A Systematic Review and Meta-analysis of Survival and Surgical Outcomes Following Neoadjuvant Chemoradiotherapy for Pancreatic Cancer

  • Jerome Martin Laurence
  • Peter Duy Tran
  • Kavita Morarji
  • Guy D. Eslick
  • Vincent Wai To Lam
  • Charbel Sandroussi
Original Article



This systematic review and meta-analysis aims to characterize the surgically important benefits and complications associated with the use of neoadjuvant chemoradiotherapy for the treatment of both resectable and initially unresectable pancreatic cancer. Studies were identified through a systematic literature search and analyzed by two independent reviewers. Survival, peri-operative complications, death rate, pancreatic fistula rate, and the incidence of involved surgical margins were analyzed and subject to meta-analysis.


Nineteen studies, involving 2,148 patients were identified. Only cohort studies were included.


The meta-analysis found that patients with unresectable pancreatic cancer who underwent neoadjuvant chemoradiotherapy achieved similar survival outcomes to patients with resectable disease, even though only 40% were ultimately resected. Neoadjuvant chemoradiotherapy was not associated with a statistically significant increase in the rate of pancreatic fistula formation or total complications.


Patients receiving neoadjuvant chemoradiotherapy were less likely to have a positive resection margin, although there was an increase in the risk of peri-operative death.


Neoadjuvant treatment Pancreatic neoplasms Chemoradiotherapy Systematic review Meta-analysis 


