Annals of Surgical Oncology

, Volume 19, Issue 4, pp 1316–1323 | Cite as

Adjuvant Radiotherapy in the Treatment of Invasive Intraductal Papillary Mucinous Neoplasm of the Pancreas: an Analysis of the Surveillance, Epidemiology, and End Results Registry

  • Mathias Worni
  • Igor Akushevich
  • Beat Gloor
  • John Scarborough
  • Junzo P. Chino
  • Danny O. Jacobs
  • Stephen M. Hahn
  • Bryan M. Clary
  • Ricardo Pietrobon
  • Anand Shah
Pancreatic Tumors



Management and outcomes of patients with invasive intraductal papillary mucinous neoplasm (IPMN) of the pancreas are not well established. We investigated whether adjuvant radiotherapy (RT) improved cancer-specific survival (CSS) and overall survival (OS) among patients undergoing surgical resection for invasive IPMN.


The Surveillance, Epidemiology, and End Results (SEER) registry was used in this retrospective cohort study. All adult patients with resection of invasive IPMN from 1988 to 2007 were included. CSS and OS were analyzed using Kaplan–Meier curves. Unadjusted and propensity-score-adjusted Cox proportional-hazards modeling were used for subgroup analyses.


972 patients were included. Adjuvant RT was administered to 31.8% (n = 309) of patients. There was no difference in overall median CSS or OS in patients who received adjuvant RT (5-year CSS: 26.5 months; 5-year OS: 23.5 months) versus those who did not (CSS: 28.5 months, P = 0.17; OS: 23.5 months, P = 0.23). Univariate predictors of survival were lymph node (LN) involvement, T4-classified tumors, and poorly differentiated tumor grade (all P < 0.05). In the propensity-score-adjusted analysis, adjuvant RT was associated with improved 5-year CSS [hazard ratio (HR): 0.67, P = 0.004] and 5-year OS (HR: 0.73, P = 0.014) among all patients with LN involvement, though further analysis by T-classification demonstrated no survival differences among patients with T1/T2 disease; patients with T3/T4-classified tumors had improved CSS (HR: 0.71, P = 0.022) but no difference in OS (HR: 0.76, P = 0.06).


On propensity-score-adjusted analysis, adjuvant RT was associated with improved survival in selected subsets of patients with invasive IPMN, particularly those with T3/T4 tumors and LN involvement.


Overall Survival Propensity Score Intraductal Papillary Mucinous Neoplasm Propensity Score Adjustment Invasive Intraductal Papillary Mucinous Neoplasm 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



This work was supported by grant PBBEP3-131567 from the Swiss National Science Foundation (M.W.) and a health services research fellowship in the Penn Department of Radiation Oncology (A.S.). The authors have no other potential conflicts of interest, including specific financial interests and relationships and affiliations relevant to the subject matter or materials discussed in the manuscript.


