Skip to main content
SpringerLink
Log in

Adjuvant Stereotactic Body Radiotherapy for Resected Pancreatic Adenocarcinoma with Close or Positive Margins

  • Original Research
  • Published:
Journal of Gastrointestinal Cancer Aims and scope Submit manuscript

Abstract

Purpose

The aim of this study was to evaluate the role of stereotactic body radiotherapy (SBRT) as adjuvant therapy for resected pancreatic adenocarcinoma with close or positive margins.

Methods

Between September 2006 and January 2010, 24 patients were treated with adjuvant SBRT following surgical resection. Eight (33.3%) patients had close margins of 1–2.5 mm to the retroperitoneal, vascular structures, and periduodenal adipose tissue. Sixteen (66.7%) patients had positive margins at retroperitoneal margin and vascular structures. Twenty-three patients received 24 Gy (20–24 Gy) in one fraction, and one had 30 Gy in three fractions. The median target volume was 11 cc (4.5–30 cc). Eighteen patients were treated with the Cyberknife® Robotic Radiosurgery System and six patients were treated with Trilogy™ intensity-modulated radiosurgery. Kaplan–Meier survival analyses were used to estimate freedom-from-local-progression (FFLP), and overall survival (OS) rates. PET/CT or CT was used to monitor disease recurrence following SBRT.

Results

The median follow-up for all patients was 12.5 months (1.4–39.5 months), and among surviving patients it was 16.3 months (2–39.5 months). The FFLP rates at 6 months, 1 and 2 years were 94.7%, 66%, and 44%, respectively. Overall, FFLP was achieved in seven (87.5%) patients with close margins, and 10 (62.5%) with positive margins. After SBRT, 19 patients resumed or started a 6-month course of gemcitabine-based chemotherapy at a median interval of 18 days (range, 9–31 days) post-SBRT. The median OS was 26.7 months and the 1- and 2-year OS rates were 80.4% and 57.2%, respectively. Of the 24 patients, 12 (50%) developed distant metastases of whom two (25%) had close margins and 10 (62.5%) had positive margins. Ten patients (41.7%) were free of progression at last follow-up (range, 3–39.5 months). Three patients (12.5%) had grade 1–2 acute GI toxicities, and two patients (8.3%) had grade 1 and 2 late toxicities. No patients experienced grade 3 or 4 toxicity, including bowel perforation, secondary to SBRT.

Conclusions

Our data suggest that adjuvant SBRT for resected pancreatic cancer can be achieved with minimal toxicity. This shorter treatment course allowed initiation of systemic chemotherapy shortly after the completion of SBRT.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. American Cancer Society. Cancer Facts & Figures 2009. Atlanta: American Cancer Society; 2009.

    Google Scholar 

  2. Li D, Xie K, Wolff R, et al. Pancreatic cancer. Lancet. 2004;363:1049–57.

    Article  PubMed  CAS  Google Scholar 

  3. Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg. 2006;244(1):10–5.

    Article  PubMed  Google Scholar 

  4. 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(3):324–9.

    Article  PubMed  Google Scholar 

  5. Wagner M, Redaelli C, Lietz M, Seiler CA, Friess H, Buchler MW. Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinoma. Br J Surg. 2004;91(5):586–94.

    Article  PubMed  CAS  Google Scholar 

  6. Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995;221(6):721–31.

    Article  PubMed  CAS  Google Scholar 

  7. Garcea G, Dennison AR, Pattenden CJ, Neal CP, Sutton CD, Berry DP. Survival following curative resection for pancreatic ductal adenocarcinoma. A systematic review of the literature. J Pancreas. 2008;9(2):99–132.

    Google Scholar 

  8. Swartz MJ, Hsu CC, Pawlik TM, et al. Adjuvant chemoradiotherapy after pancreatic resection for invasive carcinoma associated with intraductal papillary mucinous neoplasm of the pancreas. Int J Radiat Oncol Biol Phys. 2010 Mar 1;76(3):839–44.

    Article  PubMed  CAS  Google Scholar 

  9. Herman JM, Swartz MJ, Hsu CC, et al. Analysis of fluorouracil-based adjuvant chemotherapy and radiation after pancreaticoduodenectomy for ductal adenocarcinoma of the pancreas: results of a large, prospectively collected database at the Johns Hopkins Hospital. J Clin Oncol. 2008;26:3503–10.

    Article  PubMed  Google Scholar 

  10. Neoptolemos JP, Dunn JA, Stocken DD, et al. Adjuvant chemoradiotherapy and chemotherapy in resectable pancreatic cancer: a randomized controlled trial. Lancet. 2001;358(9293):1576–85.

    Article  PubMed  CAS  Google Scholar 

  11. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med. 2004;350(12):1200–10.

    Article  PubMed  CAS  Google Scholar 

  12. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine versus observation in patients undergoing curative-intent resection of pancreatic cancer. A randomized controlled trial. JAMA. 2007;297(3):267–77.

    Article  PubMed  CAS  Google Scholar 

  13. Stocken DD, Buchler MW, Dervenis C, et al. Meta-analysis of randomized adjuvant therapy trials for pancreatic cancer. Br J Cancer. 2005;92(8):1372–81.

    Article  PubMed  CAS  Google Scholar 

  14. Chang DK, Johns AL, Merrett ND, et al. Margin clearance and outcome in resected pancreatic cancer. J Clin Oncol. 2009;27:2855–62.

    Article  PubMed  Google Scholar 

  15. Heron DE, Ferris RL, Karamouzis M, et al. Stereotactic body radiotherapy for recurrent squamous cell carcinoma of the head and neck: results of a phase I dose-escalation trial. Int J Radiat Oncol Biol Phys. 2009. doi:10.1016/j.ijrobp.2008.12.075. Published on May 21, 2009.

