Advertisement

Pancreatic Cancer pp 1435-1460 | Cite as

Role of Radiotherapy in Locally Advanced Pancreatic Cancer

  • Daphna Spiegel
  • Julian Hong
  • Manisha Palta
  • Brian Czito
  • Christopher Willett
Reference work entry

Abstract

Pancreatic cancer carries a poor prognosis regardless of stage, and incidence and death rates are increasing. Pancreatic cancer is divided into four general categories, resectable, borderline resectable, locally advanced/unresectable, and metastatic. Only 15–20% of patients diagnosed with pancreatic cancer have resectable or borderline resectable disease at diagnosis. Most patients are diagnosed with more advanced disease; approximately 30–40% of patients present with locally advanced, unresectable pancreatic cancer (LAPC) at the time of diagnosis, and another 40% have distant metastatic disease. Surgery provides the only chance of cure for patients with pancreatic cancer, but the likelihood of patients with unresectable disease ultimately proceeding to surgical resection is low. The management of these patients with locally advanced, unresectable disease is controversial, and there is no internationally accepted regimen. The data for the use of radiation therapy in the setting of LAPC will be discussed in this chapter.

Keywords

Pancreatic cancer Radiation therapy Chemoradiation Hypofractionation Stereotactic body radiotherapy (SBRT) Particle therapy 

