Skip to main content

Advertisement

SpringerLink
Log in

Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors

  • Clinical
  • Published:
Cancer and Metastasis Reviews Aims and scope Submit manuscript

Abstract

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare neoplasms capable of producing hormones. The development of new treatments has improved progression-free survival, albeit with increased toxicity. Health-related quality of life (HRQoL) has become an important endpoint in clinical research to evaluate patients’ well-being in such a contradictory scenario. In this review, we examine key reported outcomes across clinical studies exploring HRQoL in patients with GEP-NETs. We have conducted a review of the literature using PubMed, The Cochrane Library, EMBASE, and Google Scholar. Selection criteria for articles were (1) publication in English between 1995 and 2014, (2) patients with GEP-NET, and (3) analysis of HRQoL, including mental health and psychological symptoms. Forty-nine studies met the inclusion criteria (31 clinical trials, 14 observational studies, and 4 developments of NET-specific HRQoL instruments). The scope and nature of the literature was diverse with 27 instruments used to measure aspects of HRQoL. EORTC QLQ-C30 was the most frequently used, in 38 of the 49 studies. Standardized measures revealed that in spite of generally good HRQoL, GEP-NET patients have specific psychological and physical complaints. The clinical benefit of somatostatin analogs and sunitinib has been clearly supported by HRQoL assessment. Improvement in HRQoL scores or symptom relief over time was also reported in 14 trials of peptide receptor radionuclide therapy, however the absence of randomized studies obviate definitive conclusions. We have also identified several unanswered questions that should be addressed in further research concerning chemotherapy, everolimus, surgery, local ablative therapies, and chemoembolization. Future research should incorporate GEP-NET-specific HRQoL instruments into phase III trials. This review may help both clinicians and researchers to select the most appropriate tools to assess changes in HRQoL in this population.

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

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Yao, J. C., Hassan, M., Phan, A., et al. (2008). One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the united states. Journal of Clinical Oncology, 26(18), 3063–3072.

    Article  PubMed  Google Scholar 

  2. Beaumont, J. L., Cella, D., Phan, A. T., Choi, S., Liu, Z., & Yao, J. C. (2012). Comparison of health-related quality of life in patients with neuroendocrine tumors with quality of life in the general US population. Pancreas, 41(3), 461–466.

    Article  CAS  PubMed  Google Scholar 

  3. Larsson, G., Sjoden, P. O., Oberg, K., Eriksson, B., & von Essen, L. (2001). Health-related quality of life, anxiety and depression in patients with midgut carcinoid tumours. Acta Oncologica, 40(7), 825–831.

    Article  CAS  PubMed  Google Scholar 

  4. US Department of Health and Human Services. (2006). Guidance for industry: patient-reported outcome measures: use in medical product development to support labeling claims: draft guidance. Health and Quality of Life Outcomes, 4, 79.

    Article  Google Scholar 

  5. Redeker, N. S., Lev, E. L., & Ruggiero, J. (2000). Insomnia, fatigue, anxiety, depression, and quality of life of cancer patients undergoing chemotherapy. Scholarly Inquiry for Nursing Practice, 14(4), 275–290. discussion 291–8.

    CAS  PubMed  Google Scholar 

  6. Cella, D. (1998). Factors influencing quality of life in cancer patients: anemia and fatigue. Seminars in Oncology, 25(3 Suppl 7), 43–46.

    CAS  PubMed  Google Scholar 

  7. Coates, A., Gebski, V., Bishop, J. F., et al. (1987). Improving the quality of life during chemotherapy for advanced breast cancer. A comparison of intermittent and continuous treatment strategies. New England Journal of Medicine, 317(24), 1490–1495.

    Article  CAS  PubMed  Google Scholar 

  8. Ganz, P. A., Lee, J. J., & Siau, J. (1991). Quality of life assessment. An independent prognostic variable for survival in lung cancer. Cancer, 67(12), 3131–3135.

    Article  CAS  PubMed  Google Scholar 

  9. Haugland, T., Vatn, M. H., Veenstra, M., Wahl, A. K., & Natvig, G. K. (2009). Health related quality of life in patients with neuroendocrine tumors compared with the general Norwegian population. Quality of Life Research, 18(6), 719–726.

    Article  PubMed  Google Scholar 

  10. Claringbold, P. G., Brayshaw, P. A., Price, R. A., & Turner, J. H. (2011). Phase II study of radiopeptide 177Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours. European Journal of Nuclear Medicine and Molecular Imaging, 38(2), 302–311.

    Article  CAS  PubMed  Google Scholar 

  11. Raymond, E., Dahan, L., Raoul, J. L., et al. (2011). Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. New England Journal of Medicine, 364(6), 501–513.

    Article  CAS  PubMed  Google Scholar 

  12. Rinke, A., Muller, H. H., Schade-Brittinger, C., et al. (2009). Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. Journal of Clinical Oncology, 27(28), 4656–4663.

    Article  CAS  PubMed  Google Scholar 

  13. Teunissen, J. J., Kwekkeboom, D. J., & Krenning, E. P. (2004). Quality of life in patients with gastroenteropancreatic tumors treated with [177Lu-DOTA0, Tyr3]octreotate. Journal of Clinical Oncology, 22(13), 2724–2729.

    Article  CAS  PubMed  Google Scholar 

  14. Kalinowski, M., Dressler, M., Konig, A., et al. (2009). Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study. Digestion, 79(3), 137–142.

    Article  PubMed  Google Scholar 

  15. Frilling, A., Weber, F., Saner, F., et al. (2006). Treatment with (90)Y- and (177)Lu-DOTATOC in patients with metastatic neuroendocrine tumors. Surgery, 140(6), 967–968.

    Article  Google Scholar 

  16. Bushnell, D. L., Jr., O’Dorisio, T. M., O’Dorisio, M. S., et al. (2010). 90Y-edotreotide for metastatic carcinoid refractory to octreotide. Journal of Clinical Oncology, 28(10), 1652–1659.

