Annals of Surgical Oncology

, Volume 21, Issue 8, pp 2801–2807

Prognostic Impact of CA 19-9 on Outcome after Neoadjuvant Chemoradiation in Patients with Locally Advanced Pancreatic Cancer

  • Stephanie E. Combs
  • Daniel Habermehl
  • Kerstin A. Kessel
  • Frank Bergmann
  • Jens Werner
  • Patrick Naumann
  • Dirk Jäger
  • Markus W. Büchler
  • Jürgen Debus
Pancreatic Tumors

Abstract

Background

To asses the impact of CA 19-9 and weight loss/gain on outcome after neoadjuvant chemoradiation (CRT) in patients with locally advanced pancreatic cancer (LAPC).

Methods

We analyzed 289 patients with LAPC treated with CRT for LAPC. All patients received concomitant chemotherapy parallel to radiotherapy and adjuvant treatments. CA 19-9 and body weight were collected as prognostic and predictive markers. All patients were included into a regular follow-up with reassessment of resectability.

Results

Median overall survival in all patients was 14 months. Actuarial overall survival was 37 % at 12 months, 12 % at 24 months, and 4 % at 36 months. Secondary resectability was achieved in 35 % of the patients. R0/R1 resection was significantly associated with increase in overall survival (p = 0.04). Intraoperative radiotherapy was applied in 50 patients, but it did not influence overall survival (p = 0.05). Pretreatment CA 19-9 significantly influenced overall survival using different cutoff values. With increase in CA 19-9 levels, the possibility of secondary surgical resection decreased from 46 % in patients with CA 19-9 levels below 90 U/ml to 31 % in the group with CA 19-9 levels higher than 269 U/ml.

Discussion

This large group of patients with LAPC treated with neoadjuvant CRT confirms that CA 19-9 and body weight are strong predictive and prognostic factors of outcome. In the future, individual patient factors should be taken into account to tailor treatment.

