title: Bone metastases and skeletal-related events from neuroendocrine tumors.
abstract: Neuroendocrine tumors (NETs) metastasize to bone; however, a multi-institution evaluation of the natural history and complications of bone metastases across multiple NET subtypes has not, to our knowledge, previously been conducted. At two tertiary academic centers, we identified patients with bone metastases from databases of patients with a diagnosis of NET between 2004 and 2008. Detection of bone metastases, occurrence of skeletal-related events (SREs), and interventions were analyzed using summary statistics and categorical methods. Time-to-event data were assessed using Kaplan-Meier estimates and log-rank tests. Between 2004 and 2008, 82 out of 691 NET patients (12%) were reported to have bone metastases. Of the 82 patients with bone metastases, 55% were men and their median age was 49. Bone metastases occurred in 25% of pheochromocytomas and paragangliomas, 20% of high-grade neuroendocrine carcinomas, 9% of carcinoid tumors, and 8% of pancreatic NETs. At time of detection of bone metastases, 60% reported symptoms, including pain; 10% developed cord compression, 9% suffered a pathological fracture, and 4% developed hypercalcemia. Occurrence of SREs did not differ significantly with regard to tumor histology. Of patients with bone metastases, 67 (82%) received at least one form of bone-directed treatment, 50% received radiation, 45% received a bisphosphonate, 18% underwent surgery, 11% received (131)I-MIBG, 5% received denosumab, and 46% were treated with more than one treatment modality. Bone metastases occur in a substantial number of patients diagnosed with NETs. Patients are often symptomatic and many develop SREs. Given the recent therapeutic advances and increasing life expectancy of patients with NETs, development of guidelines for surveillance and clinical care of bone metastases from NETs is needed.
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA katherine.vanloon@ucsf.edu.
authors.forename: Katherine
authors.initials: K
authors.lastname: Van Loon
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Keiser
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Cendy
authors.initials: C
authors.lastname: Carrasco
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Glass
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Maria-Teresa
authors.initials: MT
authors.lastname: Ramirez
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bobiak
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Eric K
authors.initials: EK
authors.lastname: Nakakura
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Alan P
authors.initials: AP
authors.lastname: Venook
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Manisha H
authors.initials: MH
authors.lastname: Shah
authors.affiliation: The UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California, San Francisco, 1600 Divisadero Street, UCSF Box 1770, San Francisco, California 94143, USAThe Ohio State University Comprehensive Cancer CenterColumbus, Ohio 43210, USANational Comprehensive Cancer NetworkFort Washington, Pennsylvania 19034, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Bergsland
keywords: bone metastases; neuroendocrine tumors; skeletal-related events