  1. 1.
    Khan S, Sclabas G, Reid-Lombardo KM. Population-based epidemiology, risk factors and screening of intraductal papillary mucinous neoplasm patients. World J Gastrointest Surg. 2010;2:314–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Riall TS, Stager VM, Nealon WH, et al. Incidence of additional primary cancers in patients with invasive intraductal papillary mucinous neoplasms and sporadic pancreatic adenocarcinomas. J Am Coll Surg. 2007;204:803–13; discussion 813–4.PubMedCrossRefGoogle Scholar
  3. 3.
    Kloppel G SE, Longnecker DS, et al. Histological typing of tumours of the exocrine pancreas. In: World Health Organization international classification of tumors. Berlin: Springer; 1996.Google Scholar
  4. 4.
    Longnecker DS AG, Hruban RH, Klöppel G. Intraductal papillary-mucinous neoplasms of the pancreas. In: Hamilton SR, Aaltonen LA, editors. WHO classification of tumours. Lyon, France: IARC Press; 2000. p. 237–40.Google Scholar
  5. 5.
    D’Angelica M, Brennan MF, Suriawinata AA, et al. Intraductal papillary mucinous neoplasms of the pancreas: an analysis of clinicopathologic features and outcome. Ann Surg. 2004;239:400–8.PubMedCrossRefGoogle Scholar
  6. 6.
    Maire F, Hammel P, Terris B, et al. Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma. Gut. 2002;51:717–22.PubMedCrossRefGoogle Scholar
  7. 7.
    Nakagohri T, Kinoshita T, Konishi M, et al. Surgical outcome of intraductal papillary mucinous neoplasms of the pancreas. Ann Surg Oncol. 2007;14:3174–80.PubMedCrossRefGoogle Scholar
  8. 8.
    Niedergethmann M, Grutzmann R, Hildenbrand R, et al. Outcome of invasive and noninvasive intraductal papillary-mucinous neoplasms of the pancreas (IPMN): a 10-year experience. World J Surg. 2008;32:2253–60.PubMedCrossRefGoogle Scholar
  9. 9.
    Schnelldorfer T, Sarr MG, Nagorney DM, et al. Experience with 208 resections for intraductal papillary mucinous neoplasm of the pancreas. Arch Surg. 2008;143:639–46; discussion 646.PubMedCrossRefGoogle Scholar
  10. 10.
    Wada K, Kozarek RA, Traverso LW. Outcomes following resection of invasive and noninvasive intraductal papillary mucinous neoplasms of the pancreas. Am J Surg. 2005;189:632–6; discussion 637.PubMedCrossRefGoogle Scholar
  11. 11.
    Yopp AC, Allen PJ. Prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas. World J Gastrointest Surg. 2010;2:359–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Turrini O, Waters JA, Schnelldorfer T, et al. Invasive intraductal papillary mucinous neoplasm: predictors of survival and role of adjuvant therapy. HPB (Oxford). 2010;12:447–55.CrossRefGoogle Scholar
  13. 13.
    Fujii H, Inagaki M, Kasai S, et al. Genetic progression and heterogeneity in intraductal papillary-mucinous neoplasms of the pancreas. Am J Pathol. 1997;151:1447–54.PubMedGoogle Scholar
  14. 14.
    Wilentz RE, Hruban RH. Pathology of cancer of the pancreas. Surg Oncol Clin North Am. 1998;7:43–65.Google Scholar
  15. 15.
    Poultsides GA, Reddy S, Cameron JL, et al. Histopathologic basis for the favorable survival after resection of intraductal papillary mucinous neoplasm-associated invasive adenocarcinoma of the pancreas. Ann Surg. 2010;251:470–6.PubMedCrossRefGoogle Scholar
  16. 16.
    Wasif N, Bentrem DJ, Farrell JJ, et al. Invasive intraductal papillary mucinous neoplasm versus sporadic pancreatic adenocarcinoma: a stage-matched comparison of outcomes. Cancer. 2010;116:3369–77.PubMedCrossRefGoogle Scholar
  17. 17.
    Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group. Cancer. 1987;59:2006–10.Google Scholar
  18. 18.
    Crane CH, Varadhachary G, Pisters PW, et al. Future chemoradiation strategies in pancreatic cancer. Semin Oncol. 2007;34:335–46.PubMedCrossRefGoogle Scholar
  19. 19.
    Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120:899–903.Google Scholar
  20. 20.
    Klinkenbijl JH, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg. 1999;230:776–82; discussion 782–4.PubMedCrossRefGoogle Scholar
  21. 21.
    McDade TP, Hill JS, Simons JP, et al. A national propensity-adjusted analysis of adjuvant radiotherapy in the treatment of resected pancreatic adenocarcinoma. Cancer. 2010;116:3257–66.PubMedCrossRefGoogle Scholar