References

  1. 1.
    Koprowski H, Herlyn M, Steplewski Z, Sears HF. Specific antigen in serum of patients with colon carcinoma. Science. 1981;212:53–5.PubMedCrossRefGoogle Scholar
  2. 2.
    Koprowski H, Steplewski Z, Mitchell K, Herlyn M, Herlyn D, Fuhrer P. Colorectal carcinoma antigens detected by hybridoma antibodies. Somatic Cell Genet. 1979;5:957–71.PubMedCrossRefGoogle Scholar
  3. 3.
    Berger AC, Garcia M Jr, Hoffman JP, Regine WF, Abrams RA, Safran H, et al. Postresection CA 19-9 predicts overall survival in patients with pancreatic cancer treated with adjuvant chemoradiation: a prospective validation by RTOG 9704. J Clin Oncol. 2008;26:5918–22.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Montgomery RC, Hoffman JP, Riley LB, Rogatko A, Ridge JA, Eisenberg BL. Prediction of recurrence and survival by post-resection CA 19-9 values in patients with adenocarcinoma of the pancreas. Ann Surg Oncol. 1997;4:551–6.PubMedCrossRefGoogle Scholar
  5. 5.
    Berger AC, Meszoely IM, Ross EA, Watson JC, Hoffman JP. Undetectable preoperative levels of serum CA 19-9 correlate with improved survival for patients with resectable pancreatic adenocarcinoma. Ann Surg Oncol. 2004;11:644–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Bauer TM, El Rayes BF, Li X, Hammad N, Philip PA, Shields AF, et al. Carbohydrate antigen 19-9 is a prognostic and predictive biomarker in patients with advanced pancreatic cancer who receive gemcitabine-containing chemotherapy: a pooled analysis of 6 prospective trials. Cancer. 2013;119:285–92.PubMedCrossRefGoogle Scholar
  7. 7.
    Naumann P, Habermehl D, Welzel T, Debus J, Combs SE. Outcome after neoadjuvant chemoradiation and correlation with nutritional status in patients with locally advanced pancreatic cancer. Strahlenther Onkol. 2013;189:745–52.PubMedCrossRefGoogle Scholar
  8. 8.
    Breslin TM, Hess KR, Harbison DB, Jean ME, Cleary KR, Dackiw AP, et al. Neoadjuvant chemoradiotherapy for adenocarcinoma of the pancreas: treatment variables and survival duration. Ann Surg Oncol. 2001;8:123–32.PubMedCrossRefGoogle Scholar
  9. 9.
    Evans DB, Varadhachary GR, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine-based chemoradiation for patients with resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3496–502.PubMedCrossRefGoogle Scholar
  10. 10.
    Gillen S, Schuster T, Meyer Zum BC, Friess H, Kleeff J. Preoperative/neoadjuvant therapy in pancreatic cancer: a systematic review and meta-analysis of response and resection percentages. PLoS Med. 2010;7:e1000267.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Habermehl D, Kessel K, Welzel T, Hof H, Abdollahi A, Bergmann F, et al. Neoadjuvant chemoradiation with gemcitabine for locally advanced pancreatic cancer. Radiat Oncol. 2012;7:28.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Morganti AG, Massaccesi M, La Torre G, Caravatta L, Piscopo A, Tambaro R, et al. A systematic review of resectability and survival after concurrent chemoradiation in primarily unresectable pancreatic cancer. Ann Surg Oncol. 2010;17:194–205.PubMedCrossRefGoogle Scholar
  13. 13.
    Mornex F, Girard N, Delpero JR, Partensky C. Radiochemotherapy in the management of pancreatic cancer—part I: neoadjuvant treatment. Semin Radiat Oncol. 2005;15:226–34.PubMedCrossRefGoogle Scholar
  14. 14.
    Varadhachary GR, Wolff RA, Crane CH, Sun CC, Lee JE, Pisters PW, et al. Preoperative gemcitabine and cisplatin followed by gemcitabine-based chemoradiation for resectable adenocarcinoma of the pancreatic head. J Clin Oncol. 2008;26:3487–95.PubMedCrossRefGoogle Scholar
  15. 15.
    White RR, Hurwitz HI, Morse MA, Lee C, Anscher MS, Paulson EK, et al. Neoadjuvant chemoradiation for localized adenocarcinoma of the pancreas. Ann Surg Oncol. 2001;8:758–65.PubMedCrossRefGoogle Scholar
  16. 16.
