Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas (original) (raw)

Abstract

Background: The use of neoadjuvant preoperative chemoradiotherapy CRT for pancreatic cancer has been advocated for its potential ability to optimize patient selection for surgical resection and to downstage locally advanced tumors. This article reports our experience with neoadjuvant CRT for localized pancreatic cancer.

Methods: Since 1995, 111 patients with radiographically localized, pathologically confirmed pancreatic adenocarcinoma have received neoadjuvant external beam radiation therapy EBRT; median, 4500 cGy with 5-flourouracil–based chemotherapy. Tumors were defined as potentially resectable PR, n = 53 in the absence of arterial involvement and venous occlusion and locally advanced LA, n = 58 with arterial involvement or venous occlusion by CT.

Results: Five patients 4.5% were not restaged due to death n = 3 or intolerance of therapy n = 2. Twenty-one patients 19% manifested distant metastatic disease on restaging CT. Twenty-eight patients with initially PR tumors 53% and 11 patients with initially LA tumors 19% were resected after CRT. Histologic examination revealed significant fibrosis in all resected specimens and two complete responses. Surgical margins were negative in 72%, and lymph nodes were negative in 70% of resected patients. Median survival in resected patients has not been reached at a median follow-up of 16 months.

Conclusions: Neoadjuvant CRT provided an opportunity for patients with occult metastatic disease to avoid the morbidity of resection and resulted in tumor downstaging in a minority of patients with LA tumors. Survival after neoadjuvant CRT and resection appears to be at least comparable to survival after resection and adjuvant postoperative CRT.

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References

  1. 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 CAS PubMed Google Scholar
  2. Kalser MH, Ellenberg SS. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection [published erratum appears in Arch Surg 1986;121:1045]. Arch Surg 1985; 120: 899–903.
    CAS PubMed Google Scholar
  3. Spitz F, Abruzzese J, Lee J, et al. Preoperative and postoperative chemoradiation strategies in patients treated with pancreaticoduodenectomy for adenocarcinoma of the pancreas. J Clin Oncol 1997; 15: 928–37.
    CAS PubMed Google Scholar
  4. Klinkenbijl JH, Jeekel J, Sahmoud T, 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;discussion 782–4.
    Article CAS PubMed Google Scholar
  5. Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiation for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2001; 8: 123–32.
    PubMed CAS Google Scholar
  6. Jeekel J, Treurniet-Donker AD. Treatment perspectives in locally advanced unresectable pancreatic cancer. Br J Surg 1991; 78: 1332–4.
    PubMed CAS Google Scholar
  7. Jessup JM, Steele G Jr, Mayer RJ, et al. Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg 1993; 128: 559–64.
    PubMed CAS Google Scholar
  8. Coia L, Hoffman J, Scher R, et al. Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum. Int J Radiat Oncol Biol Phys 1994; 30(1): 161–7.
    PubMed CAS Google Scholar
  9. 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;discussion 124–5.
    PubMed CAS Google Scholar
  10. Kamthan AG, Morris JC, Dalton J, et al. Combined modality therapy for stage II and stage III pancreatic carcinoma. J Clin Oncol 1997; 15: 2920–7.
    PubMed CAS Google Scholar
  11. Kornek GV, Schratter-Sehn A, Marczell A, 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.
    Article CAS PubMed Google Scholar
  12. 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 CAS PubMed Google Scholar
  13. White R, Lee C, Anscher M, et al. Preoperative chemoradiation for patients with locally advanced adenocarcinoma of the pancreas. Ann Surg Oncol 1999; 6: 38–45.
    PubMed Google Scholar
  14. Anonymous. Further evidence of effective adjuvant combined radiation and chemotherapy following curative resection of pancreatic cancer. Gastrointestinal Tumor Study Group Cancer 1987; 59: 2006–10.
    Google Scholar
  15. Whittington R, Bryer MP, Haller DG, et al. Adjuvant therapy of resected adenocarcinoma of the pancreas. Int J Radiat Oncol Biol Phys 1991; 21: 1137–43.
    PubMed CAS Google Scholar
  16. Foo ML, Gunderson LL, Nagorney DM, et al. Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation ±5 fluorouracil. Int J Radiat Oncol Biol Phys 1993; 26: 483–9.
    PubMed CAS Google Scholar
  17. Yeo CJ, Abrams RA, Grochow LB, et al. Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience. Ann Surg 1997; 225: 621–33;discussion 633–6.
    PubMed CAS Google Scholar
  18. Neoptolemos JP, Kerr DJ, Beger H, et al. ESPAC-1 trial progress report: the European randomized adjuvant study comparing radiochemotherapy, 6 months chemotherapy and combination therapy versus observation in pancreatic cancer. Digestion 1997; 58: 570–7.
    Article PubMed CAS Google Scholar
  19. Birkmeyer JD, Finlayson SR, Tosteson AN, et al. Effect of hospital volume on in-hospital mortality with pancreaticoduodenectomy. Surgery 1999; 125: 250–6.
    Article CAS PubMed Google Scholar
  20. Lillemoe KD, Cameron JL, Yeo CJ, et al. Pancreaticoduodenectomy. Does it have a role in the palliation of pancreatic cancer? Ann Surg 1996; 223: 718–25;discussion 725–8.
    Article CAS PubMed Google Scholar
  21. White RR, Paulson EK, Freed K, et. al, Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg 2001 in press.
  22. Gulliver D, Baker M, Cheng C, et al. Malignant biliary obstruction: efficacy of thin-section dynamic CT in determining resectability. Am J Roentgenol 1992; 159: 503–7.
    CAS Google Scholar
  23. Fuhrman G, Charnsangavej C, Abbruzzese J, et al. Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms. Am J Surg 1994; 167: 104–13.
    PubMed CAS Google Scholar
  24. Loyer EM, David CL, Dubrow RA, et al. Vascular involvement in pancreatic adenocarcinoma: reassessment by thin-section CT. Abdom Imaging 1996; 21: 202–6.
    PubMed CAS Google Scholar
  25. Espat N, Brennan M, Conlon K. Patients with laparoscopically staged unresectable pancreatic adenocarcinoma do not require subsequent surgical biliary or gastric bypass. J Am Coll Surg 1999; 188: 649–57.
    PubMed CAS Google Scholar
  26. Moertel C, Frytak S, Hahn R, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads) + 5-fluorouracil, and high-dose radiation + 5-fluorouracil. The Gastrointestinal Tumor Study Group Cancer 1981; 48: 1705–10.
    CAS Google Scholar
  27. Anonymous. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group Journal of the National Cancer Institute 1988; 80(10): 751–5.
    Google Scholar
  28. 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
  29. Wolff RA, Evans DB, Gravel DM, et al. Phase I trial of gemcitabine combined with radiation for treatment of locally advanced pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1998; 17: 283(abstract).
    Google Scholar
  30. Pisters PWT, Abbruzzese JL, Janjan NA, et al. Comparative toxicities of preoperative paclitaxel vs. 5-fluorouracil based rapid fractionation chemoradiation for resectable pancreatic adenocarcinoma. Proc Am Soc Clin Oncol 1999; 18: 224
    Google Scholar

