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Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer: An Emerging Paradigm?

  • Gastrointestinal Cancers (BG Czito, Section Editor)
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Abstract

Although neoadjuvant chemoradiotherapy has been tested for more than two decades and can be safely delivered to patients with non-metastatic pancreatic cancer, no randomised trials have been reported until now. Here we provide an overview of the first randomised trial in patients with potentially resectable cancer and of the latest developments in neoadjuvant therapy for this group of patients. It is necessary to continue to perform clinical trials in this field to accurately identify the effect on survival and quality of life in patients with potentially resectable, borderline resectable and unresectable pancreatic cancer. Aspects of imaging for restaging and clinical prognostic factors are also discussed given they will be useful instruments for future trials.

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References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  2. Crane CH, Varadhachary GR, Yordy JS, et al. Phase II trial of cetuximab, gemcitabine, and oxaliplatin followed by chemoradiation with cetuximab for locally advanced (T4) pancreatic adenocarcinoma: correlation of Smad4(Dpc4) immunostaining with pattern of disease progression. J Clin Oncol. 2011;29:3037–43.

    Article  PubMed  CAS  Google Scholar 

  3. Brunner TB, Geiger M, Grabenbauer GG, et al. Phase I trial of the human immunodeficiency virus protease inhibitor nelfinavir and chemoradiation for locally advanced pancreatic cancer. J Clin Oncol. 2008;26:2699–706.

    Article  PubMed  CAS  Google Scholar 

  4. Fokas E, Prevo R, Pollard JR, et al. Targeting ATR in vivo using the novel inhibitor VE-822 results in selective sensitization of pancreatic tumors to radiation. Cell Death Dis. 2012;3:e441.

    Article  PubMed  CAS  Google Scholar 

  5. 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;26:3496–502.

    Article  PubMed  CAS  Google Scholar 

  6. Pingpank JF, Hoffman JP, Ross EA, et al. Effect of preoperative chemoradiotherapy on surgical margin status of resected adenocarcinoma of the head of the pancreas. J Gastrointest Surg. 2001;5:121–30.

    Article  PubMed  CAS  Google Scholar 

  7. Tinkl D, Grabenbauer GG, Golcher H, et al. Downstaging of pancreatic carcinoma after neoadjuvant chemoradiation. Strahlenther Onkol. 2009;185:557–66.

    Article  PubMed  Google Scholar 

  8. Spitz FR, Abbruzzese JL, Lee JE, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol. 1997;15:928–37.

    PubMed  CAS  Google Scholar 

  9. Sohn TA, Yeo CJ, Cameron JL, et al. Resected adenocarcinoma of the pancreas-616 patients: results, outcomes, and prognostic indicators. J Gastrointest Surg. 2000;4:567–79.

    Article  PubMed  CAS  Google Scholar 

  10. Wayne JD, Wolff RA, Pisters PW, et al. Multimodality management of localized pancreatic cancer. Cancer J. 2001;7 Suppl 1:S35–46.

    PubMed  Google Scholar 

  11. Rumstadt B, Schwab M, Schuster K, et al. The role of laparoscopy in the preoperative staging of pancreatic carcinoma. J Gastrointest Surg. 1997;1:245–50.

    Article  PubMed  CAS  Google Scholar 

  12. Brunner TB, Fokas E, Eccles C, et al. A comparison of four target volume definitions for pancreatic cancer: two concepts including the lymphatics (RTOG & ARO) and two concepts only treating the primary tumour (Michigan & UK-SCALOP). Poster 2274 presented at the ASTRO annual meeting 2012, Boston.

  13. Tamm EP, Loyer EM, Faria S, et al. Staging of pancreatic cancer with multidetector CT in the setting of preoperative chemoradiation therapy. Abdom Imaging. 2006;31:568–74.

    Article  PubMed  CAS  Google Scholar 

  14. Cheng TY, Sheth K, White RR, et al. Effect of neoadjuvant chemoradiation on operative mortality and morbidity for pancreaticoduodenectomy. Ann Surg Oncol. 2006;13:66–74.

