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Annals of Oncology : Official Journal... Aug 2015Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European... (Review)
Review
Pulmonary neuroendocrine (carcinoid) tumors: European Neuroendocrine Tumor Society expert consensus and recommendations for best practice for typical and atypical pulmonary carcinoids.
BACKGROUND
Pulmonary carcinoids (PCs) are rare tumors. As there is a paucity of randomized studies, this expert consensus document represents an initiative by the European Neuroendocrine Tumor Society to provide guidance on their management.
PATIENTS AND METHODS
Bibliographical searches were carried out in PubMed for the terms 'pulmonary neuroendocrine tumors', 'bronchial neuroendocrine tumors', 'bronchial carcinoid tumors', 'pulmonary carcinoid', 'pulmonary typical/atypical carcinoid', and 'pulmonary carcinoid and diagnosis/treatment/epidemiology/prognosis'. A systematic review of the relevant literature was carried out, followed by expert review.
RESULTS
PCs are well-differentiated neuroendocrine tumors and include low- and intermediate-grade malignant tumors, i.e. typical (TC) and atypical carcinoid (AC), respectively. Contrast CT scan is the diagnostic gold standard for PCs, but pathology examination is mandatory for their correct classification. Somatostatin receptor imaging may visualize nearly 80% of the primary tumors and is most sensitive for metastatic disease. Plasma chromogranin A can be increased in PCs. Surgery is the treatment of choice for PCs with the aim of removing the tumor and preserving as much lung tissue as possible. Resection of metastases should be considered whenever possible with curative intent. Somatostatin analogs are the first-line treatment of carcinoid syndrome and may be considered as first-line systemic antiproliferative treatment in unresectable PCs, particularly of low-grade TC and AC. Locoregional or radiotargeted therapies should be considered for metastatic disease. Systemic chemotherapy is used for progressive PCs, although cytotoxic regimens have demonstrated limited effects with etoposide and platinum combination the most commonly used, however, temozolomide has shown most clinical benefit.
CONCLUSIONS
PCs are complex tumors which require a multidisciplinary approach and long-term follow-up.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bronchoscopy; Carboplatin; Carcinoid Heart Disease; Carcinoid Tumor; Cisplatin; Dacarbazine; Etoposide; Europe; Humans; Lung Neoplasms; Pneumonectomy; Positron-Emission Tomography; Receptors, Somatostatin; Societies, Medical; Temozolomide; Tomography, X-Ray Computed; Ultrasonography
PubMed: 25646366
DOI: 10.1093/annonc/mdv041 -
Cancers Jun 2022Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid... (Review)
Review
BACKGROUND
Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide.
METHODS
A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000-2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models.
RESULTS
Eight studies met inclusion criteria ( = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06-0.36]). Liver metastasis (odds ratio 2.85 [1.49-5.47]) and gender (male 0.58 [0.34-0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03-4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32-1.66]). Notably, there was no standard prophylactic octreotide strategy used.
CONCLUSIONS
Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC.
PubMed: 35740631
DOI: 10.3390/cancers14122966 -
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 -
PharmacoEconomics Nov 2021To date, the economic burden and patient-reported outcomes associated with carcinoid syndrome (CS) in patients with neuroendocrine tumor (NET) remain largely unknown.
BACKGROUND
To date, the economic burden and patient-reported outcomes associated with carcinoid syndrome (CS) in patients with neuroendocrine tumor (NET) remain largely unknown.
OBJECTIVES
The objective of this study was to perform a systematic review of economic and quality-of-life (QOL) studies related to the treatment of CS.
METHODS
Articles included in the review were extracted from PubMed, Embase, and the Cochrane Library. Studies had to be in English and published between 1 January 2000 and 2 July 2020. Other study eligibility criteria included patients with NET with CS receiving treatment for CS, study outcomes of cost or QOL, and clinical trials or population-based studies using claims or other secondary databases. The interventions included somatostatin analogs, telotristat ethyl, or other treatment for CS. To evaluate the quality and bias of the included studies, the 24-item CHEERS and 10-item Gill and Feinstein checklists were used. We report a narrative synthesis of the findings from the selected studies.
