Identification of areas for improvement in the management of bone metastases in patients with neuroendocrine neoplasms

Koi Haw Jonathan Lim, Hussain Raja, Paolo D'Arienzo, Jorge Barriuso, Mairead Mcnamara, Richard Hubner, Wasat Mansoor, Juan Valle, Angela Lamarca

Research output: Contribution to journalArticlepeer-review


Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs).

Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement.

Methods: A retrospective study of all patients with NENs, except Grade 3 (G3) lung NENs (April 2002-March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS v23.0/STATA v12.

Results: Of 1212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-enteropancreatic primary (49%, n=42) followed by lung (25%, n=21), unknown primary (20%, n=17), and “others” (6%, n=5). Two-thirds (n=57) had G1-2 neuroendocrine tumours, and 41% (n=35) had functional tumours. Overall, 28% (n=24) presented with synchronous BMs at first NEN diagnosis, and 55% (n=47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n=38), median time to development of BMs was 14.0 months. BMs were ‘widespread’ in 61% (n=52). Although only 22% (n=19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n=37). Radiotherapy and bisphosphonates were used in 34% (n=29) and 22% (n=19), respectively. Surgery was rarely performed (2%, n=2). Median OS from identification of BMs was 31.0 months, and 18.9 months from development of BMs-related symptoms.

Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients’ quality of life and survival outcomes.
Original languageEnglish
Publication statusAccepted/In press - 21 Oct 2019


  • bone metastases
  • skeletal-related events
  • Hypercalcaemia
  • bisphosphonates
  • palliative radiotherapy


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