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European Journal of Endocrinology Oct 2016To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To systematically review the incidence and factors associated with recurrences or new tumors after apparent complete resection of pheochromocytoma or thoraco-abdomino-pelvic paraganglioma.
DESIGN
A systematic review and meta-analysis of published literature was performed.
METHODS
Pubmed and Embase from 1980 to 2012 were searched for studies published in English on patients with non-metastatic pheochromocytoma or thoraco-abdomino-pelvic paraganglioma, complete tumor resection, postoperative follow-up exceeding 1 month, and recurrence or new tumor documented by pathology, hormonal dosages, or imaging tests. Incidence rates of new events after curative surgery were calculated for each study that had sufficient information and pooled using random-effect meta-analysis.
RESULTS
In total, 38 studies were selected from 3518 references, of which 36 reported retrospective cohorts from the USA, Europe, and Asia. Patient follow-up was neither standardized nor exhaustive in the included studies. A clear description of patient retrieval methods was available for nine studies and the follow-up protocol and patient flow for four studies. Only two studies used multivariable methods to assess potential predictors of postoperative events.The overall rate of recurrent disease from 34 studies was 0.98 events/100 person-years (95% confidence interval 0.71, 1.25). Syndromic diseases and paragangliomas were consistently associated with a higher risk of a new event in individual studies and in meta-regression analysis.
CONCLUSIONS
The risk of recurrent disease after complete resection of pheochromocytoma may be lower than that previously estimated, corresponding to five events for 100 patients followed up for 5 years after complete resection. Risk stratification is required to tailor the follow-up protocol after complete resection of a pheochromocytoma or paraganglioma. Large multicenter studies are needed to this end.
Topics: Adrenal Gland Neoplasms; Humans; Neoplasm Recurrence, Local; Neoplasms, Second Primary; Paraganglioma; Pheochromocytoma
PubMed: 27080352
DOI: 10.1530/EJE-16-0189 -
Frontiers in Endocrinology 2022Targeted radionuclide therapy (TRT) with [I]MIBG and [Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable...
Response to targeted radionuclide therapy with [I]MIBG AND [Lu]Lu-DOTA-TATE according to adrenal vs. extra-adrenal primary location in metastatic paragangliomas and pheochromocytomas: A systematic review.
PURPOSE
Targeted radionuclide therapy (TRT) with [I]MIBG and [Lu]Lu-DOTA-TATE is an alternative treatment to the classic schemes in slow progressive metastatic/inoperable paraganglioma (PGL) and pheochromocytoma (PHEO). There is no consensus on which treatment to administer and/or the best sequence in patients who are candidates for both therapies. To clarify these questions, this systematic review assesses the prognostic value of [I]MIBG and Lu]Lu-DOTA-TATE (PRRT-Lu) treatments in terms of progression-free survival (PFS) both globally and considering the primary location.
METHODS
This review was developed according to the PRISMA Statement with 27 final studies (608 patients). Patient characteristics, treatment procedure, and follow-up criteria were evaluated. In addition, a Bayesian linear regression model weighted according to its sample size and an alternative model, which also included an interaction between the treatment and the proportion of PHEOs, were carried out, adjusted by a Student's distribution.
RESULTS
In linear regression models, [I]MIBG overall PFS was, on average, 10 months lower when compared with PRRT-Lu. When considering the interaction between treatment responses and the proportion of PHEOs, PRRT-Lu showed remarkably better results in adrenal location. The PFS of PRRT-Lu was longer when the ratio of PHEOs increased, with a decrease in [I]MIBG PFS by 1.9 months for each 10% increase in the proportion of PHEOs in the sample.
CONCLUSION
Methodology, procedure, and PFS from the different studies are quite heterogeneous. PRRT-Lu showed better results globally and specifically in PHEOs. This fact opens the window to prospective trials comparing or sequencing [I]MIBG and PRRT-Lu.
Topics: Humans; Pheochromocytoma; 3-Iodobenzylguanidine; Bayes Theorem; Prospective Studies; Radiopharmaceuticals; Paraganglioma; Adrenal Gland Neoplasms; Iodine Radioisotopes
PubMed: 36339441
DOI: 10.3389/fendo.2022.957172 -
Interventional Neuroradiology : Journal... Jul 2023Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether... (Review)
Review
INTRODUCTION
Embolization of head and neck paragangliomas (HNPs) is a well-established treatment strategy and adjunctive therapy. However, the optimal mode of intervention, whether by direct percutaneous puncture (DP) or via transarterial embolization (TAE), remains unclear.
