A Systematic Review of Resectability and Survival After Concurrent Chemoradiation in Primarily Unresectable Pancreatic Cancer
- Alessio G. Morganti MD,
- Mariangela Massaccesi MD,
- Giuseppe La Torre MD,
- Luciana Caravatta MD,
- Adele Piscopo MD,
- Rosa Tambaro MD,
- Luigi Sofo MD,
- Giuseppina Sallustio MD,
- Marcello Ingrosso MD,
- Gabriella Macchia MD,
- Francesco Deodato MD,
- Vincenzo Picardi MD,
- Edy Ippolito MD,
- Numa Cellini MD,
- Vincenzo Valentini MD
- … show all 15 hide
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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.
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.
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.
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.
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Survival after resection for ductal adenocarcinoma of the pancreas. Br J Surg. 1996;83:625–31. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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.
- 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. CrossRef
- 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.
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- White RR, Tyler DS. Neoadjuvant therapy for pancreatic cancer: the Duke experience. Surg Oncol Clin North Am. 2004;13:675–84. CrossRef
- 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. CrossRef
- Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg. 2002;6:763–9. CrossRef
- 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. CrossRef
- 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.
- 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.
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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.
- 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.
- 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. CrossRef
- 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.
- Delpero JR, Turrini O. Locally advanced pancreatic adenocarcinoma. Chemoradiotherapy, reevaluation and secondary resection. Cancer Radiother. 2006;10:462–70.
- 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.
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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.
- 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.
- 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.
- 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. CrossRef
- Martin JL, Harvey HA, Lipton A, Martin R. Combined chemoradiotherapy for unresectable pancreatic cancer. Am J Clin Oncol. 1999;22:309–14. CrossRef
- 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.
- 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. CrossRef
- 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. CrossRef
- 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.
- 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. CrossRef
- 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.
- 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. CrossRef
- 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.
- Wong JC, Lu DS. Staging of pancreatic adenocarcinoma by imaging studies. Clin Gastroenterol Hepatol. 2008;6:1301–8. CrossRef
- 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. CrossRef
- Verbeke CS. Resection margins and R1 rates in pancreatic cancer: are we there yet? Histopathology. 2008;52:787–96. CrossRef
- 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].
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- 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. CrossRef
- Sperti C, Pasquali C, Piccoli A, Pedrazzoli S. Recurrence after resection for ductal adenocarcinoma of the pancreas. World J Surg. 1997;21:195–200. CrossRef
- Lin PW, Shan YS, Lin YJ, Hung CJ. Pancreaticoduodenectomy for pancreatic head cancer: PPPD versus Whipple procedure. Hepatogastroenterology. 2005;52:1601–4.
- 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. CrossRef
- A Systematic Review of Resectability and Survival After Concurrent Chemoradiation in Primarily Unresectable Pancreatic Cancer
Annals of Surgical Oncology
Volume 17, Issue 1 , pp 194-205
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- Alessio G. Morganti MD (1) (2)
- Mariangela Massaccesi MD (1)
- Giuseppe La Torre MD (3)
- Luciana Caravatta MD (1)
- Adele Piscopo MD (1)
- Rosa Tambaro MD (2)
- Luigi Sofo MD (4)
- Giuseppina Sallustio MD (5)
- Marcello Ingrosso MD (6)
- Gabriella Macchia MD (1)
- Francesco Deodato MD (1)
- Vincenzo Picardi MD (1)
- Edy Ippolito MD (1)
- Numa Cellini MD (7)
- Vincenzo Valentini MD (7)
- Author Affiliations
- 1. Department of Radiation Oncology, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
- 2. Department of Palliative Therapies, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
- 3. Unit of Clinical Medicine and Public Health, Sapienza University of Rome, Rome, Italy
- 4. Department of Surgery, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
- 5. Department of Radiology, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
- 6. Department of Endoscopy, “John Paul II” Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy
- 7. Department of Radiotherapy, Policlinico Universitario “A. Gemelli,” Catholic University, Rome, Italy