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Clinical Endocrinology Mar 2015The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family... (Review)
Review
BACKGROUND
The presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.
OBJECTIVE
To describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations.
METHODS
We searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease.
RESULTS
We included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members.
CONCLUSIONS
The frequency of germline mutations in SPPs is approximately 11-13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.
Topics: Female; Germ-Line Mutation; Humans; Isocitrate Dehydrogenase; Male; Membrane Proteins; Mitochondrial Proteins; Paraganglioma; Pheochromocytoma; Proto-Oncogene Proteins c-ret; Succinate Dehydrogenase; Von Hippel-Lindau Tumor Suppressor Protein
PubMed: 24954084
DOI: 10.1111/cen.12530 -
Journal of Neuroendocrinology Dec 2023Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to...
Safety and efficacy of peptide receptor radionuclide therapy in patients with advanced pheochromocytoma and paraganglioma: A single-institution experience and review of the literature.
INTRODUCTION
Despite advances in diagnosis and management, patients with advanced pheochromocytomas and paragangliomas (PPGL) face limited treatment options. This study aims to evaluate the safety and efficacy of peptide receptor radionuclide therapy (PRRT) in patients with advanced PPGL, based on a single-institution experience and provide a comprehensive review of the literature.
METHODS
A retrospective analysis was conducted on patients with advanced pheochromocytoma and paraganglioma who received PRRT at a single institution from April 2012 to March 2022. Clinical characteristics, treatment response, adverse events, and survival outcomes were assessed. A systematic literature review was also performed.
RESULTS
A total of 15 patients with advanced PPGL were included, the majority of whom had both metastatic and functional disease. Most patients received four infusions of 177Lu-DOTATATE (73%). The median therapeutic 177Lu-DOTATATE radioactivity for each infusion was 7.4 GBq. Only one patient was treated with one infusion of 90Y-DOTATATE (4.2 GBq) in addition to three infusions of Lu-177 DOTATATE. Overall, PRRT suggests a promising efficacy with disease control rate of 63.6% by RECIST v1.1. The median overall survival (OS) was not reached and the median progression free survival (PFS) was 25.9 months. In terms of safety, PRRT was well tolerated. Review of the literature revealed consistent findings, supporting the efficacy and safety of PRRT in PPGL.
CONCLUSION
This study suggests that PRRT is a safe and effective therapeutic option for patients with PPGL. Our findings align with the existing literature, providing additional evidence to support the use of PRRT in this challenging patient population.
Topics: Humans; Pheochromocytoma; Yttrium Radioisotopes; Retrospective Studies; Paraganglioma; Adrenal Gland Neoplasms; Receptors, Peptide
PubMed: 37937484
DOI: 10.1111/jne.13349 -
Therapeutic Advances in Medical Oncology 2022Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been... (Review)
Review
BACKGROUND
Cabozantinib is approved, in various settings, for the treatment of renal cell carcinoma, medullary thyroid cancer, and hepatocellular carcinoma, and it has been investigated for the treatment of other cancers. With the available evidence and the real-world performance of cabozantinib compared with clinical trial data, we performed a systematic review of cabozantinib monotherapy as treatment for solid tumors in adults.
METHODS
This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with PROSPERO (CRD42020144680). We searched for clinical and observational studies of cabozantinib monotherapy for solid tumors using Embase, MEDLINE, and Cochrane databases (October 2020), and screened relevant congress abstracts. Eligible studies reported clinical or safety outcomes, or biomarker data. Small studies ( < 25) and studies of cabozantinib combination therapies were excluded. Quality was assessed using National Institute for Health and Care Excellence methodology, and study characteristics were described qualitatively.
RESULTS
Of 2888 citations, 114 were included (52 randomized studies, 29 observational studies, 32 nonrandomized phase I or II studies or pilot trials, and 1 analysis of data from a randomized study and a nonrandomized study). Beyond approved indications, other tumors studied were castration-resistant prostate cancer, urothelial carcinoma, Ewing sarcoma, osteosarcoma, uveal melanoma, non-small-cell lung cancer, Merkel cell carcinoma, glioblastoma, pheochromocytomas and paragangliomas, cholangiocarcinoma, gastrointestinal stromal tumor, colorectal cancer, salivary gland cancer, carcinoid and pancreatic neuroendocrine tumors, and breast, endometrial and ovarian cancers. The most common adverse events were hypertension, diarrhea, and fatigue.
CONCLUSION
The identified evidence demonstrates the positive efficacy/effectiveness of cabozantinib monotherapy in various solid tumor types, with safety findings being consistent with those observed with other VEGFR-targeting tyrosine kinase inhibitors. When available, real-world findings were consistent with the data reported from clinical trials. A limitation of this review is the high proportion of abstracts; however, this allowed us to capture the most up-to-date findings.
