Skip to main content

Advertisement

SpringerLink
Log in

Outcomes of Neoadjuvant Chemotherapy Versus Chemoradiation in Localized Pancreatic Cancer: A Case–Control Matched Analysis

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

Abstract

Background

Neoadjuvant therapy is increasingly used for patients with pancreatic ductal adenocarcinoma (PDAC). It is unknown whether neoadjuvant chemoradiotherapy is more effective than chemotherapy (NCRT vs. NAC). We aim to compare pathological and survival outcomes of NCRT and NAC in patients with PDAC.

Patients and Methods

Single-center analysis of PDAC patients treated with NCRT or NAC followed by resection between December 2008 and December 2018 was performed. Average treatment effect (ATE) was estimated after case–control matching using Mahalanobis distance nearest-neighbor matching. Inverse probability weighted estimates (IPWE)-based ATE was estimated for disease-free survival (DFS) and overall survival (OS).

Results

Among the 418 patients (mean age 66.8 years, 51% female) included in the study, 327 received NAC and 91 received NCRT. NCRT patients had higher rates of locally advanced disease, number of neoadjuvant chemotherapy cycles, more chemotherapy regimen crossover (gemcitabine and 5-FU based), and were more likely to undergo open surgical procedures and/or vascular resection (all p < 0.05). After matched analysis, NCRT was associated with a significant reduction in lymph node positive disease [ATE = (−)0.24, p = 0.007] and lymphovascular invasion [ATE = (−)0.20, p = 0.02]. While NCRT was associated with significantly improved DFS by 9.5 months (p = 0.006), it did not affect OS by IPWE-based ATE after adjusting for adjuvant therapy (ATE = 5.5 months; p = 0.32).

Conclusion

Compared with NAC alone, NCRT is associated with improved pathologic surrogates and disease-free survival, but not overall survival in patients with PDAC.

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. Rawla P, Sunkara T, Gaduputi V. Epidemiology of pancreatic cancer: global trends, etiology and risk factors. World J Oncol. 2019;10(1):10–27. https://doi.org/10.14740/wjon1166.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Howlader N, Noone AM, Krapcho M, Miller D, Brest A, Yu M, Ruhl J, Tatalovich Z, Mariotto A, Lewis DR, Chen HS, Feuer EJ, Cronin KA (eds). SEER Cancer Statistics Review, 1975–2016, National Cancer Institute. Bethesda, MD, https://seer.cancer.gov/csr/1975_2016/, based on November 2018 SEER data submission, posted to the SEER web site, April 2019.

  3. Nagakawa Y, Sahara Y, Hosokawa Y et al. Clinical impact of neoadjuvant chemotherapy and chemoradiotherapy in borderline resectable pancreatic cancer: analysis of 884 patients at facilities specializing in pancreatic surgery. Ann Surg Oncol. 2019;26(6):1629–36. https://doi.org/10.1245/s10434-018-07131-8.

    Article  PubMed  Google Scholar 

  4. Youngwirth LM, Nussbaum DP, Thomas S et al. Nationwide trends and outcomes associated with neoadjuvant therapy in pancreatic cancer: an analysis of 18243 patients. J Surg Oncol. 2017;116(2):127–32. https://doi.org/10.1002/jso.24630.

    Article  CAS  PubMed  Google Scholar 

  5. Zhan HX, Xu JW, Wu D et al. Neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of prospective studies. Cancer Med. 2017;6(6):1201–19. https://doi.org/10.1002/cam4.1071.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Versteijne E, Suker M, Groothuis K et al. Preoperative chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: results of the dutch randomized phase III PREOPANC trial. J Clin Oncol. 2020; 27:JCO1902274. https://doi.org/10.1200/jco.19.02274.

    Article  CAS  Google Scholar 

  7. Macedo FI, Ryon E, Maithel SK et al. Survival outcomes associated with clinical and pathological response following neoadjuvant FOLFIRINOX or Gemcitabine/Nab-Paclitaxel chemotherapy in resected pancreatic cancer. Ann Surg. 2019;270(3):400–13. https://doi.org/10.1097/sla.0000000000003468.

