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A Meta-analysis of Randomized Clinical Trials of Chemoradiation Therapy in Locally Advanced Pancreatic Cancer

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Abstract

Objectives

Pancreatic cancer is the fourth most common cause of cancer deaths in the USA. Despite the fact that the radiotherapy in addition to chemotherapy (CT) is frequently employed, the role of chemoradiation therapy (CRT) in the treatment of locally advanced pancreatic cancer (LAPC) remains controversial. We conducted a systemic review and meta-analysis to evaluate the effect of radiation treatment in addition to CT in patients with LAPC.

Methods

Only randomized controlled trials that compared CRT to CT and reported time to event summary were included in this study. The primary end point was overall survival expressed as hazard ratio (HR). Due to significant heterogeneity, random-effects model statistics were used.

Results

Five eligible studies were included with a total of 593 patients (CT, N = 298; CRT, N = 295). Two studies demonstrated statistically significant difference in OS in favor of CRT and the rest of the studies did not demonstrate any significant differences. Meta-analysis demonstrated that there was a non-significant trend toward a survival benefit in the CRT arm; HR 0.913 (95 % CI 0.595–1.400, p = 0.675). No significant differences in overall results were seen with sensitivity analysis.

Conclusions

The addition of radiation therapy to CT in the treatment of LAPC is associated with a non-significant trend toward survival advantage. Larger randomized controlled trials using modern CT regimens and radiation techniques are needed to further clarify the role of radiation in this setting.

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References

  1. (2014) NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines): Pancreatic adenocarcinoma. Version 2.2014. In:

  2. Abrams RA, Winter KA, Regine WF, Safran H, Hoffman JP, Lustig R, et al. Failure to adhere to protocol specified radiation therapy guidelines was associated with decreased survival in RTOG 9704–a phase III trial of adjuvant chemotherapy and chemoradiotherapy for patients with resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys. 2012;82:809–16. doi:10.1016/j.ijrobp.2010.11.039.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Bardeesy N, Cheng KH, Berger JH, Chu GC, Pahler J, Olson P, et al. Smad4 is dispensable for normal pancreas development yet critical in progression and tumor biology of pancreas cancer. Genes Dev. 2006;20:3130–46. doi:10.1101/gad.1478706.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  4. Berlin JD, Catalano P, Thomas JP, Kugler JW, Haller DG, Benson 3rd AB. Phase III study of gemcitabine in combination with fluorouracil versus gemcitabine alone in patients with advanced pancreatic carcinoma: Eastern Cooperative Oncology Group Trial E2297. J Clin Oncol. 2002;20:3270–5.

    Article  CAS  PubMed  Google Scholar 

  5. Bramhall SR, Rosemurgy A, Brown PD, Bowry C, Buckels JA, Marimastat Pancreatic Cancer Study G. Marimastat as first-line therapy for patients with unresectable pancreatic cancer: a randomized trial. J Clin Oncol. 2001;19:3447–55.

    CAS  PubMed  Google Scholar 

  6. Bramhall SR, Schulz J, Nemunaitis J, Brown PD, Baillet M, Buckels JA. A double-blind placebo-controlled, randomised study comparing gemcitabine and marimastat with gemcitabine and placebo as first line therapy in patients with advanced pancreatic cancer. Br J Cancer. 2002;87:161–7. doi:10.1038/sj.bjc.6600446.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  7. Burris 3rd HA, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial. J Clin Oncol. 1997;15:2403–13.

    CAS  PubMed  Google Scholar 

  8. 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;19:1592–9. doi:10.1093/annonc/mdn281.

    Article  CAS  PubMed  Google Scholar 

  9. Chuong MD, Springett GM, Freilich JM, Park CK, Weber JM, Mellon EA, et al. Stereotactic body radiation therapy for locally advanced and borderline resectable pancreatic cancer is effective and well tolerated. Int J Radiat Oncol Biol Phys. 2013;86:516–22. doi:10.1016/j.ijrobp.2013.02.022.

    Article  PubMed  Google Scholar 

  10. 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;364:1817–25. doi:10.1056/NEJMoa1011923.

