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The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice

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Abstract

Purpose

To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs).

Methods

Seventy-four patients were recruited from four NEN centers in this observational multicenter study.

Results

Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months.

Conclusions

Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.

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Authors and Affiliations

  1. Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, 11527, Greece

    Krystallenia I. Alexandraki, Dimitrios Thomas, Denise Kolomodi, Marina Tsoli & Gregory Kaltsas

  2. Institute of Liver Studies, King’s College Hospital, London, SE5 9RS, UK

    Michail Pizanias & Rajaventhan Srirajaskanthan

  3. Neuroendocrine Tumor Unit, Endocrinology and Metabolism Department, Division of Medicine, Hadassah-Hebrew University Medical Center, P.O.B. 12000, 91120, Jerusalem, Israel

    Inbal Uri, David J. Gross & Simona Grozinsky-Glasberg

  4. The ARDEN NET Centre, University Hospitals Coventry & Warwickshire NHS Trust, Coventry, UK

    Tristan Page, Chen Sheng Low, Olu Adesanya, Harpal Randeva, Gregory Kaltsas & Martin O. Weickert

  5. Coventry University, Centre for Applied Biological & Exercise Science, Coventry, UK

    Harpal Randeva & Martin O. Weickert

  6. Clinical Sciences Research Laboratories, Division of Translational Medicine, Warwick Medical School, University Hospital, University of Warwick, CV4 7AL, Coventry, UK

    Harpal Randeva & Martin O. Weickert

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  1. Krystallenia I. Alexandraki
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Correspondence to Krystallenia I. Alexandraki.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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These authors should be considered as senior authors: Gregory Kaltsas, Martin O. Weickert

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Alexandraki, K.I., Pizanias, M., Uri, I. et al. The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice. Endocrine 64, 690–701 (2019). https://doi.org/10.1007/s12020-019-01838-8

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  • DOI: https://doi.org/10.1007/s12020-019-01838-8

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