Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis

Esmeralda Garcia-Torralba; Francesca Spada; Kok Haw Jonathan Lim; Timothy Jacobs; Jorge Barriuso; Was Mansoor; Mairéad G McNamara; Richard A Hubner; Prakash Manoharan; Nicola Fazio; Juan Valle; Angela Lamarca

doi:10.1016/j.ctrv.2021.102168

Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis

Esmeralda Garcia-Torralba, Francesca Spada, Kok Haw Jonathan Lim, Timothy Jacobs, Jorge Barriuso, Was Mansoor, Mairéad G McNamara, Richard A Hubner, Prakash Manoharan, Nicola Fazio, Juan Valle, Angela Lamarca^*

^*Corresponding author for this work

Division of Cancer Sciences (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

OBJECTIVE: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.

METHODS: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .

RESULTS: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.

CONCLUSIONS: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.

Original language	English
Article number	102168
Journal	Cancer Treatment Reviews
Volume	94
Early online date	19 Feb 2021
DOIs	https://doi.org/10.1016/j.ctrv.2021.102168
Publication status	Published - 1 Mar 2021

Keywords

Bone Neoplasms/diagnosis
Humans
Neuroendocrine Tumors/diagnosis
Bisphosphonates
Bone metastases
Radiotherapy
Skeletal-related events
Surgery

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.ctrv.2021.102168

2021-02-08-Cancer Treatment Reviews - Bone metsAccepted author manuscript, 806 KBLicence: CC BY

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Garcia-Torralba, E., Spada, F., Lim, K. H. J., Jacobs, T., Barriuso, J., Mansoor, W., McNamara, M. G., Hubner, R. A., Manoharan, P., Fazio, N., Valle, J., & Lamarca, A. (2021). Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis. Cancer Treatment Reviews, 94, Article 102168. https://doi.org/10.1016/j.ctrv.2021.102168

@article{6780b5f04ecb48fa8fd1a01b7c88f509,

title = "Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis",

abstract = "OBJECTIVE: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.METHODS: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .RESULTS: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.CONCLUSIONS: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.",

keywords = "Bone Neoplasms/diagnosis, Humans, Neuroendocrine Tumors/diagnosis, Bisphosphonates, Bone metastases, Radiotherapy, Skeletal-related events, Surgery",

author = "Esmeralda Garcia-Torralba and Francesca Spada and Lim, {Kok Haw Jonathan} and Timothy Jacobs and Jorge Barriuso and Was Mansoor and McNamara, {Mair{\'e}ad G} and Hubner, {Richard A} and Prakash Manoharan and Nicola Fazio and Juan Valle and Angela Lamarca",

year = "2021",

month = mar,

day = "1",

doi = "10.1016/j.ctrv.2021.102168",

language = "English",

volume = "94",

journal = "Cancer Treatment Reviews",

issn = "0305-7372",

publisher = "W.B. Saunders Co. Ltd",

}

TY - JOUR

T1 - Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms

T2 - A systematic review and meta-analysis

AU - Garcia-Torralba, Esmeralda

AU - Spada, Francesca

AU - Lim, Kok Haw Jonathan

AU - Jacobs, Timothy

AU - Barriuso, Jorge

AU - Mansoor, Was

AU - McNamara, Mairéad G

AU - Hubner, Richard A

AU - Manoharan, Prakash

AU - Fazio, Nicola

AU - Valle, Juan

AU - Lamarca, Angela

PY - 2021/3/1

Y1 - 2021/3/1

N2 - OBJECTIVE: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.METHODS: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .RESULTS: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.CONCLUSIONS: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.

AB - OBJECTIVE: This systematic review and meta-analysis aimed to develop an evidence-based summary of current knowledge of bone metastases (BMs) in neuroendocrine neoplasms (NENs), inform diagnosis and treatment and standardise management between institutions.METHODS: PubMed, Medline, EMBASE and meeting proceedings were searched for eligible studies reporting data on patients with BMs and NENs of any grade of differentiation and site; poorly-differentiated large/small cell lung cancer were excluded. Data were extracted and analysed using STATA v.12. Meta-analysis of proportions for calculation of estimated pooled prevalence of BM and calculation of weighted pooled frequency and weighted pooled mean for other variables of interest was performed .RESULTS: A total of 149 studies met the eligibility criteria. Pooled prevalence of BMs was 18.4% (95% CI 15.4-21.5). BMs were mainly metachronous with initial diagnosis of NEN (61.2%) and predominantly osteoblastic; around 61% were multifocal, with a predisposition in axial skeleton. PET/CT seemed to provide (together with MRI) the highest sensitivity and specificity for BM detection. Almost half of patients (46.4%) reported BM-related symptoms: pain (66%) and skeletal-related events (SREs, fracture/spinal cord compression) (26.2%; weightedweighted mean time-to-SRE 9.9 months). Management of BMs was multimodal [bisphosphonates and bone-modifying agents (45.2%), external beam radiotherapy (34.9%), surgery (14.8%)] and supported by little evidence. Overall survival (OS) from the time of diagnosis of BMs was long [weighted mean 50.9 months (95% CI 40.0-61.9)]. Patients with BMs had shorter OS [48.8 months (95% CI 37.9-59.6)] compared to patients without BMs [87.4 months (95% CI 74.9-100.0); p = 0.001]. Poor performance status and BM-related symptoms were also associated with worse OS.CONCLUSIONS: BMs in patients with NENs remain underdiagnosed and undertreated. Recommendations for management of BMs derived from current knowledge are provided. Prospective studies to inform management are required.

KW - Bone Neoplasms/diagnosis

KW - Humans

KW - Neuroendocrine Tumors/diagnosis

KW - Bisphosphonates

KW - Bone metastases

KW - Radiotherapy

KW - Skeletal-related events

KW - Surgery

U2 - 10.1016/j.ctrv.2021.102168

DO - 10.1016/j.ctrv.2021.102168

M3 - Article

C2 - 33730627

SN - 0305-7372

VL - 94

JO - Cancer Treatment Reviews

JF - Cancer Treatment Reviews

M1 - 102168

ER -

Knowns and unknowns of bone metastases in patients with neuroendocrine neoplasms: A systematic review and meta-analysis

Abstract

Keywords

UN SDGs

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