    Article  CAS  PubMed  Google Scholar 

  17. Zuetenhorst, J. M., Valdes Olmos, R. A., Muller, M., Hoefnagel, C. A., & Taal, B. G. (2004). Interferon and meta-iodobenzylguanidin combinations in the treatment of metastatic carcinoid tumours. Endocrine-Related Cancer, 11(3), 553–561.

    Article  CAS  PubMed  Google Scholar 

  18. Bajetta, E., Procopio, G., Catena, L., et al. (2006). Lanreotide autogel every 6 weeks compared with lanreotide microparticles every 3 weeks in patients with well differentiated neuroendocrine tumors: a phase III study. Cancer, 107(10), 2474–2481.

    Article  CAS  PubMed  Google Scholar 

  19. Ruszniewski, P., Ish-Shalom, S., Wymenga, M., et al. (2004). Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide. Neuroendocrinology, 80(4), 244–251.

    Article  CAS  PubMed  Google Scholar 

  20. Cwikla, J. B., Sankowski, A., Seklecka, N., et al. (2010). Efficacy of radionuclide treatment DOTATATE Y-90 in patients with progressive metastatic gastroenteropancreatic neuroendocrine carcinomas (GEP-NETs): a phase II study. Annals of Oncology, 21(4), 787–794.

    Article  CAS  PubMed  Google Scholar 

  21. Martin-Richard, M., Massuti, B., Pineda, E., et al. (2013). Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study. BMC Cancer, 13(1), 427.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  22. O’Toole, D., Ducreux, M., Bommelaer, G., et al. (2000). Treatment of carcinoid syndrome: a prospective crossover evaluation of lanreotide versus octreotide in terms of efficacy, patient acceptability, and tolerance. Cancer, 88(4), 770–776.

    Article  PubMed  Google Scholar 

  23. Kulke, M. H., Lenz, H. J., Meropol, N. J., et al. (2008). Activity of sunitinib in patients with advanced neuroendocrine tumors. Journal of Clinical Oncology, 26(20), 3403–3410.

    Article  CAS  PubMed  Google Scholar 

  24. Kvols, L. K., Oberg, K. E., O’Dorisio, T. M., et al. (2012). Pasireotide (SOM230) shows efficacy and tolerability in the treatment of patients with advanced neuroendocrine tumors refractory or resistant to octreotide LAR: results from a phase II study. Endocrine-Related Cancer, 19(5), 657–666.

    Article  CAS  PubMed  Google Scholar 

  25. Jacobsen, M. B., & Hanssen, L. E. (1995). Clinical effects of octreotide compared to placebo in patients with gastrointestinal neuroendocrine tumours. Report on a double-blind, randomized trial. Journal of Internal Medicine, 237(3), 269–275.

    Article  CAS  PubMed  Google Scholar 

  26. Virgolini, I., Britton, K., Buscombe, J., Moncayo, R., Paganelli, G., & Riva, P. (2002). In- and Y-DOTA-lanreotide: results and implications of the MAURITIUS trial. Seminars in Nuclear Medicine, 32(2), 148–155.

    Article  PubMed  Google Scholar 

  27. Waldherr, C., Pless, M., Maecke, H. R., et al. (2002). Tumor response and clinical benefit in neuroendocrine tumors after 7.4 GBq (90)Y-DOTATOC. Journal of Nuclear Medicine, 43(5), 610–616.

    CAS  PubMed  Google Scholar 

  28. Forrer, F., Waldherr, C., Maecke, H. R., & Mueller-Brand, J. (2006). Targeted radionuclide therapy with 90Y-DOTATOC in patients with neuroendocrine tumors. Anticancer Research, 26(1B), 703–707.

    CAS  PubMed  Google Scholar 

  29. Valkema, R., Pauwels, S., Kvols, L. K., et al. (2006). Survival and response after peptide receptor radionuclide therapy with [90Y-DOTA0, Tyr3]octreotide in patients with advanced gastroenteropancreatic neuroendocrine tumors. Seminars in Nuclear Medicine, 36(2), 147–156.

    Article  PubMed  Google Scholar 

  30. Bushnell, D., O’Dorisio, T., Menda, Y., et al. (2003). Evaluating the clinical effectiveness of 90Y-SMT 487 in patients with neuroendocrine tumors. Journal of Nuclear Medicine, 44(10), 1556–1560.

    PubMed  Google Scholar 

  31. Muros, M. A., Varsavsky, M., Iglesias Rozas, P., et al. (2009). Outcome of treating advanced neuroendocrine tumours with radiolabelled somatostatin analogues. Clinical and Translational Oncology, 11(1), 48–53.

    Article  CAS  PubMed  Google Scholar 

  32. Bodei, L., Cremonesi, M., Grana, C. M., et al. (2011). Peptide receptor radionuclide therapy with 177-Lu-DOTATATE: the IEO phase I–II study. European Journal of Nuclear Medicine and Molecular Imaging, 38(12), 2125–2135.

    Article  CAS  PubMed  Google Scholar 

  33. Khan, S., Krenning, E. P., van Essen, M., Kam, B. L., Teunissen, J. J., & Kwekkeboom, D. J. (2011). Quality of life in 265 patients with gastroenteropancreatic or bronchial neuroendocrine tumors treated with [177Lu-DOTA0, Tyr3]octreotate. Journal of Nuclear Medicine, 52(9), 1361–1368.

    Article  CAS  PubMed  Google Scholar 

  34. Arnold, R., Rinke, A., Klose, K. J., et al. (2005). Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial. Clinical Gastroenterology and Hepatology, 3(8), 761–771.

    Article  CAS  PubMed  Google Scholar 

  35. Gyokeres, T., Pulgar, S., Singh, N., Passos, V. Q., & Kelemen, P. (2012). Effect of octreotide LAR on quality of life of 93 Hungarian patients with neuroendocrine tumors. ASCO Meeting Abstract, 30(4_suppl), 362.

    Google Scholar 

  36. Wymenga, A. N., Eriksson, B., Salmela, P. I., et al. (1999). Efficacy and safety of prolonged-release lanreotide in patients with gastrointestinal neuroendocrine tumors and hormone-related symptoms. Journal of Clinical Oncology, 17(4), 1111.

