Use of antiresorptive therapy (ART) and skeletal-related events (SREs) in patients with bone metastases of neuroendocrine neoplasms (NEN).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 4096-4096
Author(s):  
Leonidas Apostolidis ◽  
Dirk Jaeger ◽  
Eva Caroline Winkler
Keyword(s):  
Bone Metastases ◽  
Rare Event ◽  
Neuroendocrine Neoplasms ◽  
Antiresorptive Therapy ◽  
Negative Prognostic Factor ◽  
Significant Toxicity ◽  
Osteolytic Metastases ◽  
Skeletal Related Events ◽  
Grade 3

4096 Background: Antiresorptive therapy (ART) with bisphosphonates or denosumab is effective in preventing skeletal-related events (SREs) in patients with bone metastases (BM). In neuroendocrine neoplasms (NEN), BM are a negative prognostic factor, however tend to be asymptomatic and SREs are considered a rare event. The role of ART in preventing SREs in NEN has not been investigated so far. Methods: Retrospective analysis of all patients with bone metastases in the NEN database of the National Center for Tumor Diseases who presented at our center between 12/2012 and 01/2017. Overall survival (OS) from diagnosis of BM as well as time to SRE (TTSRE) were calculated. In patients experiencing an SRE within 1 month after diagnosis (i.e. before efficacy of ART could be assessed), TTSRE was defined as the time to a subsequent SRE. Results: In a total of 513 patients in the database, 108 patients with BM could be identified. Median OS was not reached in a median follow-up of 15.2 months. ART was applied to 42.6 % of patients. OS with or without ART did not differ significantly (p = 0.2538). 28.7 % of patients experienced at least 1 SRE, 20.4 % after more than 1 month. Median TTSRE was 63.8 months with ART and 127.0 months without ART (p = 0.1751). TTSRE was shortened in grade 3 vs. grade 1+2 NEN (172 months vs. not reached, HR 4.058, p = 0.0032), as well as in lytic vs. non-lytic metastases (24.5 vs. not reached, HR 7.319, p < 0.0001), however not significantly different in oligometastatic vs. disseminated bone disease (not reached vs. 63,8 months, HR 1.415, p = 0.4287). Application of ART did not significantly change TTSRE in either of these subgroups. Significant toxicity attributable to ART was observed in 15.2 % of ART patients. Conclusions: SREs in NEN patients with BM were not uncommon, especially in patients with grade 3 NEN and osteolytic metastases. Application of ART did not significantly alter median OS or TTSRE, no subgroup with a benefit of ART could be identified. The use of ART in NEN should be questioned and evaluated prospectively.

scholarly journals Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

2019 ◽  
Vol 110 (7-8) ◽  
pp. 688-696
Author(s):  
Kok Haw Jonathan Lim ◽  
Hussain Raja ◽  
Paolo D’Arienzo ◽  
Jorge Barriuso ◽  
Mairéad G. McNamara ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Distant Metastases ◽  
Unknown Primary ◽  
Neuroendocrine Neoplasms ◽  
Global Consensus ◽  
Skeletal Related Events ◽  
Grade 3 ◽  
Review Current

Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs). Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement. Methods: A retrospective study of all patients with NENs, except Grade 3 lung NENs (April 2002 to March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 23.0/STATA v12. Results: Of 1,212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-entero-pancreatic primary (49%, n = 42) followed by lung (25%, n = 21), unknown primary (20%, n = 17), and “others” (6%, n = 5). Two-thirds (n = 57) had G1–2 neuroendocrine tumours, and 41% (n = 35) had functional tumours. Overall, 28% (n = 24) presented with synchronous BMs at first NEN diagnosis, and 55% (n = 47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n = 38), median time to development of BMs was 14.0 months. BMs were “widespread” in 61% (n = 52). Although only 22% (n = 19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n = 37). Radiotherapy and bisphosphonates were used in 34% (n = 29) and 22% (n = 19) respectively. Surgery was rarely performed (2%, n = 2). Median OS from identification of BMs was 31.0, and 18.9 months from development of BMs-related symptoms. Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients’ quality of life and survival outcomes.

