Advertisement

Radiation Therapy in Pancreatic Cancer

  • Alessio G. Morganti
  • Giambattista Siepe
  • Lucia Giaccherini
Living reference work entry
First Online:

Abstract

Pancreatic adenocarcinoma is a neoplasm with very poor prognosis due to the biological aggressiveness of this tumor and to the frequently late diagnosis. In fact, in most patients, pancreatic cancer is diagnosed in locally advanced or metastatic stage. Therefore, in the majority of cases, the purpose of therapy is to prolong survival and improve quality of life.

In patients with resectable disease, the standard treatment is surgical resection followed by adjuvant chemotherapy which may eventually combined with postoperative chemoradiation. In locally advanced tumors, the treatment is mainly based on chemotherapy, eventually combined also in this case with concurrent chemoradiation.

Patients with locally advanced tumor undergoing chemoradiation should be accurately reassessed by imaging after the treatment and during the follow-up in order to identify patients who become eligible to surgery, taking into account that the rate of pathological response can improve after 10–20 weeks after radiochemotherapy.

Stereotactic radiotherapy is an emerging technique in locally advanced pancreatic cancer, by allowing satisfactory local control of the disease with very short treatment duration. In metastatic patients, palliative radiotherapy can be used to treat symptoms caused by metastases or primary tumors, again in combination with systemic treatments.

Keywords

Pancreatic neoplasms Surgery Chemotherapy Radiotherapy Stereotactic radiotherapy 
This is a preview of subscription content, log in to check access.

