Bone Metastases in Patients with Neuroendocrine Neoplasm: Frequency and Clinical, Therapeutic, and Prognostic Relevance

Scharf, Michael E.; Petry, Vanessa; Daniel, Hanna; Rinke, Anja; Gress, Thomas M.

doi:10.1159/000457954

Cited by 51 publications

(111 citation statements)

References 23 publications

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“…The current findings suggest that the rate of BMs in patients with NENs is 7%, which appears to be lower than previously reported [6][7][8]. An explanation could be an underdiagnosis of BMs, considering most patients were followed-up using cross-sectional CT imaging, which has limited sensitivity in detecting BMs [17].…”

Section: Discussioncontrasting

confidence: 73%

“…It is well established that NENs, in particular moderate to high-grade NENs, have the ability to spread to distant sites, including bone [4,5]. Nevertheless, bone metastases (BMs) in NENs are expected to be uncommon events, with several retrospective series reporting an incidence from 12% to as high as 25% in certain subtypes of NENs [5][6][7][8]. Some studies have reported that more than half of patients with NENs with BMs were symptomatic, and that skeletal-related events (SREs) occurred in around 21% [7,8].…”

Section: Introductionmentioning

confidence: 99%

“…Nevertheless, bone metastases (BMs) in NENs are expected to be uncommon events, with several retrospective series reporting an incidence from 12% to as high as 25% in certain subtypes of NENs [5][6][7][8]. Some studies have reported that more than half of patients with NENs with BMs were symptomatic, and that skeletal-related events (SREs) occurred in around 21% [7,8]. Currently, there remain no standardised guidelines for the diagnosis and management of BMs in NENs.…”

Section: Introductionmentioning

confidence: 99%

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

Lim¹,

Raja²,

D'Arienzo³

et al. 2019

Neuroendocrinology

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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.

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Section: Discussioncontrasting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

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

Lim¹,

Raja²,

D'Arienzo³

et al. 2019

Neuroendocrinology

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“…In other survival analyses of midgut NETs, bone metastases have not been assessed separately as a prognostic factor, although in some studies they have probably been included in a miscellaneous category of "distant metastases" along with other sites of extrahepatic disease [6]. A recent paper by Scharf et al [26] including 677 patients with NETs from the EN-ETS centre in Marburg, Germany, showed that bone metastases were present in 12.6% of cases (mainly small intestinal and pancreatic primaries) and were associated with a significantly shorter OS compared to other distant metastases (49 vs. 101 months, p = 0.01).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of Clinical Prognostic Factors and Further Delineation of the Effect of Mesenteric Fibrosis on Survival in Advanced Midgut Neuroendocrine Tumours

et al. 2018

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Background: Small intestinal neuroendocrine tumours (SI NETs) represent 30–50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. Aim: The primary aim of this study was to perform a large-scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs. The secondary aim was to provide epidemiological information regarding the prevalence of MF and to evaluate its effect on OS. Results: The median OS was 101 months (95% CI 84, 118). Age > 65 years, mesenteric metastases with and without desmoplasia, liver metastases, carcinoid heart disease (CHD) and bone metastases were associated with a significantly shorter OS, while primary tumour resection was predictive of a longer OS. The benefit of surgical resection was limited to symptomatic patients. MF was present in approximately 50% of patients with mesenteric lymphadenopathy. Elevated urinary 5-HIAA levels correlated strongly with the presence of CHD (p < 0.001) and to a lesser extent (p = 0.02) with MF. MF and CHD did not usually co-exist, suggesting that different mechanisms are likely to be involved in the development of these fibrotic complications. Conclusions: This study has identified specific prognostic factors in a large cohort of 387 patients with advanced SI NETs and has provided useful epidemiological data regarding carcinoid-related fibrotic complications.

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“…The presence of carcinoid heart disease, mesenteric lymph node metastases, distant abdominal lymph node metastases, liver metastatic burden, extra-abdominal metastases, skeletal involvement and peritoneal carcinomatosis (PC) are independent prognostic factors for OS in SBNEN [157]. Bone metastases have a distinct prognostic impact to that of other distant metastases (inferior OS with the former) [158], and although occurring only in approximately 5% of metastatic GEP NEN, lung metastases have significant detriment to OS which is in addition to that presented by distant metastases at other sites [159]. Multivariate prognostic scores have been developed for both SBNEN and PanNEN in terms of OS or recurrence post-surgery [160][161][162][163].…”

Section: Therapeutic Strategiesmentioning

confidence: 99%

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

et al. 2019

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The traditionally promulgated perspectives of neuroendocrine neoplasms (NEN) as rare, indolent tumours are blunt and have been outdated for the last 2 decades. Clear increments in their incidence over the past decades render them increasingly clinically relevant, and at initial diagnosis many present with nodal and/or distant metastases (notably hepatic). The molecular pathogenesis of these tumours is increasingly yet incompletely understood. Those arising from the small bowel (SB) or pancreas typically occur sporadically; the latter may occur within the context of hereditary tumour predisposition syndromes. NENs can also be associated with endocrinopathy of hormonal hypersecretion. Tangible advances in the development of novel biomarkers, functional imaging modalities and therapy are especially applicable to this sub-set of tumours. The management of SB and pancreatic neuroendocrine tumours (NET) may be challenging, and often comprises a multidisciplinary approach wherein surgical, medical, interventional radiological and radiotherapeu-tic modalities are implemented. This review provides a comprehensive overview of the epidemiology, pathophysiology, diagnosis and treatment of SB and pancreatic NETs. Moreover, we provide an outlook of the future in these tumour types which will include the development of precision oncology frameworks for individualised therapy, multi-analyte predictive biomarkers, artificial intelligence-derived clinical decision support tools and elucidation of the role of the microbiome in NEN development and clinical behaviour.According to SEER version 18, SBNEN and PanNEN incidences are currently estimated at 1.2 and 0.7 per 100,000, respectively [5]. The overall 20-year duration prevalence of all NEN is estimated at 171,321; SBNEN constituting 32,122 patients with 3-fold fewer PanNEN (10,707) [5]. Possible attributable factors for this increase evolving epidemiology include increased use of endoscopy and also improvements in the sensitivity of widely used imaging modalities, leading to increased detection of early-stage, asymptomatic disease [5].The median overall survival (OS) for NEN (irrespective of site and grade) is 9.3 years [5]. For SB (median OS: 14 years), this ranges from 70 months (advanced disease with distant metastases) to 170 months (localised disease) and from 30 months (Grade 3) to 160 months (Grade 1). For pancreas (median OS: 3.6 years): 21 months (advanced) to 235 months (localised disease) and from 15 months (Grade 3) to 140 months (Grade 1) [5].Multivariable analyses have identified that ethnicity, age, differentiation, stage and site all have statistically significant correlations with survival. In general, Caucasian ethnicity, age (< 50 years) and localised, well-differentiated NEN exhibit the best survival. SB tumour patients are approximately 1.5 times more likely to survive longer than those with PanNEN [19]. Many of these correlations are self-evident since they pertain to degree of malignancy, disease duration and patient performance status.OS (median 5-year) app...

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Bone Metastases in Patients with Neuroendocrine Neoplasm: Frequency and Clinical, Therapeutic, and Prognostic Relevance

Cited by 51 publications

References 23 publications

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

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

Evaluation of Clinical Prognostic Factors and Further Delineation of the Effect of Mesenteric Fibrosis on Survival in Advanced Midgut Neuroendocrine Tumours

Neuroendocrine Neoplasms of the Small Bowel and Pancreas

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