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A Systematic Review of Resectability and Survival After Concurrent Chemoradiation in Primarily Unresectable Pancreatic Cancer

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

Abstract

Purpose

The objective of this study was to determine the effect on resection rate and survival of neoadjuvant chemoradiotherapy for primarily unresectable locally advanced pancreatic carcinoma.

Methods

A systematic review of recently published literature was performed. Resection rates and survival data were derived from reports published from 2000 onwards. Only recent studies, based on radiotherapy with standard dose and fractionation, have been analyzed.

Results

Thirteen studies with a total of 510 patients met selection criteria. A resection rate of 8.3–64.2% was reported (median, 26.5%). Of the operated patients, 57.1–100% (median, 87.5%) had R0 tumor resection. Most papers reported occasional pathological complete responses (CR, 3.0–8.8%). When outcome in all patients was considered, median survival ranged from 9 to 23 (median, 13.3) months, comparing favorably with literature data based on concurrent chemoradiation alone (range, 8.6–13 months). Surprisingly, in patients with unresectable tumor at presentation, median survival after surgery ranged from 16.4 to 32.3 (median, 23.6) months.

Conclusions

The finding of a high proportion of R0 resection among all resections performed confirms the activity of neoadjuvant radiochemotherapy and should not be neglected. Based on these data, patients with unresectable pancreatic cancer without disease progression after chemoradiotherapy should be considered for radical surgery.

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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006;56:106–30.

    Article  Google Scholar 

  2. Black RJ, Bray F, Ferlay J, Parkin DM. Cancer incidence and mortality in the European Union: cancer registry data and estimates of national incidence for 1990. Eur J Cancer. 1997;33:1075–107.

    Article  CAS  PubMed  Google Scholar 

  3. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Büchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004,91:586–94.

    Article  CAS  PubMed  Google Scholar 

  4. Cleary SP, Gryfe R, Guindi M, Greig P, Smith L, Mackenzie R, Strasberg S, et al. Prognostic factors in resected pancreatic adenocarcinoma: analysis of actual 5-year survivors. J Am Coll Surg. 2004;198:722–31.

    Article  PubMed  Google Scholar 

  5. Conlon KC, Klimstra DS, Brennan MF. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996;223:273–9.

    Article  CAS  PubMed  Google Scholar 

  6. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg. 1996;83:625–31.

    Article  CAS  PubMed  Google Scholar 

  7. Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, Sauter PK, et al. Resected adenocarcinoma of the pancreas—616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.

    Article  CAS  PubMed  Google Scholar 

  8. Yeo CJ, Sohn TA, Cameron JL, Hruban RH, Lillemoe KD, Pitt HA. Periampullary adenocarcinoma: analysis of 5-year survivors. Ann Surg. 1998;227:821–31.

    Article  CAS  PubMed  Google Scholar 

  9. Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, et al. Cancer statistics, 2005. CA Cancer J Clin. 2005;55:10–30.

    Article  Google Scholar 

  10. Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. J Natl Cancer Inst. 1988;80:751–5.

    Article  Google Scholar 

  11. Gastrointestinal Tumor Study Group. A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. Ann Surg. 1979;189:205–8.

    Google Scholar 

  12. Chauffert B, Mornex F, Bonnetain F, Rougier P, Mariette C, Bouché O, Bosset JF, 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;19:1592–9.

    Article  CAS  PubMed  Google Scholar 

  13. Loehrer PJ, Powell ME, Cardenes HR, Wagner L, Brell JM, Ramanathan RK, Crane CH, et al. A randomized phase III study of gemcitabine in combination with radiation therapy versus gemcitabine alone in patients with localized, unresectable pancreatic cancer: E4201 [abstract]. J Clin Oncol. 2008;26(Suppl 15):4506a.

    Google Scholar 

  14. Wanebo HJ, Glicksman AS, Vezeridis MP, Clark J, Tibbetts L, Koness RJ, Levy A. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg 2000;135:81–7.