PubMed: 35847482
DOI: 10.1177/17588359221107112 -
European Annals of Otorhinolaryngology,... Sep 2017To review the optimal techniques for localization and characterization of neck paragangliomas (PGL). (Review)
Review
OBJECTIVE
To review the optimal techniques for localization and characterization of neck paragangliomas (PGL).
MATERIAL AND METHODS
Systematic review of the literature from the PubMed/Medline database.
RESULTS
Neck PGL are hypervascular tumours essentially arising from paraganglionic tissue situated at the carotid bifurcation (carotid body) and along the vagus nerve. Morphological and functional imaging are indicated to confirm the diagnosis, identify multifocal disease and for local and regional staging. MR angiography is the noninvasive technique of choice. CT scan and especially CT angiography are excellent alternatives for diagnosis and staging. Conventional arteriography remains useful preoperatively for embolization and occlusion tests. Functional imaging allows localization and characterization of PGLs. Somatostatin receptor scintigraphy (SRS) was the reference imaging technique for staging of sporadic PGLs. The indications for PET imaging have been extended over recent years in parallel with the development of new tracers such as [F]-FDOPA PET or Gallium-labelled DOTA peptides. Gallium-labelled DOTA peptides has become the first-line imaging modality in the evaluation of cervical PGLs, regardless of the genetic background.
CONCLUSION
Morphological and functional imaging is essential for the staging of neck PGL.
Topics: Computed Tomography Angiography; Head and Neck Neoplasms; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Neoplasm Staging; Paraganglioma; Positron-Emission Tomography; Predictive Value of Tests; Radiopharmaceuticals; Sensitivity and Specificity; Tomography, X-Ray Computed
PubMed: 27887852
DOI: 10.1016/j.anorl.2016.10.003 -
Clinical Imaging Dec 2021To retrospectively evaluate the safety and technical success of pre-operative embolization (POE) of head and neck paragangliomas (HNP) in a single-center cohort over a... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To retrospectively evaluate the safety and technical success of pre-operative embolization (POE) of head and neck paragangliomas (HNP) in a single-center cohort over a 10-year period, and to benchmark our results with those derived from a systematic analysis of the available literature.
METHODS
All consecutive HNP embolized between November 2010 and April 2020 were included and reviewed. In total, there were 27 HNP in 27 patients [8 (30%) males; 19 (70%) females; mean age 53 ± 16 years; range 30-86]. Embolization technique, total procedure time, dose area product (DAP), complications, rate of HNP devascularization, and technical success (i.e. ≥80% devascularization of the HNP) were recorded and analyzed. A systematic analysis on the safety and technical success of POE was then conducted according to the Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
RESULTS
Twenty-one (21/27; 78%) HNP were treated with an endovascular approach and 6/27 (22%) with a percutaneous or combined (endovascular/percutaneous) technique. Mean total procedure time and DAP were 108 ± 48 min (range 45-235) and 92.5 ± 61.3 Gy·cm (range 19.9-276.0), respectively. Two (2/27; 7%) complications (one minor, one major) were observed. Mean HNP devascularization was 88 ± 15% (range 23-100) with technical success achieved in 24/27 (89%) HNP. Literature analysis revealed a pooled rate of complication and technical success of 3.8% (95% CI: 0.5-8.8%) and 79.0% (95% CI: 63.6-91.6%), respectively.
CONCLUSIONS
POE of HNP is safe and results in extensive devascularization in the majority of treated tumors.
Topics: Adult; Aged; Aged, 80 and over; Embolization, Therapeutic; Female; Head and Neck Neoplasms; Humans; Male; Middle Aged; Paraganglioma; Retrospective Studies; Treatment Outcome
PubMed: 34467873
DOI: 10.1016/j.clinimag.2021.08.014 -
International Forum of Allergy &... Apr 2019Paragangliomas of the nasal cavity and paranasal sinuses, although exceedingly rare, can exhibit frequent and aggressive recurrences. Our objective was to evaluate tumor...
BACKGROUND
Paragangliomas of the nasal cavity and paranasal sinuses, although exceedingly rare, can exhibit frequent and aggressive recurrences. Our objective was to evaluate tumor characteristics, clinical course, management, and associated complications of sinonasal paragangliomas METHODS: A systematic review of the literature was performed utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, searching for sinonasal paraganglioma. Studies meeting inclusion criteria were assessed for level of evidence. Patient demographics, tumor characteristics, primary intervention, and other clinical characteristics were evaluated.