  22. 22.
    Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomised controlled trial. Lancet. 2001;358:1576–85.PubMedCrossRefGoogle Scholar
  23. 23.
    Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350:1200–10.PubMedCrossRefGoogle Scholar
  24. 24.
    Edwards BK, Ward E, Kohler BA, et al. Annual report to the nation on the status of cancer, 1975–2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer. 2010;116:544–73.PubMedCrossRefGoogle Scholar
  25. 25. Accessed 10 Aug 2011.
  26. 26. Accessed 10 Aug 2011.
  27. 27.
    Tomlinson JS, Jain S, Bentrem DJ, et al. Accuracy of staging node-negative pancreas cancer: a potential quality measure. Arch Surg. 2007;142:767–73; discussion 773–4.Google Scholar
  28. 28.
    Greene FL PD, Fleming ID, et al. AJCC cancer staging handbook. Chicago, IL: Springer; 2002.Google Scholar
  29. 29.
    Artinyan A, Hellan M, Mojica-Manosa P, et al. Improved survival with adjuvant external-beam radiation therapy in lymph node-negative pancreatic cancer: a United States population-based assessment. Cancer. 2008;112:34–42.PubMedCrossRefGoogle Scholar
  30. 30.
    Lund JL, Harlan LC, Yabroff KR, Warren JL. Should cause of death from the death certificate be used to examine cancer-specific survival? A study of patients with distant stage disease. Cancer Invest. 2010;28:758–64.PubMedCrossRefGoogle Scholar
  31. 31.
    Rosenbaum PR, Rubin DB. The central role of the propensity score in observational studies for causal effects. Biometrika. 1983;70:15.CrossRefGoogle Scholar
  32. 32.
    Brookhart MA, Schneeweiss S, Rothman KJ, et al. Variable selection for propensity score models. Am J Epidemiol. 2006;163:1149–56.PubMedCrossRefGoogle Scholar
  33. 33.
    Chari ST, Yadav D, Smyrk TC, et al. Study of recurrence after surgical resection of intraductal papillary mucinous neoplasm of the pancreas. Gastroenterology. 2002;123:1500–7.PubMedCrossRefGoogle Scholar
  34. 34.
    Neoptolemos JP, Cunningham D, Friess H, et al. Adjuvant therapy in pancreatic cancer: historical and current perspectives. Ann Oncol Official J Eur Soc Med Oncol. 2003;14:675–92.CrossRefGoogle Scholar
  35. 35.
    Miller RC, Iott MJ, Corsini MM. Review of adjuvant radiochemotherapy for resected pancreatic cancer and results from Mayo Clinic for the 5th JUCTS symposium. Int J Radiat Oncol Biol, Phys. 2009;75:364–8.CrossRefGoogle Scholar
  36. 36.
    Salvia R, Fernandez-del Castillo C, Bassi C, et al. Main-duct intraductal papillary mucinous neoplasms of the pancreas: clinical predictors of malignancy and long-term survival following resection. Ann Surg. 2004;239:678–85; discussion 685–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Sohn TA, Yeo CJ, Cameron JL, et al. Intraductal papillary mucinous neoplasms of the pancreas: an updated experience. Ann Surg. 2004;239:788–97; discussion 797–9.PubMedCrossRefGoogle Scholar
  38. 38.
    Woo SM, Ryu JK, Lee SH, et al. Survival and prognosis of invasive intraductal papillary mucinous neoplasms of the pancreas: comparison with pancreatic ductal adenocarcinoma. Pancreas. 2008;36:50–5.PubMedCrossRefGoogle Scholar
  39. 39.
    Yopp AC, Katabi N, Janakos M, et al. Invasive carcinoma arising in intraductal papillary mucinous neoplasms of the pancreas: a matched control study with conventional pancreatic ductal adenocarcinoma. Ann Surg. 2011.Google Scholar

Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Mathias Worni
    • 1
    • 2
  • Igor Akushevich
    • 3
  • Beat Gloor
    • 2
  • John Scarborough
    • 4
  • Junzo P. Chino
    • 5
  • Danny O. Jacobs
    • 4
  • Stephen M. Hahn
    • 6
  • Bryan M. Clary
    • 4
  • Ricardo Pietrobon
    • 1
  • Anand Shah
    • 6
  1. 1.Research on Research, Department of SurgeryDuke University Medical CenterDurhamUSA
  2. 2.Department of Visceral Surgery and MedicineUniversity of BernBernSwitzerland
  3. 3.Center for Population Health and AgingDuke UniversityDurhamUSA
  4. 4.Department of SurgeryDuke University Medical CenterDurhamUSA
  5. 5.Department of Radiation OncologyDuke University Medical CenterDurhamUSA
  6. 6.Department of Radiation OncologyHospital of the University of PennsylvaniaPhiladelphiaUSA

Personalised recommendations