Skip to main content
Top
Published in: Annals of Surgical Oncology 9/2006

01-09-2006

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

Authors: Paolo Massucco, MD, Lorenzo Capussotti, MD, Antonella Magnino, MD, Elisa Sperti, MD, Marco Gatti, MD, Andrea Muratore, MD, Enrico Sgotto, MD, Pietro Gabriele, MD, Massimo Aglietta, MD

Published in: Annals of Surgical Oncology | Issue 9/2006

Login to get access

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.
Literature
1.
go back to reference Moertel CG, Childs DS, Reitemeier RJ, et al. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 1969; 2:865–7PubMedCrossRef Moertel CG, Childs DS, Reitemeier RJ, et al. Combined 5-fluorouracil and supervoltage radiation therapy of locally unresectable gastrointestinal cancer. Lancet 1969; 2:865–7PubMedCrossRef
2.
go back to reference 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; 48:1705–10PubMedCrossRef 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; 48:1705–10PubMedCrossRef
3.
go back to reference 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; 3:373–8PubMed 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; 3:373–8PubMed
4.
go back to reference 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; 80:751–5CrossRef 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; 80:751–5CrossRef
5.
go back to reference Kamthan AG, Morris JC, Dalton J, et al. Combined modality therapy for stage II and stage III pancreatic carcinoma. J Clin Oncol 1997; 15:2920–7PubMed Kamthan AG, Morris JC, Dalton J, et al. Combined modality therapy for stage II and stage III pancreatic carcinoma. J Clin Oncol 1997; 15:2920–7PubMed
6.
go back to reference 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; 2:159–66PubMedCrossRef 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; 2:159–66PubMedCrossRef
7.
go back to reference 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; 45:285–9PubMed 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; 45:285–9PubMed
8.
go back to reference 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; 82:98–103PubMedCrossRef 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; 82:98–103PubMedCrossRef
9.
go back to reference White RR, Hurwitz HI, Morse MA, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol 2001; 8:758–65PubMedCrossRef White RR, Hurwitz HI, Morse MA, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol 2001; 8:758–65PubMedCrossRef
10.
go back to reference 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; 24:155–9PubMedCrossRef 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; 24:155–9PubMedCrossRef
11.
go back to reference Safran H, Moore T, Iannitti D, et al. Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2001; 49:1275–9PubMed Safran H, Moore T, Iannitti D, et al. Paclitaxel and concurrent radiation for locally advanced pancreatic cancer. Int J Radiat Oncol Biol Phys 2001; 49:1275–9PubMed
12.
go back to reference 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):25–8 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):25–8
13.
go back to reference 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; 52:1293–302PubMedCrossRef 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; 52:1293–302PubMedCrossRef
14.
go back to reference 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; 34:107–16PubMedCrossRef 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; 34:107–16PubMedCrossRef
15.
go back to reference 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; 26:30–6PubMedCrossRef 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; 26:30–6PubMedCrossRef
16.
go back to reference 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; 27:51–6PubMedCrossRef 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; 27:51–6PubMedCrossRef
17.
go back to reference 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; 60:1494–1501PubMed 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; 60:1494–1501PubMed
18.
go back to reference 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; 28:1011–8PubMedCrossRef 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; 28:1011–8PubMedCrossRef
19.
go back to reference 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; 68:493–9PubMedCrossRef 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; 68:493–9PubMedCrossRef
20.
go back to reference 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; 138:1316–22PubMedCrossRef 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; 138:1316–22PubMedCrossRef
21.
go back to reference Sobin LH, Wittekind Ch, eds. UICC TNM Classification of Malignant Tumours, 6th ed. New York: John Wiley & Sons, 2002 Sobin LH, Wittekind Ch, eds. UICC TNM Classification of Malignant Tumours, 6th ed. New York: John Wiley & Sons, 2002
22.
go back to reference Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg 2002; 6:763–9PubMedCrossRef Kim HJ, Czischke K, Brennan MF, Conlon KC. Does neoadjuvant chemoradiation downstage locally advanced pancreatic cancer? J Gastrointest Surg 2002; 6:763–9PubMedCrossRef
23.
go back to reference Wanebo HJ, Glicksman AS, Vezeridis MP, et al. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg 2000; 135:81–8PubMedCrossRef Wanebo HJ, Glicksman AS, Vezeridis MP, et al. Preoperative chemotherapy, radiotherapy, and surgical resection of locally advanced pancreatic cancer. Arch Surg 2000; 135:81–8PubMedCrossRef
24.
go back to reference 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; 167:104–11PubMedCrossRef 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; 167:104–11PubMedCrossRef
25.
go back to reference Freeny PC, Traverso LW, Ryan JA. Diagnosis and staging of pancreatic adenocarcinoma with dynamic computed tomography. Am J Surg 1993; 165:600–6PubMedCrossRef Freeny PC, Traverso LW, Ryan JA. Diagnosis and staging of pancreatic adenocarcinoma with dynamic computed tomography. Am J Surg 1993; 165:600–6PubMedCrossRef
26.
go back to reference Tseng JF, Raut CP, Lee JE, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004; 8:935–50PubMedCrossRef Tseng JF, Raut CP, Lee JE, et al. Pancreaticoduodenectomy with vascular resection: margin status and survival duration. J Gastrointest Surg 2004; 8:935–50PubMedCrossRef
27.
go back to reference Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2001; 8:123–32PubMedCrossRef Breslin TM, Hess KR, Harbison DB, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol 2001; 8:123–32PubMedCrossRef
28.
go back to reference 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; 60:437–43PubMed 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; 60:437–43PubMed
29.
go back to reference White RR, Xie HB, Gottfried MR, et al. Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. Ann Surg Oncol 2005; 12:214–21PubMedCrossRef White RR, Xie HB, Gottfried MR, et al. Significance of histological response to preoperative chemoradiotherapy for pancreatic cancer. Ann Surg Oncol 2005; 12:214–21PubMedCrossRef
30.
go back to reference 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; 5:121–30PubMedCrossRef 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; 5:121–30PubMedCrossRef
31.
go back to reference White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg 2001; 5:626–33PubMedCrossRef White RR, Paulson EK, Freed KS, et al. Staging of pancreatic cancer before and after neoadjuvant chemoradiation. J Gastrointest Surg 2001; 5:626–33PubMedCrossRef
32.
go back to reference 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; 15:928–37PubMed 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; 15:928–37PubMed
33.
go back to reference 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 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
Metadata
Title
Pancreatic Resections after Chemoradiotherapy for Locally Advanced Ductal Adenocarcinoma: Analysis of Perioperative Outcome and Survival
Authors
Paolo Massucco, MD
Lorenzo Capussotti, MD
Antonella Magnino, MD
Elisa Sperti, MD
Marco Gatti, MD
Andrea Muratore, MD
Enrico Sgotto, MD
Pietro Gabriele, MD
Massimo Aglietta, MD
Publication date
01-09-2006
Publisher
Springer-Verlag
Published in
Annals of Surgical Oncology / Issue 9/2006
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-006-9032-x

Other articles of this Issue 9/2006

Annals of Surgical Oncology 9/2006 Go to the issue