scholarly journals Bone metastases and skeletal-related events from neuroendocrine tumors

2015 ◽  
Vol 4 (1) ◽  
pp. 9-17 ◽  
Author(s):  
Katherine Van Loon ◽  
Li Zhang ◽  
Jennifer Keiser ◽  
Cendy Carrasco ◽  
Katherine Glass ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Neuroendocrine Tumors ◽  
Clinical Care ◽  
Cord Compression ◽  
Time To Event ◽  
Time To Event Data ◽  
Kaplan Meier ◽  
Number Of Patients ◽  
Skeletal Related Events ◽  
Neuroendocrine Carcinomas

Neuroendocrine tumors (NETs) metastasize to bone; however, a multi-institution evaluation of the natural history and complications of bone metastases across multiple NET subtypes has not, to our knowledge, previously been conducted. At two tertiary academic centers, we identified patients with bone metastases from databases of patients with a diagnosis of NET between 2004 and 2008. Detection of bone metastases, occurrence of skeletal-related events (SREs), and interventions were analyzed using summary statistics and categorical methods. Time-to-event data were assessed using Kaplan–Meier estimates and log-rank tests. Between 2004 and 2008, 82 out of 691 NET patients (12%) were reported to have bone metastases. Of the 82 patients with bone metastases, 55% were men and their median age was 49. Bone metastases occurred in 25% of pheochromocytomas and paragangliomas, 20% of high-grade neuroendocrine carcinomas, 9% of carcinoid tumors, and 8% of pancreatic NETs. At time of detection of bone metastases, 60% reported symptoms, including pain; 10% developed cord compression, 9% suffered a pathological fracture, and 4% developed hypercalcemia. Occurrence of SREs did not differ significantly with regard to tumor histology. Of patients with bone metastases, 67 (82%) received at least one form of bone-directed treatment, 50% received radiation, 45% received a bisphosphonate, 18% underwent surgery, 11% received 131I-MIBG, 5% received denosumab, and 46% were treated with more than one treatment modality. Bone metastases occur in a substantial number of patients diagnosed with NETs. Patients are often symptomatic and many develop SREs. Given the recent therapeutic advances and increasing life expectancy of patients with NETs, development of guidelines for surveillance and clinical care of bone metastases from NETs is needed.

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 Practical update for the use of bone-targeted agents in patients with bone metastases from metastatic breast cancer or castration-resistant prostate cancer

2020 ◽  
Vol 27 (4) ◽  
Author(s):  
D. Southcott ◽  
A. Awan ◽  
K. Ghate ◽  
M. Clemons ◽  
R. Fernandes
Keyword(s):  
Prostate Cancer ◽  
Bone Metastases ◽  
Metastatic Breast ◽  
Pathologic Fracture ◽  
Dose Schedule ◽  
Cord Compression ◽  
Targeted Agents ◽  
Castration Resistant Prostate Cancer ◽  
Skeletal Related Events ◽  
Breast And Prostate Cancer

Bone metastases are a significant source of morbidity and mortality for patients with breast and prostate cancer. In this review, we discuss key practical themes regarding the use of bone-targeted agents (btas) such as bisphospho­nates and denosumab for managing bony metastatic disease. The btas both delay the onset and reduce the incidence of skeletal-related events (sres), defined as any or all of a need for radiation therapy or surgery to bone, pathologic fracture, spinal cord compression, or hypercalcemia of malignancy. They have more modest benefits for pain and other quality-of-life measures. Regardless of the benefits of btas, it should always be remembered that the palliative management of meta­static bone disease is multimodal and multidisciplinary. The collaboration of all disciplines is essential for optimal patient care. Special consideration is given to these key questions: What are btas, and what is their efficacy? What are their common toxicities? When should they be initiated? How do we choose the appropriate bta? What is the appropriate dose, schedule, and duration of btas?

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.

scholarly journals Dealing with Bone Metastases from Breast Cancer - A Pathological and Clinical Overview

2018 ◽  
Vol 1 (Supplement) ◽  
pp. 25
Author(s):  
O. Munteanu ◽  
A. Dumitru ◽  
O. Bodean ◽  
L. Arsene ◽  
D. Voicu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Bone Metastases ◽  
Malignant Tumors ◽  
Cord Compression ◽  
Pathological Fractures ◽  
Future Directions ◽  
Skeletal Related Events ◽  
Frequent Site ◽  
Clinical Overview

Abstract From breast malignant tumors, bone is the most frequent site of metastasis. Bone metastases from breast cancer are correlated with pathological fractures, spinal cord compression and other skeletal-related events as well as bone pain and hypercalcemia. These lead to impaired mobility, decreased quality of life, and overall decrease in survival. Clarification of mechanisms regulating bone metastasis has advanced greatly in the last years and this has translated into plentiful unused therapeutic options. Greater understanding of the pathophysiology of bone metastases has led to the detection and clinical efficiency of bone-targeted agents. This review summarizes the key evidence for current clinical practice and future directions.