    Article  CAS  PubMed  Google Scholar 

  15. Snady H, Bruckner H, Cooperman A, Paradiso J, Kiefer L. Survival advantage of combined chemoradiotherapy compared with resection as the initial treatment of patients with regional pancreatic carcinoma. An outcomes trial. Cancer 2000; 89:314–27.

    Article  CAS  PubMed  Google Scholar 

  16. Ammori JB, Colletti LM, Zalupski MM, Eckhauser FE, Greenson JK, Dimick J, Lawrence TS, McGinn CJ. Surgical resection following radiation therapy with concurrent gemcitabine in patients with previously unresectable adenocarcinoma of the pancreas. J Gastrointest Surg. 2003;7:766–72.

    Article  PubMed  Google Scholar 

  17. Aristu J, Cañón R, Pardo F, Martínez-Monge R, Martin-Algarra S, Manuel Ordoñez J, Villafranca E, et al. Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer. Am J Clin Oncol (CCT). 2003;26:30–6.

    Article  Google Scholar 

  18. Sa Cunha A, Rault A, Laurent C, Adhoute X, Vendrely V, Béllannée G, Brunet R, et al. Surgical resection after radiochemotherapy in patients with unresectable adenocarcinoma of the pancreas. J Am Coll Surg. 2005;201:359–65.

    Article  PubMed  Google Scholar 

  19. Adhoute X, Smith D, Vendrely V, Rault A, Sa Cunha A, Legoux JL, Belleannée G, et al. Subsequent resection of locally advanced pancreatic carcinoma after chemoradiotherapy. Gastroenterol Clin Biol. 2006;30:224–30.

    Article  PubMed  Google Scholar 

  20. White RR, Tyler DS. Neoadjuvant therapy for pancreatic cancer: the Duke experience. Surg Oncol Clin North Am. 2004;13:675–84.

    Article  Google Scholar 

  21. Kornek GV, Schratter-Sehn A, Marczell A, Depisch D, Karner J, Krauss G, Haider K, et al. Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucovorin and cisplatin. Br J Cancer. 2000;82:98–103.

    Article  CAS  PubMed  Google Scholar 

  22. Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg. 2002;6:763–9.

    Article  PubMed  Google Scholar 

  23. Crane CH, Abbruzzese JL, Evans DB, Wolff RA, Ballo MT, Delclos M, Milas L, et al. Is the therapeutic index better with gemcitabine-based chemoradiation than with 5-fluorouracil-based chemoradiation in locally advanced pancreatic cancer? Int J Radiat Oncol Biol Phys. 2002;52:1293–302.

    Article  CAS  PubMed  Google Scholar 

  24. Zimmermann FB, Schuhmacher C, Lersch C, Bernhardt B, Pickel P, Siewert JR, Molls M, et al. Sequential and/or concurrent hypofractionated radiotherapy and concurrent chemotherapy in neoadjuvant treatment of advanced adenocarcinoma of the pancreas. Outcome and patterns of failure. Hepatogastroenterology. 2004;51:1842–6.

    PubMed  Google Scholar 

  25. Grading systems and levels of evidence and grades of recommendation. SIGN guideline development handbook: SIGN 50 Available at: http://www.sign.ac.uk/pdf/sign50.pdf.

  26. White RR, Hurwitz HI, Morse MA, Lee C, Anscher MS, Paulson EK, Gottfried MR, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol. 2001;8:758–65.

    Article  CAS  PubMed  Google Scholar 

  27. Brunner TB, Grabenbauer GG, Kastl S, Herrmann O, Baum U, Fietkau R, Klein P, et al. Preoperative chemoradiation in locally advanced pancreatic carcinoma: a phase II study. Onkologie. 2000;23:436–42.

