Skip to main content
PMC home page
Annals of Surgery logoLink to Annals of Surgery
. 1997 May;225(5):621–636. doi: 10.1097/00000658-199705000-00018

Pancreaticoduodenectomy for pancreatic adenocarcinoma: postoperative adjuvant chemoradiation improves survival. A prospective, single-institution experience.

C J Yeo 1, R A Abrams 1, L B Grochow 1, T A Sohn 1, S E Ord 1, R H Hruban 1, M L Zahurak 1, W C Dooley 1, J Coleman 1, P K Sauter 1, H A Pitt 1, K D Lillemoe 1, J L Cameron 1
PMCID: PMC1190807  PMID: 9193189

Abstract

OBJECTIVE: This study was designed to evaluate prospectively survival after pancreaticoduodenectomy for pancreatic adenocarcinoma, comparing two different postoperative adjuvant chemoradiation protocol to those of no adjuvant therapy. SUMMARY BACKGROUND DATA: Based on limited data from the Gastrointestinal Tumor Study Group, adjuvant chemoradiation therapy has been recommended after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancrease. However, many patients continue to receive no such therapy. METHODS: From October 1991 through September 1995, all patients with resected, pathologically confirmed adenocarcinoma of the head, neck, or uncinate process of the pancreas were reviewed by a multidisciplinary group (surgery, radiation oncology, medical oncology, and pathology) and were offered three options for postoperative treatment after pancreaticoduodenectomy: 1) standard therapy: external beam radiation therapy to the pancreatic bed (4000-4500 cGy) given with two 3-day fluorouracil (5-FU) courses and followed by weekly bolus 5-FU (500 mg/m2 per day) for 4 months; 2) intensive therapy: external beam radiation therapy to the pancreatic bed (5040-5760 cGy) with prophylactic hepatic irradiation (2340-2700 cGy) given with and followed by infusional 5-FU (200 mg/m2 per day) plus leucovorin (5 mg/m2 per day) for 5 of 7 days for 4 months; or 3) no therapy: no postoperative radiation therapy or chemotherapy. RESULTS: Pancreaticoduodenectomy was performed in 174 patients, with 1 in-hospital death (0.6%). Ninety-nine patients elected standard therapy, 21 elected intensive therapy, and 53 patients declined therapy. The three groups were comparable with respect to race, gender, intraoperative blood loss, tumor differentiation, lymph node status, tumor diameter, and resection margin status. Univariate analyses indicated that tumor diameter < 3 cm, intraoperative blood loss < 700 mL, absence of intraoperative blood transfusions, and use of adjuvant chemoradiation therapy were associated with significantly longer survival (p < 0.05). By Cox proportional hazards survival analysis, the most powerful predictors of outcome were tumor diameter, intraoperative blood loss, status of resection margins, and use of postoperative adjuvant therapy. The use of postoperative adjuvant chemoradiation therapy was a predictor of improved survival (median survival, 19.5 months compared to 13.5 months without therapy; p = 0.003). The intensive therapy group had no survival advantage when compared to that of the standard therapy group (median survival, 17.5 months vs. 21 months, p = not significant). CONCLUSIONS: Adjuvant chemoradiation therapy significantly improves survival after pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Based on these survival data, standard adjuvant chemoradiation therapy appears to be indicated for patients treated by pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas. Intensive therapy conferred no survival advantage over standard therapy in this analysis.