    CAS  PubMed  Google Scholar 

  37. Caplin, M. E., Pavel, M., Cwikła, J. B., et al. (2014). Lanreotide in metastatic enteropancreatic neuroendocrine tumors. New England Journal of Medicine, 371(3), 224–233.

    Article  PubMed  CAS  Google Scholar 

  38. Pavel, M., Unger, N., Borbath, I., et al. (2014). Safety and quality-of-life (QOL) assessments in the open-label, multicenter, phase 3b, expanded access study of everolimus in patients with advanced neuroendocrine tumors (NET). Pancreas, 43(3), 500–501.

    Google Scholar 

  39. Delpassand, E. S., Samarghandi, A., Zamanian, S., et al. (2014). Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience. Pancreas, 43(4), 518–525.

    Article  CAS  PubMed  Google Scholar 

  40. Frojd, C., Larsson, G., Lampic, C., & von Essen, L. (2007). Health related quality of life and psychosocial function among patients with carcinoid tumours. A longitudinal, prospective, and comparative study. Health and Quality of Life Outcomes, 5, 18.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Larsson, G., von Essen, L., & Sjoden, P. O. (1999). Health-related quality of life in patients with endocrine tumours of the gastrointestinal tract. Acta Oncologica, 38(4), 481–490.

    Article  CAS  PubMed  Google Scholar 

  42. Berglund, G., Liden, A., Hansson, M. G., Oberg, K., Sjoden, P. O., & Nordin, K. (2003). Quality of life in patients with multiple endocrine neoplasia type 1 (MEN 1). Familial Cancer, 2(1), 27–33.

    Article  CAS  PubMed  Google Scholar 

  43. Larsson, G., Haglund, K., & Von Essen, L. (2003). Distress, quality of life and strategies to “keep a good mood” in patients with carcinoid tumours: patient and staff perceptions. European Journal of Cancer Care, 12(1), 46–57.

    Article  CAS  PubMed  Google Scholar 

  44. Von Essen, L., Larsson, G., Oberg, K., & Sjoden, P. O. (2002). “Satisfaction with care”: associations with health-related quality of life and psychosocial function among Swedish patients with endocrine gastrointestinal tumours. European Journal of Cancer Care, 11(2), 91–99.

    Article  Google Scholar 

  45. Pezzilli, R., Campana, D., Morselli-Labate, A. M., Fabbri, M. C., Brocchi, E., & Tomassetti, P. (2009). Patient-reported outcomes in subjects with neuroendocrine tumors of the pancreas. World Journal of Gastroenterology, 15(40), 5067–5073.

    Article  PubMed Central  PubMed  Google Scholar 

  46. Van der Horst-Schrivers, A. N., van Ieperen, E., Wymenga, A. N., et al. (2009). Sexual function in patients with metastatic midgut carcinoid tumours. Neuroendocrinology, 89(2), 231–236.

    Article  PubMed  CAS  Google Scholar 

  47. You, Y. N., Thompson, G. B., Young, W. F., Jr., et al. (2007). Pancreatoduodenal surgery in patients with multiple endocrine neoplasia type 1: operative outcomes, long-term function, and quality of life. Surgery, 142(6), 829–836. discussion 836.e1.

    Article  PubMed  Google Scholar 

  48. Korse, C. M., Bonfrer, J. M. G., Aaronson, N. K., Hart, A. A. M., & Taal, B. G. (2009). Chromogranin A as an alternative to 5-hydroxyindoleacetic acid in the evaluation of symptoms during treatment of patients with neuroendocrine tumors. Neuroendocrinology, 89(3), 296–301.

    Article  CAS  PubMed  Google Scholar 

  49. Davies, A. H., Larsson, G., Ardill, J., et al. (2006). Development of a disease-specific quality of life questionnaire module for patients with gastrointestinal neuroendocrine tumours. European Journal of Cancer, 42(4), 477–484.

    Article  CAS  PubMed  Google Scholar 

  50. Vinik, E., Carlton, C. A., Silva, M. P., & Vinik, A. I. (2009). Development of the Norfolk quality of life tool for assessing patients with neuroendocrine tumors. Pancreas, 38(3), e87–e95.

    Article  PubMed  Google Scholar 

  51. Yadegarfar, G., Friend, L., Jones, L., et al. (2013). Validation of the EORTC QLQ-GINET21 questionnaire for assessing quality of life of patients with gastrointestinal neuroendocrine tumours. British Journal of Cancer, 108(2), 301–310.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Vinik, E., Silva, M. P., & Vinik, A. I. (2011). Measuring the relationship of quality of life and health status, including tumor burden, symptoms, and biochemical measures in patients with neuroendocrine tumors. Endocrinology and Metabolism Clinics of North America, 40(1), 97–109.

    Article  CAS  PubMed  Google Scholar 

  53. Vinik, A., Bang, Y., Raoul, J., et al. (2010). Patient-reported outcomes (PROs) in patients (pts) with pancreatic neuroendocrine tumors (NET) receiving sunitinib (SU) in a phase III trial. ASCO Meeting Abstract, 28(15_suppl), 4003.

    Google Scholar 

  54. Haugland, T., Veenstra, M., Vatn, M. H., & Wahl, A. K. (2013). Improvement in stress, general self-efficacy, and health related quality of life following patient education for patients with neuroendocrine tumors: a pilot study. Nursing Research Practice, 2013, 695820.

    Article  PubMed Central  PubMed  Google Scholar 

  55. Larsson, G., von Essen, L., & Sjoden, P. O. (1998). Quality of life in patients with endocrine tumors of the gastrointestinal tract: patient and staff perceptions. Cancer Nursing, 21(6), 411–420.

    Article  CAS  PubMed  Google Scholar 

  56. Larsson, G., Sjoden, P. O., Oberg, K., & von Essen, L. (1999). Importance-satisfaction discrepancies are associated with health-related quality of life in five-year survivors of endocrine gastrointestinal tumours. Annals of Oncology, 10(11), 1321–1327.

    Article  CAS  PubMed  Google Scholar 

  57. Ramage, J. K., Davies, A. H., & Group EQ of L. (2003). Measurement of quality of life in carcinoid/neuroendocrine tumours. Endocrine-Related Cancer, 10(4), 483–486.

