Skip to main content
SpringerLink
Log in

Alkaline Phosphatase Predicts Survival in Patients with Metastatic Neuroendocrine Tumors

  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

The clinical course of patients with metastatic neuroendocrine tumors is highly variable. While some patients experience an indolent clinical course over many years, other patients may rapidly succumb to their disease. Little is known about prognostic factors in these patients, making decisions regarding their management more difficult.

We performed a retrospective analysis of 137 patients with metastatic neuroendocrine tumors referred to our institution for treatment. Potential prognostic factors were evaluated using multivariate survival analysis. The median overall survival of patients in our cohort was 6.0 years, although the range of survival times was broad (48 days to 23.4 years). Alkaline phosphatase levels above normal were predictive of shorter survival in both univariate and multivariate analysis. Elevated chromogranin A levels were also associated with shorter survival in univariate analysis; in a multivariate analysis, however, this correlation was no longer significant. There was no association between survival and gender, primary tumor site, or presence or absence of carcinoid syndrome. Elevated alkaline phosphatase is a robust adverse prognostic factor for survival in patients with metastatic neuroendocrine tumors and may be superior to chromogranin A in this setting. Close monitoring of alkaline phosphatase levels may be useful when considering initiation or changes of therapy in patients with metastatic neuroendocrine tumors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Yu F, Venzon DJ, Serrano J, et al.: Prospective study of the clinical course, prognostic factors, causes of death, and survival in patients with long–standing Zollinger–Ellison syndrome. J Clin Oncol 17(2):615–630, 1999 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids=10080607)

    Google Scholar 

  2. Clements D, Elias E: Regression of metastatic vipoma with somatostatin analogue SMS 201–995. Lancet 1(8433):874–875, 1985 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2858733)

  3. Frank M, Klose KJ, Wied M, Ishaque N, Schade-Brittinger C, Arnold R: Combination therapy with octreotide and alpha-interferon: effect on tumor growth in metastatic endocrine gastroenteropancreatic tumors. Am J Gastroenterol 94(5):1381–1387, 1999 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10235222)

  4. Arnold R, Neuhaus C, Benning R, et al.: Somatostatin analog sandostatin and inhibition of tumor growth in patients with metastatic endocrine gastroenteropancreatic tumors. World J Surg 17(4):511–518, 1993 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids=8395752)

  5. Saltz L, Trochanowski B, Buckley M, et al.: Octreotide as an antineoplastic agent in the treatment of functional and nonfunctional neuroendocrine tumors. Cancer 72(1):244–248, 1993 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& db=PubMed&dopt=Citation&list_uids=8389666)

    Google Scholar 

  6. Arnold R, Trautmann ME, Creutzfeldt W, et al.: Somatostatin analogue octreotide and inhibition of tumour growth in metastatic endocrine gastroenteropancreatic tumours. Gut 38(3):430–438, 1996 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=8675099)

  7. Faiss S, Pape UF, Bohmig M, et al.: Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors—-the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol 21(14):2689–2696, 2003 (available at: http://www.ncbi.nlm.nih. gov/entrez/query. fcgi?cmd=Retrieve& db=PubMed& dopt=Citation&list_ uids=12860945)

  8. Faiss S, Rath U, Mansmann U, et al.: Ultra-high-dose lanreotide treatment in patients with metastatic neuroendocrine gastroenteropancreatic tumors. Digestion 60(5):469–476, 1999 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10473972)

    Google Scholar 

  9. Chu QD, Hill HC, Douglass HO Jr, et al.: Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas. Ann Surg Oncol 9(9):855–862, 2002 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12417506)

    Google Scholar 

  10. Harpole DH Jr, Feldman JM, Buchanan S, Young WG, Wolfe WG: Bronchial carcinoid tumors: a retrospective analysis of 126 patients. Ann Thorac Surg 54(1):50–54, discussion 54–55, 1992 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1610254)

    Google Scholar 

  11. Nobels FR, Kwekkeboom DJ, Bouillon R, Lamberts SW: Chromogranin A: its clinical value as marker of neuroendocrine tumours. Eur J Clin Invest 28(6):431–440, 1998 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& db=PubMed&dopt=Citation&list_uids=9693933)

  12. O’Connor DT, Deftos LJ: Secretion of chromogranin A by peptide-producing endocrine neoplasms. N Engl J Med 314(18):1145–1551, 1986 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3007986)

  13. Bajetta E, Ferrari L, Martinetti A, et al.: Chromogranin A, neuron specific enolase, carcinoembryonic antigen, and hydroxyindole acetic acid evaluation in patients with neuroendocrine tumors. Cancer 86(5):858–865, 1999 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& !db=PubMed&dopt=Citation&list_uids=10463986)

    Google Scholar 

  14. Baudin E, Gigliotti A, Ducreux M, et al.: Neuron-specific enolase and chromogranin A as markers of neuroendocrine tumours. Br J Cancer 78(8):1102–1107, 1998 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& db=PubMed&dopt=Citation&list_uids=9792158)

    Google Scholar 

  15. Seregni E, Ferrari L, Bajetta E, Martinetti A, Bombardieri E: Clinical significance of blood chromogranin A measurement in neuroendocrine tumours. Ann Oncol 12 (Suppl 2):S69–S72, 2001 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11762355)

  16. Stridsberg M, Oberg K, Li Q, Engstrom U, Lundqvist G: Measurements of chromogranin A, chromogranin B (secretogranin I), chromogranin C (secretogranin II) and pancreastatin in plasma and urine from patients with carcinoid tumours and endocrine pancreatic tumours. J Endocrinol 144(1):49–58, 1995 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& db=PubMed&dopt=Citation&list_uids=7891024)

