Skip to main content

Advertisement

Log in

Preoperative Capecitabine and Concurrent Radiation for Borderline Resectable Pancreatic Cancer

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

Abstract

Background

Patients with borderline resectable pancreatic ductal adenocarcinoma (PDA) represent a high-risk group of patients due to tumor or patient-related characteristics. The optimal management of these patients has not been fully defined.

Materials and Methods

All patients undergoing evaluation for PDA between 2005 and 2008 were identified. Clinical, radiographic, and pathological data were retrospectively reviewed. Patients were staged as borderline resectable using the M.D. Anderson Cancer Center (MDACC) classification.

Results

A total of 170 patients with PDA were identified, 40 with borderline resectable disease. Of these, 34 borderline resectable patients (85%) completed neoadjuvant therapy and were restaged; pancreatic resection was completed in 16 patients (46%). Also, 8 patients completed 50 Gy of radiation in 28 fractions in 6 weeks, whereas 8 patients received 50 Gy in 20 fractions in 4 weeks plus chronomodulated capecitabine. An R0 resection was achieved in 12 of the 16 patients (75%). Also, 5 patients (63%) treated in 20 fractions had >90% pathologic response versus 1 (13%) treated in 28 fractions (P < .05). Borderline resectable patients completing surgery had similar survival to patients with resectable disease who underwent surgery. Patients receiving accelerated fractionation radiation had improved survival compared with patients treated with standard fractionation protocol.

Conclusions

A neoadjuvant approach to borderline resectable PDA identifies patients who are most likely to benefit from pancreatic resection. Preoperative capecitabine-based chemoradiation is an effective, well-tolerated treatment for these patients. Neoadjuvant therapy for borderline resectable PDA warrants further investigation using treatment schedules that can safely intensify irradiation dose.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, et al. Cancer statistics, 2008. CA Cancer J Clin. 2008;58:71–96.

    Article  PubMed  Google Scholar 

  2. Mehta VK, Fisher G, Ford JA, Poen JC, Vierra MA, Oberhelman H, et al. Preoperative chemoradiation for marginally resectable adenocarcinoma of the pancreas. J Gastrointest Surg. 2001;5:27–35.

    Article  PubMed  CAS  Google Scholar 

  3. Raut CP, Tseng JF, Sun CC, Wang H, Wolff RA, Crane CH, et al. Impact of resection status on pattern of failure and survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg. 2007;246:52–60.

    Article  PubMed  Google Scholar 

  4. Millikan KW, Deziel DJ, Silverstein JC, Kanjo TM, Christein JD, Doolas A, et al. Prognostic factors associated with resectable adenocarcinoma of the head of the pancreas. Am Surg. 1999;65:618–23; discussion 623–4.

    PubMed  CAS  Google Scholar 

  5. Sohn TA, Yeo CJ, Cameron JL, Koniaris L, Kaushal S, Abrams RA, 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 

  6. Benassai G, Mastrorilli M, Quarto G, Cappiello A, Giani U, Mosella G. Survival after pancreaticoduodenectomy for ductal adenocarcinoma of the head of the pancreas. Chir Ital. 2000;52:263–70.

    PubMed  CAS  Google Scholar 

  7. Neoptolemos JP, Stocken DD, Dunn JA, Almond J, Beger HG, Pederzoli P, et al. Influence of resection margins on survival for patients with pancreatic cancer treated by adjuvant chemoradiation and/or chemotherapy in the ESPAC-1 randomized controlled trial. Ann Surg. 2001;234:758–68.

    Article  PubMed  CAS  Google Scholar 

  8. Takai S, Satoi S, Toyokawa H, Yanagimoto H, Sugimoto N, Tsuji K, et al. Clinicopathologic evaluation after resection for ductal adenocarcinoma of the pancreas: a retrospective, single-institution experience. Pancreas. 2003;26:243–9.

    Article  PubMed  CAS  Google Scholar 

  9. Varadhachary GR, Tamm EP, Abbruzzese JL, Xiong HQ, Crane CH, Wang H, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13:1035–46.

    Article  PubMed  Google Scholar 

  10. Katz MH, Pisters PW, Evans DB, Sun CC, Lee JE, Fleming JB, 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 

  11. Brown KM, Siripurapu V, Davidson M, Cohen SJ, Konski A, Watson JC, et al. Chemoradiation followed by chemotherapy before resection for borderline pancreatic adenocarcinoma. Am J Surg. 2008;195:318–21.

    Article  PubMed  CAS  Google Scholar 

  12. Bilimoria KY, Bentrem DJ, Ko CY, Ritchey J, Stewart AK, Winchester DP, et al. Validation of the 6th edition AJCC Pancreatic Cancer Staging System: report from the National Cancer Database. Cancer. 2007;110:738–44.

    Article  PubMed  Google Scholar 

  13. Evans DB, Rich TA, Byrd DR, Cleary KR, Connelly JH, Levin B, et al. Preoperative chemoradiation and pancreaticoduodenectomy for adenocarcinoma of the pancreas. Arch Surg. 1992;127:1335–9.