References

  1. 1.
    Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.CrossRefGoogle Scholar
  2. 2.
    Cress RD, Yin D, Clarke L, Bold R, Holly EA. Survival among patients with adenocarcinoma of the pancreas: a population-based study (United States). Cancer Causes Control. 2006;17(4):403–9.CrossRefGoogle Scholar
  3. 3.
    Hammel P, Huguet F, van Laethem JL, Goldstein D, Glimelius B, Artru P, et al. 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
  4. 4.
    Conroy T, Desseigne F, Ychou M, Bouche O, Guimbaud R, Becouarn Y, et al. FOLFIRINOX versus gemcitabine for metastatic pancreatic cancer. N Engl J Med. 2011;364(19):1817–25.CrossRefGoogle Scholar
  5. 5.
    Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369(18):1691–703.CrossRefGoogle Scholar
  6. 6.
    Baumgartner JM, Krasinskas A, Daouadi M, Zureikat A, Marsh W, Lee K, et al. Distal pancreatectomy with en bloc celiac axis resection for locally advanced pancreatic adenocarcinoma following neoadjuvant therapy. J Gastrointest Surg. 2012;16(6):1152–9.CrossRefGoogle Scholar
  7. 7.
    Christians KK, Pilgrim CH, Tsai S, Ritch P, George B, Erickson B, et al. Arterial resection at the time of pancreatectomy for cancer. Surgery. 2014;155(5):919–26.CrossRefGoogle Scholar
  8. 8.
    Evans DB, George B, Tsai S. Non-metastatic pancreatic cancer: resectable, borderline resectable, and locally advanced-definitions of increasing importance for the optimal delivery of multimodality therapy. Ann Surg Oncol. 2015;22(11):3409–13.CrossRefGoogle Scholar
  9. 9.
    Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med. 2014;371(11):1039–49.CrossRefGoogle Scholar
  10. 10.
    Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, Group EGW. Pancreatic adenocarcinoma: ESMO-ESDO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012;23(Suppl 7):vii33–40.CrossRefGoogle Scholar
  11. 11.
    Moertel CG, Childs Jr DS, Reitemeier RJ, Colby Jr MY, Holbrook MA. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet. 1969;2(7626):865–7.CrossRefGoogle Scholar
  12. 12.
    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):205–8.Google Scholar
  13. 13.
    Moertel CG, Frytak S, Hahn RG, O'Connell MJ, Reitemeier RJ, Rubin J, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: the Gastrointestinal Tumor Study Group. Cancer. 1981;48(8):1705–10.CrossRefGoogle Scholar
  14. 14.
    Cohen SJ, Dobelbower Jr R, Lipsitz S, Catalano PJ, Sischy B, Smith TJ, et al. A randomized phase III study of radiotherapy alone or with 5-fluorouracil and mitomycin-C in patients with locally advanced adenocarcinoma of the pancreas: Eastern Cooperative Oncology Group study E8282. Int J Radiat Oncol Biol Phys. 2005;62(5):1345–50.CrossRefGoogle Scholar
  15. 15.
    Sultana A, Tudur Smith C, Cunningham D, Starling N, Tait D, Neoptolemos JP, et al. Systematic review, including meta-analyses, on the management of locally advanced pancreatic cancer using radiation/combined modality therapy. Br J Cancer. 2007;96(8):1183–90.CrossRefGoogle Scholar
  16. 16.
    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):751–5.Google Scholar
  17. 17.
    Klaassen DJ, MacIntyre JM, Catton GE, Engstrom PF, Moertel CG. Treatment of locally unresectable cancer of the stomach and pancreas: a randomized comparison of 5-fluorouracil alone with radiation plus concurrent and maintenance 5-fluorouracil – an Eastern Cooperative Oncology Group study. J Clin Oncol. 1985;3(3):373–8.CrossRefGoogle Scholar
  18. 18.
    Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouche O, 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.CrossRefGoogle Scholar
  19. 19.
    Loehrer Sr PJ, Feng Y, Cardenes H, Wagner L, Brell JM, Cella D, et al. 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.CrossRefGoogle Scholar
  20. 20.
    Huguet F, Andre T, Hammel P, Artru P, Balosso J, Selle F, et al. Impact of chemoradiotherapy after disease control with chemotherapy in locally advanced pancreatic adenocarcinoma in GERCOR phase II and III studies. J Clin Oncol. 2007;25(3):326–31.CrossRefGoogle Scholar
  21. 21.
    Mahadevan A, Miksad R, Goldstein M, Sullivan R, Bullock A, Buchbinder E, et al. Induction gemcitabine and stereotactic body radiotherapy for locally advanced nonmetastatic pancreas cancer. Int J Radiat Oncol Biol Phys. 2011;81(4):e615–22.CrossRefGoogle Scholar
  22. 22.
    Radiation therapy combined with Adriamycin or 5-fluorouracil for the treatment of locally unresectable pancreatic carcinoma. Gastrointestinal Tumor Study Group. Cancer. 1985;56(11):2563–8.Google Scholar