    Katz A, Hanlon A, Lanciano R, Hoffman J, Coia L. Prognostic value of CA 19-9 levels in patients with carcinoma of the pancreas treated with radiotherapy. Int J Radiat Oncol Biol Phys. 1998;41:393–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Krempien R, Muenter MW, Huber PE, Nill S, Friess H, Timke C, et al. Randomized phase II–study evaluating EGFR targeting therapy with cetuximab in combination with radiotherapy and chemotherapy for patients with locally advanced pancreatic cancer—PARC: study protocol [ISRCTN56652283]. BMC Cancer. 2005;5:131.PubMedCentralPubMedCrossRefGoogle Scholar
  18. 18.
    Combs SE, Habermehl D, Kessel K, Bergmann F, Werner J, Brecht IG, et al. Intensity modulated radiotherapy (IMRT) for the treatment of patients with locally advanced pancreatic cancer as neoadjuvant chemoradiation: outcome analysis and comparison with a 3D-treated patient cohort. Strahlenther Onkol. 2013;189:738–44.Google Scholar
  19. 19.
    Roeder F, Timke C, Uhl M, Habl G, Hensley FW, Buechler MW, et al. Aggressive local treatment containing intraoperative radiation therapy (IORT) for patients with isolated local recurrences of pancreatic cancer: a retrospective analysis. BMC Cancer. 2012;12:295.PubMedCentralPubMedCrossRefGoogle Scholar
  20. 20.
    Valentini V, Calvo F, Reni M, Krempien R, Sedlmayer F, Buchler MW, et al. Intra-operative radiotherapy (IORT) in pancreatic cancer: joint analysis of the ISIORT–Europe experience. Radiother Oncol. 2009;91:54–9.PubMedCrossRefGoogle Scholar
  21. 21.
    Habermehl D, Lindel K, Rieken S, Haase K, Goeppert B, Buchler MW, et al. Chemoradiation in patients with unresectable extrahepatic and hilar cholangiocarcinoma or at high risk for disease recurrence after resection: analysis of treatment efficacy and failure in patients receiving postoperative or primary chemoradiation. Strahlenther Onkol. 2012;188:795–801.PubMedCrossRefGoogle Scholar
  22. 22.
    Berger AC, Winter K, Hoffman JP, Regine WF, Abrams RA, Safran H, et al. Five year results of US intergroup/RTOG 9704 with postoperative CA 19-9 </=90 U/mL and comparison to the CONKO-001 trial. Int J Radiat Oncol Biol Phys. 2012;84:e291–7.PubMedCrossRefGoogle Scholar
  23. 23.
    Esposito I, Kleeff J, Bergmann F, Reiser C, Herpel E, Friess H, et al. Most pancreatic cancer resections are R1 resections. Ann Surg Oncol. 2008;15:1651–60.PubMedCrossRefGoogle Scholar
  24. 24.
    Strobel O, Hartwig W, Hackert T, Hinz U, Berens V, Grenacher L, et al. Re-resection for isolated local recurrence of pancreatic cancer is feasible, safe, and associated with encouraging survival. Ann Surg Oncol. 2013;20:964–72.PubMedCrossRefGoogle Scholar
  25. 25.
    Strobel O, Berens V, Hinz U, Hartwig W, Hackert T, Bergmann F, et al. Resection after neoadjuvant therapy for locally advanced, “unresectable” pancreatic cancer. Surgery. 2012;152:S33–42.PubMedCrossRefGoogle Scholar
  26. 26.
    Vainshtein JM, Schipper M, Zalupski MM, Lawrence TS, Abrams R, Francis IR, et al. Prognostic significance of carbohydrate antigen 19-9 in unresectable locally advanced pancreatic cancer treated with dose-escalated intensity modulated radiation therapy and concurrent full-dose gemcitabine: analysis of a prospective phase 1/2 dose escalation study. Int J Radiat Oncol Biol Phys. 2013;86:96–101.PubMedCentralPubMedCrossRefGoogle Scholar
  27. 27.
    Oettle H, Post S, Neuhaus P, Gellert K, Langrehr J, Ridwelski K, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA. 2007;297:267–77.PubMedCrossRefGoogle Scholar
  28. 28.
    Kondo N, Murakami Y, Uemura K, Hayashidani Y, Sudo T, Hashimoto Y, et al. Prognostic impact of perioperative serum CA 19-9 levels in patients with resectable pancreatic cancer. Ann Surg Oncol. 2010;17:2321–9.PubMedCrossRefGoogle Scholar
  29. 29.
    Kinsella TJ, Seo Y, Willis J, Stellato TA, Siegel CT, Harpp D, et al. The impact of resection margin status and postoperative CA19-9 levels on survival and patterns of recurrence after postoperative high-dose radiotherapy with 5-FU-based concurrent chemotherapy for resectable pancreatic cancer. Am J Clin Oncol. 2008;31:446–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Ehrsson YT, Langius-Eklof A, Laurell G. Nutritional surveillance and weight loss in head and neck cancer patients. Support Care Cancer. 2012;20:757–65.PubMedCentralPubMedCrossRefGoogle Scholar