Bone Metastases in Medullary Thyroid Carcinoma: High Morbidity and Poor Prognosis Associated With Osteolytic Morphology

2020 ◽  
Vol 105 (6) ◽  
pp. e2239-e2246 ◽  
Author(s):  
Theresa Vogel ◽  
Julia Wendler ◽  
Karin Frank-Raue ◽  
Michael C Kreissl ◽  
Christine Spitzweg ◽  
...  
Keyword(s):  
Thyroid Carcinoma ◽  
Bone Metastases ◽  
Medullary Thyroid Carcinoma ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
High Morbidity ◽  
Medullary Thyroid ◽  
Kaplan Meier ◽  
Osteolytic Metastases ◽  
Skeletal Related Events

Abstract Context The clinical relevance of bone metastases (BM) in advanced medullary thyroid carcinoma (MTC) is poorly described. Objective The objectives of this work are to describe the prevalence of BM, frequency of skeletal related events (SREs), and impact of BM morphology and SREs on prognosis, and to assess the role of antiresorptive treatment (ART). Design A retrospective cohort study was conducted. Setting This study was conducted at 4 German referral centers. Patients A total of 1060 MTC patients were included. Main Outcome Measure Main outcome measures include descriptive statistics, overall survival (OS) by the Kaplan-Meier method, and risk factors by Cox proportional hazards modeling. Results A total of 120 of 416 patients (29%) with metastatic MTC had BM, of which 97% had concurrent nonosseous metastases. BM occurred 2.1 years (median, range –0.1 to 20.6 years) after initial diagnosis, were multifocal in 79%, and were located preferentially in the spine (86%) and pelvis (60%). BM morphology was osteolytic in 32%, osteoblastic in 25%, and mixed in 22% of cases (unknown: 21%). Within a median observation period of 26.6 months (range, 0-188 months) after BM diagnosis, 47% of patients experienced one or more SREs (bone radiation 50%, pathological fractures 32%), of which 42% occurred in osteolytic and 17% in osteoblastic BM (P = .047). Presence of osteolytic metastases (hazard ratio 3.85, 95% CI 1.52-9.77, P = .005) but not occurrence of SREs was associated with impaired OS. Among the 36 patients who received ART (no ART: n = 71), SREs were significantly less frequent than in untreated patients (P = .04). Conclusion BM are common in metastatic MTC and most often with an osteolytic morphology and an unfavorable prognosis. The majority of SREs occur in osteolytic metastases and may be prevented by ART.

scholarly journals Morbidity and mortality of bone metastases in advanced adrenocortical carcinoma: a multicenter retrospective study

2019 ◽  
Vol 180 (5) ◽  
pp. 311-320 ◽  
Author(s):  
Alfredo Berruti ◽  
Rossella Libè ◽  
Marta Laganà ◽  
Hester Ettaieb ◽  
Mohamad Anas Sukkari ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Bone Metastases ◽  
Adrenocortical Carcinoma ◽  
Bone Fractures ◽  
The United States ◽  
Cord Compression ◽  
Risk Of Death ◽  
Skeletal Related Events ◽  
Improve Patient

Introduction Adrenocortical carcinoma (ACC) is a rare cancer that commonly spreads to the liver, lungs and lymph nodes. Bone metastases are infrequent. Objective The aim of this report was to describe the clinical characteristics, survival perspective, prognostic factors and frequency of adverse skeletal-related events (SREs) in patients with ACC who developed bone metastasis. Methods This is a retrospective, observational, multicenter, multinational study of patients diagnosed with bone metastases from ACC who were treated and followed up in three European countries (France, Italy and The Netherlands) and one center in the United States. Results Data of 156 patients were captured. The median overall survival was 11 months. SREs occurred in 47% of patients: 17% bone fractures, 17% spinal cord compression, 1% hypercalcemia, 12% developed more than one SRE. In multivariate analysis, cortisol hypersecretion was the only prognostic factor significantly associated with a higher mortality risk (hazard ratio (HR) 2.24, 95% confidence interval (CI): 1.19–4.23, P = 0.013) and with the development of a SREs (of border line significance). The administration of antiresorptive therapies (bisphosphonates and denosumab) was associated with a lower risk of death, even if not significant, and their survival benefit appeared confined in patients attaining serum mitotane levels within the therapeutic range. Conclusion Bone metastases in ACC patients are associated with poor prognosis and high risk of SREs. Cortisol hypersecretion was the only prognostic factor suggesting a potential benefit from antisecretory medications. The therapeutic role of bisphosphonates and denosumab to improve patient outcome deserves to be tested in a prospective clinical trial.