  23. 23.
    Li CP, Chao Y, Chi KH, Chan WK, Teng HC, Lee RC, et al. Concurrent chemoradiotherapy treatment of locally advanced pancreatic cancer: gemcitabine versus 5-fluorouracil, a randomized controlled study. Int J Radiat Oncol Biol Phys. 2003;57(1):98–104.CrossRefGoogle Scholar
  24. 24.
    O’Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, et al. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014;32(18):1927–34.CrossRefGoogle Scholar
  25. 25.
    Schneider BJ, Ben-Josef E, McGinn CJ, Chang AE, Colletti LM, Normolle DP, et al. Capecitabine and radiation therapy preceded and followed by combination chemotherapy in advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2005;63(5):1325–30.CrossRefGoogle Scholar
  26. 26.
    Stokes JB, Nolan NJ, Stelow EB, Walters DM, Weiss GR, de Lange EE, et al. Preoperative capecitabine and concurrent radiation for borderline resectable pancreatic cancer. Ann Surg Oncol. 2011;18(3):619–27.CrossRefGoogle Scholar
  27. 27.
    Mukherjee S, Hurt CN, Bridgewater J, Falk S, Cummins S, Wasan H, et al. Gemcitabine-based or capecitabine-based chemoradiotherapy for locally advanced pancreatic cancer (SCALOP): a multicentre, randomised, phase 2 trial. Lancet Oncol. 2013;14(4):317–26.CrossRefGoogle Scholar
  28. 28.
    Wong AA, Delclos ME, Wolff RA, Evans DB, Abbruzzese JL, Tamm EP, et al. Radiation dose considerations in the palliative treatment of locally advanced adenocarcinoma of the pancreas. Am J Clin Oncol. 2005;28(3):227–33.CrossRefGoogle Scholar
  29. 29.
    Zimmermann FB, Jeremic B, Lersch C, Geinitz H, Hennig M, Molls M. Dose escalation of concurrent hypofractionated radiotherapy and continuous infusion 5-FU-chemotherapy in advanced adenocarcinoma of the pancreas. Hepatogastroenterology. 2005;52(61):246–50.PubMedGoogle Scholar
  30. 30.
    Cai S, Hong TS, Goldberg SI, Fernandez-del Castillo C, Thayer SP, Ferrone CR, et al. Updated long-term outcomes and prognostic factors for patients with unresectable locally advanced pancreatic cancer treated with intraoperative radiotherapy at the Massachusetts General Hospital, 1978 to 2010. Cancer. 2013;119(23):4196–204.CrossRefGoogle Scholar
  31. 31.
    Brown MW, Ning H, Arora B, Albert PS, Poggi M, Camphausen K, et al. A dosimetric analysis of dose escalation using two intensity-modulated radiation therapy techniques in locally advanced pancreatic carcinoma. Int J Radiat Oncol Biol Phys. 2006;65(1):274–83.CrossRefGoogle Scholar
  32. 32.
    Spalding AC, Jee KW, Vineberg K, Jablonowski M, Fraass BA, Pan CC, et al. Potential for dose-escalation and reduction of risk in pancreatic cancer using IMRT optimization with lexicographic ordering and gEUD-based cost functions. Med Phys. 2007;34(2):521–9.CrossRefGoogle Scholar
  33. 33.
    Ben-Josef E, Shields AF, Vaishampayan U, Vaitkevicius V, El-Rayes BF, McDermott P, et al. Intensity-modulated radiotherapy (IMRT) and concurrent capecitabine for pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;59(2):454–9.CrossRefGoogle Scholar
  34. 34.
    Milano MT, Chmura SJ, Garofalo MC, Rash C, Roeske JC, Connell PP, et al. Intensity-modulated radiotherapy in treatment of pancreatic and bile duct malignancies: toxicity and clinical outcome. Int J Radiat Oncol Biol Phys. 2004;59(2):445–53.CrossRefGoogle Scholar
  35. 35.
    Murphy JD, Adusumilli S, Griffith KA, Ray ME, Zalupski MM, Lawrence TS, et al. Full-dose gemcitabine and concurrent radiotherapy for unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2007;68(3):801–8.CrossRefGoogle Scholar
  36. 36.
    Ben-Josef E, Schipper M, Francis IR, Hadley S, Ten-Haken R, Lawrence T, et al. A phase I/II trial of intensity modulated radiation (IMRT) dose escalation with concurrent fixed-dose rate gemcitabine (FDR-G) in patients with unresectable pancreatic cancer. Int J Radiat Oncol Biol Phys. 2012;84(5):1166–71.CrossRefGoogle Scholar
  37. 37.
    Krishnan S, Chadha AS, Suh Y, Chen HC, Rao A, Das P, et al. Focal radiation therapy dose escalation improves overall survival in locally advanced pancreatic cancer patients receiving induction chemotherapy and consolidative chemoradiation. Int J Radiat Oncol Biol Phys. 2016;94(4):755–65.CrossRefGoogle Scholar
  38. 38.
    Blomgren H, Lax I, Naslund I, Svanstrom R. Stereotactic high dose fraction radiation therapy of extracranial tumors using an accelerator. Clinical experience of the first thirty-one patients. Acta Oncol. 1995;34(6):861–70.CrossRefGoogle Scholar