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 Proposals on Kaplan–Meier plots in medical research and a survey of stakeholder views: KMunicate

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030215 ◽  
Author(s):  
Tim P Morris ◽  
Christopher I Jarvis ◽  
William Cragg ◽  
Patrick P J Phillips ◽  
Babak Choodari-Oskooei ◽  
...  
Keyword(s):  
Outcome Measures ◽  
Event Data ◽  
Time To Event ◽  
Web Based ◽  
Time To Event Data ◽  
Kaplan Meier ◽  
Starting Point ◽  
Wide Range ◽  
International Participation ◽  
Over Time

ObjectivesTo examine reactions to the proposed improvements to standard Kaplan–Meier plots, the standard way to present time-to-event data, and to understand which (if any) facilitated better depiction of (1) the state of patients over time, and (2) uncertainty over time in the estimates of survival.DesignA survey of stakeholders’ opinions on the proposals.SettingA web-based survey, open to international participation, for those with an interest in visualisation of time-to-event data.Participants1174 people participated in the survey over a 6-week period. Participation was global (although primarily Europe and North America) and represented a wide range of researchers (primarily statisticians and clinicians).Main outcome measuresTwo outcome measures were of principal importance: (1) participants’ opinions of each proposal compared with a ‘standard’ Kaplan–Meier plot; and (2) participants’ overall ranking of the proposals (including the standard).ResultsMost proposals were more popular than the standard Kaplan–Meier plot. The most popular proposals in the two categories, respectively, were an extended table beneath the plot depicting the numbers at risk, censored and having experienced an event at periodic timepoints, and CIs around each Kaplan–Meier curve.ConclusionsThis study produced a high response number, reflecting the importance of graphics for time-to-event data. Those producing and publishing Kaplan–Meier plots—both authors and journals—should, as a starting point, consider using the combination of the two favoured proposals.

Burden of hospitalizations associated with skeletal related events in patients with breast cancer or lung cancer and bone metastases or multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 17083-17083 ◽  
Author(s):  
M. Lage ◽  
D. J. Harrison ◽  
B. Barber ◽  
S. Jun
Keyword(s):  
Breast Cancer ◽  
Lung Cancer ◽  
Multiple Myeloma ◽  
Bone Metastases ◽  
Index Date ◽  
Opioid Analgesic ◽  
Cord Compression ◽  
Continuous Coverage ◽  
Diagnosis Of Cancer ◽  
Skeletal Related Events

17083 Background: Patients with bone metastases secondary to cancer often experience skeletal related events (SREs) including pathological fracture, spinal cord compression, hypercalcemia, bone surgery or radiotherapy, or initiation of opioid analgesic use. These SREs result in major morbidity and reduced quality of life. This research examines hospitalizations associated with SREs. Methods: Data for this study were obtained from i3 LabRx Database (05/01/2000 to 03/31/2005). Individuals were included in the analyses if they had at least two diagnoses of breast cancer (based upon an ICD-9 code of 174.xx), lung cancer (162.xx), or multiple myeloma (203.0x) and had at least two diagnoses of bone metastases (198.5x) after the first diagnosis of cancer. In addition, individuals were required to have at least one SRE (based upon a previously published algorithm) on or after their initial diagnosis of bone metastases (their index date). Individuals were required to be continuously insured for at least 6 months prior to, and at least one month post their index date. Data were analyzed until 03/31/2005 or until the end of their continuous coverage, whichever occurred first. Descriptive statistics for each of these cohorts are provided. Results: A total of 1,204 individuals with breast cancer, 1,094 with lung cancer, and 258 with multiple myeloma were included in the study. The vast majority of individuals with breast cancer (96.5%), lung cancer (95.9%), or multiple myeloma (96.8%) were hospitalized. All three patient groups were likely to have SRE-related hospitalizations; multiple myeloma 43.4%, breast cancer 36.2% and lung cancer 35.6%. The average number of days per patient year that patients were hospitalized related to a diagnosis or procedure for a SRE was 6.75 days for patients with lung cancer, 6.56 days for patients with multiple myeloma, and 3.75 days for patients with breast cancer. Conclusion: Hospitalizations related to SREs are common and the number of days per year is substantial. No significant financial relationships to disclose.