    Article  CAS  PubMed  Google Scholar 

  58. Frojd, C., Lampic, C., Larsson, G., & von Essen, L. (2009). Is satisfaction with doctors’ care related to health-related quality of life, anxiety and depression among patients with carcinoid tumours? A longitudinal report. Scandinavian Journal of Caring Sciences, 23(1), 107–116.

    Article  PubMed  Google Scholar 

  59. Kulke, M.H., O’Dorisio, T., Yang Qi, M., et al. (2015). Patient-reported symptom experiences following participation in a study of telotristat etiprate for patients with carcinoid tumor and octreotide-refractory diarrhea. Available at: http://www.nanets.net/nanets_cd/2013/pdfs/C13-kulkeabstract2.pdf.Accessed 20 June 2015.

  60. Cheung, Y. B., Goh, C., Thumboo, J., Khoo, K. S., & Wee, J. (2005). Variability and sample size requirements of quality-of-life measures: a randomized study of three major questionnaires. Journal of Clinical Oncology, 23(22), 4936–4944.

    Article  PubMed  Google Scholar 

  61. Kemmler, G., Holzner, B., Kopp, M., et al. (1999). Comparison of two quality-of-life instruments for cancer patients: the functional assessment of cancer therapy-general and the European Organization for Research and Treatment of Cancer quality of life questionnaire-C30. Journal of Clinical Oncology, 17(9), 2932–2940.

    CAS  PubMed  Google Scholar 

  62. Aaronson, N. K., Ahmedzai, S., Bergman, B., et al. (1993). The European Organization for Research and Treatment of Cancer QLQ-C30: a quality-of-life instrument for use in international clinical trials in oncology. Journal of the National Cancer Institute, 85(5), 365–376.

    Article  CAS  PubMed  Google Scholar 

  63. Fayers, P. M., Aaronson, N. K., Bjordal, K., Groenvold, M., Curran, D., & Bottomley, A. (2001). The EORTC QLQ-C30 scoring manual. Brussels: European Organisation for Research and Treatment of Cancer.

    Google Scholar 

  64. Bredart, A., Bottomley, A., Blazeby, J. M., et al. (2005). An international prospective study of the EORTC cancer in-patient satisfaction with care measure (EORTC IN-PATSAT32). European Journal of Cancer, 41(14), 2120–2131.

    Article  CAS  PubMed  Google Scholar 

  65. Osoba, D., Zee, B., Pater, J., Warr, D., Kaizer, L., & Latreille, J. (1994). Psychometric properties and responsiveness of the EORTC quality of life questionnaire (QLQ-C30) in patients with breast, ovarian and lung cancer. Quality of Life Research, 3(5), 353–364.

    Article  CAS  PubMed  Google Scholar 

  66. Groenvold, M., Klee, M. C., Sprangers, M. A., & Aaronson, N. K. (1997). Validation of the EORTC QLQ-C30 quality of life questionnaire through combined qualitative and quantitative assessment of patient-observer agreement. Journal of Clinical Epidemiology, 50(4), 441–450.

    Article  CAS  PubMed  Google Scholar 

  67. Ringdal, G. I., & Ringdal, K. (1993). Testing the EORTC quality of life questionnaire on cancer patients with heterogeneous diagnoses. Quality of Life Research, 2(2), 129–140.

    Article  CAS  PubMed  Google Scholar 

  68. McLachlan, S. A., Devins, G. M., & Goodwin, P. J. (1999). Factor analysis of the psychosocial items of the EORTC QLQ-C30 in metastatic breast cancer patients participating in a psychosocial intervention study. Quality of Life Research, 8(4), 311–317.

    Article  CAS  PubMed  Google Scholar 

  69. Kaasa, S., Bjordal, K., Aaronson, N., et al. (1995). The EORTC core quality of life questionnaire (QLQ-C30): validity and reliability when analysed with patients treated with palliative radiotherapy. European Journal of Cancer, 31A(13–14), 2260–2263.

    Article  CAS  PubMed  Google Scholar 

  70. Arraras, J. I., Arias, F., Tejedor, M., et al. (2002). The EORTC QLQ-C30 (version 3.0) quality of life questionnaire: validation study for Spain with head and neck cancer patients. Psychooncology, 11(3), 249–256.

    Article  CAS  PubMed  Google Scholar 

  71. Bjordal, K., de Graeff, A., Fayers, P. M., et al. (2000). A 12 country field study of the EORTC QLQ-C30 (version 3.0) and the head and neck cancer specific module (EORTC QLQ-H&N35) in head and neck patients. EORTC Quality of Life Group. European Journal of Cancer, 36(14), 1796–1807.

    Article  CAS  PubMed  Google Scholar 

  72. Whistance, R. N., Conroy, T., Chie, W., et al. (2009). Clinical and psychometric validation of the EORTC QLQ-CR29 questionnaire module to assess health-related quality of life in patients with colorectal cancer. European Journal of Cancer, 45(17), 3017–3026.

    Article  CAS  PubMed  Google Scholar 

  73. Fayers, P., Aaronson, N., Bjordal, K., et al. (2001). The EORTC QLQ-C30 scoring manual (3rd ed.). Brussels: European Organisation for Research and Treatment of Cancer.

    Google Scholar 

  74. Kulke, M. H., Stuart, K., Enzinger, P. C., et al. (2006). Phase II study of temozolomide and thalidomide in patients with metastatic neuroendocrine tumors. Journal of Clinical Oncology, 24(3), 401–406.

    Article  CAS  PubMed  Google Scholar 

  75. Guyatt, G. H., Feeny, D. H., & Patrick, D. L. (1993). Measuring health-related quality of life. Annals of Internal Medicine, 118(8), 622–629.

    Article  CAS  PubMed  Google Scholar 

  76. Smith, K. W., Avis, N. E., & Assmann, S. F. (1999). Distinguishing between quality of life and health status in quality of life research: a meta-analysis. Quality of Life Research, 8(5), 447–459.