    Article  PubMed  Google Scholar 

  15. •• Brunner TB, Golcher H, Witzigmann H, et al. Results of a multicenter randomized phase II trial of resection ± neoadjuvant chemoradiation therapy in pancreatic cancer. Int J Radiat Oncol Biol Phys. 2012;84:S90–1. This is the first multicentre randomised controlled trial comparing primary resection versus neoadjuvant chemoradiotherapy followed by resection in pancreatic cancer. Median overall survival of patients with resected tumours was 25 versus 18 months, preoperative therapy was safe and the clear resection rate was higher after pretreatment.

    Article  Google Scholar 

  16. Lu DS, Reber HA, Krasny RM, et al. 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.

    Article  PubMed  CAS  Google Scholar 

  17. Brunner TB, Merkel S, Grabenbauer GG, et al. Definition of elective lymphatic target volume in ductal carcinoma of the pancreatic head based upon histopathologic analysis. Int J Radiat Oncol Biol Phys. 2005;62:1021–9.

    Article  PubMed  Google Scholar 

  18. Dindo D, Demartines N, Clavien PA. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240:205–13.

    Article  PubMed  Google Scholar 

  19. Huguet F, Andre T, Hammel P, 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;25:326–31.

    Article  PubMed  CAS  Google Scholar 

  20. •• Gillen S, Schuster T, Meyer Zum Buschenfelde C, et al. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267. This is an important meta-analysis on neoadjuvant chemoradiotherapy for both resectable and non-resectable tumours.

    Article  PubMed  Google Scholar 

  21. Boeck S, Bruns CJ, Sargent M, et al. Current oncological treatment of patients with pancreatic cancer in germany: results from a national survey on behalf of the Arbeitsgemeinschaft Internistische Onkologie and the Chirurgische Arbeitsgemeinschaft Onkologie of the Germany Cancer Society. Oncology. 2009;77:40–8.

    Article  PubMed  Google Scholar 

  22. Assifi MM, Lu X, Eibl G, et al. Neoadjuvant therapy in pancreatic adenocarcinoma: a meta-analysis of phase II trials. Surgery. 2011;150:466–73.

    Article  PubMed  Google Scholar 

  23. Iacobuzio-Donahue CA, Fu B, Yachida S, 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.

    Article  PubMed  CAS  Google Scholar 

  24. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–47.

    Article  PubMed  CAS  Google Scholar 

  25. Hoffman JP, Lipsitz S, Pisansky T, et al. Phase II trial of preoperative radiation therapy and chemotherapy for patients with localized, resectable adenocarcinoma of the pancreas: an Eastern Cooperative Oncology Group Study. J Clin Oncol. 1998;16:317–23.

    PubMed  CAS  Google Scholar 

  26. Staley CA, Lee JE, Cleary KR, et al. Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Am J Surg. 1996;171:118–24.

    Article  PubMed  CAS  Google Scholar 

  27. Pisters PW, Abbruzzese JL, Janjan NA, et al. Rapid-fractionation preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for resectable pancreatic adenocarcinoma. J Clin Oncol. 1998;16:3843–50.

    PubMed  CAS  Google Scholar 

  28. Moutardier V, Magnin V, Turrini O, et al. Assessment of pathologic response after preoperative chemoradiotherapy and surgery in pancreatic adenocarcinoma. Int J Radiat Oncol Biol Phys. 2004;60:437–43.

    Article  PubMed  Google Scholar 

  29. Le Scodan R, Mornex F, Girard N, et al. Preoperative chemoradiation in potentially resectable pancreatic adenocarcinoma: feasibility, treatment effect evaluation and prognostic factors, analysis of the SFRO-FFCD 9704 trial and literature review. Ann Oncol. 2009;20:1387–96.

    Article  PubMed  Google Scholar 

  30. Zhu CP, Shi J, Chen YX, et al. Gemcitabine in the chemoradiotherapy for locally advanced pancreatic cancer: a meta-analysis. Radiother Oncol. 2011;99:108–13.

    Article  PubMed  CAS  Google Scholar 

  31. • Papalezova KT, Tyler DS, Blazer 3rd DG, et al. Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer? J Surg Oncol. 2012;106:111–8. This is a large retrospective comparison of 144 patients with resectable PDAC who had preoperative chemoradiotherapy with 92 patients who had immediate surgery. Median overall survival of resected patients was 26 versus 17 months (p = 0.04).

