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 131I-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.

The Impact of 68Ga-DOTATATE PET/CT Imaging on Management of Patients with Neuroendocrine Tumors: Experience from a National Referral Center in the United Kingdom

“…In the present study a significant difference in median survival was observed between patients with bone metastases and those with soft-tissue metastases (59.6 vs. 84.1 mo, P , 0.0001); median survival for those without metastatic disease was 96.7 mo. Our findings are in agreement with a recent study in which median survival for patients with both liver and bone metastases from NETs was 15.4-62.1 mo, compared with 18.2-166.3 mo in patients with liver metastases and no detected bone metastases (P , 0.0001), the variations depending on histologic subtype and grade of differentiation (24).…”

“…In our study, we did not attempt to correlate the SUV, as a semiquantitative marker of SSTR expression, with survival, as it is part of a separate study. Bone metastases were once considered exceedingly rare in patients with NETs but more recent studies have shown that they may be detected in 12% of overall NET populations and approximately 25% in some subgroups (24). In the present study a significant difference in median survival was observed between patients with bone metastases and those with soft-tissue metastases (59.6 vs. 84.1 mo, P , 0.0001); median survival for those without metastatic disease was 96.7 mo.…”

ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, Pancreatic, Bronchial Neuroendocrine Neoplasms (NEN) and NEN of Unknown Primary Site

“…Metastases are predominantly found in the liver and/or lymph nodes. In contrast, bone metastases are reported in <15% of cases [5,6]; however, the true prevalence of bony metastases is probably underestimated, since the reported figures are not based on the most sensitive imaging methods such as bone MRI or 68 Ga-DOTATOC/NOC/TATE PET/CT. Other rare disease sites include the lung, brain and peritoneum, which have also been covered in guidelines [6,7,8,9].…”

Reviewing the Osteotropism in Neuroendocrine Tumors: The Role of Epithelial-Mesenchymal Transition

“…In fact, although in a small postmortem study bone involvement was found in 42% of patients [9], the clinical detection of skeletal metastases is usually reported in <18% of patients with advanced disease [10,11,12,13,14]. Foregut and hindgut tumors are apparently prone to metastasize to the bone as compared with midgut carcinoids [8,15,16], although no preferential primary tumor site has been identified in a recent retrospective study [14].…”

“…Foregut and hindgut tumors are apparently prone to metastasize to the bone as compared with midgut carcinoids [8,15,16], although no preferential primary tumor site has been identified in a recent retrospective study [14]. Skeletal metastases are asymptomatic in 40% of patients [13] and are usually discovered incidentally during tumor staging [11]. However, they result in significant morbidity and severely reduce quality of life due to the emergence of skeletal-related events (SREs), such as pathological fractures, spinal cord compression, need for orthopedic surgery or radiotherapy to bone and/or hypercalcemia [13].…”