    Article  CAS  PubMed  Google Scholar 

  11. Faris JE, Blaszkowsky LS, McDermott S, Guimaraes AR, Szymonifka J, Huynh MA, Ferrone CR, Wargo JA, Allen JN, Dias LE, Kwak EL, Lillemoe KD, Thayer SP, Murphy JE, Zhu AX, Sahani DV, Wo JY, Clark JW, Fernandez-del Castillo C, Ryan DP, Hong TS (2013) FOLFIRINOX in locally advanced pancreatic cancer: the Massachusetts General Hospital Cancer Center experience. Oncologist 18: p 543–548.

  12. 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 

  13. Hazel JJ, Thirlwell MP, Huggins M, Maksymiuk A, MacFarlane JK. Multi-drug chemotherapy with and without radiation for carcinoma of the stomach and pancreas: a prospective randomized trial. J Can Assoc Radiol. 1981;32:164–5.

    CAS  PubMed  Google Scholar 

  14. Huguet F, Goodman KA, Azria D, Racadot S, Abrams RA. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations. Int J Radiat Oncol Biol Phys. 2012;83:1355–64. doi:10.1016/j.ijrobp.2011.11.050.

    Article  PubMed  Google Scholar 

  15. Iacobuzio-Donahue CA, Fu B, Yachida S, Luo M, Abe H, Henderson CM, et al. DPC4 gene status of the primary carcinoma correlates with patterns of failure in patients with pancreatic cancer. J Clin Oncol. 2009;27:1806–13. doi:10.1200/JCO.2008.17.7188.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. 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;3:373–8.

    CAS  PubMed  Google Scholar 

  17. Li D, Xie K, Wolff R, Abbruzzese JL. Pancreatic cancer. Lancet. 2004;363:1049–57. doi:10.1016/S0140-6736(04)15841-8.

    Article  CAS  PubMed  Google Scholar 

  18. 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;29:4105–12. doi:10.1200/JCO.2011.34.8904.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Pascal Hammel FH, Jean-Luc Van Laethem, David Goldstein, Bengt Glimelius, Pascal Artru, Ivan Borbath, Oliver Bouche, Jenny Shannon, Thierry Andre, Laurent Mineur, Benoist Chibaudel, Franck Bonnetain and Christophe Louvet (2013) Comparison of chemoradiotherapy (CRT) and chemotherapy in patients with locally advanced pancreatic cancer (LAPC) controlled after 4 months of gemcitabine with or without erlotinib: final results of the international phase III LAP 07 study. J Clin Oncol 31.

  20. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29. doi:10.3322/caac.21208.

    Article  PubMed  Google Scholar 

  21. 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;96:1183–90. doi:10.1038/sj.bjc.6603719.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Tierney JF, Stewart LA, Ghersi D, Burdett S, Sydes MR. Practical methods for incorporating summary time-to-event data into meta-analysis. Trials. 2007;8:16. doi:10.1186/1745-6215-8-16.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Torres-Roca JF. A molecular assay of tumor radiosensitivity: a roadmap towards biology-based personalized radiation therapy. Pers Med. 2012;9:547–57. doi:10.2217/pme.12.55.

    Article  CAS  Google Scholar 

  24. Trakul N, Koong AC, Chang DT. Stereotactic body radiotherapy in the treatment of pancreatic cancer. Semin Radiat Oncol. 2014;24:140–7. doi:10.1016/j.semradonc.2013.11.008.

    Article  PubMed  Google Scholar 

  25. Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet. 2011;378:607–20. doi:10.1016/S0140-6736(10)62307-0.

    Article  PubMed Central  PubMed  Google Scholar 

  26. 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;369:1691–703. doi:10.1056/NEJMoa1304369.

    Article  Google Scholar 

  27. Yeo TP, Hruban RH, Leach SD, Wilentz RE, Sohn TA, Kern SE, et al. Pancreatic cancer. Curr Probl Cancer. 2002;26:176–275.

    Article  PubMed  Google Scholar 

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Correspondence to Amit Mahipal.

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Ambe, C., Fulp, W., Springett, G. et al. A Meta-analysis of Randomized Clinical Trials of Chemoradiation Therapy in Locally Advanced Pancreatic Cancer. J Gastrointest Canc 46, 284–290 (2015). https://doi.org/10.1007/s12029-015-9734-z

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  • DOI: https://doi.org/10.1007/s12029-015-9734-z

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