    PubMed  CAS  Google Scholar 

  14. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc. 1958;53:457–81.

    Article  Google Scholar 

  15. Ammori JB, Colletti LM, Zalupski MM, Eckhauser FE, Greenson JK, Dimick J, et al. 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 

  16. Richter A, Niedergethmann M, Sturm JW, Lorenz D, Post S, Trede M. Long-term results of partial pancreaticoduodenectomy for ductal adenocarcinoma of the pancreatic head: 25-year experience. World J Surg. 2003;27:324–9.

    Article  PubMed  Google Scholar 

  17. Kuhlmann KF, de Castro SM, Wesseling JG, ten Kate FJ, Offerhaus GJ, Busch OR, et al. Surgical treatment of pancreatic adenocarcinoma; actual survival and prognostic factors in 343 patients. Eur J Cancer. 2004;40:549–58.

    Article  PubMed  CAS  Google Scholar 

  18. Pingpank JF, Hoffman JP, Ross EA, Cooper HS, Meropol NJ, Freedman G, 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 

  19. Sasson AR, Wetherington RW, Hoffman JP, Ross EA, Cooper H, Meropol NJ, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: analysis of histopathology and outcome. Int J Gastrointest Cancer. 2003;34:121–8.

    Article  PubMed  Google Scholar 

  20. Talamonti MS, Small W, Jr., Mulcahy MF, Wayne JD, Attaluri V, Colletti LM, et al. A multi-institutional phase II trial of preoperative full-dose gemcitabine and concurrent radiation for patients with potentially resectable pancreatic carcinoma. Ann Surg Oncol. 2006;13:150–8.

    Article  PubMed  Google Scholar 

  21. Pilepich MV, Miller HH. Preoperative irradiation in carcinoma of the pancreas. Cancer. 1980;46:1945–9.

    Article  PubMed  CAS  Google Scholar 

  22. Jessup JM, Steele G, Jr., Mayer RJ, Posner M, Busse P, Cady B, et al. Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg. 1993;128:559–64.

    PubMed  CAS  Google Scholar 

  23. Hoffman JP, Weese JL, Solin LJ, Engstrom P, Agarwal P, Barber LW, et al. A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas. Am J Surg. 1995;169:71–7; discussion 77–8.

    Article  PubMed  CAS  Google Scholar 

  24. Hoffman JP, Lipsitz S, Pisansky T, Weese JL, Solin L, Benson AB 3rd. 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 

  25. 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  PubMed  CAS  Google Scholar 

  26. Crane CH, Abbruzzese JL, Evans DB, Wolff RA, Ballo MT, Delclos M, 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  PubMed  CAS  Google Scholar 

  27. 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 

  28. Safran H, Dipetrillo T, Iannitti D, Quirk D, Akerman P, Cruff D, et al. Gemcitabine, paclitaxel, and radiation for locally advanced pancreatic cancer: a Phase I trial. Int J Radiat Oncol Biol Phys. 2002;54:137–41.

    PubMed  CAS  Google Scholar 

  29. Crane CH, Ellis LM, Abbruzzese JL, Amos C, Xiong HQ, Ho L, 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  PubMed  CAS  Google Scholar 

  30. Pisters PW, Wolff RA, Janjan NA, Cleary KR, Charnsangavej C, Crane CN, et al. Preoperative paclitaxel and concurrent rapid-fractionation radiation for resectable pancreatic adenocarcinoma: toxicities, histologic response rates, and event-free outcome. J Clin Oncol. 2002;20:2537–44.

    Article  PubMed  CAS  Google Scholar 

  31. Crane C, Janjan N, Evans D, Wolff R, Ballo M, Milas L, et al. Toxicity and efficacy of concurrent gemcitabine and radiotherapy for locally advanced pancreatic cancer. Int J Gastrointest Cancer. 2001;29:9–18.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  33. Joensuu TK, Kiviluoto T, Karkkainen P, Vento P, Kivisaari L, Terhunen M, et al. Phase I-II trial of twice-weekly gemcitabine and concomitant irradiation in patients undergoing pancreaticoduodenectomy with extended lymphadenectomy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;60:444–52.

    Article  PubMed  CAS  Google Scholar 

  34. Pipas JM, Barth RJ, Jr., Zaki B, Tsapakos MJ, Suriawinata AA, Bettmann MA, et al. Docetaxel/Gemcitabine followed by gemcitabine and external beam radiotherapy in patients with pancreatic adenocarcinoma. Ann Surg Oncol. 2005;12:995–1004.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors thank Sara Adair for her assistance in the data analysis and Aimee Strong and Lori Fitzgerald for assistance in collection of the clinical data. Sources of financial support: NIH Research Training Grant T32 HL007849 (JBS).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jayme B. Stokes MD.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplemental Table 1 (DOC 56 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stokes, J.B., Nolan, N.J., Stelow, E.B. et al. Preoperative Capecitabine and Concurrent Radiation for Borderline Resectable Pancreatic Cancer. Ann Surg Oncol 18, 619–627 (2011). https://doi.org/10.1245/s10434-010-1456-7

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-010-1456-7

Keywords

Navigation