The prognosis and management of neuroendocrine neoplasms-related metastatic bone disease: lessons from clinical practice

• Published in: Endocrine 2019-06, Vol.64 (3), p.690-701
• Main Authors: Alexandraki, Krystallenia I., Pizanias, Michail, Uri, Inbal, Thomas, Dimitrios, Page, Tristan, Kolomodi, Denise, Low, Chen Sheng, Adesanya, Olu, Tsoli, Marina, Gross, David J., Randeva, Harpal, Srirajaskanthan, Rajaventhan, Grozinsky-Glasberg, Simona, Kaltsas, Gregory, Weickert, Martin O.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Aged, 80 and over; Bisphosphonates; Bone diseases; Bone Neoplasms - diagnostic imaging; Bone Neoplasms - secondary; Bone Neoplasms - therapy; Computed tomography; Diabetes; Diphosphonates - therapeutic use; Disease Management; Endocrinology; Female; Humanities and Social Sciences; Humans; Immunotherapy; Internal Medicine; Intestinal Neoplasms - diagnostic imaging; Intestinal Neoplasms - pathology; Intestinal Neoplasms - therapy; Male; Medical prognosis; Medicine; Medicine & Public Health; Metastases; Metastasis; Middle Aged; Monoclonal antibodies; multidisciplinary; Multivariate analysis; Neuroendocrine tumors; Neuroendocrine Tumors - diagnostic imaging; Neuroendocrine Tumors - secondary; Neuroendocrine Tumors - therapy; Original Article; Pancreas; Pancreatic Neoplasms - diagnostic imaging; Pancreatic Neoplasms - pathology; Pancreatic Neoplasms - therapy; Patients; Prognosis; Radiation therapy; Science; Small intestine; Somatostatin; Survival; Thymus; Tomography, X-Ray Computed; Tumors; Young Adult
• ISSN: 1355-008X; 1559-0100
• DOI: 10.1007/s12020-019-01838-8

Purpose To study the evolution and optimal management of metastatic bone disease (mBD) in patients with neuroendocrine neoplasms (NENs). Methods Seventy-four patients were recruited from four NEN centers in this observational multicenter study. Results Pancreas and small bowel were the most common primaries (30 and 27%, respectively). Almost all gastrointestinal (GI)-NENs were grades 1 and 2, whereas bronchopulmonary-thymic were atypical carcinoids. Thirty-two (43%) patients had synchronous metastatic bone disease (mBD) and three patients reported bone-specific symptoms; metachronous mBD developed at a median of 35 (range: 4–395) months. Thirty-six (86%) of patients with metachronous mBD had stage IV disease at diagnosis. Somatostatin receptor functional imaging and computed tomography were the modalities mostly used for mBD identification. Fifty-two patients received assessable bone-related therapy (bisphosphonates, denosumab, local radiotherapy, and radionuclide treatment). Improvement in mBD was seen in 5, stable disease in 22, and deterioration in 25 patients. The presence of synchronous mBD and the negative outcome of bone-related therapy negatively affected overall survival (OS). In the multivariate analysis, the stronger predictor of OS was the outcome of bone-related therapy (HR: 4.753; 95% CI: 1.589–14.213). Bisphosphonates therapy was the mostly used bone-specific treatment but its monthly administration did not affect OS. At last follow-up, 39 patients were alive with OS 50 (14–463) months. Conclusions Early investigation for mBD offers a prognostic marker of patients with NENs, since synchronous mBD has a negative impact on survival. The outcome of bone-related therapy affects OS but the monthly administration of bisphosphonates did not show a benefit over less intense schemes.