RESULTS
Forty-five relevant studies encompassing 54 patients with sinonasal paraganglioma were identified. The most common tumor locations were the nasal cavity (66.7%), ethmoid sinuses (22.2%), maxillary sinuses (7.4%), and sphenoid sinuses (3.7%). Common presenting symptoms included recurrent epistaxis (68.5%), nasal obstruction (53.7%), and headache (13.0%). Tumors were malignant in 28.6% of patients. Only 4 cases (7.4%) involved functional tumors. Initial management was always surgical, via either an open (63.0%) or endoscopic (33.3%) approach. Radiotherapy was used as adjunctive treatment in 10 cases (18.5%). Recurrence rate was 21.7% and occurred between 12 to 156 months after initial resection. The overall survival was 87.0% with a metastatic rate of 8.7%.
CONCLUSION
Sinonasal paragangliomas are vascular neoplasms manifesting clinically with recurrent epistaxis and nasal obstruction. Management goals are total resection with clear margins and long-term follow-up due to tendency for local recurrence. Radiotherapy has been utilized as adjuvant therapy with variable results. Further randomized controlled studies may be invaluable in elucidating these findings.
Topics: Humans; Paraganglioma; Paranasal Sinus Neoplasms
PubMed: 30570216
DOI: 10.1002/alr.22261 -
Journal of Pediatric Surgery Sep 2018Gastrointestinal stromal tumors (GIST) are extremely rare in children. Imaging plays a key role in staging and monitoring therapy (surgical and with tyrosine kinase... (Review)
Review
BACKGROUND
Gastrointestinal stromal tumors (GIST) are extremely rare in children. Imaging plays a key role in staging and monitoring therapy (surgical and with tyrosine kinase inhibitors). The vast majority of articles addressing imaging of GIST base on adults and are based on CT. The subtype "pediatric GIST" - if at all - is only mentioned in a dependent clause. Although the imaging features in children and adults are similar, histology, clinical course and thus imaging approach are different.
METHODS
A PubMed search using the search terms "Gastrointestinal stromal tumor, GIST, WT GIST, children, pediatric, carney's triad, imaging, staging, follow-up, MRI, CEUS, ultrasonography, Positron emission tomography" was conducted. Studies that reported on laparoscopy, endoscopy and surgical techniques only were excluded.
RESULTS
Based on our selective literature review, we present alternative radiological imaging strategies using MRI, contrast enhanced ultrasound (CEUS) and PET-CT to stage and follow-up pediatric GIST patients. As pediatric GIST often is a chronic disease, minimizing exposure to ionizing radiation is mandatory.
CONCLUSION
MRI, contrast enhanced ultrasound and PET-CT instead of CT are the imaging modalities to evaluate pediatric GIST.
TYPE OF STUDY
Systematic review LEVEL OF EVIDENCE: III.
Topics: Child; Chondroma; Contrast Media; Female; Gastrointestinal Stromal Tumors; Humans; Leiomyosarcoma; Lung Neoplasms; Magnetic Resonance Imaging; Male; Multimodal Imaging; Paraganglioma, Extra-Adrenal; Positron Emission Tomography Computed Tomography; Stomach Neoplasms; Tomography, X-Ray Computed
PubMed: 29685489
DOI: 10.1016/j.jpedsurg.2018.03.022 -
Biomedicines Mar 2023We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive... (Review)
Review
Efficacy and Safety of [Lu]Lu-DOTA-TATE in Adults with Inoperable or Metastatic Somatostatin Receptor-Positive Pheochromocytomas/Paragangliomas, Bronchial and Unknown Origin Neuroendocrine Tumors, and Medullary Thyroid Carcinoma: A Systematic Literature Review.
BACKGROUND
We have performed a systematic review to evaluate the efficacy and safety of [Lu]Lu-DOTA-TATE, a radioligand therapy, in advanced somatostatin receptor-positive pheochromocytoma/paraganglioma (PPGL), thymic neuroendocrine tumor (NET), bronchial NET, unknown primary NET, or medullary thyroid carcinoma (MTC).
METHODS
Studies identified in PubMed from inception to 13 May 2021 must have assessed [Lu]Lu-DOTA-TATE as a single agent and reported outcome data for the specific NET types of interest.
RESULTS
Two independent reviewers performed the screening and data extraction, resulting in 16 publications: PPGL ( = 7), bronchial NETs ( = 6; one also included NETs of unknown origin), and MTC ( = 3). Overall, [Lu]Lu-DOTA-TATE offers encouraging antitumor activity (overall tumor response rates and disease control rates) across NET types. Safety was favorable with most adverse events mild to moderate in severity, transient, and consistent with those seen in patients with gastroenteropancreatic (GEP)-NETs.