    Article  PubMed  Google Scholar 

  28. Wilkowski R, Thoma M, Schauer R, Wagner A, Heinemann V. Effect of chemoradiotherapy with gemcitabine and cisplatin on locoregional control in patients with primary inoperable pancreatic cancer. World J Surg. 2004;28:1011–8.

    Article  PubMed  Google Scholar 

  29. Wilkowski R, Thoma M, Bruns C, Wagner A, Heinemann V. Chemoradiotherapy with gemcitabine and continuous 5-FU in patients with primary inoperable pancreatic cancer. JOP. 2006;7:349–60.

    PubMed  Google Scholar 

  30. Macchia G, Valentini V, Mattiucci GC, Mantini G, Alfieri S, Digesù C, Deodato F. Preoperative chemoradiation and intra-operative radiotherapy for pancreatic carcinoma. Tumori. 2007;93:53–60.

    CAS  PubMed  Google Scholar 

  31. Lind PA, Isaksson B, Almström M, Johnsson A, Albiin N, Byström P, Permert J. Efficacy of preoperative radiochemotherapy in patients with locally advanced pancreatic carcinoma. Acta Oncol. 2008;47:413–20.

    Article  CAS  PubMed  Google Scholar 

  32. Milandri C, Polico R, Gardini A, Passardi A, Romeo A, Zaccaroni A, Rosetti A, et al. Chemoradiotherapy for unresectable locally advanced pancreatic cancer: a pilot study [abstract]. J Clin Oncol. 2008;26(Suppl 15):15630a.

    Google Scholar 

  33. Delpero JR, Turrini O. Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection. Cancer Radiother. 2006;10:462–70.

    PubMed  Google Scholar 

  34. Wilkowski R, Stoffregen C, Rau H-G, Heiss MM, Thoma M, Dühmke E, Langer F, Heinemann V. Chemoradiation with gemcitabine (G) in primary inoperable pancreatic cancer. Proc Am Soc Clin Oncol. 2001;20:A2317.

    Google Scholar 

  35. Massucco P, Capussotti L, Magnino A, Sperti E, Gatti M, Muratore A, Sgotto E, et al. Pancreatic resections after chemoradiotherapy for locally advanced ductal adenocarcinoma: analysis of perioperative outcome and survival. Ann Surg Oncol. 2006;13:1201–8.

    Article  PubMed  Google Scholar 

  36. Marti JL, Hochster HS, Hiotis SP, Donahue B, Ryan T, Newman E. Phase I/II trial of induction chemotherapy followed by concurrent chemoradiotherapy and surgery for locoregionally advanced pancreatic cancer. Ann Surg Oncol. 2008;15:3521–31.

    Article  PubMed  Google Scholar 

  37. Small W, Berlin J, Freedman GM, Lawrence T, Talamonti M, et al. Full-dose gemcitabine with concurrent radiation therapy in patient with nonmetastatic pancreatic cancer. A multicenter phase II trial. J Clin Oncol. 2008;26:942–7.

    Article  CAS  PubMed  Google Scholar 

  38. Katz MHG, Pisters PWT, Evans DB, Sun CC, Lee JE, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46.

    Article  PubMed  Google Scholar 

  39. Crane CH, Ellis LM, Abbruzzese JL, et al. Phase I trial evaluating the safety of bevacizumab with concurrent radiotherapy and capecitabine in locally advanced pancreatic cancer. J Clin Oncol. 2006;24:1145–51.

    Article  CAS  PubMed  Google Scholar 

  40. Rich T, Harris J, Abrams R, et al. Phase II study of external irradiation and weekly paclitaxel for nonmetastatic, unresectable pancreatic cancer: RTOG-98-12. Am J Clin Oncol. 2004;27:51–6.

    Article  CAS  PubMed  Google Scholar 

  41. Rich T, Myerson R, Harris J, et al. A randomized phase II trial of weekly gemcitabine (G), paclitaxel (P), and external irradiation followed by the farnesyl transferase inhibitor R115777 (NSC#702818) for locally advanced pancreatic cancer (RTOG 0020) [abstract]. Proc Gastrointest Cancers Symp. 2006:A-121.

