Annals of Surgical Oncology

, Volume 13, Issue 9, pp 1201–1208 | Cite as

Pancreatic Resections after Chemoradiotherapy for Locally Advanced Ductal Adenocarcinoma: Analysis of Perioperative Outcome and Survival

  • Paolo Massucco
  • Lorenzo Capussotti
  • Antonella Magnino
  • Elisa Sperti
  • Marco Gatti
  • Andrea Muratore
  • Enrico Sgotto
  • Pietro Gabriele
  • Massimo Aglietta
Article

Abstract

Background

The most accepted treatment for locally advanced pancreatic cancer is chemoradiotherapy. However, indications to and results of pancreatic resections after chemoradiation are not yet defined.

Methods

From June 1999 to December 2003, 28 patients with locally advanced pancreatic cancer (group 1) were enrolled for institutional trials of gemcitabine-based chemoradiotherapy. Tumors were stratified as unresectable or borderline resectable according to the pattern of vascular involvement at pretreatment computed tomographic scan. Patients with partial response or stable disease and in-range Ca19-9 were surgically explored. Perioperative outcome and survival of group 1 were compared with 44 patients primary resected for localized cancer with or without adjuvant treatment in the same time period (group 2).

Results

Only one unresectable tumor was successfully resected compared to 7 out of 18 (39%) that were borderline resectable. Operations after chemoradiation were 1 hour longer and postoperative stays 5 days longer, but transfusion rate, morbidity, and mortality were not significantly different. Median survival was 15.4 months for group 1 (>21 for resected vs. 10 for not resected, P < 0.01) and 14 months for group 2. In both groups, a disease-free survival beyond 24 months was recorded only among patients resected with negative margins.

Conclusions

The conversion of an unresectable cancer to a resectable one is a rare event. On the contrary, the resection of a borderline resectable tumor was successfully accomplished in one-third of cases. Chemoradiotherapy did not increase the operative risk, but the interventions were more technically demanding and required a longer postoperative stay. Patients resected after chemoradiation for a locally advanced tumor had at least the same survival as those primary resected for a localized one. Only R0 resections in both groups gave the chance of disease-free survival longer than 24 months.