    Article  PubMed  Google Scholar 

  32. •• Callery MP, Chang KJ, Fishman EK, et al. Pretreatment assessment of resectable and borderline resectable pancreatic cancer: expert consensus statement. Ann Surg Oncol. 2009;16:1727–33. This article provides the expert consensus definition of resectable, borderline resectable and non-resectable pancreatic tumours which should be employed to classify patients with localised pancreatic tumours.

    Article  PubMed  Google Scholar 

  33. Tempero M, Arnoletti J, Behrman S, et al. NCCN clinical practice guidelines in oncology. Pancreatic adenocarcinoma. 2010, pp 1–52

  34. Snady H, Bruckner H, Cooperman A, et al. 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  PubMed  CAS  Google Scholar 

  35. Golcher H, Brunner T, Grabenbauer G, et al. Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy. Eur J Surg Oncol. 2008;34:756–64.

    Article  PubMed  CAS  Google Scholar 

  36. Katz MH, Fleming JB, Bhosale P, et al. Response of borderline resectable pancreatic cancer to neoadjuvant therapy is not reflected by radiographic indicators. Cancer. 2012;118:5749–56.

    Article  PubMed  Google Scholar 

  37. Katz MH, Pisters PW, Evans DB, et al. Borderline resectable pancreatic cancer: the importance of this emerging stage of disease. J Am Coll Surg. 2008;206:833–46. discussion 846–8.

    Article  PubMed  Google Scholar 

  38. 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 

  39. Chatterjee D, Katz MH, Rashid A, et al. Histologic grading of the extent of residual carcinoma following neoadjuvant chemoradiation in pancreatic ductal adenocarcinoma: a predictor for patient outcome. Cancer. 2012;118:3182–90.

    Article  PubMed  Google Scholar 

  40. Bang S, Chung HW, Park SW, et al. The clinical usefulness of 18-fluorodeoxyglucose positron emission tomography in the differential diagnosis, staging, and response evaluation after concurrent chemoradiotherapy for pancreatic cancer. J Clin Gastroenterol. 2006;40:923–9.

    Article  PubMed  Google Scholar 

  41. Choi M, Heilbrun LK, Venkatramanamoorthy R, et al. Using 18F-fluorodeoxyglucose positron emission tomography to monitor clinical outcomes in patients treated with neoadjuvant chemo-radiotherapy for locally advanced pancreatic cancer. Am J Clin Oncol. 2010;33:257–61.

    PubMed  Google Scholar 

  42. Heinrich S, Schafer M, Weber A, et al. Neoadjuvant chemotherapy generates a significant tumor response in resectable pancreatic cancer without increasing morbidity: results of a prospective phase II trial. Ann Surg. 2008;248:1014–22.

    Article  PubMed  Google Scholar 

  43. Topkan E, Parlak C, Kotek A, et al. Predictive value of metabolic 18FDG-PET response on outcomes in patients with locally advanced pancreatic carcinoma treated with definitive concurrent chemoradiotherapy. BMC Gastroenterol. 2011;11:123.

    Article  PubMed  CAS  Google Scholar 

  44. Tzeng CW, Fleming JB, Lee JE, et al. Defined clinical classifications are associated with outcome of patients with anatomically resectable pancreatic adenocarcinoma treated with neoadjuvant therapy. Ann Surg Oncol. 2012;19:2045–53.

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Radiation Oncology, Freiburg University, Robert-Koch-Str. 3, 79106, Freiburg, Germany

    Thomas B. Brunner

  2. Gray Institute for Radiation Oncology and Biology, Department of Oncology, Oxford University, Oxford, UK

    Thomas B. Brunner

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Correspondence to Thomas B. Brunner.

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Brunner, T.B. Neoadjuvant Therapy for Potentially Resectable Pancreatic Cancer: An Emerging Paradigm?. Curr Oncol Rep 15, 162–169 (2013). https://doi.org/10.1007/s11912-012-0291-3

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  • DOI: https://doi.org/10.1007/s11912-012-0291-3

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