  39. 39.
    Adler Jr JR, Chang SD, Murphy MJ, Doty J, Geis P, Hancock SL. The Cyberknife: a frameless robotic system for radiosurgery. Stereotact Funct Neurosurg. 1997;69(1–4 Pt 2):124–8.CrossRefGoogle Scholar
  40. 40.
    Schweikard A, Glosser G, Bodduluri M, Murphy MJ, Adler JR. Robotic motion compensation for respiratory movement during radiosurgery. Comput Aided Surg. 2000;5(4):263–77.CrossRefGoogle Scholar
  41. 41.
    Chang BK, Timmerman RD. Stereotactic body radiation therapy: a comprehensive review. Am J Clin Oncol. 2007;30(6):637–44.CrossRefGoogle Scholar
  42. 42.
    Koong AC, Le QT, Ho A, Fong B, Fisher G, Cho C, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58(4):1017–21.CrossRefGoogle Scholar
  43. 43.
    Schellenberg D, Goodman KA, Lee F, Chang S, Kuo T, Ford JM, et al. Gemcitabine chemotherapy and single-fraction stereotactic body radiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2008;72(3):678–86.CrossRefGoogle Scholar
  44. 44.
    Schellenberg D, Kim J, Christman-Skieller C, Chun CL, Columbo LA, Ford JM, et al. Single-fraction stereotactic body radiation therapy and sequential gemcitabine for the treatment of locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2011;81(1):181–8.CrossRefGoogle Scholar
  45. 45.
    de Lange SM, van Groeningen CJ, Meijer OW, Cuesta MA, Langendijk JA, van Riel JM, et al. Gemcitabine-radiotherapy in patients with locally advanced pancreatic cancer. Eur J Cancer. 2002;38(9):1212–7.CrossRefGoogle Scholar
  46. 46.
    Willett CG, Del Castillo CF, Shih HA, Goldberg S, Biggs P, Clark JW, et al. Long-term results of intraoperative electron beam irradiation (IOERT) for patients with unresectable pancreatic cancer. Ann Surg. 2005;241(2):295–9.CrossRefGoogle Scholar
  47. 47.
    Hoyer M, Roed H, Sengelov L, Traberg A, Ohlhuis L, Pedersen J, et al. Phase-II study on stereotactic radiotherapy of locally advanced pancreatic carcinoma. Radiother Oncol. 2005;76(1):48–53.CrossRefGoogle Scholar
  48. 48.
    Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker-Prietz A, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121(7):1128–37.CrossRefGoogle Scholar
  49. 49.
    Moningi S, Marciscano AE, Rosati LM, Ng SK, Teboh Forbang R, Jackson J, et al. Stereotactic body radiation therapy in pancreatic cancer: the new frontier. Expert Rev Anticancer Ther. 2014;14(12):1461–75.CrossRefGoogle Scholar
  50. 50.
    Hsiung-Stripp DC, McDonough J, Masters HM, Levin WP, Hahn SM, Jones HA, et al. Comparative treatment planning between proton and X-ray therapy in pancreatic cancer. Med Dosim. 2001;26(3):255–9.CrossRefGoogle Scholar
  51. 51.
    Zurlo A, Lomax A, Hoess A, Bortfeld T, Russo M, Goitein G, et al. The role of proton therapy in the treatment of large irradiation volumes: a comparative planning study of pancreatic and biliary tumors. Int J Radiat Oncol Biol Phys. 2000;48(1):277–88.CrossRefGoogle Scholar
  52. 52.
    Kozak KR, Kachnic LA, Adams J, Crowley EM, Alexander BM, Mamon HJ, et al. Dosimetric feasibility of hypofractionated proton radiotherapy for neoadjuvant pancreatic cancer treatment. Int J Radiat Oncol Biol Phys. 2007;68(5):1557–66.CrossRefGoogle Scholar
  53. 53.
    Linstadt D, Quivey JM, Castro JR, Andejeski Y, Phillips TL, Hannigan J, et al. Comparison of helium-ion radiation therapy and split-course megavoltage irradiation for unresectable adenocarcinoma of the pancreas. Final report of a Northern California Oncology Group randomized prospective clinical trial. Radiology. 1988;168(1):261–4.CrossRefGoogle Scholar
  54. 54.
    Tsujii H, Mizoe J, Kamada T, Baba M, Tsuji H, Kato H, et al. Clinical results of carbon ion radiotherapy at NIRS. J Radiat Res. 2007;48(Suppl A):A1–A13.CrossRefGoogle Scholar
  55. 55.
    Okada T, Kamada T, Tsuji H, Mizoe JE, Baba M, Kato S, et al. Carbon ion radiotherapy: clinical experiences at National Institute of Radiological Science (NIRS). J Radiat Res. 2010;51(4):355–64.CrossRefGoogle Scholar
  56. 56.
    Shinoto M, Yamada S, Terashima K, Yasuda S, Shioyama Y, Honda H, et al. Carbon ion radiation therapy with concurrent gemcitabine for patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2016;95(1):498–504.CrossRefGoogle Scholar
  57. 57.
    Jayachandran P, Minn AY, Van Dam J, Norton JA, Koong AC, Chang DT. Interfractional uncertainty in the treatment of pancreatic cancer with radiation. Int J Radiat Oncol Biol Phys. 2010;76(2):603–7.CrossRefGoogle Scholar