RESULTS
A total of 12 economic and 12 QOL studies met the inclusion criteria and were included for review. Patients with uncontrolled CS symptoms had 23-92% higher costs than those with controlled CS; mostly, ambulatory/outpatient services were the primary drivers of the costs. The use of telotristat ethyl may be cost effective if the societal willingness to pay is as high as $US150,000 per quality-adjusted life-year in the USA. Of the 12 QOL papers, only three case-control studies assessed QOL at baseline and more than two follow-up time points. Seven studies evaluated QOL at two or more time points but lacked a control group, obscuring direct intervention effects on patients' well-being.
CONCLUSIONS
We observed wide variations in the reviewed studies evaluating the economic burden and patient-reported outcomes, in terms of cost and QOL, of patients with CS. Although QOL is consistently impaired and costs are consistently increased by CS, the numbers of both cost and QOL studies among this patient population remain sparse, and many of the existing studies indicated an important need for quality improvement.
Topics: Cost-Benefit Analysis; Humans; Malignant Carcinoid Syndrome; Patient Reported Outcome Measures; Quality of Life; Quality-Adjusted Life Years
PubMed: 34378163
DOI: 10.1007/s40273-021-01071-0 -
Frontiers in Endocrinology 2022Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy,...
BACKGROUND
Ovarian strumal carcinoid is a rare tumor in which thyroid (struma) and carcinoid components coexist. The disease is generally considered to be a borderline malignancy, however, cases with metastatic disease have been described. No data in the literature are available to guide diagnosis and therapy.
METHODS
We performed a pooled analysis and a systematic review of histopathological-confirmed strumal carcinoid cases published in the literature using the following keywords: "strumal carcinoid of the ovary", "strumal carcinoid case report". A case of strumal carcinoid tumor diagnosed and followed-up at the Medical Oncology Unit of Spedali Civili (Brescia, Italy) was also described and included.
RESULTS
Sixty-six eligible publications were identified, providing data from one hundred and seventeen patients, plus a case diagnosed at our institution. At presentation, among the eighty-eight patients with symptomatic disease, 37% of patients suffered from abdominal distention and 49% from pain due to a growing abdominal tumor mass, 37% from constipation (peptide YY was analyzed in only nine of them, resulting above the physiologic range). Surgery was the primary therapy in 99% of the patients. Three patients had metastatic disease at diagnosis and five patients underwent recurrence after radical surgery. Histology at disease recurrence concerned the thyroid component in two patients, the carcinoid component in two patients, both histologies in one patient. Median disease-free survival and overall survival in this series were not attained.
CONCLUSION
Strumal carcinoid of the ovary generally presents a benign behavior and surgery is curative in most cases. However, a small group of patients with this disease can undergo disease recurrence due to both the thyroid and the neuroendocrine (carcinoid) components. A follow-up in radically operated patients is therefore needed, particularly in those with a voluminous disease at diagnosis.
Topics: Carcinoid Tumor; Female; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Struma Ovarii
PubMed: 35528006
DOI: 10.3389/fendo.2022.871210 -
Lung Cancer (Amsterdam, Netherlands) Aug 2019The treatment of pulmonary carcinoid has changed over the last decades. Although surgical resection is still the gold standard, minimally invasive endobronchial... (Meta-Analysis)
Meta-Analysis
The treatment of pulmonary carcinoid has changed over the last decades. Although surgical resection is still the gold standard, minimally invasive endobronchial procedures have emerged as a parenchyma sparing alternative for tumors located in the central airways. This review was performed to identify the optimal treatment strategy for pulmonary carcinoid, with a particular focus on the feasibility and outcome of parenchyma sparing techniques versus surgical resection. A systematic review of the literature was carried out using MEDLINE, Embase and the Cochrane databases, based on the Preferred Reporting Items for Systematic Reviews and Meta-Analysis statement. Two separate searches of publications in endobronchial and surgical treatment in patients with pulmonary carcinoid, were performed. Outcomes were overall survival, disease free survival, recurrence rate, complications, quality of life, and healthcare costs. Combining the two main searches for endobronchial therapy and surgical therapy yielded 3111 records. Finally, 43 studies concerning surgical treatment and 9 studies related to endobronchial treatment for pulmonary carcinoid were included. Assessment of included studies showed that lymph node involvement, histological grade, tumor location and tumor diameter were identified as poor prognostic factors and seem to be important for patients with pulmonary carcinoid. For patients with a more favorable prognosis, tumor location and tumor diameter are important factors that can help decide on the optimal treatment strategy. Centrally located small intraluminal pulmonary carcinoids, without signs of metastasis can be treated with minimally invasive alternatives such as endobronchial treatment or parenchyma sparing surgical resection. Patients with parenchyma sparing resections should be followed with long term follow up to exclude recurrence of disease. In a multidisciplinary setting, it should be determined whether individual patients are eligible for parenchyma sparing procedures or anatomical resection. Overall evidence is of low quality and future studies should focus on prospective trials in the treatment of pulmonary carcinoid.