Full text

PDF
624

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Allison D. C., Bose K. K., Hruban R. H., Piantadosi S., Dooley W. C., Boitnott J. K., Cameron J. L. Pancreatic cancer cell DNA content correlates with long-term survival after pancreatoduodenectomy. Ann Surg. 1991 Dec;214(6):648–656. doi: 10.1097/00000658-199112000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison D. C., Bose K. K., Hruban R. H., Piantadosi S., Dooley W. C., Boitnott J. K., Cameron J. L. Pancreatic cancer cell DNA content correlates with long-term survival after pancreatoduodenectomy. Ann Surg. 1991 Dec;214(6):648–656. doi: 10.1097/00000658-199112000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andrén-Sandberg A., Ihse I. Factors influencing survival after total pancreatectomy in patients with pancreatic cancer. Ann Surg. 1983 Nov;198(5):605–610. doi: 10.1097/00000658-198311000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Ardalan B., Ucar A., Reddy R., Livingstone A. S., Markoe A., Schwade J., Richman S. P., Donofrio K. Phase I trial of low dose N-phosphonacetyl-L-aspartic acid and high dose 5-fluorouracil administered concomitantly with radiation therapy for unresectable localized adenocarcinoma of the pancreas. Cancer. 1994 Oct 1;74(7):1869–1873. doi: 10.1002/1097-0142(19941001)74:7<1869::aid-cncr2820740707>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
  5. Bakkevold K. E., Arnesjø B., Dahl O., Kambestad B. Adjuvant combination chemotherapy (AMF) following radical resection of carcinoma of the pancreas and papilla of Vater--results of a controlled, prospective, randomised multicentre study. Eur J Cancer. 1993;29A(5):698–703. doi: 10.1016/s0959-8049(05)80349-1. [DOI] [PubMed] [Google Scholar]
  6. Bosset J. F., Pavy J. J., Gillet M., Mantion G., Pelissier E., Schraub S. Conventional external irradiation alone as adjuvant treatment in resectable pancreatic cancer: results of a prospective study. Radiother Oncol. 1992 Jul;24(3):191–194. doi: 10.1016/0167-8140(92)90379-9. [DOI] [PubMed] [Google Scholar]
  7. Bukowski R. M., Fleming T. R., Macdonald J. S., Oishi N., Taylor S. A., Baker L. H. Evaluation of combination chemotherapy and phase II agents in pancreatic adenocarcinoma. A Southwest Oncology Group study. Cancer. 1993 Jan 15;71(2):322–325. doi: 10.1002/1097-0142(19930115)71:2<322::aid-cncr2820710209>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  8. Burrows L., Tartter P. Effect of blood transfusions on colonic malignancy recurrent rate. Lancet. 1982 Sep 18;2(8299):662–662. doi: 10.1016/s0140-6736(82)92764-7. [DOI] [PubMed] [Google Scholar]
  9. Böttger T. C., Störkel S., Wellek S., Stöckle M., Junginger T. Factors influencing survival after resection of pancreatic cancer. A DNA analysis and a histomorphologic study. Cancer. 1994 Jan 1;73(1):63–73. doi: 10.1002/1097-0142(19940101)73:1<63::aid-cncr2820730113>3.0.co;2-p. [DOI] [PubMed] [Google Scholar]
  10. Cameron J. L., Crist D. W., Sitzmann J. V., Hruban R. H., Boitnott J. K., Seidler A. J., Coleman J. Factors influencing survival after pancreaticoduodenectomy for pancreatic cancer. Am J Surg. 1991 Jan;161(1):120–125. doi: 10.1016/0002-9610(91)90371-j. [DOI] [PubMed] [Google Scholar]
  11. Carducci M. A., Abrams R. A., Yeo C. J., Hruban R. H., Zahurak M. L., Cameron J. L., Grochow L. B. Early evaluation of abdominal/hepatic irradiation and 5-fluorouracil/leucovorin infusion after pancreaticoduodenectomy. Int J Radiat Oncol Biol Phys. 1996 Apr 1;35(1):143–150. doi: 10.1016/s0360-3016(96)85023-1. [DOI] [PubMed] [Google Scholar]
  12. Coia L., Hoffman J., Scher R., Weese J., Solin L., Weiner L., Eisenberg B., Paul A., Hanks G. Preoperative chemoradiation for adenocarcinoma of the pancreas and duodenum. Int J Radiat Oncol Biol Phys. 1994 Aug 30;30(1):161–167. doi: 10.1016/0360-3016(94)90531-2. [DOI] [PubMed] [Google Scholar]
