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 independently and analysed using STATA v.12.
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%; weighted-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 pooled 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.
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 independently and analysed using STATA v.12.
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%; weighted-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 pooled 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 |
|---|---|
| Journal | Cancer Treatment Reviews |
| Publication status | Accepted/In press - 5 Feb 2021 |