References

  1. Benedict SH, Yenice KM, Followill D, Galvin JM, Hinson W, Kavanagh B, Keall P, Lovelock M, Meeks S, Papiez L, Purdie T, Sadagopan R, Schell MC, Salter B, Schlesinger DJ, Shiu AS, Solberg T, Song DY, Stieber V, Timmerman R, Tomé WA, Verellen D, Wang L, Yin FF. Stereotactic body radiation therapy: the report of AAPM Task Group 101. Med Phys. 2010;37(8):4078–101.CrossRefPubMedGoogle Scholar
  2. Bilimoria KY, et al. Multimodality therapy for pancreatic cancer in the U.S.: utilization, outcomes, and the effect of hospital volume. Cancer. 2007;110:1227–34.CrossRefPubMedGoogle Scholar
  3. 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):1592–9.CrossRefPubMedGoogle Scholar
  4. Chen KT, Devarajan K, Milestone BN, Cooper HS, Denlinger C, Cohen SJ, Meyer JE, Hoffman JP. Neoadjuvant chemoradiation and duration of chemotherapy before surgical resection for pancreatic cancer: does time interval between radiotherapy and surgery matter? Ann Surg Oncol. 2014;21(2):662–9.CrossRefPubMedGoogle Scholar
  5. Corsini MM, Miller RC, Haddock MG, et al. Adjuvant radiotherapy and chemotherapy for pancreatic carcinoma: the Mayo Clinic experience (1975–2005). J Clin Oncol. 2008;26(21):3511–6.CrossRefPubMedGoogle Scholar
  6. Didolkar MS, Coleman CW, Brenner MJ, et al. Image guided stereotactic radiosurgery for locally advanced pancreatic adenocarcinoma results of first 85 patients. J Gastrointest Surg. 2010;14(10):1547–59.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. Farnell MB, et al. A prospective randomized trial comparing standard pancreatectomy with pancreatectomy with extended lymphadenectomy in resectable pancreatic head adenocarcinoma. Surgery. 2005;138:618–30.CrossRefPubMedGoogle Scholar
  9. Gillen S, Schuster T, Meyer Zum Büschenfelde 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.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Hall WA, Colbert LE, Liu Y, et al. The influence of adjuvant radiotherapy dose on overall survival in patients with resected pancreatic adenocarcinoma. Cancer. 2013;119(12):2350–7.CrossRefPubMedPubMedCentralGoogle Scholar
  11. Hammel P, Huguet F, van Laethem JL, et al. LAP07 Trial Group. Effect of chemoradiotherapy vs chemotherapy on survival in patients with locally advanced pancreatic cancer controlled after 4 months of gemcitabine with or without erlotinib: the LAP07 randomized clinical trial. JAMA. 2016;315(17):1844–53.CrossRefGoogle Scholar
  12. Hazard L, Tward JD, Szabo A, Shrieve DC. Radiation therapy is associated with improved survival in patients with pancreatic adenocarcinoma: results of a study from the Surveillance, Epidemiology, and End Results (SEER) registry data. Cancer. 2007;110(10):2191–201.CrossRefPubMedGoogle Scholar
  13. Herman JM, Swartz MJ, Hsu CC, et al. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008;26(21):3503–10.CrossRefPubMedPubMedCentralGoogle Scholar
  14. Hishinuma S, Ogata Y, Tomikawa M, Ozawa I, Hirabayashi K, Igarashi S. Patterns of recurrence after curative resection of pancreatic cancer, based on autopsy findings. J Gastrointest Surg. 2006;10(4):511–8.CrossRefPubMedGoogle Scholar
  15. Hsu CC, Herman JM, Corsini MM, et al. Adjuvant chemoradiation for pancreatic adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Ann Surg Oncol. 2010;17(4):981–90.CrossRefPubMedPubMedCentralGoogle Scholar
  16. Hurt CN, Mukherjee S, Bridgewater J, Falk S, Crosby T, McDonald A, Joseph G, Staffurth J, Abrams RA, Blazeby JM, Bridges S, Dutton P, Griffiths G, Maughan T, Johnson C. Health-related quality of life in SCALOP, a randomized phase 2 trial comparing chemoradiation therapy regimens in locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2015;93(4):810–8.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985;120(9):899–903.PubMedGoogle Scholar
  18. Kayahara M, Nagakawa T, Ueno K, et al. An evaluation of radical resection for pancreatic cancer based on the mode of recurrence as determined by autopsy and diagnostic imaging. Cancer. 1993;72(7):2118–23.CrossRefPubMedGoogle Scholar
  19. Khanna A, Walker GR, Livingstone AS, et al. Is adjuvant 5-FU-based chemoradiotherapy for resectable pancreatic adenocarcinoma beneficial? A meta-analysis of an unanswered question. J Gastrointest Surg. 2006;10(5):689–97.CrossRefPubMedGoogle Scholar
  20. Kindler HL, et al. Gemcitabine plus bevacizumab compared to gemcitabine plus placebo in patients with advanced pancreatic cancer: phase III trial of Cancer and Leukemia Group B (CALBG 80303). J Clin Oncol. 2010;28:3617–22.CrossRefPubMedPubMedCentralGoogle Scholar
  21. Klein AP, et al. Familial pancreatic cancer. Cancer J. 2001;7:266–73.PubMedGoogle Scholar
  22. 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(6):776–82.CrossRefPubMedPubMedCentralGoogle Scholar
  23. Kooby DA, Gillespie TW, Liu Y, et al. Impact of adjuvant radiotherapy on survival after pancreatic cancer resection: an appraisal of data from the national cancer data base. Ann Surg Oncol. 2013;20(11):3634–42.CrossRefPubMedPubMedCentralGoogle Scholar