Clinical Usefulness of Bisphosphonates in Oncology: Treatment of Bone Metastases, antitumoral Activity and Effect on Bone Resorption Markers

2007 ◽  
Vol 22 (1) ◽  
pp. 24-33 ◽  
Author(s):  
A. Verì ◽  
M.R. D'Andrea ◽  
P. Bonginelli ◽  
G. Gasparini
Keyword(s):  
Bone Metastases ◽  
Advanced Disease ◽  
Cord Compression ◽  
Antitumoral Activity ◽  
Pathological Fractures ◽  
Antiangiogenic Activity ◽  
Treatment And Prevention ◽  
Oncology Treatment ◽  
Skeletal Related Events

The present article overviews the role of bisphosphonates for the treatment and prevention of bone metastases and their antiangiogenic effects and antitumoral activity. The skeleton is a frequent and clinically relevant site of metastasis in cancer patients. The major events related to bone metastases include bone pain, bone loss, hypercalcemia, spinal cord compression, and fractures. On the basis of their radiographic features, bone metastases are classified as osteoblastic, osteoclastic, or mixed. The primary goals of treatment of bone metastases are reduction of the risk of pathological fractures and other skeletal-related events, and pain control. Bisphosphonates are used to prevent pathological fractures by inhibition of osteoclasts. Recent studies suggest that bisphosphonates have some direct antitumoral activity, mainly mediated through the blockade of angiogenic pathways. Further clinical studies are needed to determine the optimal treatment duration, timing and schedule of bisphosphonates, assess their role as adjuvant therapy for the prevention of bone metastases, and establish their antiangiogenic activity in association with standard cytotoxic and hormonal drugs for treatment of patients with advanced disease.

scholarly journals Evaluating the Role of Theranostics in Grade 3 Neuroendocrine Neoplasms

2019 ◽  
Vol 60 (7) ◽  
pp. 882-891 ◽  
Author(s):  
Najeff Waseem ◽  
Carina Mari Aparici ◽  
Pamela L. Kunz
Keyword(s):  
Neuroendocrine Neoplasms ◽  
Grade 3

scholarly journals Denosumab: A comprehensive review

2013 ◽  
Vol 02 (04) ◽  
pp. 272-277 ◽  
Author(s):  
Prasad Narayanan
Keyword(s):  
Bone Resorption ◽  
Bone Metastases ◽  
Human Monoclonal Antibody ◽  
Bone Destruction ◽  
Clinical Trial Data ◽  
Osteoclast Formation ◽  
Future Challenges ◽  
Formation Function ◽  
Skeletal Related Events

AbstractThe clinical sequelae from bone metastases, termed skeletal-related events (SREs), are among the most frequent and debilitating complications in patients with advanced cancer. Bone metastases are characterized by pathologically increased osteoclast activity, and accumulating evidence indicates that tumor cells interact within the bone to stimulate the receptor activator of nuclear factor kB (RANK)-RANK ligand (RANKL) pathway. RANKL is an essential mediator of osteoclast formation, function, and survival. Because of the central role of RANKL in cancer-induced bone destruction, the inhibition of RANKL has the potential to result in the reduction of pathologic bone resorption. Denosumab is a fully human monoclonal antibody specific for RANKL that inhibits the formation, activation, and survival of osteoclasts. This in turn decreases bone resorption and reduces cancer-induced bone destruction. In this review, we give an overview of the drug Denosumab with its history, mechanism of action, clinical trial data, adverse effects, and future challenges.

