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Horm Metab Res 2023; 55(12): 827-834
DOI: 10.1055/a-2159-5548
Original Article: Endocrine Care

Bone Metastases in Patients with Pancreatic NETs: Prevalence and Prognosis

Annie Mathew
1   Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany
,
Wolfgang P. Fendler
2   Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
,
Jens Theysohn
3   Institute for Diagnostics and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany
,
Ken Herrmann
2   Department of Nuclear Medicine, University Hospital Essen, Essen, Germany
,
Dagmar Führer
1   Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany
,
Harald Lahner
1   Department of Endocrinology, Diabetes and Metabolism and Division of Laboratory Research, University Hospital Essen, Essen, Germany
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Abstract

The clinical relevance of bone metastases (BM) in advanced pancreatic neuroendocrine tumors (PanNETs) is poorly described. We analyzed 314 consecutive PanNET patients treated at the European Neuroendocrine Tumour Society (ENETS) Center Essen between 2009 and 2021 in terms of the occurrence and clinical and prognostic impact of BM using hybrid imaging with 68Ga-DOTATOC PET/CT. According to UICC staging, 171/314 (54.5%) patients had stage IV PanNETs. BM was diagnosed in 62/171 (36.3%) patients. Initially, 35% of BMs were visible by pathological tracer uptake only. Skeletal-related events (SREs) were detected in 11 of the 62 patients (17.7%). Patients with antiresorptive therapy had a significantly lower rate of SRE (2/36, 5.6%) than individuals without bone-specific therapy (9/26, 34.6%) (odds ratio 9.0, p=0.0054, Fisher’s exact test). The median overall survival (OS) was 82 months (53.6–110.4, 95% CI) in the stage IV PanNET cohort. The median OS was significantly lower for patients with BM (63 months; 49.9–76.0, 95% CI) than for patients with distant metastases other than BM (116 months; 87.6–144.3, 95% CI) (p=0.016, log-rank test). BM occurs in more than one-third of advanced PanNETs and is associated with an unfavorable prognosis. One in five patients experiences a persistent quality-of-life-lowering SRE. Antiresorptive therapy is associated with a more favorable risk of SREs and should be offered to all patients with BM in PanNETs.

Key words

pancreas - neuroendocrine tumour - bone metastases


Publication History

Received: 02 June 2023

Accepted after revision: 23 August 2023

Accepted Manuscript online:
23 August 2023

Article published online:
01 December 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
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  • References

  • 1 Dasari A, Shen C, Halperin D. et al. Trends in the incidence, prevalence, and survival outcomes in patients with neuroendocrine tumors in the United States. JAMA Oncol 2017; 3: 1335-1342
    CrossrefPubMedGoogle Scholar
  • 2 Yao JC, Hassan M, Phan A. et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol 2008; 26: 3063-3072
    CrossrefPubMedGoogle Scholar
  • 3 Lloyd RVOR, Klöppel G, Rosai J. WHO classification of tumours of endocrine organs. IARC Press; 2017
    Google Scholar
  • 4 Riihimaki M, Hemminki A, Sundquist K. et al. The epidemiology of metastases in neuroendocrine tumors. Int J Cancer 2016; 139: 2679-2686
    CrossrefPubMedGoogle Scholar
  • 5 Albanus DR, Apitzsch J, Erdem Z. et al. Clinical value of (6)(8)Ga-DOTATATE-PET/CT compared to stand-alone contrast enhanced CT for the detection of extra-hepatic metastases in patients with neuroendocrine tumours (NET). Eur J Radiol 2015; 84: 1866-1872
    CrossrefPubMedGoogle Scholar
  • 6 Sadowski SM, Neychev V, Millo C. et al. Prospective study of 68Ga-DOTATATE positron emission tomography/computed tomography for detecting gastro-entero-pancreatic euroendocrine tumors and unknown primary Sites. J Clin Oncol 2016; 34: 588-596
    CrossrefPubMedGoogle Scholar
  • 7 Zheng Z, Chen C, Jiang L. et al. Incidence and risk factors of gastrointestinal neuroendocrine neoplasm metastasis in liver, lung, bone, and brain: A population-based study. Cancer Med 2019; 8: 7288-7298
    CrossrefPubMedGoogle Scholar
  • 8 Nunez-Valdovinos B, Carmona-Bayonas A, Jimenez-Fonseca P. et al. Neuroendocrine tumor heterogeneity adds uncertainty to the world health organization 2010 classification: real-world data from the Spanish tumor registry (R-GETNE). Oncologist 2018; 23: 422-432
    CrossrefPubMedGoogle Scholar
  • 9 Scharf M, Petry V, Daniel H. et al. Bone metastases in patients with neuroendocrine neoplasm: frequency and clinical, therapeutic, and prognostic relevance. Neuroendocrinology 2018; 106: 30-37
    CrossrefPubMedGoogle Scholar
  • 10 Kavecansky J, Wei L, Caronia L. et al. Bone metastases in well-to-moderately differentiated neuroendocrine tumors: a single institutional review from the Ohio State University Medical Center. Pancreas 2015; 44: 198-203
    CrossrefPubMedGoogle Scholar
  • 11 Van Loon K, Zhang L, Keiser J. et al. Bone metastases and skeletal-related events from neuroendocrine tumors. Endocr Connect 2015; 4: 9-17
    CrossrefPubMedGoogle Scholar
  • 12 Reher D, Fehrenbach U, Kayser A. et al. Localization defines streptozotocin/5-FU response in primary pancreatic neuroendocrine tumours. Neuroendocrinology 2022; 112: 595-605
    CrossrefPubMedGoogle Scholar
  • 13 Lombard-Bohas C, Mitry E, O’Toole D. et al. Thirteen-month registration of patients with gastroenteropancreatic endocrine tumours in France. Neuroendocrinology 2009; 89: 217-222
    CrossrefPubMedGoogle Scholar
  • 14 Garcia-Carbonero R, Capdevila J, Crespo-Herrero G. et al. Incidence, patterns of care and prognostic factors for outcome of gastroenteropancreatic neuroendocrine tumors (GEP-NETs): results from the National Cancer Registry of Spain (RGETNE). Ann Oncol 2010; 21: 1794-1803
    CrossrefPubMedGoogle Scholar