Topics: Bronchoscopy; Carcinoid Tumor; Health Care Costs; Humans; Lung Neoplasms; Organ Sparing Treatments; Pneumonectomy; Postoperative Complications; Prognosis; Quality of Life; Recurrence; Treatment Outcome
PubMed: 31320001
DOI: 10.1016/j.lungcan.2019.04.016 -
Przeglad Gastroenterologiczny 2018Knowledge about oesophageal carcinoids is based primarily on case reports, and therefore information about them is incomplete. (Review)
Review
INTRODUCTION
Knowledge about oesophageal carcinoids is based primarily on case reports, and therefore information about them is incomplete.
AIM
To collect information on oesophageal carcinoid tumours in a systematic review study.
MATERIAL AND METHODS
Databases including PubMed, Scopus, and Web of Science were searched for the characteristics of oesophageal carcinoid tumour. Studies included original articles, case series, or case reports, reporting at least one of the characteristics of benign carcinoid tumour or carcinoid tumour.
RESULTS
Out of 670 studies searched, after evaluation and excluding non-relevant studies, 14 studies were included and analysed in the systematic review. These studies included 19 patients with carcinoid tumour of whom 57.9% were males with a mean age of 55.5 years. Dysphagia and weight loss were the most prevalent symptoms and signs in the patients. Lower oesophagus was the most prevalent site of tumour.
CONCLUSIONS
This meta-analysis showed that the mean age at diagnosis of oesophageal carcinoid was around 55 years, with 1.4 times greater prevalence among males, and located mainly in the distal oesophagus. The mean tumour size was 2.4 cm. The main symptoms and signs of this disease were dysphagia, weight loss, and reflux. The tumour behaviour was mainly non-aggressive except for cases associated with adenocarcinoma.
PubMed: 30302162
DOI: 10.5114/pg.2018.78285 -
Current Urology Apr 2017The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular... (Review)
Review
PURPOSE
The purpose of this study is to study the main epidemiological, clinical, para clinical, pathological, therapeutic, and evolutionary features of patients with testicular neuroendocrine tumors (TNET).
MATERIALS AND METHODS
Nine case series and sixteen case reports were identified by searching PubMed database and qualified for inclusion in this study. We added the data of one case treated in the department of urology in Habib Bourguiba Hospital in Sfax, to the published cases.
RESULTS
A total of 132 cases were collected. Median age at diagnosis was 39 years old (range 10- 83 years). The most common presenting symptom was either a testicular mass or a swelling in 38.46% of cases. Carcinoid syndrome was documented in 10.60% of patients. The clinical examination revealed a palpable mass in 44.70% of patients. This mass was painless and firm in most cases. Serum tumor markers (β-gonadotrophine chorionique humaine, α-feto protein, and lactate dehydrogenase) were within normal limits in all patients except in one case. Most testicular neuroendocrine tumors (76.52%) were primary and pure. The tumors were positive for chromogranin (100%), synaptophysin (100%) and cytokeratin (93.10%). Metastases were detected at time of diagnosis in eight cases (6.06%). The main treatment was radical orchiectomy performed in 127 patients (96.21%). The 5-year overall survival rate was 78.70% and the 5-year specific survival rate was 84.30%.
CONCLUSION
The diagnosis of testicular carcinoids is based on the immunohistochemistry study. The treatment of choice for these tumors is radical orchiectomy. Somatostatin analogues were reported to be effective in patients with carcinoid syndrome.