    Article  PubMed  Google Scholar 

  8. Al Abbas AI, Zenati M, Reiser CJ et al. Serum CA19-9 Response to neoadjuvant therapy predicts tumor size reduction and survival in pancreatic adenocarcinoma. Ann Surg Oncol. 2020. https://doi.org/10.1245/s10434-019-08156-3.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Tempero MA, Malafa MP, Chiorean EG et al. Pancreatic adenocarcinoma, Version 1.2019. J Natl Compr Cancer Netw. 2019;17(3):202–10. https://doi.org/10.6004/jnccn.2019.0014.

    Article  Google Scholar 

  10. Landau E, Kalnicki S. The evolving role of radiation in pancreatic cancer. Surg Clin North Am. 2018;98(1):113–25. https://doi.org/10.1016/j.suc.2017.09.008.

    Article  PubMed  Google Scholar 

  11. Neoptolemos JP, Dunn JA, Stocken DD et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358(9293):1576–85.

    Article  CAS  Google Scholar 

  12. Neoptolemos JP, Stocken DD, Friess H et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. . 2004;350(12):1200–10.

    Article  CAS  Google Scholar 

  13. 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(9):1019–26. https://doi.org/10.1001/jama.299.9.1019.

    Article  CAS  PubMed  Google Scholar 

  14. Neoptolemos JP, Palmer DH, Ghaneh P, et al. European study group for pancreatic cancer. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): a multicentre, open-label, randomised, phase 3 trial. Lancet. 2017;389(10073):1011–24. https://doi.org/10.1016/s0140-6736(16)32409-6.

    Article  CAS  PubMed  Google Scholar 

  15. 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  Google Scholar 

  16. Conroy T, Hammel P, Hebbar M, Ben Abdelghani M, Wei AC, Raoul JL, Choné L, Francois E, Artru P, Biagi JJ, Lecomte T, Assenat E, Faroux R, Ychou M, Volet J, Sauvanet A, Breysacher G, Di Fiore F, Cripps C, Kavan P, Texereau P, Bouhier-Leporrier K, Khemissa-Akouz F, Legoux JL, Juzyna B, Gourgou S, O’Callaghan CJ, Jouffroy-Zeller C, Rat P, Malka D, Castan F, Bachet JB. Canadian cancer trials group and the unicancer-GI-PRODIGE. Group FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379:2395–406.

    Article  CAS  Google Scholar 

  17. Regine WF, Winter KA, Abrams R et al. Fluorouracil‐based chemoradiation with either gemcitabine or fluorouracil chemotherapy after resection of pancreatic adenocarcinoma: 5‐year analysis of the US Intergroup/RTOG 9704 phase III trial. Ann Surg Oncol. 2011;18:1319–26.

    Article  Google Scholar 

  18. Wu L, Zhou Y, Fan Y et al. Consolidative chemoradiotherapy after induced chemotherapy is an optimal regimen for locally advanced pancreatic cancer. Front Oncol. 2020;21(9):1543. https://doi.org/10.3389/fonc.2019.01543.

    Article  Google Scholar 

  19. Chen-Zhao X, Hernando O, López M et al. A prospective observational study of the clinical and pathological impact of stereotactic body radiotherapy (SBRT) as a neoadjuvant strategy of chemoradiation in pancreatic cancer. Clin Transl Oncol. 2020. https://doi.org/10.1007/s12094-020-02287-w.

    Article  PubMed  Google Scholar 

  20. National Comprehensive Cancer Network. Pancreatic cancer (Version 1.2020). https://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed 26 Feb 2020.

  21. Chun YS, Pawlik TM, Vauthey JN. 8th Edition of the AJCC cancer staging manual: pancreas and hepatobiliary cancers. Ann Surg Oncol. 2018;25(4):845–7.

    Article  Google Scholar 

  22. Kakar S, Shi C, Adsay V et al. Protocol for the examination of specimens from patients with carcinoma of the pancreas, [Internet], version Pancreas Exocrine 4.0.0.1. CAP, 2017. https://documents.cap.org/protocols/cp-gihepatobiliary-pancreas-exocrine17protocol4001.pdf.

