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Head & Neck Aug 2019The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The aim of this study is to investigate and summarize the treatment efficacy and adverse effects (AEs) of sorafenib in the treatment of metastatic medullary thyroid carcinomas (MTCs).
METHODS
We included studies reporting the treatment efficacy or drug toxicity of sorafenib as a single therapeutic agent in MTCs. Pooled incidence and its 95% confidence interval (CI) for complete response, partial response (PR), stable disease (SD), and sorafenib-related AEs were calculated using random-effect model.
RESULTS
Eight trials with 101 metastatic MTCs were included for meta-analyses. The overall PR and SD were 21% (95% CI = 9-33) and 58% (95% CI = 41-75), respectively. Hand-foot syndrome, diarrhea, alopecia, mucositis, skin rash, fatigue, and hypertension were the most commonly observed AEs.
CONCLUSION
Our results show that sorafenib treatment has a modest effect and might be a candidate treatment in patients with metastatic MTCs who have failed other therapeutic regimens.
Topics: Antineoplastic Agents; Carcinoma, Neuroendocrine; Humans; Sorafenib; Thyroid Neoplasms
PubMed: 31162772
DOI: 10.1002/hed.25832 -
Radiotherapy and Oncology : Journal of... Jul 2019In order to clarify the role of external beam radiotherapy in the management of medullary thyroid cancer (MTC), a systematic review was undertaken.
OBJECTIVE
In order to clarify the role of external beam radiotherapy in the management of medullary thyroid cancer (MTC), a systematic review was undertaken.
PATIENTS AND INTERVENTIONS
Patients with MTC of any stage receiving radiotherapy, either as adjuvant postoperative treatment or as primary treatment for unresectable disease.
DESIGN
Electronic searching Medline and ProQuest databases for randomised or non-randomised studies. A risk of bias assessment (ROBINS-I) was carried out for each study.
MAIN OUTCOME MEASURES
Overall survival, rates of locoregional recurrence, locoregional relapse-free survival.
RESULTS
There were no randomised studies. Twenty-seven non-randomised studies were identified. Within four cohort studies, radiotherapy had no significant effect on overall survival. Within one prospective and 22 retrospective studies (of approximately 1200 patients), radiotherapy similarly had no consistent effect on overall survival but there was evidence that radiotherapy reduces the risk of locoregional relapse, particularly in those with nodal involvement, extrathyroidal extension or residual disease. In a meta-analysis of patients within four studies, radiotherapy reduced the risk of locoregional relapse by at least 38%. Evidence supports the use of doses of 60 Gy or greater and an interval between surgery and radiotherapy of less than two months. Thirteen of 63 patients (21%) treated for unresectable disease achieved a complete response. Acute morbidity was observed in relation to difficulty swallowing, xerostomia and skin reactions. Late morbidity was infrequent with a low incidence of xerostomia.
CONCLUSIONS
Radiotherapy should be considered for those at high risk of locoregional relapse, in particular those with nodal involvement, extrathyroidal extension or residual disease (microscopic or macroscopic).
Topics: Carcinoma, Neuroendocrine; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Radiotherapy; Thyroid Neoplasms; Xerostomia
PubMed: 31015112
DOI: 10.1016/j.radonc.2019.03.033 -
Health Technology Assessment... Feb 2019Medullary thyroid cancer (MTC) is a rare form of cancer that affects patients' health-related quality of life (HRQoL) and survival. Cabozantinib (Cometriq; Ipsen, Paris,...
BACKGROUND
Medullary thyroid cancer (MTC) is a rare form of cancer that affects patients' health-related quality of life (HRQoL) and survival. Cabozantinib (Cometriq; Ipsen, Paris, France) and vandetanib (Caprelsa; Sanofi Genzyme, Cambridge, MA, USA) are currently the treatment modality of choice for treating unresectable progressive and symptomatic MTC.
OBJECTIVES
(1) To evaluate the clinical effectiveness and safety of cabozantinib and vandetanib. (2) To estimate the incremental cost-effectiveness of cabozantinib and vandetanib versus each other and best supportive care. (3) To identify key areas for primary research. (4) To estimate the overall cost of these treatments in England.
DATA SOURCES
Peer-reviewed publications (searched from inception to November 2016), European Public Assessment Reports and manufacturers' submissions.
REVIEW METHODS
A systematic review [including a network meta-analysis (NMA)] was conducted to evaluate the clinical effectiveness and safety of cabozantinib and vandetanib. The economic analysis included a review of existing analyses and the development of a de novo model.