  24. Lim JE, Chien MW, Earle CC. Prognostic factors following curative resection for pancreatic adenocarcinoma: a population-based, linked database analysis of 396 patients. Ann Surg. 2003;237(1):74–85.CrossRefPubMedPubMedCentralGoogle Scholar
  25. Loehrer PJ Sr, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, Flynn P, Ramanathan RK, Crane CH, Alberts SR, Benson AB 3rd. Gemcitabine alone versus gemcitabine plus radiotherapy in patients with locally advanced pancreatic cancer: an Eastern Cooperative Oncology Group trial. J Clin Oncol. 2011;29(31):4105–12.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 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(13):3257–66.CrossRefPubMedGoogle Scholar
  27. Merchant NB, Rymer J, Koehler EA, et al. Adjuvant chemoradiation therapy for pancreatic adenocarcinoma: who really benefits? J Am Coll Surg. 2009;208(5):829–38.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Morganti AG, Trodella L, Valentini V, et al. Pain relief with short-term irradiation in locally advanced carcinoma of the pancreas. J Palliat Care. 2003;19(4):258–62.PubMedGoogle Scholar
  29. 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.CrossRefPubMedGoogle Scholar
  30. Morganti AG, Falconi M, Van Stiphout RG, Mattiucci GC, Alfieri S, Calvo FA, Dubois JB, Fastner G, Herman JM, Maidment BW 3rd, Miller RC, Regine WF, Reni M, Sharma NK, Ippolito E, Valentini V. Multi-institutional pooled analysis on adjuvant chemotherapy in pancreatic cancer. Int J Radiat Oncol Biol Phys. 2014;90(4):911–7.CrossRefPubMedGoogle Scholar
  31. National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology. Pancreatic adenocarcinoma version 2.2017. http://www.nccn.org/professionals/physician_gls/pdf/pancreatic.pdf. Accessed June 2017.
  32. Neoptolemos JP, Stocken DD, Friess H, et al. European Study Group for Pancreatic Cancer. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.CrossRefPubMedGoogle Scholar
  33. Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, Faluyi O, O’Reilly DA, Cunningham D, Wadsley J, Darby S, Meyer T, Gillmore R, Anthoney A, Lind P, Glimelius B, Falk S, Izbicki JR, Middleton GW, Cummins S, Ross PJ, Wasan H, McDonald A, Crosby T, Ma YT, Patel K, Sherriff D, Soomal R, Borg D, Sothi S, Hammel P, Hackert T, Jackson R, Büchler MW, 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;389:1011–24.CrossRefGoogle Scholar
  34. Palta M, Willett CG, Czito BG. Chapter 59, Pancreatic cancer. In: Halperin EC, et al., editors. Perez and Brady’s principles and practice of radiation oncology. 6th ed. Philadelphia: Lippincott Williams & Wilkins, a Wolters Kluwer Business; 2013. p. 1189–201.Google Scholar
  35. Philip PA, et al. Phase III study comparing gemcitabine plus cetuximab versus gemcitabine in patients with advanced adenocarcinoma pancreatic: Southwest Oncology Group-directed intergroup trial S0205. J Clin Oncol. 2010;28:3605–10.CrossRefPubMedPubMedCentralGoogle Scholar
  36. Rahib L, Smith BD, Aizenberg R, Rosenzweig AB, Fleshman JM, Matrisian LM. Projecting cancer incidence and death to 2030: the unespected burden of thyroid, liver, and pancreas cancer in the United States. Cancer Res. 2014;74(11):2913–21.CrossRefGoogle Scholar
  37. Rwimega JC, Parikh SD, Heron DE, et al. Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas. Am J Clin Oncol. 2011;24(1):63–9.Google Scholar
  38. Shen ZT, Wu XH, Li B, Wang L, Zhu XX. Preliminary efficacy of CyberKnife radiosurgery for locally advanced pancreatic cancer. Chin J Cancer. 2010;29(9):802–9.CrossRefPubMedGoogle Scholar
  39. Takahashi H, Ohigashi H, Gotoh K, et al. Preoperative gemcitabine-based chemoradiation therapy for resectable and borderline resectable pancreatic cancer. Ann Surg. 2013;258(6):1040–50.CrossRefPubMedGoogle Scholar
  40. Turrini O, Ychou M, Moureau-Zabotto L, et al. Neoadjuvant docetaxel-based chemoradiation for resectable adenocarcinoma of the pancreas: new neoadjuvant regimen was safe and provided an interesting pathologic response. Eur J Surg Oncol. 2010;36(10):987–92.CrossRefPubMedGoogle Scholar
  41. Vanderveen KA, Chen SL, Yin D, et al. Benefit of postoperative adjuvant therapy for pancreatic cancer: a population-based analysis. Cancer. 2009;115(11):2420–9.CrossRefPubMedPubMedCentralGoogle Scholar
  42. 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(5):621–33.CrossRefPubMedPubMedCentralGoogle Scholar
  43. Yovino S, Poppe M, Jabbour S, et al. Intensity-modulated radiation therapy significantly improves acute gastrointestinal toxicity in pancreatic and ampullary cancers. Int J Radiat Oncol Biol Phys. 2011;79(1):158–62.CrossRefPubMedGoogle Scholar
  44. Zeng Y, Rucki AA, Che X, Zheng L. Shifting paradigm of developing biologics for the treatment of pancreatic adenocarcinoma. J Gastrointest Oncol. 2017;8:441–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Alessio G. Morganti
    • 1
  • Giambattista Siepe
    • 1
  • Lucia Giaccherini
    • 2
  1. 1.Radiotherapy CenterBologna University, Policlinico Universitario S. Orsola-MalpighiBolognaItaly
  2. 2.Radiation Oncology Unit, Department of Oncology and Advanced TechnologyAUSL-IRCCSReggio EmiliaItaly

Personalised recommendations

Cite entry