Skeletal related events in patients with metastatic renal cell carcinoma: A retrospective review

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16118-e16118
Author(s):  
M. Secter ◽  
M. J. MacKenzie ◽  
P. O'Brien ◽  
F. Whiston
Keyword(s):  
Renal Cell Carcinoma ◽  
Bone Metastases ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Retrospective Review ◽  
Renal Cell ◽  
Length Of Hospital Stay ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Skeletal Related Events

e16118 Background: Approximately one third of patients with renal cell carcinoma (RCC) will develop bone metastases during the course of their disease. Previous studies suggest that the rate of skeletal related events (SREs) in patients with metastatic renal cell carcinoma is high, and that bisphosphonate therapy can lower the rate of SREs. We conducted a retrospective review of patients with metastatic renal cell carcinoma and bone metastases seen at our academic cancer centre. Methods: After approval by the Research Ethics Board, a retrospective review of all patients seen at the London Regional Cancer Centre with a diagnosis of RCC between January 2006 and December 2008 was performed. Data points collected included the number of patients with bone metastases, number of SREs, length of hospital stay, and treatments related to SREs. A SRE was defined as one of the following: pathologic fracture, spinal cord compression, radiotherapy or surgery to bone, or hypercalcemia in the presence of bone metastases. Results: 196 patients with metastatic RCC were identified. Of these, 63 (32%) had bone metastases. 75% of these patients with bone metastases received medical therapies including sunitinib, sorafenib or temsirolimus. 66% of patients received at least one dose of bisphosponate therapy. Common sites of metastases were vertebra (66%), pelvis (50%), and femur (42%). Of those with bone metastases, 61 (95%) experienced at least one SRE. 42% sustained a pathologic fracture; 28% suffered a spinal cord compression or cauda equina syndrome; 22% had surgery for bone metastases; 87.5% required radiotherapy and 27% had hypercalcemia. 40% of patients were hospitalized due to an SRE, and the mean length of hospital stay was 21 days (range 1–120 days). Conclusions: Despite significant recent improvements in the overall care of RCC, and expansion of the number of therapeutic options, bone metastases and consequent SREs continue to cause significant morbidity. These SREs come with frequent and prolonged hospitalizations. Our rate of SREs is actually higher than that documented in the placebo arm of a randomized trial of a bisphosphonate in RCC from the pre-tyrosine kinase era. Bone-related morbidity in mRCC remains a clinical problem with a significant unmet medical need. [Table: see text]

Incidence and natural history of bone metastases in neuroendocrine tumors.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 340-340 ◽  
Author(s):  
Jennifer Keiser ◽  
Eric K. Nakakura ◽  
Laurel Imhoff ◽  
Margaret A. Mayorga ◽  
Sarah Bobiak ◽  
...  
Keyword(s):  
Natural History ◽  
Bone Metastases ◽  
Neuroendocrine Tumors ◽  
Stage Iv ◽  
Pathologic Fracture ◽  
Cord Compression ◽  
Unknown Primary ◽  
Eligibility Criteria ◽  
History Of ◽  
Using Data

340 Background: Bone metastases (BM) occur in carcinoids and other neuroendocrine tumors (NET), however, a comparative analysis of the incidence and natural history of BM across different NET subtypes has not been performed. We retrospectively characterized BM incidence, complications, and management across five subtypes: carcinoid/unknown primary (CARC), pancreatic NET (PNET), pheochromocytomas/paragangliomas (PHEO), adrenal cortical carcinoma (ACC) and high grade NET (HGNET) using data collected in the context of the NCCN NET Outcomes Database. Methods: 296 NET patients (pts) presenting at UCSF from 2004 to 2007 were retrospectively identified. Eligibility criteria included presentation on or after Jan 1, 2004, continued management at UCSF within one year of consultation, age over 18, and pathological confirmation of an eligible NET subtype. BM identified radiographically and/or pathologically, and classified as symptomatic (pain, pathologic fracture, or spinal cord compression) or asymptomatic. BM treatments (tx) included radiation, surgery, bisphosphonate and/or denosumab. Results: BM identified in 36/296 (12%): 29% pts with HGNET (5/17), 10% pts with CARC (12/121), 7.4% pts with PNET (6/81), 17% pt with PHEO (11/66), 18% pt with ACC (2/11). BM occurred in 21 men/15 women; median age 54. 30/36 (83%) had stage IV disease at diagnosis (dx); 69% had BM at dx. 69% pts were eventually symptomatic: bone pain (24/25, 96%), cord compression (3/25, 12%) and/or pathologic fracture (6/25, 24%); 8/25 (32%) had more than one symptom from BM. Median survival from BM: 28 mo (21.1 mo if symptomatic; 34.3 mo if asymptomatic). Overall, 81% (29/36) pt received tx for BM: 53% XRT (19/36), 25% surgery (9/36), 39% bisphosphonate (14/36), and/or 11% denosumab (4/36). Conclusions: 12% of pts with NET in this database developed BM. Most pts with BM experienced pain. Serious complications such as cord compression and/or pathological fracture occurred in 36% (9/25) suggesting that bisphosphonate and/or denosumab tx may be of value in these patients. Accrual to the database is ongoing.

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