    Article  CAS  PubMed  Google Scholar 

  77. Covinsky, K. E., Wu, A. W., Landefeld, C. S., et al. (1999). Health status versus quality of life in older patients: does the distinction matter? American Journal of Medicine, 106(4), 435–440.

    Article  CAS  PubMed  Google Scholar 

  78. Ware, J. E., Jr., & Sherbourne, C. D. (1992). The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care, 30(6), 473–483.

    Article  PubMed  Google Scholar 

  79. Ware, J., Kosinski, M., & Keller, S. D. (1996). A 12-item short-form health survey: construction of scales and preliminary tests of reliability and validity. Medical Care, 34(3), 220–233.

    Article  PubMed  Google Scholar 

  80. Cella, D., Beaumont, J. L., Liu, Z., Phan, A. T., Choi, S., & Yao, J. C. (2010). Neuroendocrine tumor disease state and PROMIS health-related quality of life scores. ASCO Meeting Abstract, 28(15_suppl), 6118.

    Google Scholar 

  81. Bucquet, D., Condon, S., & Ritchie, K. (1990). The French version of the Nottingham health profile. A comparison of items weights with those of the source version. Social Science and Medicine, 30(7), 829–835.

    Article  CAS  PubMed  Google Scholar 

  82. Larsson, G., & Janson, E. T. (2008). Anemia in patients with midgut carcinoid, treated with alpha interferon: effects by erythropoietin treatment on the perceived quality of life. European Journal of Cancer Care, 17(2), 200–204.

    Article  CAS  PubMed  Google Scholar 

  83. Webster, K., Cella, D., & Yost, K. (2003). The functional assessment of chronic illness therapy (FACIT) measurement system: properties, applications, and interpretation. Health and Quality of Life Outcomes, 1, 79.

    Article  PubMed Central  PubMed  Google Scholar 

  84. Yellen, S. B., Cella, D. F., Webster, K., Blendowski, C., & Kaplan, E. (1997). Measuring fatigue and other anemia-related symptoms with the functional assessment of cancer therapy (FACT) measurement system. Journal of Pain and Symptom Management, 13(2), 63–74.

    Article  CAS  PubMed  Google Scholar 

  85. Schell, S. R., Camp, E. R., Caridi, J. G., & Hawkins, I. F., Jr. (2002). Hepatic artery embolization for control of symptoms, octreotide requirements, and tumor progression in metastatic carcinoid tumors. Journal of Gastrointestinal Surgery, 6(5), 664–670.

    Article  PubMed  Google Scholar 

  86. Boudreaux, J. P., Putty, B., Frey, D. J., et al. (2005). Surgical treatment of advanced-stage carcinoid tumors: lessons learned. Annals of Surgery, 241(6), 839–845.

    Article  PubMed Central  PubMed  Google Scholar 

  87. Gulec, S. A., Mountcastle, T. S., Frey, D., et al. (2002). Cytoreductive surgery in patients with advanced-stage carcinoid tumors. American Surgeon, 68(8), 667–671.

    PubMed  Google Scholar 

  88. Knox, C. D., Feurer, I. D., Wise, P. E., et al. (2004). Survival and functional quality of life after resection for hepatic carcinoid metastasis. Journal of Gastrointestinal Surgery, 8(6), 653–659.

    Article  PubMed  Google Scholar 

  89. Oken, M. M., Creech, R. H., Tormey, D. C., et al. (1982). Toxicity and response criteria of the Eastern Cooperative Oncology group. American Journal of Clinical Oncology, 5(6), 649–655.

    Article  CAS  PubMed  Google Scholar 

  90. Karnofsky, D. A., & Burchenal, J. H. (1949). The clinical evaluation of chemotherapeutic agents in cancer. New York: Columbia University Press.

    Google Scholar 

  91. Blazeby, J. M., Fayers, P., Conroy, T., et al. (2009). Validation of the European Organization for Research and Treatment of Cancer QLQ-LMC21 questionnaire for assessment of patient-reported outcomes during treatment of colorectal liver metastases. British Journal of Surgery, 96(3), 291–298.

    Article  CAS  PubMed  Google Scholar 

  92. Derogatis, L. R. (1986). The psychosocial adjustment to illness scale (PAIS). Journal of Psychosomatic Research, 30(1), 77–91.

    Article  CAS  PubMed  Google Scholar 

  93. Horowitz, M., Wilner, N., & Alvarez, W. (1979). Impact of event scale: a measure of subjective stress. Psychosomatic Medicine, 41(3), 209–218.

    Article  CAS  PubMed  Google Scholar 

  94. Scheier, M. F., Carver, C. S., & Bridges, M. W. (1994). Distinguishing optimism from neuroticism (and trait anxiety, self-mastery, and self-esteem): a reevaluation of the Life Orientation Test. Journal of Personality and Social Psychology, 67(6), 1063–1078.

    Article  CAS  PubMed  Google Scholar 

  95. Vodermaier, A., Linden, W., & Siu, C. (2009). Screening for emotional distress in cancer patients: a systematic review of assessment instruments. Journal of the National Cancer Institute, 101(21), 1464–1488.

    Article  PubMed Central  PubMed  Google Scholar 

  96. Hatton, M. Q., & Reed, N. S. (1997). Chemotherapy for neuroendocrine tumors: the Beatson Oncology Centre experience. Clinical Oncology (Royal College of Radiologists), 9(6), 385–389.

    Article  CAS  Google Scholar 

  97. Khan, M. S., & Caplin, M. E. (2011). Therapeutic management of patients with gastroenteropancreatic neuroendocrine tumours. Endocrine-Related Cancer, 18(Suppl 1), S53–S74.

    Article  CAS  PubMed  Google Scholar 

  98. Sarmiento, J. M., Heywood, G., Rubin, J., Ilstrup, D. M., Nagorney, D. M., & Que, F. G. (2003). Surgical treatment of neuroendocrine metastases to the liver: a plea for resection to increase survival. Journal of the American College of Surgery, 197(1), 29–37.

    Article  Google Scholar 

  99. Touzios, J. G., Kiely, J. M., Pitt, S. C., et al. (2005). Neuroendocrine hepatic metastases: does aggressive management improve survival? Annals of Surgery, 241(5), 775–776.

