictors of survival for resected pancreatic adenocarcinoma. World J Surg. 2010;34(4):768-75. doi: 10.1007/s00268-009-0336-4

    Article  PubMed  Google Scholar 

  12. La Torre M, Cavallini M, Ramacciato G, et al. Role of the lymph node ratio in pancreatic ductal adenocarcinoma. Impact on patient stratification and prognosis. J Surg Oncol. 2011;104(6):629-33.

    Article  PubMed  Google Scholar 

  13. Murakami Y, Uemura K, Sudo T, et al. Number of metastatic lymph nodes, but not lymph node ratio, is an independent prognostic factor after resection of pancreatic carcinoma. J Am Coll Surg. 2010;211(2):196-204.

    Article  PubMed  Google Scholar 

  14. Pawlik TM, Gleisner AL, Cameron JL, et al. Prognostic relevance of lymph node ratio following pancreaticoduodenectomy for pancreatic cancer. Surgery. 2007;141(5):610-8.

    Article  PubMed  Google Scholar 

  15. Slidell MB, Chang DC, Cameron JL, et al. Impact of total lymph node count and lymph node ratio on staging and survival after pancreatectomy for pancreatic adenocarcinoma: a large, population-based analysis. Ann Surg Oncol. 2008;15(1):165-74.

    Article  PubMed  Google Scholar 

  16. Caricato M, Ausania F, De Dominicis E, et al. Tumor regression in mesorectal lymphnodes after neoadjuvant chemoradiation for rectal cancer. Eur J Surg Oncol. 2007;33(6):724-8.

    Article  CAS  PubMed  Google Scholar 

  17. Dominici LS, Negron Gonzalez VM, Buzdar AU, et al. Cytologically proven axillary lymph node metastases are eradicated in patients receiving preoperative chemotherapy with concurrent trastuzumab for HER2-positive breast cancer. Cancer. 2010;116(12):2884-9.

    Article  PubMed  Google Scholar 

  18. Chun YS, Cooper HS, Cohen SJ, et al. Significance of pathologic response to preoperative therapy in pancreatic cancer. Ann Surg Oncol. 2011;18(13):3601-3607.

    Article  PubMed  Google Scholar 

  19. Estrella JS, Rashid A, Fleming JB, et al. Post-therapy pathologic stage and survival in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant chemoradiation. Cancer. 2012;118(1):268-77.

    Article  PubMed  Google Scholar 

  20. Hwang RF, Wang H, Lara A, et al. Development of an integrated biospecimen bank and multidisciplinary clinical database for pancreatic cancer. Ann Surg Oncol. 2008;15(5):1356-66.

    Article  PubMed  Google Scholar 

  21. Yen TW, Abdalla EK, Pisters PW, Evans DB. Pancreaticoduodenectomy. Sandury: Jones and Bartlett; 2005.

    Google Scholar 

  22. Katz MH, Wang H, Balachandran A, et al. Effect of neoadjuvant chemoradiation and surgical technique on recurrence of localized pancreatic cancer. J Gastrointest Surg. 2012;16(1):68-78; discussion 78-9.

    Article  PubMed  Google Scholar 

  23. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti III A. AJCC cancer staging manual. New York: Springer; 2009.

    Google Scholar 

  24. 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(5):833-46; discussion 846-8.

    Article  PubMed  Google Scholar 

  25. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13(8):1035-46.

    Article  PubMed  Google Scholar 

  26. Katz MH, Wang H, Fleming JB, et al. Long-term survival after multidisciplinary management of resected pancreatic adenocarcinoma. Ann Surg Oncol. 2009;16(4):836-47.

    Article  PubMed Central  PubMed  Google Scholar 

  27. Oettle H, Neuhaus P, Hochhaus A, et al. Adjuvant chemotherapy with gemcitabine and long-term outcomes among patients with resected pancreatic cancer: the CONKO-001 randomized trial. JAMA. 2013;310(14):1473-81.

    Article  CAS  PubMed  Google Scholar 

  28. Sinn M, Striefler JK, Sinn BV, et al. Does long-term survival in patients with pancreatic cancer really exist? Results from the CONKO-001 study. J Surg Oncol. 2013;108(6):398-402.

    Article  CAS  PubMed  Google Scholar 

  29. Valsangkar NP, Bush DM, Michaelson JS, et al. N0/N1, PNL, or LNR? The effect of lymph node number on accurate survival prediction in pancreatic ductal adenocarcinoma. J Gastrointest Surg. 2013;17(2):257-66.

    Article  PubMed Central  PubMed  Google Scholar 

  30. Kadera BE, Sunjaya DB, Isacoff WH, et al. Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival. JAMA Surg. 2014;149(2):145-53.

    Article  PubMed  Google Scholar 

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Acknowledgment

This research has been supported by the Khalifa Bin Zayed Al Nahyan Foundation and the various donor pancreatic cancer research funds at the University of Texas MD Anderson Cancer Center and the Ruth L. Kirschstein National Research Service Award NIH T32 CA009599. The authors thank Joel Cox for his management of our departmental pancreatic cancer database.

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Authors and Affiliations

  1. Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA

    Christina L. Roland MD, Anthony D. Yang MD, Matthew H. G. Katz MD, Jean N. Vauthey MD, Peter W. Pisters MD, Jeffrey E. Lee MD & Jason B. Fleming MD

  2. Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Deyali Chatterjee MD & Huamin Wang MD

  3. Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Heather Lin PhD

  4. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Gauri R. Varadhachary MD & Robert A. Wolff MD

  5. Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Christopher H. Crane MD

  6. Department of Surgery, University of California-Davis Health System, Sacramento, CA, USA

    Anthony D. Yang MD

Authors
  1. Christina L. Roland MD
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  2. Anthony D. Yang MD
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  3. Matthew H. G. Katz MD
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  4. Deyali Chatterjee MD
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  5. Huamin Wang MD
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  7. Jean N. Vauthey MD
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  9. Gauri R. Varadhachary MD
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  13. Jason B. Fleming MD
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Corresponding author

Correspondence to Jason B. Fleming MD.

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Christina L. Roland and Anthony D. Yang have equal contributions.

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Roland, C.L., Yang, A.D., Katz, M.H.G. et al. Neoadjuvant Therapy is Associated with a Reduced Lymph Node Ratio in Patients with Potentially Resectable Pancreatic Cancer. Ann Surg Oncol 22, 1168–1175 (2015). https://doi.org/10.1245/s10434-014-4192-6

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  • DOI: https://doi.org/10.1245/s10434-014-4192-6

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