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Authors and Affiliations

  1. Department of Surgery, Duke University Medical Center, Durham, North Carolina
    Rebekah R. White MD, Bryan M. Clary MD, Theodore N. Pappas MD & Douglas S. Tyler MD
  2. Department of Medicine, Duke University Medical Center, Durham, North Carolina
    Herbert I. Hurwitz MD, Michael A. Morse MD, John Baillie MB, ChB, Malcolm S. Branch MD, Paul S. Jowell MB, ChB & Kevin M. McGrath MD
  3. Department of Radiation Oncology, Duke University Medical Center, Durham, North Carolina
    Catherine Lee MD & Mitchell S. Anscher MD
  4. Department of Radiology, Duke University Medical Center, Durham, North Carolina
    Erik K. Paulson MD
  5. Department of Pathology, Duke University Medical Center, Durham, North Carolina
    Marcia R. Gottfried MD
  6. Duke University Medical Center, Box 3118, Durham, NC, 27710
    Douglas S. Tyler MD

Authors

  1. Rebekah R. White MD
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  2. Herbert I. Hurwitz MD
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  3. Michael A. Morse MD
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  4. Catherine Lee MD
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  5. Mitchell S. Anscher MD
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  6. Erik K. Paulson MD
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  7. Marcia R. Gottfried MD
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  8. John Baillie MB, ChB
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  9. Malcolm S. Branch MD
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  10. Paul S. Jowell MB, ChB
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  11. Kevin M. McGrath MD
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  12. Bryan M. Clary MD
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  13. Theodore N. Pappas MD
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  14. Douglas S. Tyler MD
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Corresponding author

Correspondence toDouglas S. Tyler MD.

Additional information

Presented at the 54th Annual Meeting of the Society of Surgical Oncology, Washington, DC, March 15-18, 2001.

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White, R.R., Hurwitz, H.I., Morse, M.A. et al. Neoadjuvant Chemoradiation for Localized Adenocarcinoma of the Pancreas.Ann Surg Oncol 8, 758–765 (2001). https://doi.org/10.1007/s10434-001-0758-1

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