PubMed: 28559773
DOI: 10.1159/000447146 -
Endocrine-related Cancer Mar 2019Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms,... (Meta-Analysis)
Meta-Analysis
Carcinoid syndrome (CS) is a debilitating disease caused by functional neuroendocrine tumors. Several treatment options are available to alleviate the hormonal symptoms, but their relative efficacy is unknown. Online databases were searched for publications on the treatment of CS symptoms. Independent reviewers assessed relevant publications for study quality and outcome. Meta-analysis of the outcomes of the intervention on CS-related symptoms was stratified by the type of treatment. We found 3682 therapeutic interventions on CS-specific outcomes were collected from 93 studies. Overall, the study qualities were poor with only six randomized controlled clinical trials. The somatostatin analogs octreotide and lanreotide induced symptomatic improvement in 65-72% and biochemical response in 45-46% of patients. An increase in dose or frequency or interclass switch led to a reduction of flushes and/or diarrhea in 72-84% of cases. Retrospective, institutional series showed that liver-directed therapy can improve symptoms in 82% of CS patients with a liver-dominant disease. The serotonin synthesis inhibitor telotristat ethyl reduced bowel movements in 40% of patients with diarrhea refractory to somatostatin analogs. Interferon-alpha controlled CS symptoms in 45-63% of cases. Favorable response has been noted after radionuclide therapy in subgroup analyses of studies not specifically involving CS patients. Chemotherapy and everolimus did not induce a significant response in the CS. We conclude that several treatment lines can be offered to patients suffering from the carcinoid syndrome. Initiation of randomized controlled trials with a primary outcome on carcinoid syndrome symptoms is strongly recommended.
Topics: Female; Humans; Male; Malignant Carcinoid Syndrome; Neuroendocrine Tumors; Treatment Outcome
PubMed: 30608900
DOI: 10.1530/ERC-18-0495 -
World Journal of Gastroenterology Feb 2015To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo... (Review)
Review
AIM
To review literature on efficacy and safety of octreotide-long-acting repeatable (LAR) used at doses higher than the Food and Drug Administration (FDA)-approved 30 mg/mo for treatment of neuroendocrine tumors (NETs).
METHODS
We searched PubMed and Cochrane Library from 1998-2012, 5 conferences (American Society of Clinical Oncology, Endocrine Society, European Neuroendocrine Tumor Society, European Society for Medical Oncology, North American Neuroendocrine Tumor Society) from 2000-2013 using MeSH and keyterms including neuroendocrine tumors, carcinoid tumor, carcinoma, neuroendocrine, and octreotide. Bibliographies of accepted articles were also searched. Two reviewers reviewed titles, abstracts, and full-length articles. Studies that reported data on efficacy and safety of ≥ 30 mg/mo octreotide-LAR for NETs in human subjects, published in any language were included in the review.
RESULTS
The search identified 1086 publications, of which 238 underwent full-text review (20 were translated into English); 17 were included in the review. Studies varied in designs, subjects, octreotide-LAR regimens, and definition of outcomes. Eleven studies reported use of higher doses to control symptoms and tumor progression, although symptom severity and formal quality-of-life analysis were not quantitatively measured. Ten studies reported efficacy, describing 260 subjects with doses ranging from 40 mg/mo or 30 mg/3 wk up to 120 mg/mo. Eight studies reported expert clinical opinion that supported dose escalation of octreotide-LAR up to 60 mg/mo for symptom control and suggested increased doses may be effective at preventing tumor progression. Eight studies reported safety; there was no evidence of increased toxicity associated with doses of octreotide-LAR > 30 mg/mo.
CONCLUSION
As reported in this review, octreotide-LAR at doses > 30 mg/mo is being prescribed for symptom and tumor control in NET patients. Furthermore, expert clinical opinion provided support for escalation of somatostatin analogs for refractory hormonal symptoms.
Topics: Antineoplastic Agents, Hormonal; Gastrointestinal Neoplasms; Humans; Neuroendocrine Tumors; Octreotide; Treatment Outcome
PubMed: 25684964
DOI: 10.3748/wjg.v21.i6.1945