  1. 1.
    Jemal A, Siegel R, Xu J, et al. Cancer statistics, 2010. CA Cancer J Clin 2010; 60 (5): 277–300.PubMedCrossRefGoogle Scholar
  2. 2.
    A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group. Ann Surg 1979; 189 (2): 205–208.Google Scholar
  3. 3.
    Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Inst 1988; 80 (10): 751–755.CrossRefGoogle Scholar
  4. 4.
    Chauffert B, Mornex F, Bonnetain F, et al. Phase III trial comparing intensive induction chemoradiotherapy (60 Gy, infusional 5-FU and intermittent cisplatin) followed by maintenance gemcitabine with gemcitabine alone for locally advanced unresectable pancreatic cancer. Definitive results of the 2000–01 FFCD/SFRO study. Ann Oncol 2008; 19 (9): 1592–1599.PubMedCrossRefGoogle Scholar
  5. 5.
    Brunner TB, Grabenbauer GG, Meyer T, et al. Primary resection versus neoadjuvant chemoradiation followed by resection for locally resectable or potentially resectable pancreatic carcinoma without distant metastasis. A multi-centre prospectively randomised phase II-study of the Interdisciplinary Working Group Gastrointestinal Tumours (AIO, ARO, and CAO). BMC Cancer 2007; 7: 41.PubMedCrossRefGoogle Scholar
  6. 6.
    Gillen S, Schuster T, Meyer Zum Buschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med 2010; 7 (4): e1000267.PubMedCrossRefGoogle Scholar
  7. 7.
    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 (1): 194–205.PubMedCrossRefGoogle Scholar
  8. 8.
    Delpero JR, Turrini O. [Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection]. Cancer Radiother 2006; 10 (6–7): 462–470.PubMedCrossRefGoogle Scholar
  9. 9.
    Higgins JPT GS. Cochrane Handbook for Systematic Reviews of Interventions Version 5.02, 2009.Google Scholar
  10. 10.
    Higgins JP, Thompson SG, Deeks JJ, et al. Measuring inconsistency in meta-analyses. BMJ 2003; 327 (7414): 557–560.PubMedCrossRefGoogle Scholar
  11. 11.
    Macaskill P, Walter SD, Irwig L. A comparison of methods to detect publication bias in meta-analysis. Stat Med 2001; 20 (4): 641–654.PubMedCrossRefGoogle Scholar
  12. 12.
    Egger M, Davey Smith G, Schneider M, et al. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315 (7109): 629–634.PubMedCrossRefGoogle Scholar
  13. 13.
    Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analyses of the published literature for survival endpoints. Stat Med 1998; 17 (24): 2815–2834.PubMedCrossRefGoogle Scholar
  14. 14.
    Tierney JF, Stewart LA, Ghersi D, et al. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials 2007; 8: 16.PubMedCrossRefGoogle Scholar
  15. 15.
    Al-Sukhun S, Zalupski MM, Ben-Josef E, et al. Chemoradiotherapy in the treatment of regional pancreatic carcinoma: a phase II study. Am J Clin Oncol 2003; 26 (6): 543–549.PubMedCrossRefGoogle Scholar
  16. 16.
    Allendorf JD, Lauerman M, Bill A, et al. Neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic adenocarcinoma: feasibility, efficacy, and survival. J Gastrointest Surg 2008; 12 (1): 91–100.PubMedCrossRefGoogle Scholar
  17. 17.
    Bruckner HW, Kalnicki S, Dalton J, et al. Survival after combined modality therapy for pancreatic cancer. J Clin Gastroenterol 1993; 16 (3): 199–203.PubMedCrossRefGoogle Scholar
  18. 18.
    Chao C, Hoffman JP, Ross EA, et al. Pancreatic carcinoma deemed unresectable at exploration may be resected for cure: an institutional experience. Am Surg 2000; 66 (4): 378–385; discussion 386.PubMedGoogle Scholar
  19. 19.
    Golcher H, Brunner T, Grabenbauer G, et al. Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy. Eur J Surg Oncol 2008; 34 (7): 756–764.PubMedCrossRefGoogle Scholar
  20. 20.
    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 (3): 451–457.PubMedCrossRefGoogle Scholar
  21. 21.
    Ishikawa O, Ohigashi H, Imaoka S, et al. Is the long-term survival rate improved by preoperative irradiation prior to Whipple's procedure for adenocarcinoma of the pancreatic head? Arch Surg 1994; 129 (10): 1075–1080.PubMedGoogle Scholar
  22. 22.
    Jessup JM, Steele G, Jr., Mayer RJ, et al. Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg 1993; 128 (5): 559–564.PubMedGoogle Scholar
  23. 23.
    Kim HJ, Czischke K, Brennan MF, et al. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg 2002; 6 (5): 763–769.PubMedCrossRefGoogle Scholar
  24. 24.
    Lind PA, Isaksson B, Almstrom M, et al. Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma. Acta Oncol 2008; 47 (3): 413–420.PubMedCrossRefGoogle Scholar
  25. 25.
    Massucco P, Capussotti L, Magnino A, et al. Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival. Ann Surg Oncol 2006; 13 (9): 1201–1208.PubMedCrossRefGoogle Scholar
  26. 26.
    Pendurthi TK, Hoffman JP, Ross E, et al. Preoperative versus postoperative chemoradiation for patients with resected pancreatic adenocarcinoma. Am Surg 1998; 64 (7): 686–692.PubMedGoogle Scholar
  27. 27.
    Pingpank JF, Hoffman JP, Ross EA, et al. Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg 2001; 5 (2): 121–130.PubMedCrossRefGoogle Scholar
  28. 28.
    Piperdi M, McDade TP, Shim JK, et al. A neoadjuvant strategy for pancreatic adenocarcinoma increases the likelihood of receiving all components of care: lessons from a single-institution database. HPB (Oxford) 2010; 12 (3): 204–210.Google Scholar
  29. 29.
    Satoi S, Yanagimoto H, Toyokawa H, et al. Surgical results after preoperative chemoradiation therapy for patients with pancreatic cancer. Pancreas 2009; 38 (3): 282–288.PubMedCrossRefGoogle Scholar
  30. 30.
    Snady H, Bruckner H, Cooperman A, et al. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer 2000; 89 (2): 314–327.PubMedCrossRefGoogle Scholar
  31. 31.
    Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 1997; 15 (3): 928–937.PubMedGoogle Scholar
  32. 32.
    Vento P, Mustonen H, Joensuu T, et al. Impact of preoperative chemoradiotherapy on survival in patients with resectable pancreatic cancer. World J Gastroenterol 2007; 13 (21): 2945–2951.PubMedGoogle Scholar
  33. 33.
    Grading systems and levels of evidence and grade of recommendation. SIGN guideline development handbook: SIGN 50.Google Scholar
  34. 34.
    White RR, Kattan MW, Haney JC, et al. Evaluation of preoperative therapy for pancreatic cancer using a prognostic nomogram. Ann Surg Oncol 2006; 13 (11): 1485–1492.PubMedCrossRefGoogle Scholar
  35. 35.
    Abrams RA, Lowy AM, O'Reilly EM, et al. Combined modality treatment of resectable and borderline resectable pancreas cancer: expert consensus statement. Ann Surg Oncol 2009; 16 (7): 1751–1756.PubMedCrossRefGoogle Scholar
  36. 36.
    Hoffman JP. Status of neoadjuvant therapy for resectable pancreatic cancer. Surg Oncol Clin N Am 2010; 19 (2): 411–418.PubMedCrossRefGoogle Scholar
  37. 37.
    Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol 2009; 16 (7): 1727–1733.PubMedCrossRefGoogle Scholar
  38. 38.
    Sasson AR, Wetherington RW, Hoffman JP, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: analysis of histopathology and outcome. Int J Gastrointest Cancer 2003; 34 (2–3): 121–128.PubMedCrossRefGoogle Scholar
  39. 39.
    Ishikawa O, Ohigashi H, Imaoka S, et al. Concomitant benefit of preoperative irradiation in preventing pancreas fistula formation after pancreatoduodenectomy. Arch Surg 1991; 126 (7): 885–889.PubMedGoogle Scholar

Copyright information

© The Society for Surgery of the Alimentary Tract 2011

Authors and Affiliations

  • Jerome Martin Laurence
    • 1
    • 2
    • 3
  • Peter Duy Tran
    • 4
  • Kavita Morarji
    • 4
  • Guy D. Eslick
    • 5
  • Vincent Wai To Lam
    • 1
    • 3
  • Charbel Sandroussi
    • 1
    • 2
    • 6
  1. 1.Department of SurgeryUniversity of SydneySydneyAustralia
  2. 2.Royal Prince Alfred HospitalSydneyAustralia
  3. 3.Westmead HospitalSydneyAustralia
  4. 4.Liverpool HospitalSydneyAustralia
  5. 5.The Whiteley-Martin Research Centre, Discipline of SurgeryThe University of Sydney, Nepean HospitalSydneyAustralia
  6. 6.Surgical Outcomes Resource Centre (SOuRCe)The University of SydneySydneyAustralia

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