METHODS
The aim of this study was to complete a systematic literature review and meta-analysis to compare the safety and efficacy of DP versus TAE for HNP embolization. The Cochrane Library and MEDLINE databases were used to identify studies describing the clinical outcomes of either DP or TAE for HNP embolization. Outcome measures included: complete angiographic devascularization, major complications, and minor complications. Pooled rates were calculated for each variable which were then compared with meta-regression using a random effects model.
RESULTS
Thirty-one retrospective studies met inclusion criteria, detailing 394 patients with 411 HNPs. Overall, DP was associated with a higher rate of complete devascularization (91.5%, 95% confidence interval [CI]: 85.6% to 97.4%; = 0%) when compared to TAE technique (40.1%, CI: 27.2% to 58.9%; = 93%). However, there was no difference regarding major complication rates between DP (6%, CI:1.3% to 10.8%; = 0%) and TAE for HNP embolization (3.3%, CI: 1.4% to 5.3%; = 0%) (p = 0.370), nor in minor complications between the techniques (p = 0.211). Subgroup analysis of TAE embolic agents revealed that particle embolics were associated with a significantly lower rate of major complications (2.5%; 0.4% to 4.6%; = 0%) when compared to liquid embolics (10.6%, CI:4% to 17.3%; = 48%; p = 0.022).
CONCLUSIONS
A DP approach for HNP embolization results in a higher rate of complete devascularization and with a similar complication profile when compared to TAE. These findings also suggest that particle embolics are associated with fewer major complications compared to liquid embolics when TAE is utilized.
PubMed: 37455341
DOI: 10.1177/15910199231188859 -
Cancers Feb 2019Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia,... (Review)
Review
The Value of Histological Algorithms to Predict the Malignancy Potential of Pheochromocytomas and Abdominal Paragangliomas-A Meta-Analysis and Systematic Review of the Literature.
Pheochromocytomas (PCCs) and abdominal paragangliomas (PGLs), collectively abbreviated PPGLs, are neuroendocrine tumors of the adrenal medulla and paraganglia, respectively. These tumors exhibit malignant potential but seldom display evidence of metastatic spread, the latter being the only widely accepted evidence of malignancy. To counter this, pre-defined histological algorithms have been suggested to stratify the risk of malignancy: Pheochromocytoma of the Adrenal Gland Scaled Score (PASS) and the Grading system for Adrenal Pheochromocytoma and Paraganglioma (GAPP). The PASS algorithm was originally intended for PCCs whereas the GAPP model is proposed for stratification of both PCCs and PGLs. In parallel, advances in terms of coupling overtly malignant PPGLs to the underlying molecular genetics have been made, but there is yet no combined risk stratification model based on histology and the overall mutational profile of the tumor. In this review, we systematically meta-analyzed previously reported cohorts using the PASS and GAPP algorithms and acknowledge a "rule-out" way of approaching these stratification models rather than a classical "rule-in" strategy. Moreover, the current genetic panorama regarding possible molecular adjunct markers for PPGL malignancy is reviewed. A combined histological and genetic approach will be needed to fully elucidate the malignant potential of these tumors.
PubMed: 30769931
DOI: 10.3390/cancers11020225 -
World Neurosurgery May 2022Primary spine paragangliomas are rare tumors. Surgical resection plays a role, but aggressive lesions are challenging. We reviewed the literature on primary spine... (Review)
Review
BACKGROUND
Primary spine paragangliomas are rare tumors. Surgical resection plays a role, but aggressive lesions are challenging. We reviewed the literature on primary spine paragangliomas.
METHODS
PubMed, Scopus, Web of Science, and Cochrane were searched following the PRISMA guidelines to include studies on primary spine paragangliomas. Clinical-radiologic features, treatments, and outcomes were analyzed and compared between cauda equina versus non-cauda equina tumors.
RESULTS
We included 143 studies comprising 334 patients. Median age was 46 years (range, 6-85 years). The most frequent symptoms were lower back (64.1%) and radicular (53.9%) pain, and sympathetic in 18 patients (5.4%). Cauda equina paragangliomas (84.1%) had frequently lumbar (49.1%) or lumbosacral (29%) locations. Non-cauda equina tumors were mostly in the thoracic (11.4%), thoracolumbar (5.1%), and cervical (3.6%) spine. Median tumor diameter was 2.5 cm (range, 0.5-13.0 cm). Surgical resection (98.5%) was preferred over biopsy (1.5%). Decompressive laminectomy (53%) and spine fusion (6.9%) were also performed. Adjuvant radiotherapy was delivered in 39 patients (11.7%) with aggressive tumors. Posttreatment symptomatic improvement was described in 86.2% cases. Median follow-up was 19.5 months (range, 0.1-468.0 months), and 23 patients (3.9%) had tumor recurrences. No significant differences were found between cauda equina versus non-cauda equina tumors.
