Krystallenia I Alexandraki1, Michail Pizanias2, Inbal Uri3, Dimitrios Thomas4, Tristan Page5, Denise Kolomodi4, Chen Sheng Low5, Olu Adesanya5, Marina Tsoli4, David J Gross3, Harpal Randeva5,6,7, Rajaventhan Srirajaskanthan2, Simona Grozinsky-Glasberg3, Gregory Kaltsas4,5, Martin O Weickert5,6,7. 1. Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, 11527, Greece. alexandrakik@gmail.com. 2. Institute of Liver Studies, King's College Hospital, London, SE5 9RS, UK. 3. Neuroendocrine Tumor Unit, Endocrinology and Metabolism Department, Division of Medicine, Hadassah-Hebrew University Medical Center, P.O.B. 12000, 91120, Jerusalem, Israel. 4. Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Mikras Asias 75, Athens, 11527, Greece. 5. The ARDEN NET Centre, University Hospitals Coventry & Warwickshire NHS Trust, Coventry, UK. 6. Coventry University, Centre for Applied Biological & Exercise Science, Coventry, UK. 7. Clinical Sciences Research Laboratories, Division of Translational Medicine, Warwick Medical School, University Hospital, University of Warwick, CV4 7AL, Coventry, UK.
Abstract
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.
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.
Entities:
Keywords:
Bisphosphonates; Denosumab; Metastatic bone disease; Neuroendocrine neoplasms
Authors: Aurel Perren; Anne Couvelard; Jean-Yves Scoazec; Frederico Costa; Ivan Borbath; Gianfranco Delle Fave; Vera Gorbounova; David Gross; Ashley Grossma; Robert T Jense; Matthew Kulke; Kjell Oeberg; Guido Rindi; Halfdan Sorbye; Staffan Welin Journal: Neuroendocrinology Date: 2017-02-11 Impact factor: 4.914
Authors: David H A Nguyen; Pauline T Truong; Caroline V Walter; Emily Hayashi; Jennifer L Christie; Cheryl Alexander Journal: Ann Surg Oncol Date: 2012-04-03 Impact factor: 5.344
Authors: R Lebtahi; G Cadiot; N Delahaye; R Genin; D Daou; M C Peker; D Chosidow; M Faraggi; M Mignon; D Le Guludec Journal: J Nucl Med Date: 1999-10 Impact factor: 10.057
Authors: F Gibril; J L Doppman; J C Reynolds; C C Chen; V E Sutliff; F Yu; J Serrano; D J Venzon; R T Jensen Journal: J Clin Oncol Date: 1998-03 Impact factor: 44.544
Authors: Juraj Kavecansky; Lai Wei; Lisa Caronia; Maria-Teresa Ramirez; Mark Bloomston; Manisha H Shah Journal: Pancreas Date: 2015-03 Impact factor: 3.327