    Article  Google Scholar 

  100. Ahmed, A., Turner, G., King, B., et al. (2009). Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study. Endocrine-Related Cancer, 16(3), 885–894.

    Article  CAS  PubMed  Google Scholar 

  101. Mayo, S. C., de Jong, M. C., Bloomston, M., et al. (2011). Surgery versus intra-arterial therapy for neuroendocrine liver metastasis: a multicenter international analysis. Annals of Surgical Oncology, 18(13), 3657–3665.

    Article  PubMed  Google Scholar 

  102. Meranze, S. G., Bream, P. R., & Grzeszczak, E. (2007). Phase II clinical trial of yttrium-90 resin microspheres for the treatment of metastatic neuroendocrine tumor. Presented as a poster at the society of interventional radiology (SIR) 32nd annual scientific meeting 2007; Abs 422. Journal of Vascular and Interventional Radiology, 18(1), S150–S151.

    Article  Google Scholar 

  103. Osborne, D. A., Zervos, E. E., Strosberg, J., et al. (2006). Improved outcome with cytoreduction versus embolization for symptomatic hepatic metastases of carcinoid and neuroendocrine tumors. Annals of Surgical Oncology, 13(4), 572–581.

    Article  PubMed  Google Scholar 

  104. Hung, J. S., Chang, M. C., Lee, P. H., & Tien, Y. W. (2007). Is surgery indicated for patients with symptomatic nonfunctioning pancreatic neuroendocrine tumor and unresectable hepatic metastases? World Journal of Surgery, 31(12), 2392–2397.

    Article  PubMed  Google Scholar 

  105. Saxena, A., Chua, T. C., Perera, M., Chu, F., & Morris, D. L. (2012). Surgical resection of hepatic metastases from neuroendocrine neoplasms: a systematic review. Surgical Oncology, 21(3), e131–e141.

    Article  PubMed  Google Scholar 

  106. Drougas, J. G., Anthony, L. B., Blair, T. K., et al. (1998). Hepatic artery chemoembolization for management of patients with advanced metastatic carcinoid tumors. American Journal of Surgery, 175(5), 408–412.

    Article  CAS  PubMed  Google Scholar 

  107. Loewe, C., Schindl, M., Cejna, M., Niederle, B., Lammer, J., & Thurnher, S. (2003). Permanent transarterial embolization of neuroendocrine metastases of the liver using cyanoacrylate and lipiodol: assessment of mid- and long-term results. AJR American Journal of Roentgenology, 180(5), 1379–1384.

    Article  PubMed  Google Scholar 

  108. Diamandidou, E., Ajani, J. A., Yang, D. J., et al. (1998). Two-phase study of hepatic artery vascular occlusion with microencapsulated cisplatin in patients with liver metastases from neuroendocrine tumors. American Journal of Roentgenology, 170(2), 339–344.

    Article  CAS  PubMed  Google Scholar 

  109. Wessels, F. J., & Schell, S. R. (2001). Radiofrequency ablation treatment of refractory carcinoid hepatic metastases. Journal of Surgical Research, 95(1), 8–12.

    Article  CAS  PubMed  Google Scholar 

  110. Maire, F., Lombard-Bohas, C., O’Toole, D., et al. (2012). Hepatic arterial embolization versus chemoembolization in the treatment of liver metastases from well-differentiated midgut endocrine tumors: a prospective randomized study. Neuroendocrinology, 96(4), 294–300.

    Article  CAS  PubMed  Google Scholar 

  111. Rajekar, H., Bogammana, K., & Stubbs, R. S. (2011). Selective internal radiation therapy for gastrointestinal neuroendocrine tumour liver metastases: a new and effective modality for treatment. International Journal of Hepatology, 2011, 404916.

    Article  PubMed Central  PubMed  Google Scholar 

  112. Chambers, A. J., Pasieka, J. L., Dixon, E., & Rorstad, O. (2008). The palliative benefit of aggressive surgical intervention for both hepatic and mesenteric metastases from neuroendocrine tumors. Surgery, 144(4), 643–645.

    Article  Google Scholar 

  113. Karnofsky, D. A., Abelmann, W. H., Craver, L. F., & Burchenal, J. H. (1948). The use of the nitrogen mustards in the palliative treatment of carcinoma. With particular reference to bronchogenic carcinoma. Cancer, 1(4), 634–656.

    Article  Google Scholar 

  114. Pavel, M., Baudin, E., Couvelard, A., et al. (2012). ENETS consensus guidelines for the management of patients with liver and other distant metastases from neuroendocrine neoplasms of foregut, midgut, hindgut, and unknown primary. Neuroendocrinology, 95(2), 157–176.

    Article  CAS  PubMed  Google Scholar 

  115. Yang, T. X., Chua, T. C., & Morris, D. L. (2012). Radioembolization and chemoembolization for unresectable neuroendocrine liver metastases - a systematic review. Surgical Oncology, 21(4), 299–308.

    Article  PubMed  Google Scholar 

  116. Elias, D., Goere, D., Leroux, G., et al. (2009). Combined liver surgery and RFA for patients with gastroenteropancreatic endocrine tumors presenting with more than 15 metastases to the liver. European Journal of Surgical Oncology, 35(10), 1092–1097.

    Article  CAS  PubMed  Google Scholar 

  117. Huang, Y.-Z., Zhou, S.-C., Zhou, H., & Tong, M. (2013). Radiofrequency ablation versus cryosurgery ablation for hepatocellular carcinoma: a meta-analysis. Hepato-Gastroenterology, 60(125), 1131–1135.

    PubMed  Google Scholar 

  118. Akyildiz, H. Y., Mitchell, J., Milas, M., Siperstein, A., & Berber, E. (2010). Laparoscopic radiofrequency thermal ablation of neuroendocrine hepatic metastases: long-term follow-up. Surgery, 148(6), 1288–1293.

    Article  PubMed  Google Scholar 

  119. National Cancer Institute (2015). Common terminology criteria for adverse effects (CTCAE) v3.0. Available at: http://ctep.cancer.gov/reporting/ctc.html. Accessed: 20 June 2015.