RESULTS
The systematic review identified two placebo-controlled trials. The Efficacy of XL184 (Cabozantinib) in Advanced Medullary Thyroid Cancer (EXAM) trial evaluated the efficacy and safety of cabozantinib in patients with unresectable locally advanced, metastatic and progressive MTC. The ZETA trial evaluated the efficacy and safety of vandetanib in patients with unresectable locally advanced or metastatic MTC. Both drugs significantly improved progression-free survival (PFS) more than the placebo ( < 0.001). The NMA suggested that, within the symptomatic and progressive MTC population, the effects on PFS were similar (vandetanib vs. cabozantinib: hazard ratio 1.14, 95% credible interval 0.41 to 3.09). Neither trial demonstrated a significant overall survival benefit for cabozantinib or vandetanib versus placebo, although data from ZETA were subject to potential confounding. Both cabozantinib and vandetanib demonstrated significantly better objective response rates and calcitonin (CTN) and carcinoembryonic antigen (CEA) response rates than placebo. Both cabozantinib and vandetanib produced frequent adverse events, often leading to dose interruption or reduction. The assessment group model indicates that, within the EU-label population (symptomatic and progressive MTC), the incremental cost-effectiveness ratios (ICERs) for cabozantinib and vandetanib are > £138,000 per quality-adjusted life-year (QALY) gained. Within the restricted EU-label population (symptomatic and progressive MTC with CEA/CTN doubling times of ≤ 24 months), the ICER for vandetanib is expected to be > £66,000 per QALY gained. The maximum annual budget impact within the symptomatic and progressive population is estimated to be ≈£2.35M for cabozantinib and ≈£5.53M for vandetanib. The costs of vandetanib in the restricted EU-label population are expected to be lower.
LIMITATIONS
The intention-to-treat populations of the EXAM and ZETA trials are notably different. The analyses of ZETA subgroups may be subject to confounding as a result of differences in baseline characteristics and open-label vandetanib use. Attempts to statistically adjust for treatment switching were unsuccessful. No HRQoL evidence was identified for the MTC population.
CONCLUSIONS
The identified trials suggest that cabozantinib and vandetanib improve PFS more than the placebo; however, significant OS benefits were not demonstrated. The economic analyses indicate that within the EU-label population, the ICERs for cabozantinib and vandetanib are > £138,000 per QALY gained. Within the restricted EU-label population, the ICER for vandetanib is expected to be > £66,000 per QALY gained.
FUTURE RESEARCH PRIORITIES
(1) Primary research assessing the long-term effectiveness of cabozantinib and vandetanib within relevant subgroups. (2) Reanalyses of the ZETA trial to investigate the impact of adjusting for open-label vandetanib use using appropriate statistical methods. (3) Studies assessing the impact of MTC on HRQoL.
STUDY REGISTRATION
This study is registered as PROSPERO CRD42016050403.
FUNDING
The National Institute for Health Research Health Technology Assessment programme.
Topics: Anilides; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Neuroendocrine; Cost-Benefit Analysis; England; Humans; Models, Economic; Piperidines; Pyridines; Quality-Adjusted Life Years; Quinazolines; Technology Assessment, Biomedical; Thyroid Neoplasms
PubMed: 30821231
DOI: 10.3310/hta23080 -
Auris, Nasus, Larynx Jun 2019The survival benefit of prophylactic lateral neck dissection in medullary thyroid carcinomas remains unclear; thus, recent clinical guidelines have deferred the...
OBJECTIVE
The survival benefit of prophylactic lateral neck dissection in medullary thyroid carcinomas remains unclear; thus, recent clinical guidelines have deferred the recommendation of lateral neck dissection. This review is to assess the role of lateral neck dissection in treatment of clinically overt medullary thyroid carcinoma.
METHODS
A meta-analysis was performed on full-text publications written in English sourced using Embase and Medline databases. Publications with data regarding lateral neck dissection and clinical outcome were included.
RESULTS
The frequently performed central neck dissection was significantly correlated with a higher biological cure rate (p=0.047) and lower structural recurrence rate (p=0.002). The frequency of ipsilateral lateral neck dissection was significantly negatively correlated with the rate of died of disease (p=0.017).
CONCLUSION
The frequency of lateral neck dissections and rate of died of disease had a reverse correlation suggesting that prophylactic lateral neck dissection has a significant impact on survival.
Topics: Carcinoma, Medullary; Humans; Neck Dissection; Survival Rate; Thyroid Neoplasms
PubMed: 30237011
DOI: 10.1016/j.anl.2018.08.017 -
Endocrinology and Metabolism (Seoul,... Jun 2018Calcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have...
BACKGROUND
Calcitonin measurement is pivotal in the management of medullary thyroid carcinoma (MTC), but several pitfalls can affect its reliability. Other potential markers have been proposed, and procalcitonin (ProCT) has been reported as promising. The present study was undertaken to summarize the published data and provide more robust estimates on the reliability of ProCT as marker in the management of patients with MTC.