scholarly journals The prognostic role of morphology and Ki67 in grade 3 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NEN)

2018 ◽  
Vol 29 ◽  
pp. viii472-viii473
Author(s):  
A.R. Hayes ◽  
M. Furnace ◽  
C. Rundell ◽  
R. Shah ◽  
G. Muller ◽  
...  
Keyword(s):  
Neuroendocrine Neoplasms ◽  
Prognostic Role ◽  
Grade 3

scholarly journals Challenges in High-grade Neuroendocrine Neoplasms and Mixed Neuroendocrine/Non-neuroendocrine Neoplasms

2021 ◽  
Author(s):  
Stefano La Rosa
Keyword(s):  
Diagnostic Criteria ◽  
Digestive System ◽  
Labelling Index ◽  
Differential Diagnoses ◽  
Neuroendocrine Neoplasms ◽  
High Grade ◽  
Immunohistochemical Profile ◽  
Grade 3

AbstractThe growth in knowledge of the pathogenesis, molecular background, and immunohistochemical profile of neuroendocrine neoplasms (NENs) has led not only to an increased awareness of these diseases but also to several changes of the nomenclature. In particular, the concept and terminology of high-grade (grade 3) NENs and mixed neoplasms have changed considerably over the last 20 years, creating some confusion among pathologists and clinicians. The aim of this review is to elucidate the diagnostic criteria, including the most important differential diagnoses of high-grade NENs and mixed neuroendocrine/non-neuroendocrine neoplasms (MiNENs). The role of the Ki67 labelling index and morphology, used to define grade 3 NENs of the digestive system and lungs, is also discussed. The evolution of the concepts and terminology of MiNENs is revised, including the most important differential diagnoses.

The Role of Ki-67 Index Cut-off of 55% and Differentiation in Redefining NET and NEC for Grade 3 Gastrointestinal Neuroendocrine Neoplasms

2020 ◽  
Vol 24 (10) ◽  
pp. 2302-2305
Author(s):  
Huiying Shi ◽  
Luohai Chen ◽  
Lingjun Meng ◽  
Qin Zhang ◽  
Yuan Lin ◽  
...  
Keyword(s):  
Neuroendocrine Neoplasms ◽  
Ki 67 ◽  
Grade 3

scholarly journals An institutional evaluation of radiotherapy with concurrent and adjuvant temozolomide exclusively in grade III gliomas

2021 ◽  
Author(s):  
Naga Chandra Sekhar Darisi ◽  
V. L. Anusha Konakalla ◽  
Venkata Pradeep Babu Koyyala
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Progression Free Survival ◽  
Complete Response ◽  
Who Grade ◽  
Medical College ◽  
Significant Toxicity ◽  
Grade 3 ◽  
Grade Iii

Background: Gliomas are the most common tumors that develop from glial cells in the brain. As per WHO classification, grade III (high-grade) gliomas are usually treated by surgery followed by radiotherapy. Concurrent and adjuvant chemotherapy with temozolomide (TMZ) is showing new hope in the management.Methods: Prospective study was conducted in 20 WHO grade III glioma patients at GSL medical college and general hospital for a period of 2 years (August 2019 to July 2021) to evaluate the role of concurrent and adjuvant TMZ with radiation in the treatment of grade III gliomas. The primary objectives of the study were to determine toxicity and response rates in our set of patients. The secondary objectives were to determine progression-free survival and overall survival.Results: Majority were males (80%) in the age group of 30 to 49 (75%). 40% of gliomas were in the temporal lobe. Headache was the most presenting symptom (60%) followed by seizures (35%).70 to 80 Karnofsky performance status/ KPS score was seen in 70% of cases. None of the patients in the study had grade 3 or 4 toxicities. 40% had a complete response according to MacDonald’s criteria. At a median follow-up of 10 months, 25% of patients had disease progression and 1yr overall survival was 95%.Conclusions: TMZ combined with radiation was well tolerated in our set of patients with grade III gliomas without any significant toxicity.

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