St. Agnes Health Care, Baltimore, MD
Paula Bruges , Ian Schonman , Marianna Zahurak , Daniel A. Laheru , Jin He , Fabian McCartney Johnston , Jonathan Greer , Lilja Solnes , Ana De Jesus-Acosta
Background: The clinical implications and management of bone metastases in patients (pts) with gastrointestinal neuroendocrine tumors (GI-NETs) is poorly characterized. In this study we investigated the frequency of bone metastases and skeletal-related events (SRE) in pts with GI-NETs. Methods: Retrospective review of ptswith GI-NETs seen at our institution between 2010-2022. We collected clinicopathologic data including tumor primary site, tumor differentiation, grade using Ki-67 labeling index (G1, G2, or G3), time of diagnosis of metastatic GI-NET, and development of bone metastases (synchronous or metachronous). Diagnosis of metastatic bone disease was assessed by contrast imaging (CT, MRI) and/or functional imaging studies (FDG or DOTATATE PET). SRE were defined as bone pain, spinal cord compression, pathological fracture or tumor-related hypercalcemia. Bone directed therapy was defined as use of bisphosphonates, radiation therapy, and surgical intervention. Results: We identified a total of 865 pts with metastatic GI-NETs. Of these, 122 pts (14%) had evidence of bone metastases. In pts with bone metastases, median age was 60 y/o and 72 pts (59%) were male. Primary tumor sites included pancreas (n=52, 47%), small bowel (n=50, 45%), rectum (n=4, 4%), colon (n=3, 3%), and gallbladder (n=1, 1%). Tumors were G1 (n=31, 28%), G2 (n=51, 47%), G3 (n=27, 25%). The majority of pts had well-differentiated tumors (n=103, 84%). Imaging for initial diagnosis of bone metastasis included PET (n=65, 53%), MRI (n=29, 24%), and CT (n=28, 23%). Synchronous metastases occurred in 34 pts (28%). Metachronous bone metastasis occurred in 88 pts (72%) with a median time to developing bone metastasis of 38 months. SRE occurred in 46 pts (38%), with 36 pts (30%) experiencing bone pain, 5 pts (4%) experiencing pathological fracture, 5 pts (4%) experiencing spinal cord compression, and 2 pts (2%) experiencing hypercalcemia. Thirty-six pts (30%) received bone-directed therapy, including bisphosphonates (n=25, 20%), radiation (n=19, 16%), or surgical intervention (n=4, 3%). Median overall survival (OS) was 83.3 months. Factors associated with increased probability of SRE included younger age, non-white race, low tumor grade, synchronous presentation, and poorly differentiated tumor. Risk factors for decreased OS included male gender, intermediate or high-grade disease, and spinal cord involvement. Bisphosphonate therapy was the most frequently used bone-directed treatment (n=25, 20%). Conclusions: Bone metastases occurred in 14% of pts with GI-NETs and SRE occurred in 38% of these pts. SRE were more likely to occur in pts with synchronous metastatic bone disease, intermediate/high grade tumors or poorly differentiated tumors. Further studies evaluating interventions to decrease SRE and impact in quality of life in pts with GI-NETs are warranted.
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