METHODS
The systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The sources comprised studies published through May 2018. Journal Articles that reported series of MTC patients undergone ProCT during postoperative follow-up were searched. A random-effects model was used for statistical pooling of the data. The I² index was used to quantify the consistency among the studies. The Egger test evaluated the possible presence of significant publication bias. Quality assessment of the studies was performed according to Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).
RESULTS
According to inclusion and exclusion criteria five papers, reporting 296 MTC patients undergone ProCT evaluation, were finally selected. The number of MTC with recurrence was 140. The pooled sensitivity of ProCT in detecting recurrence was 96% (95% confidence interval [CI], 92% to 99%), with neither heterogeneity (I²=0%) nor publication bias (Egger test, 3.16; P=0.99). The pooled specificity was 96% (95% CI, 87% to 100%) with mild heterogeneity (I²=66.6%), while Egger test was not calculable.
CONCLUSION
The present meta-analysis provides evidence that ProCT is reliable to manage MTC patients during their postoperative follow-up.
PubMed: 29947178
DOI: 10.3803/EnM.2018.33.2.204 -
Frontiers in Endocrinology 2018Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we...
BACKGROUND
Vandetanib is the most largely used tyrosine kinase inhibitor (TKI) in patients with locally advanced and/or metastatic medullary thyroid cancer (MTC). Here, we conducted a systematic review on its efficacy and attempted to perform a meta-analysis adopting standardized RECIST criteria as end-points.
METHODS
The terms "medullary thyroid" and "protein kinase inhibitor" (then including all TKIs) were searched in PubMed, ClinicalTrials.gov, and CENTRAL. Only original studies reporting the use of Vandetanib as single agent in MTC were included. The last search was performed on October 31, 2017 and registered in PROSPERO on December 12, 2017 (n = CRD42017081537).
RESULTS
The search revealed 487 articles, and, after removing duplicates, reading title and abstract, and screening the eligible papers, 10 studied were finally included. Two papers were randomized controlled trials and eight were observational longitudinal studies. No data were available for overall survival. No heterogeneity nor publication bias were recorded in the pooled rate of complete response (0.7%) and stable disease (47%). Mild to moderate heterogeneity were recorded in the pooled rate of other endpoints. Data of the studies did not allow to perform a meta-analysis of time-to-event outcomes.
CONCLUSION
Vandetanib should be considered as a promising treatment in advanced MTC. However, data based on RECIST endpoints do not currently provide high-level evidence on its efficacy.
PubMed: 29774010
DOI: 10.3389/fendo.2018.00224 -
Endocrine-related Cancer Jun 2018There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at... (Meta-Analysis)
Meta-Analysis
There are ongoing debates with respect to the prognostic roles of molecular biomarkers in sporadic medullary thyroid carcinoma (MTC). In this study, we aimed at investigating the prognostic value of and mutations - the two most common mutations in sporadic MTCs. A search was conducted in four electronic databases. Relevant data were extracted and pooled into odds ratios (OR), mean differences (MD) and corresponding 95% confidence intervals (CI) using the random-effect model. We used Egger's regression test and visual of funnel plots to assess the publication bias. From 2581 studies, we included 23 studies with 964 MTCs for meta-analysis. Overall, the presence of mutation was associated with an elevated risk for lymph node metastasis (OR = 3.61; 95% CI = 2.33-5.60), distant metastasis (OR = 2.85; 95% CI = 1.64-4.94), advanced tumor stage (OR = 3.25; 95% CI = 2.02-5.25), tumor recurrence (OR = 3.01; 95% CI = 1.65-5.48) and patient mortality (OR = 2.43; 95% CI = 1.06-5.57). mutation had no significant prognostic value in predicting tumor aggressiveness. To summarize, our results affirmed that mutation is a reliable molecular biomarker to identify a group of highly aggressive sporadic MTCs. It can help clinicians better assess patient prognosis and select appropriate treatment decisions.
Topics: Carcinoma, Neuroendocrine; Humans; Lymphatic Metastasis; Mutation; Neoplasm Recurrence, Local; Proto-Oncogene Proteins c-ret; Proto-Oncogene Proteins p21(ras); Thyroid Neoplasms
PubMed: 29615431
DOI: 10.1530/ERC-18-0056 -
European Thyroid Journal Jan 2018Positron emission tomography (PET) and PET/CT are functional imaging methods that are widely used in diagnostic procedures in oncology.
BACKGROUND
Positron emission tomography (PET) and PET/CT are functional imaging methods that are widely used in diagnostic procedures in oncology.
OBJECTIVES
The objective of this study was to assess the patient-relevant benefit of PET or PET/CT in patients with thyroid cancer based on a literature review and meta-analysis.