  42. Ko AH, Quivey JM, Venook AP, et al. A phase II study of fixed-ose rate gemcitabine plus low-dose cisplatin followed by consolidative chemoradiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2007;68:809–16.

    CAS  PubMed  Google Scholar 

  43. Crane CH, Winter K, Regine W, et al. A phase II study of bevacizumab with concurrent capecitabine and radiation followed by maintenance gemcitabine and bevacizumab for locally advanced pancreatic cancer [abstract]. Int J Radiat Oncol Biol Phys. 2007;67(Suppl 77):136a.

    Google Scholar 

  44. Duffy A, Kortmansky J, Schwartz GK, et al. A phase I study of erlotinib in combination with gemcitabine and radiation in locally advanced, non-operable pancreatic adenocarcinoma. Ann Oncol. 2008;19:86–91.

    Article  CAS  PubMed  Google Scholar 

  45. Martin JL, Harvey HA, Lipton A, Martin R. Combined chemoradiotherapy for unresectable pancreatic cancer. Am J Clin Oncol. 1999;22:309–14.

    Article  CAS  PubMed  Google Scholar 

  46. Safran H, Cioffi W, Iannitti D, Mega A, Akerman P. Paclitaxel and concurrent radiation for locally advanced pancreatic carcinoma. Front Biosci. 1998;3:204–6.

    Google Scholar 

  47. Ishii H, Okada S, Tokuuye K, Nose H, Okusaka T, Yoshimori M, Nagahama H, et al. Protracted 5-fluorouracil infusion with concurrent radiotherapy as a treatment for locally advanced pancreatic carcinoma. Cancer. 1997;79:1516–20.

    Article  CAS  PubMed  Google Scholar 

  48. White RR, Paulson EK, Freed KS, Keogan MT, Hurwitz HI, Lee C, Morse MA, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg. 2001;5:626–33.

    Article  CAS  PubMed  Google Scholar 

  49. Hoffman JP, O’Dwyer P, Agarwal P, Salazar H, Ahmad N. Preoperative chemoradiotherapy for localized pancreatic carcinoma A perspective. Cancer. 1996;78(Suppl 3):592–7.

    CAS  PubMed  Google Scholar 

  50. Lall CG, Howard TJ, Skandarajah A, DeWitt JM, Aisen AM, Sandrasegaran K. New concepts in staging and treatment of locally advanced pancreatic head cancer. AJR Am J Roentgenol. 2007;189:1044–50.

    Article  PubMed  Google Scholar 

  51. National Comprehensive Cancer Network (NCCN). Pancreatic adenocarcinoma. Practice guidelines in oncology. V. 2008. Fort Washington, PA. Available at http://www.nccn.org/professionals/physician_gls/PDF/pancreatic.pdf.

  52. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13:1035–46.

    Article  PubMed  Google Scholar 

  53. Lu DSK, Reber HA, Krasny RM, Kadell BM, Sayre J. Local staging of pancreatic cancer: criteria for unresectability of major vessels as revealed by pancreatic-phase, thin-section helical CT. AJR Am J Roentgenol. 1997;168:1439–43.

    CAS  PubMed  Google Scholar 

  54. Wong JC, Lu DS. Staging of pancreatic adenocarcinoma by imaging studies. Clin Gastroenterol Hepatol. 2008;6:1301–8.

    Article  PubMed  Google Scholar 

  55. Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, Friess H, Schirmacher P, Büchler MW. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.