Keywords

Pancreatic neoplasm Combined modality therapy Surgery Locally advanced cancer 

References

  1. 1.
    Moertel CG, Childs DS, Reitemeier RJ, et al. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 1969; 2:865–7PubMedCrossRefGoogle Scholar
  2. 2.
    Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomised comparison of high dose (6000 rads) radiation alone, moderate dose radiation (400 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: Gastrointestinal Tumour Study Group. Cancer 1981; 48:1705–10PubMedCrossRefGoogle Scholar
  3. 3.
    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; 3:373–8PubMedGoogle Scholar
  4. 4.
    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; 80:751–5CrossRefGoogle Scholar
  5. 5.
    Kamthan AG, Morris JC, Dalton J, et al. Combined modality therapy for stage II and stage III pancreatic carcinoma. J Clin Oncol 1997; 15:2920–7PubMedGoogle Scholar
  6. 6.
    Todd KE, Gloor B, Lane JS, Isacoff WH, Reber HA. Resection of locally advanced pancreatic cancer after downstaging with continuous-infusion 5-fluorouracil, mitomycin-C, leucovorin, and dipyridamole. J Gastrointest Surg 1998; 2:159–66PubMedCrossRefGoogle Scholar
  7. 7.
    Bajetta E, Di Bartolomeo M, Stani SC, et al. Chemoradiotherapy as preoperative treatment in locally advanced unresectable pancreatic cancer patients: results of a feasibility study. Int J Radiat Oncol Biol Phys 1999; 45:285–9PubMedGoogle Scholar
  8. 8.
    Kornek GV, Schratter-Sehn A, Marczell A, et al. Treatment of unresectable, locally advanced pancreatic adenocarcinoma with combined radiochemotherapy with 5-fluorouracil, leucoverin and cisplatin. Br J Cancer 2000; 82:98–103PubMedCrossRefGoogle Scholar
  9. 9.
    White RR, Hurwitz HI, Morse MA, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol 2001; 8:758–65PubMedCrossRefGoogle Scholar
  10. 10.
    Mehta VK, Poen JC, Ford JM, et al. Protracted venous infusion 5-fluorouracil with concomitant radiotherapy compared with bolus 5-fluorouracil for unresectable pancreatic cancer. Am J Clin Oncol 2001; 24:155–9PubMedCrossRefGoogle Scholar
  11. 11.
    Safran H, Moore T, Iannitti D, et al. Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2001; 49:1275–9PubMedGoogle Scholar
  12. 12.
    Blackstock AW, Melin SA, Butler JM, et al. Irinotecan/gemcitabine followed by twice-weekly gemcitabine/radiation in locally advanced pancreatic cancer. Oncology (Huntingt) 2002; 16(Suppl 5):25–8Google Scholar
  13. 13.
    Crane CH, Abbruzzese JL, Evans DB, 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; 52:1293–302PubMedCrossRefGoogle Scholar
  14. 14.
    Blackstock AW, Tepper JE, Niedwiecki D, Hollis DR, Mayer RJ, Tempero MA. Cancer and leukemia group B (CALGB) 89805: phase II chemoradiation trial using gemcitabine in patients with locoregional adenocarcinoma of the pancreas. Int J Gastrointest Cancer 2003; 34:107–16PubMedCrossRefGoogle Scholar
  15. 15.
    Aristu J, Canon R, Pardo F, et al. Surgical resection after preoperative chemoradiotherapy benefits selected patients with unresectable pancreatic cancer. Am J Clin Oncol 2003; 26:30–6PubMedCrossRefGoogle Scholar
  16. 16.
    Rich T, Harris J, Abrams R, et al. Phase II study of external irradiation and weekly paclitaxel for nonmetastatic, unresectable pancreatic cancer: RTOG-98-12. Am J Clin Oncol 2004; 27:51–6PubMedCrossRefGoogle Scholar
  17. 17.
    Chung HW, Bang SM, Park SW, et al. A prospective randomized study of gemcitabine with doxifluridine versus paclitaxel with doxifluridine in concurrent chemoradiotherapy for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2004; 60:1494–1501PubMedGoogle Scholar
  18. 18.
    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; 28:1011–8PubMedCrossRefGoogle Scholar
  19. 19.
    Magnino A, Gatti M, Massucco P, et al. Phase II trial of primary radiation therapy and concurrent chemotherapy for patients with locally advanced pancreatic cancer. Oncology 2005; 68:493–9PubMedCrossRefGoogle Scholar
  20. 20.
    Capussotti L, Massucco P, Ribero D, Viganò L, Muratore A, Calgaro M. Extended lymphadenectomy and vein resection for pancreatic head cancer. Outcomes and implications for therapy. Arch Surg 2003; 138:1316–22PubMedCrossRefGoogle Scholar
  21. 21.
    Sobin LH, Wittekind Ch, eds. UICC TNM Classification of Malignant Tumours, 6th ed. New York: John Wiley & Sons, 2002Google Scholar
  22. 22.
    Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg 2002; 6:763–9PubMedCrossRefGoogle Scholar
  23. 23.
    Wanebo HJ, Glicksman AS, Vezeridis MP, et al. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg 2000; 135:81–8PubMedCrossRefGoogle Scholar
  24. 24.
    Fuhrman GM, Charnsangavej C, Abruzzese JL, et al. Thin-section contrast-enhanced computed tomography accurately predicts the resectability of malignant pancreatic neoplasms. Am J Surg 1994; 167:104–11PubMedCrossRefGoogle Scholar
  25. 25.
    Freeny PC, Traverso LW, Ryan JA. Diagnosis and staging of pancreatic adenocarcinoma with dynamic computed tomography. Am J Surg 1993; 165:600–6PubMedCrossRefGoogle Scholar
  26. 26.
    Tseng JF, Raut CP, Lee JE, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004; 8:935–50PubMedCrossRefGoogle Scholar
  27. 27.
    Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2001; 8:123–32PubMedCrossRefGoogle Scholar
  28. 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; 60:437–43PubMedGoogle Scholar
  29. 29.
    White RR, Xie HB, Gottfried MR, et al. Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. Ann Surg Oncol 2005; 12:214–21PubMedCrossRefGoogle Scholar
  30. 30.
    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; 5:121–30PubMedCrossRefGoogle Scholar
  31. 31.
    White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg 2001; 5:626–33PubMedCrossRefGoogle Scholar
  32. 32.
    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; 15:928–37PubMedGoogle Scholar
  33. 33.
    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; 89:314–27Google Scholar

Copyright information

© Society of Surgical Oncology 2006

Authors and Affiliations

  • Paolo Massucco
    • 1
  • Lorenzo Capussotti
    • 1
  • Antonella Magnino
    • 2
  • Elisa Sperti
    • 2
  • Marco Gatti
    • 3
  • Andrea Muratore
    • 1
  • Enrico Sgotto
    • 1
  • Pietro Gabriele
    • 3
  • Massimo Aglietta
    • 2
  1. 1.Unit of Surgical OncologyInstitute for Research and Cure of CancerCandioloItaly
  2. 2.Unit of Medical OncologyInstitute for Research and Cure of CancerCandioloItaly
  3. 3.Unit of Radiation TherapyInstitute for Research and Cure of CancerCandioloItaly

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