Characterizing bone metastases and skeletal-related events in patients with well-differentiated neuroendocrine neoplasms utilizing 68Gallium-DOTATATE positron emission tomography

Tumors of neuroendocrine origin are a heterogenous group of related neoplasms which can arise from anywhere in the body. Neuroendocrine neoplasms (NENs) are categorized by site of origin, differentiation status and grade (Ki-67 expression and/or mitotic rate), with significant prognostic variability accordingly. Historically, the prevalence of bone metastasis is reported to be 6%–12% based on “first generation” (i.e., ¹¹¹Indium pentetreotide [Octreoscan®]) somatostatin receptor imaging (SSRI). We conducted a retrospective cohort study including patients with well-differentiated NENs to determine the clinical and imaging characteristics of osseous metastases when evaluated with higher-sensitivity ⁶⁸Gallium-DOTATATE positron emission tomography (PET) scans, as well as determining fracture prevalence in selected sub-cohorts. We also developed a risk score analysis to assess risk of fracture in this cohort. Four hundred twenty-four patients were identified for inclusion. The median age was 61 years. Most patients were asymptomatic (64%), had sclerotic lesions (77%), Krenning 4 (71%), and had >3 sites (69%) of osseous disease. A high proportion of patients had osseous metastases at sites with high risk for fracture, including vertebra (82%), pelvis (63%), and peri-trochanteric femur (34%). Fifty-seven patients (13%) in the entire cohort suffered a fracture. Fracture prevalence was significantly lower in small bowel neuroendocrine tumors (NETs, 7%) and Grades 1 and 2 disease (8% and 9%, respectively), with higher prevalence in pancreatic NETs, paragangliomas/pheochromocytomas, lung carcinoid, and Grade 3 disease (≥20% for each; p-values <.05). Our study showed that the rate of osseous metastatic disease approximates 20% in well-differentiated NENs. Most bone metastases are asymptomatic and the risk of fracture is variable based on the primary site of disease and tumor grade. Our novel risk score analysis for fracture was designed to assist clinician decision making as to management of bone metastasis in this patient population.