  23. Evans DB, Rich TA, Byrd DR et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127(11):1335–9.

    Article  CAS  Google Scholar 

  24. Stuart EA. Matching methods for causal inference: a review and a look forward. Stat Sci. 2010;25:1.

    Article  Google Scholar 

  25. Austin PC. Variance estimation when using inverse probability of treatment weighting (IPTW) with survival analysis. Stat Med. 2016;35(30):5642–55. https://doi.org/10.1002/sim.7084.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Schorn S, Demir IE, Reyes CM et al. The impact of neoadjuvant therapy on the histopathological features of pancreatic ductal adenocarcinoma—a systematic review and meta-analysis. Cancer Treat Rev. 2017;55:96–106. https://doi.org/10.1016/j.ctrv.2017.03.003.

    Article  CAS  PubMed  Google Scholar 

  27. Chatterjee D, Katz MH, Rashid A et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome. Cancer. 2012;118(12):3182–90.

    Article  Google Scholar 

  28. Shinde A, Verma V, Li R et al. The role of sequential radiation following adjuvant chemotherapy in resected pancreatic cancer. J Gastrointest Oncol. 2019;10(3):462–73. https://doi.org/10.21037/jgo.2019.01.19.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Rutter CE, Park HS, Corso CD et al. Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base. Cancer. 2015;121(23):4141–9. https://doi.org/10.1002/cncr.29652.

    Article  CAS  PubMed  Google Scholar 

  30. Khattab A, Patruni S, Abel S et al. Long-term outcomes by response to neoadjuvant chemotherapy or chemoradiation in patients with resected pancreatic adenocarcinoma. J Gastrointest Oncol. 2019;10(5):918–27. https://doi.org/10.21037/jgo.2019.07.02.

    Article  PubMed  PubMed Central  Google Scholar 

  31. di Sebastiano P, Grottola T, di Mola FF. Borderline resectable pancreatic cancer and the role of neoadjuvant chemoradiotherapy. Updates Surg. 2016;68(3):235–9.

    Article  Google Scholar 

  32. Reames BN, Blair AB, Krell RW et al. Management of locally advanced pancreatic cancer: results of an international survey of current practice. Ann Surg. 2019. https://doi.org/10.1097/sla.0000000000003568.

    Article  Google Scholar 

  33. Cloyd JM, Chen HC, Wang X et al. Chemotherapy versus chemoradiation as preoperative therapy for resectable pancreatic ductal adenocarcinoma: a propensity score adjusted analysis. Pancreas. 2019;48(2):216–22. https://doi.org/10.1097/mpa.0000000000001231.

    Article  CAS  PubMed  Google Scholar 

  34. Versteijne E, Vogel JA, Besselink MG et al. Meta-analysis comparing upfront surgery with neoadjuvant treatment in patients with resectable or borderline resectable pancreatic cancer. Br J Surg. 2018;105(8):946–58. https://doi.org/10.1002/bjs.10870.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Murata Y, Mizuno S, Kishiwada M et al. Impact of histological response after neoadjuvant chemoradiotherapy on recurrence-free survival in UICC-T3 pancreatic adenocarcinoma but not in UICC-T4. Pancreas. 2012;41(1):130–6. https://doi.org/10.1097/mpa.0b013e3182236442.

    Article  CAS  PubMed  Google Scholar 

  36. Jiang W, Haque W, Verma V, Butler EB, Teh BS. Neoadjuvant stereotactic body radiation therapy for nonmetastatic pancreatic adenocarcinoma. Acta Oncol. 2019;58(9):1259–66. https://doi.org/10.1080/0284186x.2019.1631472.