CONCLUSIONS
Surgical resection is effective and safe in treating primary spine paragangliomas; however, adjuvant treatments may be needed for aggressive lesions.
Topics: Cauda Equina; Humans; Lumbosacral Region; Middle Aged; Neoplasm Recurrence, Local; Paraganglioma; Paraganglioma, Extra-Adrenal; Spinal Neoplasms; Spine
PubMed: 35123022
DOI: 10.1016/j.wneu.2022.01.110 -
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 -
The Oncologist Jul 2016Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs).... (Review)
Review
BACKGROUND
Everolimus, an oral mTOR (mammalian target of rapamycin) inhibitor, is currently approved for the treatment of progressive pancreatic neuroendocrine tumors (NETs). Although promising, only scattered data, often from nondedicated studies, are available for extrapancreatic NETs.
PATIENTS AND METHODS
A systematic review of the published data was performed concerning the use of everolimus in extrapancreatic NET, with the aim of summarizing the current knowledge on its efficacy and tolerability. Moreover, the usefulness of everolimus was evaluated according to the different sites of the primary.
RESULTS
The present study included 22 different publications, including 874 patients and 456 extrapancreatic NETs treated with everolimus. Nine different primary sites of extrapancreatic NETs were found. The median progression-free survival ranged from 12.0 to 29.9 months. The median time to progression was not reached in a phase II prospective study, and the interval to progression ranged from 12 to 36 months in 5 clinical cases. Objective responses were observed in 7 prospective studies, 2 retrospective studies, and 2 case reports. Stabilization of the disease was obtained in a high rate of patients, ranging from 67.4% to 100%. The toxicity of everolimus in extrapancreatic NETs is consistent with the known safety profile of the drug. Most adverse events were either grade 1 or 2 and easy manageable with a dose reduction or temporary interruption and only rarely requiring discontinuation.
CONCLUSION
Treatment with everolimus in patients with extrapancreatic NETs appears to be a promising strategy that is safe and well tolerated. The use of this emerging opportunity needs to be validated with clinical trials specifically designed on this topic.
IMPLICATIONS FOR PRACTICE
The present study reviewed all the available published data concerning the use of everolimus in 456 extrapancreatic neuroendocrine tumors (NETs) and summarized the current knowledge on the efficacy and safety of this drug, not yet approved except for pancreatic NETs. The progression-free survival rates and some objective responses seem promising and support the extension of the use of this drug. The site-by-site analysis seems to suggest that some subtypes of NETs, such as colorectal, could be more sensitive to everolimus than other primary NETs. No severe adverse events were usually reported and discontinuation was rarely required; thus, everolimus should be considered a valid therapeutic option for extrapancreatic NETs.
Topics: Adrenal Gland Neoplasms; Antineoplastic Agents; Carcinoma, Neuroendocrine; Colorectal Neoplasms; Disease-Free Survival; Everolimus; Humans; Ileal Neoplasms; Lung Neoplasms; Neuroendocrine Tumors; Pheochromocytoma; Stomach Neoplasms; Thyroid Neoplasms
PubMed: 27053503
DOI: 10.1634/theoncologist.2015-0420 -
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 -
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 -
Head & Neck May 2023Pre-operative embolization prior to surgical resection of carotid body tumors was meant to decrease intraoperative blood loss and operative time. Yet, potential... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-operative embolization prior to surgical resection of carotid body tumors was meant to decrease intraoperative blood loss and operative time. Yet, potential confounders such as different Shamblin classes have never been analyzed. Aim of our meta-analysis was to investigate effectiveness of a pre-operative embolization according to different Shamblin classes.
METHODS
Five studies comprising 245 patients were included. A random effects model meta-analysis was conducted, and the I statistic was used to assessment for heterogeneity.
RESULTS
Pre-operative embolization was associated with a significant reduction in blood loss (WM: 276.4 mL; 95% CI, 201.9-378.3, p < 0.01); an absolute mean reduction, though not statistically significant, was observed in both Shamblin 2 and 3 classes. No difference in operative time was found between the two strategies (WM: 192.0 min; 95% CI, 157.7-234.1, p = 1.0).
CONCLUSIONS
Embolization proved an overall significant reduction in perioperative bleeding, which did not reach threshold for statistical significance when Shamblin classes were singularly considered.
Topics: Humans; Carotid Body Tumor; Vascular Surgical Procedures; Retrospective Studies; Embolization, Therapeutic; Blood Loss, Surgical; Treatment Outcome
PubMed: 36896854
DOI: 10.1002/hed.27318