  17. Weber HC, Venzon DJ, Lin JT, et al.: Determinants of metastatic rate and survival in patients with Zollinger–Ellison syndrome: a prospective long-term study. Gastroenterology 108(6):1637–1648, 1995 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7768367)

    Google Scholar 

  18. Nobels FR, Kwekkeboom DJ, Coopmans W, et al.: Chromogranin A as serum marker for neuroendocrine neoplasia: comparison with neuron-specific enolase and the alpha-subunit of glycoprotein hormones. J Clin Endocrinol Metab 82(8):2622–2628, 1997 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9253344)

    Google Scholar 

  19. Janson ET, Holmberg L, Stridsberg M, et al.: Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol 8(7):685–690, 1997 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9296223)

    Google Scholar 

  20. Hsiao RJ, Seeger RC, Yu AL, O’Connor DT: Chromogranin A in children with neuroblastoma. Serum concentration parallels disease stage and predicts survival. J Clin Invest 85(5):1555–1558, 1990 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=2332506)

  21. Sarmiento JM, Heywood G, Rubin J, Ilstrup DM, Nagorney DM, Que FG: Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. J Am Coll Surg 197(1):29–37, 2003 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids=12831921)

    Google Scholar 

  22. Grama D, Eriksson B, Martensson H, et al.: Clinical characteristics, treatment and survival in patients with pancreatic tumors causing hormonal syndromes. World J Surg 16(4):632–638, 1992 (available at:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=1357829)

    Google Scholar 

  23. Moinuddin M, Dean P, Vander Zwaag R, Dragutsky M: The limitation of liver function tests in metastatic carcinoid tumors. Cancer 59(7):1304–1306, 1987 (available at: http://www.ncbi.nlm. nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=3545433)

    Google Scholar 

  24. Lahr CJ, Soong SJ, Cloud G, Smith JW, Urist MM, Balch CM: A multifactorial analysis of prognostic factors in patients with liver metastases from colorectal carcinoma. J Clin Oncol 1(11):720–726, 1983 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=6668490)

  25. Eriksson B, Oberg K, Stridsberg M: Tumor markers in neuroendocrine tumors. Digestion 62(Suppl 1):33–38, 2000 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& db=PubMed&dopt=Citation&list_uids=10940685)

    Google Scholar 

  26. Taupenot L, Harper KL, O’Connor DT: The chromogranin-secretogranin family. N Engl J Med 348(12):1134–1148, 2003 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=12646671)

    Google Scholar 

  27. Broughan TA, Leslie JD, Soto JM, Hermann RE: Pancreatic islet cell tumors. Surgery 99(6):671–678, 1986 (available at: http://www. ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed& dopt=Citation&list_uids=2424108)

    Google Scholar 

  28. Lo CY, van Heerden JA, Thompson GB, Grant CS, Soreide JA, Harmsen WS: Islet cell carcinoma of the pancreas. World J Surg 20(7):878–883, discussion 884, 1996 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve& db=PubMed& dopt=Citation&list_uids=8678966)

    Google Scholar 

  29. White TJ, Edney JA, Thompson JS, Karrer FW, Moor BJ: Is there a prognostic difference between functional and nonfunctional islet cell tumors?Am J Surg 168(6):627–629, discussion 629–630, 1994 (available at:http://www.ncbi.nlm.nih. gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=7978008)

    Google Scholar 

  30. Onaitis MW, Kirshbom PM, Hayward TZ, et al.: Gastrointestinal carcinoids: characterization by site of origin and hormone production. Ann Surg 232(4):549–556, 2000 (available at: http://www. ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed& dopt=Citation&list_uids=10998653)

    Google Scholar 

  31. Modlin IM, Sandor A: An analysis of 8305 cases of carcinoid tumors. Cancer 79(4):813–288, 1997 (available at:http://www.ncbi. nlm.nih.gov/ entrez/ query.fcgi? cmd=Retrieve&db=PubMed& dopt=Citation&list_uids=9024720)

  32. Shebani KO, Souba WW, Finkelstein DM, et al.: Prognosis and survival in patients with gastrointestinal tract carcinoid tumors. Ann Surg 229(6):815–821, discussion 822–823, 1999 (available at: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=10363895)

    Google Scholar 

  33. McDermott EW, Guduric B, Brennan MF: Prognostic variables in patients with gastrointestinal carcinoid tumours. Br J Surg 81(7):1007–1008, 1994 (available at:http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation& list_uids=7922047)

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, USA

    Thomas E. Clancy MD

  2. Department of Medical Oncology, Dana Farber Cancer Institute, Boston, Massachusetts, USA

    Tanya P. Sengupta, Jessica Paulus & Matthew H. Kulke MD

  3. Analysis Group, Inc., Boston, Massachusetts, USA

    Fawzia Ahmed & Mei-Sheng Duh

  4. Department of Surgery, Brigham and Women's Hospital, 75 Francis Street, Boston, Massachusetts, 02115, USA

    Thomas E. Clancy MD

Authors
  1. Thomas E. Clancy MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tanya P. Sengupta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jessica Paulus
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fawzia Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mei-Sheng Duh
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Matthew H. Kulke MD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas E. Clancy MD.

Additional information

Matthew Kulke is supported in part by NIH grants K23 CA 093401, K30 HL04095, and gifts from Dr. Raymond and Beverly Sackler, the Caring for Carcinoid Foundation, and the Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Clancy, T.E., Sengupta, T.P., Paulus, J. et al. Alkaline Phosphatase Predicts Survival in Patients with Metastatic Neuroendocrine Tumors. Dig Dis Sci 51, 877–884 (2006). https://doi.org/10.1007/s10620-006-9345-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-006-9345-4

Key Words

Search

Navigation