  120. Krabbe, P. F., Peerenboom, L., Langenhoff, B. S., & Ruers, T. J. (2004). Responsiveness of the generic EQ-5D summary measure compared to the disease-specific EORTC QLQ C-30. Quality of Life Research, 13(7), 1247–1253.

    Article  PubMed  Google Scholar 

  121. Fayers, P. M., & Sprangers, M. A. (2002). Understanding self-rated health. Lancet, 359(9302), 187–188.

    Article  PubMed  Google Scholar 

  122. Maton, P. N., Gardner, J. D., & Jensen, R. T. (1989). Use of long-acting somatostatin analog SMS 201-995 in patients with pancreatic islet cell tumors. Digestive Diseases and Sciences, 34(3 Suppl), 28S–39S.

    Article  CAS  PubMed  Google Scholar 

  123. Oberg, K., Kvols, L., Caplin, M., et al. (2004). Consensus report on the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Annals of Oncology, 15(6), 966–973.

    Article  CAS  PubMed  Google Scholar 

  124. Capdevila, J., Sevilla, I., Alonso, V., et al. (2015). Evaluation of the efficacy and safety of lanreotide in combination with targeted therapies in patients with neuroendocrine tumours in clinical practice: a retrospective cross-sectional analysis. BMC Cancer, 15, 495.

  125. Moertel, C. G., Lefkopoulo, M., Lipsitz, S., Hahn, R. G., & Klaassen, D. (1992). Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. New England Journal of Medicine, 326(8), 519–523.

    Article  CAS  PubMed  Google Scholar 

  126. Moertel, C. G., Kvols, L. K., O’Connell, M. J., & Rubin, J. (1991). Treatment of neuroendocrine carcinomas with combined etoposide and cisplatin. Evidence of major therapeutic activity in the anaplastic variants of these neoplasms. Cancer, 68(2), 227–232.

    Article  CAS  PubMed  Google Scholar 

  127. Eriksson, B., Skogseid, B., Lundqvist, G., Wide, L., Wilander, E., & Oberg, K. (1990). Medical treatment and long-term survival in a prospective study of 84 patients with endocrine pancreatic tumors. Cancer, 65(9), 1883–1890.

    Article  CAS  PubMed  Google Scholar 

  128. Ramanathan, R. K., Cnaan, A., Hahn, R. G., Carbone, P. P., & Haller, D. G. (2001). Phase II trial of dacarbazine (DTIC) in advanced pancreatic islet cell carcinoma. Study of the Eastern Cooperative Oncology Group-E6282. Annals of Oncology, 12(8), 1139–1143.

    Article  CAS  PubMed  Google Scholar 

  129. Strosberg, J. R., Fine, R. L., Choi, J., et al. (2011). First-line chemotherapy with capecitabine and temozolomide in patients with metastatic pancreatic endocrine carcinomas. Cancer, 117(2), 268–275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. Fine, R. L., Gulati, A. P., Krantz, B. A., et al. (2013). Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: the Pancreas Center at Columbia University experience. Cancer Chemotheraphy and Pharmacology, 71(3), 663–670.

    Article  CAS  Google Scholar 

  131. Lopez-Lopez, C., Jimenez, P., Crespo, G., et al. (2013). Temozolamide plus capecitabine as salvage treatment for patients with advanced neuroendocrine tumors (NETs) in the community setting. ASCO Meeting Abstract, 31(15_suppl), e15169.

    Google Scholar 

  132. Maire, F., Hammel, P., Faivre, S., et al. (2009). Temozolomide: a safe and effective treatment for malignant digestive endocrine tumors. Neuroendocrinology, 90(1), 67–72.

    Article  CAS  PubMed  Google Scholar 

  133. Ekeblad, S., Sundin, A., Janson, E. T., et al. (2007). Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors. Clinical Cancer Research, 13(10), 2986–2991.

    Article  CAS  PubMed  Google Scholar 

  134. Chan, J. A., Stuart, K., Earle, C. C., et al. (2012). Prospective study of bevacizumab plus temozolomide in patients with advanced neuroendocrine tumors. Journal of Clinical Oncology, 30(24), 2963–2968.

    Article  CAS  PubMed  Google Scholar 

  135. Oberg, K., Casanovas, O., Castaño, J. P., et al. (2013). Molecular pathogenesis of neuroendocrine tumors: implications for current and future therapeutic approaches. Clinical Cancer Research, 19(11), 2842–2849.

    Article  CAS  PubMed  Google Scholar 

  136. Benavent, M., de Miguel, M. J., & Garcia-Carbonero, R. (2012). New targeted agents in gastroenteropancreatic neuroendocrine tumors. Targeted Oncology, 7(2), 99–106.

    Article  PubMed  Google Scholar 

  137. Missiaglia, E., Dalai, I., Barbi, S., et al. (2010). Pancreatic endocrine tumors: expression profiling evidences a role for AKT-mTOR pathway. Journal of Clinical Oncology, 28(2), 245–255.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  138. Pavel, M., Hainsworth, J. D., Baudin, E., Peeters, M., & Hobday, T. J. (2010). A randomized, double-blind, placebo-controlled, multicenter phase III trial of everolimus + octreotide LAR vs placebo + octreotide LAR in patients with neuroendocrine tumors (NET). Annals of Oncology, 21, viii–4.

    Google Scholar 

  139. Yao, J. C., Shah, M. H., Ito, T., et al. (2011). Everolimus for advanced pancreatic neuroendocrine tumors. New England Journal of Medicine, 364(6), 514–523.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  140. Yao, J. C., Hainsworth, J. D., Wolin, E. M., et al. (2012). Multivariate analysis including biomarkers in the phase III RADIANT-2 study of octreotide LAR plus everolimus (E + O) or placebo (P + O) among patients with advanced neuroendocrine tumors (NET). ASCO Meeting Abstract, 30(4_suppl), 157.