  13. Conlon K. C., Klimstra D. S., Brennan M. F. Long-term survival after curative resection for pancreatic ductal adenocarcinoma. Clinicopathologic analysis of 5-year survivors. Ann Surg. 1996 Mar;223(3):273–279. doi: 10.1097/00000658-199603000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Crist D. W., Sitzmann J. V., Cameron J. L. Improved hospital morbidity, mortality, and survival after the Whipple procedure. Ann Surg. 1987 Sep;206(3):358–365. doi: 10.1097/00000658-198709000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Crowe J. P., Gordon N. H., Fry D. E., Shuck J. M., Hubay C. A. Breast cancer survival and perioperative blood transfusion. Surgery. 1989 Nov;106(5):836–841. [PubMed] [Google Scholar]
  16. Foo M. L., Gunderson L. L., Nagorney D. M., McLlrath D. C., van Heerden J. A., Robinow J. S., Kvols L. K., Garton G. R., Martenson J. A., Cha S. S. Patterns of failure in grossly resected pancreatic ductal adenocarcinoma treated with adjuvant irradiation +/- 5 fluorouracil. Int J Radiat Oncol Biol Phys. 1993 Jun 15;26(3):483–489. doi: 10.1016/0360-3016(93)90967-z. [DOI] [PubMed] [Google Scholar]
  17. Fortner J. G., Klimstra D. S., Senie R. T., Maclean B. J. Tumor size is the primary prognosticator for pancreatic cancer after regional pancreatectomy. Ann Surg. 1996 Feb;223(2):147–153. doi: 10.1097/00000658-199602000-00006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fuhrman G. M., Leach S. D., Staley C. A., Cusack J. C., Charnsangavej C., Cleary K. R., El-Naggar A. K., Fenoglio C. J., Lee J. E., Evans D. B. Rationale for en bloc vein resection in the treatment of pancreatic adenocarcinoma adherent to the superior mesenteric-portal vein confluence. Pancreatic Tumor Study Group. Ann Surg. 1996 Feb;223(2):154–162. doi: 10.1097/00000658-199602000-00007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Geer R. J., Brennan M. F. Prognostic indicators for survival after resection of pancreatic adenocarcinoma. Am J Surg. 1993 Jan;165(1):68–73. doi: 10.1016/s0002-9610(05)80406-4. [DOI] [PubMed] [Google Scholar]
  20. Herrera M. F., van Heerden J. A., Katzmann J. A., Weiland L. H., Nagorney D. M., Ilstrup D. Evaluation of DNA nuclear pattern as a prognostic determinant in resected pancreatic ductal adenocarcinoma. Ann Surg. 1992 Feb;215(2):120–124. doi: 10.1097/00000658-199202000-00005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hoffman J. P., Weese J. L., Solin L. J., Engstrom P., Agarwal P., Barber L. W., Guttmann M. C., Litwin S., Salazar H., Eisenberg B. L. A pilot study of preoperative chemoradiation for patients with localized adenocarcinoma of the pancreas. Am J Surg. 1995 Jan;169(1):71–78. doi: 10.1016/s0002-9610(99)80112-3. [DOI] [PubMed] [Google Scholar]
  22. Ishikawa O., Ohigashi H., Imaoka S., Sasaki Y., Iwanaga T., Matayoshi Y., Inoue T. Is the long-term survival rate improved by preoperative irradiation prior to Whipple's procedure for adenocarcinoma of the pancreatic head? Arch Surg. 1994 Oct;129(10):1075–1080. doi: 10.1001/archsurg.1994.01420340089017. [DOI] [PubMed] [Google Scholar]
  23. Jessup J. M., Steele G., Jr, Mayer R. J., Posner M., Busse P., Cady B., Stone M., Jenkins R., Osteen R. Neoadjuvant therapy for unresectable pancreatic adenocarcinoma. Arch Surg. 1993 May;128(5):559–564. doi: 10.1001/archsurg.1993.01420170093014. [DOI] [PubMed] [Google Scholar]
  24. Johnstone P. A., Sindelar W. F. Patterns of disease recurrence following definitive therapy of adenocarcinoma of the pancreas using surgery and adjuvant radiotherapy:correlations of a clinical trial. Int J Radiat Oncol Biol Phys. 1993 Nov 15;27(4):831–834. doi: 10.1016/0360-3016(93)90456-6. [DOI] [PubMed] [Google Scholar]
