Impact on symptoms and survival of bone metastases in patients with small‐intestinal neuroendocrine tumours

We aimed to assess the symptoms and impact on overall survival (OS) from bone metastases (BM) diagnosed on Gallium-68-labelled DOTA tyrosine octreotide positron emission tomography with computed tomography (⁶⁸Ga-DOTATOC-PET/CT) in patients with well-differentiated small intestinal neuroendocrine tumours (Si-NETs). Patients with well-differentiated Si-NETs, who underwent ⁶⁸Ga-DOTATOC-PET/CT between 2010 and 2023 at two tertiary referral centres in Sweden, were included. Their number of BM, ≤5 BM versus >5 BM, symptoms and need for analgesics were recorded. To further assess the impact of BM on OS, we used a control group of age- and sex-matched Si-NET patients with liver metastases (Stage IV disease) but without BM. The prevalence of BM in Si-NET patients was 23% (175/753); among these, complete clinical data were available in 138 patients. Synchronous BM were found in 33% (46/138). Sixty-one patients (44%) showed >5 BM at the time of BM detection. Fractures were diagnosed in 4% (n = 6) and 14% (n = 20) needed analgesics for BM-associated pain. In univariable analysis, patients with >5 BM experienced shorter OS from the time of BM detection compared to those with ≤5 BM (18 months vs. 75 months, p < .001). Among patients with Stage IV disease with and without BM, OS was shorter in patients with BM compared to patients with no BM (72 months vs. 288 months, p = .002). In multivariable analysis of patients with BM, higher Ki-67% (hazard ratio [HR] = 1.06, p = .007), older age (HR = 1.07, p < .01), presence of >5 BM (HR = 1.93, p = .021) and synchronous BM (HR = 2.14, p = .016) were identified as independent prognostic factors for shorter OS. In the matched cohort of patients with Stage IV disease with and without BM, presence of BM (HR = 1.94, p = .009), age at diagnosis of Stage IV (HR = 1.08, p < .001) and locoregional surgical resection (HR = 0.47, p = .015) were independent prognostic factors for survival. BM are detected in approximately 25% of Si-NET patients subjected to ⁶⁸Ga-DOTATOC-PET/CT. Pain occurs in approximately 14% and fractures in 4%. The presence of BM among Stage IV patients, the extent of bone disease (>5 BM) and synchronous BM are independent prognostic factors for shorter OS.