METHODS
A systematic review including studies that had been published until December 2013 was performed. To be included, studies had to prospectively investigate patients with thyroid cancer in a clinical setting of staging, restaging, or diagnosing tumour recurrence.
RESULTS
Out of 3,506 potentially relevant articles, 29 studies were included. No study directly evaluated the benefits of PET. Twenty-eight studies dealt with the diagnostic accuracy of PET or PET/CT, and 1 study evaluated the prognostic value of PET/CT. The authors showed that a positive result of PET/CT in restaging patients with differentiated thyroid cancer yielded a significant decrease in overall survival (hazard ratio, HR 5.01, CI 3.41-6.62). In patients with suspected recurrence of differentiated thyroid cancer, meta-analysis showed higher sensitivity of PET (89.7%, CI 78-99%) and PET/CT (94.3%, CI 87-97%) compared with conventional imaging (65.4%, CI 32-88%) and comparable results for specificity. Due to the low numbers of studies and patients, meta-analyses on medullary carcinoma did not produce meaningful results.
CONCLUSION
The patient-relevant benefits of PET or PET/CT in thyroid cancer could not be evaluated satisfactorily based on the included studies. It remains unclear whether higher diagnostic test accuracy leads to changes in therapeutic strategies and better patient-relevant outcomes.
PubMed: 29594049
DOI: 10.1159/000481707 -
Hormones (Athens, Greece) Oct 2017Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Several articles have demonstrated the high diagnostic performance of somatostatin receptor positron emission tomography (PET) in patients with neuroendocrine tumours (NETs). On the other hand, only a few studies have evaluated the detection rate (DR) of this imaging method in recurrent medullary thyroid carcinoma (MTC). We aimed to perform a systematic review and a meta-analysis of the DR of somatostatin receptor PET or PET/CT in patients with recurrent MTC to add evidence-based data to this setting.
METHODS
A comprehensive computer literature search of studies published in PubMed/MEDLINE and the Cochrane Library Database through May 2017 and regarding somatostatin receptor PET or PET/CT in patients with recurrent MTC was carried out. DR was determined on a per patient-basis. A sub-analysis considering serum calcitonin (Ctn) values was also performed.
RESULTS
Nine studies on the diagnostic performance of somatostatin receptor PET or PET/CT in detecting recurrent MTC were discussed in the systematic review. The meta-analysis of these selected studies provided the following DR on a per patient-based analysis: 63.5% [95% confidence interval (95%CI): 49-77]. Heterogeneity among the selected studies was found. DR of somatostatin receptor PET or PET/CT increased in patients with higher serum Ctn levels (83% for Ctn >500 ng/L).
CONCLUSIONS
In patients with recurrent MTC, somatostatin receptor PET or PET/CT demonstrated a non-optimal DR which increased in patients with higher serum Ctn values. The diagnostic performance of somatostatin receptor PET or PET/CT in recurrent MTC is lower compared to that of the same imaging method in the majority of NETs.
Topics: Carcinoma, Neuroendocrine; Humans; Neoplasm Recurrence, Local; Positron-Emission Tomography; Receptors, Somatostatin; Thyroid Neoplasms
PubMed: 29518756
DOI: 10.14310/horm.2002.1756 -
International Journal of Oral and... Jan 2018Surgery is the most well established mode of initial definitive treatment for the majority of oral cancers. The most important decision in terms of tumour ablation in... (Meta-Analysis)
Meta-Analysis Review
Surgery is the most well established mode of initial definitive treatment for the majority of oral cancers. The most important decision in terms of tumour ablation in oral cancers when the jaws are potentially involved is the management of the mandible. The aim of this study was to explore the differences in survival rate and disease control between patients undergoing marginal mandibulectomy and patients undergoing segmental mandibulectomy using a systematic review and meta-analysis approach. A total of 15 cohort studies, including 1672 participants, were identified. Meta-analysis provided weak evidence in favour of segmental mandibulectomy for local control. Segmental mandibulectomy gave 73% better disease-free survival than marginal mandibulectomy when the marrow was invaded (P=0.04). The overall survival rate was evaluated, and no statistically significant difference was found between the two different mandibulectomy approaches, although the results showed a trend in favour of segmental mandibulectomy which could increase the overall survival by 23%. Based on these findings regarding the survival rate and efficacy of disease control, this study indicates that a marginal mandibulectomy may be recommended for cases with no invasion or superficial invasion of the mandibular cortex, and a segmental mandibulectomy may be a more reasonable choice for patients with extensive mandibular cortex invasion or medullary invasion.
Topics: Carcinoma, Squamous Cell; Humans; Mandibular Osteotomy; Mouth Neoplasms; Survival Rate
PubMed: 28823905
DOI: 10.1016/j.ijom.2017.07.019