  25. Kalser M. H., Ellenberg S. S. Pancreatic cancer. Adjuvant combined radiation and chemotherapy following curative resection. Arch Surg. 1985 Aug;120(8):899–903. doi: 10.1001/archsurg.1985.01390320023003. [DOI] [PubMed] [Google Scholar]
  26. Kato H., Wakasugi H., Yokota M., Furukawa M., Mukuta T., Yamada Y., Funakoshi A. Effectiveness of chemotherapy for advanced adenocarcinoma of the pancreas in combined modality therapy. Intern Med. 1994 Mar;33(3):142–146. doi: 10.2169/internalmedicine.33.142. [DOI] [PubMed] [Google Scholar]
  27. Komaki R., Wadler S., Peters T., Byhardt R. W., Order S., Gallagher M. J., Herskovic A., Pederson J. High-dose local irradiation plus prophylactic hepatic irradiation and chemotherapy for inoperable adenocarcinoma of the pancreas. A preliminary report of a multi-institutional trial (Radiation Therapy Oncology Group Protocol 8801). Cancer. 1992 Jun 1;69(11):2807–2812. doi: 10.1002/1097-0142(19920601)69:11<2807::aid-cncr2820691128>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  28. Lillemoe K. D. Current management of pancreatic carcinoma. Ann Surg. 1995 Feb;221(2):133–148. doi: 10.1097/00000658-199502000-00003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mao C., Domenico D. R., Kim K., Hanson D. J., Howard J. M. Observations on the developmental patterns and the consequences of pancreatic exocrine adenocarcinoma. Findings of 154 autopsies. Arch Surg. 1995 Feb;130(2):125–134. doi: 10.1001/archsurg.1995.01430020015001. [DOI] [PubMed] [Google Scholar]
  30. Staley C. A., Lee J. E., Cleary K. R., Abbruzzese J. L., Fenoglio C. J., Rich T. A., Evans D. B. Preoperative chemoradiation, pancreaticoduodenectomy, and intraoperative radiation therapy for adenocarcinoma of the pancreatic head. Am J Surg. 1996 Jan;171(1):118–125. doi: 10.1016/S0002-9610(99)80085-3. [DOI] [PubMed] [Google Scholar]
  31. Trede M., Schwall G., Saeger H. D. Survival after pancreatoduodenectomy. 118 consecutive resections without an operative mortality. Ann Surg. 1990 Apr;211(4):447–458. doi: 10.1097/00000658-199004000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Tsuchiya R., Noda T., Harada N., Miyamoto T., Tomioka T., Yamamoto K., Yamaguchi T., Izawa K., Tsunoda T., Yoshino R. Collective review of small carcinomas of the pancreas. Ann Surg. 1986 Jan;203(1):77–81. doi: 10.1097/00000658-198601000-00013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Yeo C. J., Barry M. K., Sauter P. K., Sostre S., Lillemoe K. D., Pitt H. A., Cameron J. L. Erythromycin accelerates gastric emptying after pancreaticoduodenectomy. A prospective, randomized, placebo-controlled trial. Ann Surg. 1993 Sep;218(3):229–238. doi: 10.1097/00000658-199309000-00002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Yeo C. J., Cameron J. L., Lillemoe K. D., Sitzmann J. V., Hruban R. H., Goodman S. N., Dooley W. C., Coleman J., Pitt H. A. Pancreaticoduodenectomy for cancer of the head of the pancreas. 201 patients. Ann Surg. 1995 Jun;221(6):721–733. doi: 10.1097/00000658-199506000-00011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yeo C. J., Cameron J. L., Maher M. M., Sauter P. K., Zahurak M. L., Talamini M. A., Lillemoe K. D., Pitt H. A. A prospective randomized trial of pancreaticogastrostomy versus pancreaticojejunostomy after pancreaticoduodenectomy. Ann Surg. 1995 Oct;222(4):580–592. doi: 10.1097/00000658-199510000-00014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Yeung R. S., Weese J. L., Hoffman J. P., Solin L. J., Paul A. R., Engstrom P. F., Litwin S., Kowalyshyn M. J., Eisenberg B. L. Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase II Study. Cancer. 1993 Oct 1;72(7):2124–2133. doi: 10.1002/1097-0142(19931001)72:7<2124::aid-cncr2820720711>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]

Articles from Annals of Surgery are provided here courtesy of Lippincott, Williams, and Wilkins

RESOURCES