    Article  PubMed  Google Scholar 

  37. Mellon EA, Strom TJ, Hoffe SE et al. Favorable perioperative outcomes after resection of borderline resectable pancreatic cancer treated with neoadjuvant stereotactic radiation and chemotherapy compared with upfront pancreatectomy for resectable cancer. J Gastrointest Oncol. 2016;7(4):547–55. https://doi.org/10.21037/jgo.2016.03.15.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Xiang M, Heestand GM, Chang DT, Pollom EL. Neoadjuvant treatment strategies for resectable pancreas cancer: A propensity-matched analysis of the National Cancer Database. Radiother Oncol. 2020;143:101–7. https://doi.org/10.1016/j.radonc.2020.01.007.

    Article  CAS  PubMed  Google Scholar 

  39. Tchelebi LT, Lehrer EJ, Trifiletti DM et al. Conventionally fractionated radiation therapy versus stereotactic body radiation therapy for locally advanced pancreatic cancer (CRiSP): an international systematic review and meta-analysis. Cancer. 2020. https://doi.org/10.1002/cncr.32756.

    Article  PubMed  Google Scholar 

  40. Gao S, Zhu X, Shi X et al. Comparisons of different neoadjuvant chemotherapy regimens with or without stereotactic body radiation therapy for borderline resectable pancreatic cancer: study protocol of a prospective, randomized phase II trial (BRPCNCC-1). Radiat Oncol. 2019;14(1):52. https://doi.org/10.1186/s13014-019-1254-8.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Holyoake DL, Ward E, Grose D et al. A phase-I trial of pre-operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the ‘SPARC’ trial protocol. BMC Cancer. 2016;16(1):728. https://doi.org/10.1186/s12885-016-2765-4.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Lei Huang, Lina Jansen, Yesilda Balavarca et al. Stratified survival of resected and overall pancreatic cancer patients in europe and the USA in the early twenty-first century: a large, international population-based study. BMC Med. 2018;16(1):125. https://doi.org/10.1186/s12916-018-1120-9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

Melissa Hogg—Grant money from SAGES and Intuitive Surgical. No funding.

Author information

Authors and Affiliations

  1. Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA

    Asmita Chopra MBBS, David Bartlett MD, Kenneth K. Lee MD, Michael T. Lotze MD, Alessandro Paniccia MD & Amer H. Zureikat MD

  2. Wolff Center at UPMC, Pittsburgh, PA, USA

    Jacob C. Hodges MS

  3. Department of Radiation Oncology, University of Pittsburgh, Pittsburgh, PA, USA

    Adam Olson MD, MS, Steve Burton MD & Susannah G. Ellsworth MD

  4. Department of Medical Oncology, University of Pittsburgh, Pittsburgh, PA, USA

    Nathan Bahary MD

  5. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA

    Aatur D. Singhi MD, PhD

  6. Department of Surgery, West Virginia University, Morgantown, WV, USA

    Brian A. Boone MD

  7. Department of Surgery, Ohio State University, Columbus, OH, USA

    Joal D. Beane MD

  8. Department of Surgery, North Shore Hospital, Chicago, IL, USA

    Melissa E. Hogg MD

  9. Department of Surgery, University of Texas Southwestern, Dallas, TX, USA

    Herbert Zeh MD

  10. Surgery, Division of Surgical Oncology, Pancreatic Cancer Center, University of Pittsburgh Medical Center, Pittsburgh, PA, USA

    Amer H. Zureikat MD

Authors
  1. Asmita Chopra MBBS
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacob C. Hodges MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Adam Olson MD, MS
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Steve Burton MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Susannah G. Ellsworth MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathan Bahary MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Aatur D. Singhi MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Brian A. Boone MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Joal D. Beane MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David Bartlett MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kenneth K. Lee MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Melissa E. Hogg MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michael T. Lotze MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Alessandro Paniccia MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Herbert Zeh MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Amer H. Zureikat MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Amer H. Zureikat MD.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Chopra, A., Hodges, J.C., Olson, A. et al. Outcomes of Neoadjuvant Chemotherapy Versus Chemoradiation in Localized Pancreatic Cancer: A Case–Control Matched Analysis. Ann Surg Oncol 28, 3779–3788 (2021). https://doi.org/10.1245/s10434-020-09391-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-020-09391-9

Search

Navigation