  31. 31.
    Lee SE, Lee JH, Ryu KW, Nam B, Kim CG, Park SR, et al. Changing pattern of postoperative body weight and its association with recurrence and survival after curative resection for gastric cancer. Hepatogastroenterology. 2012;59:430–5.PubMedCrossRefGoogle Scholar
  32. 32.
    Skipworth J, Foster J, Raptis D, Hughes F. The effect of preoperative weight loss and body mass index on postoperative outcome in patients with esophagogastric carcinoma. Dis Esophagus. 2009;22:559–63.PubMedCrossRefGoogle Scholar
  33. 33.
    Thivat E, Therondel S, Lapirot O, Abrial C, Gimbergues P, Gadea E, et al. Weight change during chemotherapy changes the prognosis in non metastatic breast cancer for the worse. BMC Cancer. 2010;10:648.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Tsai S, Choti MA, Assumpcao L, Cameron JL, Gleisner AL, Herman JM, et al. Impact of obesity on perioperative outcomes and survival following pancreaticoduodenectomy for pancreatic cancer: a large single-institution study. J Gastrointest Surg. 2010;14:1143–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Valentini V, Marazzi F, Bossola M, Micciche F, Nardone L, Balducci M, et al. Nutritional counselling and oral nutritional supplements in head and neck cancer patients undergoing chemoradiotherapy. J Hum Nutr Diet. 2012;25:201–8.PubMedCrossRefGoogle Scholar
  36. 36.
    Williams TK, Rosato EL, Kennedy EP, Chojnacki KA, Andrel J, Hyslop T, et al. Impact of obesity on perioperative morbidity and mortality after pancreaticoduodenectomy. J Am Coll Surg. 2009;208:210–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Fleming JB, Gonzalez RJ, Petzel MQ, Lin E, Morris JS, Gomez H, et al. Influence of obesity on cancer-related outcomes after pancreatectomy to treat pancreatic adenocarcinoma. Arch Surg. 2009;144:216–21.PubMedCrossRefGoogle Scholar
  38. 38.
    Gaujoux S, Torres J, Olson S, Winston C, Gonen M, Brennan MF, et al. Impact of obesity and body fat distribution on survival after pancreaticoduodenectomy for pancreatic adenocarcinoma. Ann Surg Oncol. 2012;19:2908–16.PubMedCrossRefGoogle Scholar
  39. 39.
    Bachmann J, Heiligensetzer M, Krakowski-Roosen H, Buchler MW, Friess H, Martignoni ME. Cachexia worsens prognosis in patients with resectable pancreatic cancer. J Gastrointest Surg. 2008;12:1193–201.PubMedCrossRefGoogle Scholar
  40. 40.
    Pausch T, Hartwig W, Hinz U, Swolana T, Bundy BD, Hackert T, et al. Cachexia but not obesity worsens the postoperative outcome after pancreatoduodenectomy in pancreatic cancer. Surgery. 2012;152:S81–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Boone BA, Steve J, Krasinskas AM, Zureikat AH, Lembersky BC, Gibson MK, et al. Outcomes with FOLFIRINOX for borderline resectable and locally unresectable pancreatic cancer. J Surg Oncol. 2013;108:236–41.PubMedCrossRefGoogle Scholar
  42. 42.
    Conroy T, Gavoille C, Samalin E, Ychou M, Ducreux M. The role of the FOLFIRINOX regimen for advanced pancreatic cancer. Curr Oncol Rep. 2013;15:182–9.PubMedCrossRefGoogle Scholar
  43. 43.
    Von Hoff DD, Ervin T, Arena FP, Chiorean EG, Infante J, Moore M, et al. Increased survival in pancreatic cancer with nab-paclitaxel plus gemcitabine. N Engl J Med. 2013;369:1691–703.CrossRefGoogle Scholar

Copyright information

© Society of Surgical Oncology 2014

Authors and Affiliations

  • Stephanie E. Combs
    • 1
    • 5
  • Daniel Habermehl
    • 1
  • Kerstin A. Kessel
    • 5
  • Frank Bergmann
    • 2
  • Jens Werner
    • 1
    • 2
    • 3
    • 4
  • Patrick Naumann
    • 1
  • Dirk Jäger
    • 4
  • Markus W. Büchler
    • 3
  • Jürgen Debus
    • 1
  1. 1.Department of Radiation OncologyUniversity Hospital of HeidelbergHeidelbergGermany
  2. 2.Department of PathologyUniversity Hospital of HeidelbergHeidelbergGermany
  3. 3.Department of SurgeryUniversity Hospital of HeidelbergHeidelbergGermany
  4. 4.National Center for Tumor DiseasesUniversity Hospital of HeidelbergHeidelbergGermany
  5. 5.Department of Radiation OncologyTechnische Universität München (TUM)MunichGermany

Personalised recommendations