    Google Scholar 

  141. Burris, H. A., 3rd, Lebrun, F., Rugo, H. S., et al. (2013). Health-related quality of life of patients with advanced breast cancer treated with everolimus plus exemestane versus placebo plus exemestane in the phase 3, randomized, controlled, BOLERO-2 trial. Cancer, 119(10), 1908–1915.

    Article  CAS  PubMed  Google Scholar 

  142. Motzer, R. J., Escudier, B., Oudard, S., et al. (2008). Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet, 372(9637), 449–456.

    Article  CAS  PubMed  Google Scholar 

  143. Strosberg, J. R., Lincy, J., Winkler, R. E., & Wolin, E. M. (2011). Everolimus in patients with advanced pancreatic neuroendocrine tumors (pNET): updated results of a randomized, double-blind, placebo-controlled, multicenter, phase III trial (RADIANT-3). ASCO Meeting Abstract, 29(15_suppl), 4009.

    Google Scholar 

  144. Phan, A. T. (2013). Metastatic pancreatic neuroendocrine tumors (pNET): placing current findings into perspective. Cancer Treatment Reviews, 39(1), 3–9.

    Article  PubMed  Google Scholar 

  145. Raymond, E., Hammel, P., Dreyer, C., et al. (2012). Sunitinib in pancreatic neuroendocrine tumors. Targeted Oncology, 7(2), 117–125.

    Article  PubMed  Google Scholar 

  146. Oberstein, P. E., & Saif, M. W. (2012). Safety and efficacy of everolimus in adult patients with neuroendocrine tumors. Clinical Medicine Insights Oncology, 6, 41–51.

    PubMed Central  CAS  PubMed  Google Scholar 

  147. Grande, E., Capdevila, J., Castellano, D., et al. (2015). Pazopanib in pretreated advanced neuroendocrine tumors: a phase II, open-label trial of the Spanish Task Force Group for Neuroendocrine Tumors (GETNE). Annals of Oncology, pii: mdv252. [Epub ahead of print]

  148. Jiao, Y., Shi, C., Edil, B. H., et al. (2011). DAXX/ATRX, MEN1, and mTOR pathway genes are frequently altered in pancreatic neuroendocrine tumors. Science, 331(6021), 1199–1203.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  149. Yao, J. C., Pavel, M., Phan, A. T., et al. (2011). Chromogranin A and neuron-specific enolase as prognostic markers in patients with advanced pNET treated with everolimus. Journal of Clinical Endocrinology and Metabolism, 96(12), 3741–3749.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

The authors thank Nature Publishing Group Iberoamerica and Javier Mas, MD, PhD, for editing the manuscript and for editorial assistance.

Conflicts of interest

None

Funding source

This project was funded in part by a restricted educational grant from Novartis Spain and by support from the Spanish Neuroendocrine Tumor Group (GETNE).

Author information

Authors and Affiliations

  1. Department of Medical Oncology, Central Asturias University Hospital, C/ Avenida de Roma sn, Oviedo, 33011, Asturias, Spain

    P. Jiménez-Fonseca

  2. Department of Hematology and Medical Oncology, Morales Meseguer University Hospital, Murcia, Spain

    A. Carmona-Bayonas

  3. Department of General Surgery, La Princesa University Hospital, Madrid, Spain

    E. Martín-Pérez

  4. Department of Medical Oncology, Burgos University Hospital, Burgos, Spain

    G. Crespo

  5. Department of Medical Oncology, Reina Sofia University Hospital, Córdoba, Spain

    R. Serrano

  6. Department of Medical Oncology, Canarias University Hospital, Tenerife, Spain

    M. Llanos

  7. Department of Endocrinology, Bellvitge University Hospital, Hospitalet de Llobregat, Barcelona, Spain

    C. Villabona

  8. Department of Medical Oncology, Virgen del Rocio University Hospital, Instituto de Biomedicina de Sevilla (IBIS) [Universidad de Sevilla, CSIC, HUVR], Center affiliated with the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Sevilla, Spain

    R. García-Carbonero

  9. Department of Endocrinology, Puerta de Hierro University Hospital, Madrid, Spain

    J. Aller

  10. Department of Medical Oncology, Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Center affiliated with the Red Temática de Investigación Cooperativa en Cancer (RTICC), Instituto Carlos III, Spanish Ministry of Science and Innovation, Barcelona, Spain

    J. Capdevila

  11. Department of Medical Oncology, Ramon y Cajal University Hospital, Madrid, Spain

    E. Grande

Authors
  1. P. Jiménez-Fonseca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. Carmona-Bayonas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. E. Martín-Pérez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. G. Crespo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R. Serrano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. Llanos
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C. Villabona
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. R. García-Carbonero
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. J. Aller
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J. Capdevila
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. E. Grande
    View author publications

    You can also search for this author in PubMed Google Scholar

Consortia

On behalf of the Spanish Neuroendocrine Tumor Group (GETNE)

Corresponding author

Correspondence to P. Jiménez-Fonseca.

Additional information

Key points

1. Patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs) have good overall health-related quality of life (HRQoL) in both the early and late phases of the disease.

2. The potential benefit on HRQoL of surgery to remove liver metastases and other locoregional liver-targeted interventions has not yet been rigorously demonstrated; thus, further research is warranted.

3. Improved quality of life has been generally reported in patients treated with PRRT but randomized studies are needed to support these data.

4. Three phase III clinical trials have confirmed the efficacy of octreotide LAR, lanreotide PR and sunitinib in patients with GEP-NETs with no treatment-related HRQoL impairment.

5. Prolongation of overall survival and improvement in quality of life has not yet been demonstrated for chemotherapy in patients with GEP-NETs, which is essential to assess the benefit to risk ratio.

6. The randomized phase III RADIANT-3 trial did not include specific HRQoL analyses. However, a subsequent expanded access study has suggested that HRQoL may remain stable throughout everolimus therapy.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiménez-Fonseca, P., Carmona-Bayonas, A., Martín-Pérez, E. et al. Health-related quality of life in well-differentiated metastatic gastroenteropancreatic neuroendocrine tumors. Cancer Metastasis Rev 34, 381–400 (2015). https://doi.org/10.1007/s10555-015-9573-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10555-015-9573-1

Keywords

Search

Navigation