  58. 58.
    Taniguchi CM, Murphy JD, Eclov N, Atwood TF, Kielar KN, Christman-Skieller C, et al. Dosimetric analysis of organs at risk during expiratory gating in stereotactic body radiation therapy for pancreatic cancer. Int J Radiat Oncol Biol Phys. 2013;85(4):1090–5.CrossRefGoogle Scholar
  59. 59.
    Fletcher JG, Wiersema MJ, Farrell MA, Fidler JL, Burgart LJ, Koyama T, et al. Pancreatic malignancy: value of arterial, pancreatic, and hepatic phase imaging with multi-detector row CT. Radiology. 2003;229(1):81–90.CrossRefGoogle Scholar
  60. 60.
    Schellenberg D, Quon A, Minn AY, Graves EE, Kunz P, Ford JM, et al. 18Fluorodeoxyglucose PET is prognostic of progression-free and overall survival in locally advanced pancreas cancer treated with stereotactic radiotherapy. Int J Radiat Oncol Biol Phys. 2010;77(5):1420–5.CrossRefGoogle Scholar
  61. 61.
    Dholakia AS, Chaudhry M, Leal JP, Chang DT, Raman SP, Hacker-Prietz A, et al. Baseline metabolic tumor volume and total lesion glycolysis are associated with survival outcomes in patients with locally advanced pancreatic cancer receiving stereotactic body radiation therapy. Int J Radiat Oncol Biol Phys. 2014;89(3):539–46.CrossRefGoogle Scholar
  62. 62.
    Scorsetti M, Alongi F, Castiglioni S, Clivio A, Fogliata A, Lobefalo F, et al. Feasibility and early clinical assessment of flattening filter free (FFF) based stereotactic body radiotherapy (SBRT) treatments. Radiat Oncol. 2011;6:113.CrossRefGoogle Scholar
  63. 63.
    High or standard intensity radiation therapy after gemcitabine hydrochloride and Nab-paclitaxel in treating patients with pancreatic cancer that cannot be removed by surgery. 14 Aug 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01921751
  64. 64.
    A randomized phase III study evaluating modified FOLFIRINOX (mFFX) with or without stereotactic body radiotherapy (SBRT) in the treatment of locally advanced pancreatic cancer. 14 Aug 2016. Available from: https://clinicaltrials.gov/ct2/show/NCT01926197
  65. 65.
    Laheru D, Lutz E, Burke J, Biedrzycki B, Solt S, Onners B, et al. Allogeneic granulocyte macrophage colony-stimulating factor-secreting tumor immunotherapy alone or in sequence with cyclophosphamide for metastatic pancreatic cancer: a pilot study of safety, feasibility, and immune activation. Clin Cancer Res. 2008;14(5):1455–63.CrossRefGoogle Scholar
  66. 66.
    Finkelstein SE, Timmerman R, McBride WH, Schaue D, Hoffe SE, Mantz CA, et al. The confluence of stereotactic ablative radiotherapy and tumor immunology. Clin Dev Immunol. 2011;2011:439752.CrossRefGoogle Scholar
  67. 67.
    Polistina F, Costantin G, Casamassima F, et al. Unresectable locally advanced pancreatic cancer: a multimodal treatment using neoadjuvant chemoradiotherapy (gemcitabine plus stereotactic radiosurgery) and subsequent surgical exploration. Ann Surg Oncol. 2010;17(8):2092–2101.CrossRefGoogle Scholar
  68. 68.
    Gurka MK, Collins SP, Slack R, et al. Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety. Radiat Oncol. 2013;8(1):44.CrossRefGoogle Scholar
  69. 69.
    Tozzi A, Comito T, Alongi F, et al. SBRT in unresectable advanced pancreatic cancer: preliminary results of a mono-institutional experience. Radiat Oncol. 2013;8(1):148.CrossRefGoogle Scholar
  70. 70.
    Herman JM, Chang DT, Goodman KA, et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121(7):1128–1137.CrossRefGoogle Scholar
  71. 71.
    Koong AC, Christofferson E, Le Q-T, et al. Phase II study to assess the efficacy of conventionally fractionated radiotherapy followed by a stereotactic radiosurgery boost in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2005;63(2):320–323.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Daphna Spiegel
    • 1
  • Julian Hong
    • 1
  • Manisha Palta
    • 1
  • Brian Czito
    • 1
  • Christopher Willett
    • 1
  1. 1.Department of Radiation OncologyDuke UniversityDurhamUSA

Section editors and affiliations

  • John Neoptolemos
    • 1
  • Raul A. Urrutia
    • 2
  • James L. Abbruzzese
    • 3
  • Markus W. Büchler
    • 4
  1. 1.Division of Surgery and OncologyUniversity of LiverpoolLiverpoolUK
  2. 2.Mayo Clinic Cancer CenterMayo ClinicRochesterUSA
  3. 3.Duke University Medical CenterDurhamUSA
  4. 4.Department of General, Visceral and Transplantation SurgeryUniversity of HeidelbergHeidelbergGermany

Personalised recommendations