    Article  PubMed  Google Scholar 

  56. Verbeke CS. Resection margins and R1 rates in pancreatic cancer: are we there yet? Histopathology. 2008;52:787–96.

    Article  CAS  PubMed  Google Scholar 

  57. Van den Broeck A, Sergeant G, Ectors N, Van Steenbergen W, Aerts R, Topal B. Patterns of recurrence after curative resection of pancreatic ductal adenocarcinoma. Eur J Surg Oncol. 2009 Jan 6. [Epub ahead of print].

  58. Klinkenbijl JH, Jeekel J, Sahmoud T, van Pel R, Couvreur ML, Veenhof CH, Arnaud JP, 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.

    Article  CAS  PubMed  Google Scholar 

  59. Neoptolemos JP, Stocken DD, Friess H, Bassi C, Dunn JA, Hickey H, Beger 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;350:1200–10.

    Article  CAS  PubMed  Google Scholar 

  60. Kosuge T, Kiuchi T, Mukai K, Kakizoe T. Japanese Study Group of Adjuvant Therapy for Pancreatic Cancer (JSAP). A multicenter randomized controlled trial to evaluate the effect of adjuvant cisplatin and 5-fluorouracil therapy after curative resection in cases of pancreatic cancer. Jpn J Clin Oncol. 2006;36:159–65.

    Article  PubMed  Google Scholar 

  61. Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, Schramm H, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.

    Article  CAS  PubMed  Google Scholar 

  62. Neoptolemos JP, Stocken DD, Tudur Smith C, Bassi C, Ghaneh P, Owen E, Moore M, et al. Adjuvant 5-fluorouracil and folinic acid vs observation for pancreatic cancer: composite data from the ESPAC-1 and -3(v1) trials. Br J Cancer. 2009;100:246–50.

    Article  CAS  PubMed  Google Scholar 

  63. Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200.

    Article  CAS  PubMed  Google Scholar 

  64. Lin PW, Shan YS, Lin YJ, Hung CJ. Pancreaticoduodenectomy for pancreatic head cancer: PPPD versus Whipple procedure. Hepatogastroenterology. 2005;52:1601–4.

    PubMed  Google Scholar 

  65. Tran KT, Smeenk HG, van Eijck CH, Kazemier G, Hop WC, Greve JW, Terpstra OT, et al. Pylorus preserving pancreaticoduodenectomy versus standard Whipple procedure: a prospective, randomized, multicenter analysis of 170 patients with pancreatic and periampullary tumors. Ann Surg. 2004;240:738–45.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy

    Alessio G. Morganti MD, Mariangela Massaccesi MD, Luciana Caravatta MD, Adele Piscopo MD, Gabriella Macchia MD, Francesco Deodato MD, Vincenzo Picardi MD & Edy Ippolito MD

  2. Department of Palliative Therapies, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy

    Alessio G. Morganti MD & Rosa Tambaro MD

  3. Unit of Clinical Medicine and Public Health, Sapienza University of Rome, Rome, Italy

    Giuseppe La Torre MD

  4. Department of Surgery, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy

    Luigi Sofo MD

  5. Department of Radiology, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy

    Giuseppina Sallustio MD

  6. Department of Endoscopy, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy

    Marcello Ingrosso MD

  7. Department of Radiotherapy, Policlinico Universitario “A. Gemelli,” Catholic University, Rome, Italy

    Numa Cellini MD & Vincenzo Valentini MD

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  1. Alessio G. Morganti MD
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  2. Mariangela Massaccesi MD
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  3. Giuseppe La Torre MD
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  5. Adele Piscopo MD
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  6. Rosa Tambaro MD
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  7. Luigi Sofo MD
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  8. Giuseppina Sallustio MD
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  9. Marcello Ingrosso MD
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  10. Gabriella Macchia MD
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  11. Francesco Deodato MD
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  12. Vincenzo Picardi MD
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  14. Numa Cellini MD
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  15. Vincenzo Valentini MD
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Correspondence to Gabriella Macchia MD.

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Morganti, A.G., 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 17, 194–205 (2010). https://doi.org/10.1245/s10434-009-0762-4

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