    PubMed  Google Scholar 

  16. Rwigema JC, Heron DE, Ferris RL, et al. Fractionated stereotactic body radiation therapy in the treatment of previously-irradiated recurrent head and neck carcinoma—updated report of the University of Pittsburgh experience. Am J Clin Oncol. 2010;33(3):286–93.

    PubMed  Google Scholar 

  17. Rwigema JC, Heron DE, Ferris RL, Andrade RS, Gibson MK, Yang Y, Ozhasoglu C, Argiris AE, Grandis JR, Burton SA. The impact of tumor volume and radiotherapy dose on outcome in previously-irradiated recurrent squamous-cell carcinoma of the head and neck treated with stereotactic body radiation therapy. Am J Clin Oncol. 2010 Oct [In Press].

  18. Rwigema JC, Parikh SD, Heron DE, Howell M, Zeh H, Moser AJ, et al. Stereotactic body radiotherapy in the treatment of advanced adenocarcinoma of the pancreas. Am J Clin Oncol. 2010;33(3):286–93.

    PubMed  Google Scholar 

  19. Chang DT, Schellenberg D, Shen J, et al. Stereotactic radiotherapy for unresectable adenocarcinoma of the pancreas. Cancer. 2009;115:665–72.

    Article  PubMed  Google Scholar 

  20. Koong AC, Le QT, Ho A, et al. Phase I study of stereotactic radiosurgery in patients with locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys. 2004;58:1017–21.

    Article  PubMed  Google Scholar 

  21. Mahadevan A, Jain S, Goldstein M, Miksad R, Pleskow D, Sawhney M, Brennan D, Callery M, Vollmer C. Stereotactic Body Radiotherapy and Gemcitabine for Locally Advanced Pancreatic Cancer. Int J Radiat Oncol Biol Phys. 2010 Feb 18. [Epub ahead of print]

  22. Sanders MK, Khalid A, Fasanella KE, et al. EUS-guided fiducial placement for stereotactic radiosurgery in pancreatic cancer. EUS-guided fiducial placement for stereotactic radiosurgery in pancreatic cancer. Gastrointest Endosc. 2008;67(5):AB201.

    Article  Google Scholar 

  23. Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United States. N Engl J Med. 2002;346(15):1128–37.

    Article  PubMed  Google Scholar 

  24. Buchler MW, Friess H, Wagner M, Kulli C, Wagener V, Z’graggen K. Pancreatic fistula after pancreatic head resection. Br J Surg. 2000;87(7):883–9.

    Article  PubMed  CAS  Google Scholar 

  25. van Heek NT, Kuhlmann KF, Scholten RJ, et al. Hospital volume and mortality after pancreatic resection: a systematic review and an evaluation of intervention in the Netherlands. Ann Surg. 2005;242(6):781–8.

    Article  PubMed  Google Scholar 

  26. Shah AP, Strauss JB, Abrams RA. Review and commentary on the role of radiation therapy in the adjuvant management of pancreatic cancer. Am J Clin Oncol. 2010;33(1):101–6.

    Article  PubMed  CAS  Google Scholar 

  27. Griffin JF, Smalley SR, Jewell W, et al. Patterns of failure after curative resection of pancreatic carcinoma. Cancer. 1990;66:56–61.

    Article  PubMed  CAS  Google Scholar 

  28. Tepper J, Nardi G, Sutt H. Carcinoma of the pancreas: review of MGH experience from 1963 to 1973. Analysis of surgical failure and implications for radiation therapy. Cancer. 1976;37:1519–24.

    Article  PubMed  CAS  Google Scholar 

  29. Varadhachary GR, Tamm EP, Abbruzzese JL, et al. Borderline resectable pancreatic cancer: definitions, management, and role of preoperative therapy. Ann Surg Oncol. 2006;13(8):1035–46. Epub 2006 Jul 24.

    Article  PubMed  Google Scholar 

  30. 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 

  31. 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 

  32. Winter JM, Cameron JL, Campbell KA, Arnold MA, Chang DC, Coleman J, et al. 1423 pancreaticoduodenectomies for pancreatic cancer: a single-institution experience. J Gastrointest Surg. 2006;10:1199–210.

    Article  PubMed  Google Scholar 

  33. 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 

  34. Westgaard A, Tafjord S, Farstad IN, Cvancarova M, Eide TJ, Mathisen O, et al. Resectable adenocarcinomas in the pancreatic head: the retroperitoneal resection margin is an independent prognostic factor. BMC Cancer. 2008;8:5.

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the American Society for Radiation Oncology.

Conflict of Interest Notification

The authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Radiation Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jean-Claude M. Rwigema, Dwight E. Heron, Simul D. Parikh, Karlotta Ashby & Steven A. Burton

  2. Division of Surgical Oncology, Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Herbert J. Zeh III & James A. Moser

  3. Division of Hematology Oncology, Department of Medicine, University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Nathan Bahary

  4. UPMC Cancer Pavilion, 5th Floor, 5150 Centre Avenue, Pittsburgh, PA, 15232, USA

    Dwight E. Heron

Authors
  1. Jean-Claude M. Rwigema
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dwight E. Heron
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Simul D. Parikh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Herbert J. Zeh III
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James A. Moser
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nathan Bahary
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Karlotta Ashby
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Steven A. Burton
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dwight E. Heron.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rwigema, JC.M., Heron, D.E., Parikh, S.D. et al. Adjuvant Stereotactic Body Radiotherapy for Resected Pancreatic Adenocarcinoma with Close or Positive Margins. J Gastrointest Canc 43, 70–76 (2012). https://doi.org/10.1007/s12029-010-9203-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12029-010-9203-7

Keywords

Search

Navigation