CONCLUSIONS
[Lu]Lu-DOTA-TATE has been used effectively in clinical practice to treat NETs of non-GEP origin.
PubMed: 37189646
DOI: 10.3390/biomedicines11041024 -
Frontiers in Endocrinology 2023In patients with bilateral pheochromocytoma, partial adrenalectomy offers the chance to preserve adrenal function and avoid the need for lifelong steroid... (Meta-Analysis)
Meta-Analysis
BACKGROUND
In patients with bilateral pheochromocytoma, partial adrenalectomy offers the chance to preserve adrenal function and avoid the need for lifelong steroid supplementation. However, the risk of tumour recurrence raises questions about this procedure. The aim of our study was to compare partial and total adrenalectomy in bilateral pheochromocytoma through a systematic review with meta-analysis.
METHODS
A systematic search was carried out using databases (MEDLINE, EMBASE, Scopus, Web of Science, CENTRAL) and registers of clinical trials (ClinicalTrials.gov, European Trials Register, WHO International Trials Registry Platform). This meta-analysis included studies up to July 2022 without language restrictions. A random effects model meta-analysis was performed to assess the risk of tumor recurrence, steroid dependence and morbidity in these patients.
RESULTS
Twenty-five studies were included in the analysis involving 1444 patients. The relative risk (RR) of loss of adrenal hormone function during follow-up and the need for steroid therapy was 0.32 in patients after partial adrenalectomy: RR 0.32, 95% Confidence Interval (CI): 0.26-0.38, P < 0.00001, I2 = 21%. Patients undergoing partial adrenalectomy had a lower odds ratio (OR) for developing acute adrenal crisis: OR 0.3, 95% CI: 0.1-0.91, P=0.03, I2 = 0%. Partial adrenalectomy was associated with a higher risk of recurrence than total adrenalectomy: OR 3.72, 95% CI: 1.54-8.96, P=0.003, I2 = 28%.
CONCLUSION
Partial adrenalectomy for bilateral pheochromocytoma is a treatment that offers a chance of preserving adrenal hormonal function, but is associated with a higher risk of local tumor recurrence. There was no difference for the risk of metastasis and in overall mortality among the group with bilateral pheochromocytomas undergoing total or partial adrenalectomy. This study is in line with PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and AMSTAR (A Measurement Tool to Assess Systematic Reviews) Guidelines (10, 11).
SYSTEMATIC REVIEW REGISTRATION
https://osf.io/zx3se.
Topics: Humans; Pheochromocytoma; Neoplasm Recurrence, Local; Adrenalectomy; Adrenal Gland Neoplasms
PubMed: 36998480
DOI: 10.3389/fendo.2023.1127676 -
International Journal of Urology :... Jun 2024This work aims to assess the diagnostic value of chromogranin A (CgA) in the laboratory diagnosis of neuroendocrine tumors classified as pheochromocytoma and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This work aims to assess the diagnostic value of chromogranin A (CgA) in the laboratory diagnosis of neuroendocrine tumors classified as pheochromocytoma and paraganglioma (PPGL).
METHODS
A comprehensive search was performed in PubMed, Embase, the Cochrane Library, and Web of Science databases to obtain relevant studies reporting the diagnostic accuracy of CgA in patients with PPGL. The search involved studies written in English between the time of library inception and May 1, 2023. We computed the pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Additionally, the receiver operating characteristic curve and area under the curve (AUC) were determined. The heterogeneity was assessed using the Chi-square test and the I test. The subgroup analyses were performed to investigate the origins of heterogeneity. Stata 15.1 statistical software was used in all data analyses.
RESULTS
This meta-analysis included 13 studies involving 1470 patients. CgA had a pooled diagnostic sensitivity of 0.86 (95% CI 0.81-0.91), a specificity of 0.90 (95% CI 0.81-0.95), and a DOR of 57 (95% CI 23-142). CgA had an AUC of 0.93. The studies did not reveal any threshold effect (r = -0.165; p > 0.05). The subgroup analyses revealed that the control group category and the detection method caused the overall heterogeneity.
CONCLUSIONS
Our study suggests that CgA is a helpful PPGL biomarker. However, relying solely on CgA for diagnosis is not advisable. A comprehensive approach is essential for accurate diagnosis. Future large-scale research is needed to refine CgA's clinical application.
Topics: Humans; Pheochromocytoma; Chromogranin A; Adrenal Gland Neoplasms; Paraganglioma; Biomarkers, Tumor; Sensitivity and Specificity; ROC Curve
PubMed: 38380475
DOI: 10.1111/iju.15423