Histopathological diagnosis of appendiceal neuroendocrine neoplasms: when to perform a right hemicolectomy? A systematic review and meta-analysis

A broad spectrum of novel targeted therapies with prime antitumor activity and/or ample control of hormonal symptoms together with an overall acceptable safety profile have emerged for patients with metastatic neuroendocrine neoplasms (NENs). In this systematic review and quantitative meta-analysis, the PubMed, EMBASE, Cochrane Central Register of Controlled Trials and clinicaltrials.gov databases were searched to assess and compare the safety profile of NEN treatments with special focus on the cardiovascular adverse effects of biotherapy and molecular targeted therapies (MTTs). Quality/risk of bias were assessed using GRADE criteria. Placebo-controlled randomized clinical trials (RCTs) in patients with metastatic NENs, including medullary thyroid cancer (MTC) were included. A total of 3695 articles and 122 clinical trials registered in clinicaltrials.gov were screened. We included sixteen relevant RCTs comprising 3408 unique patients assigned to different treatments compared with placebo. All the included studies had a low risk of bias. We identified four drug therapies for NENs with eligible placebo-controlled RCTs: somatostatin analogs (SSAs), tryptophan hydroxylase (TPH) inhibitors, mTOR inhibitors and tyrosine kinase inhibitors (TKI). Grade 3 and 4 adverse effects (AE) were more often encountered in patients treated with mTOR inhibitors and TKI (odds ratio [OR]: 2.42, 95% CI: 1.87–3.12 and OR: 3.41, 95% CI: 1.46–7.96, respectively) as compared to SSAs (OR:0.77, 95% CI: 0.47–1.27) and TPH inhibitors (OR:0.77, 95% CI: 0.35–1.69). MTOR inhibitors had the highest risk for serious cardiac AE (OR:3.28, 95% CI: 1.66–6.48) followed by TKIs (OR:1.51, 95% CI: 0.59–3.83). Serious vascular AE were more often encountered in NEN patients treated with mTOR inhibitors (OR: 1.72, 95% CI: 0.64–4.64) and TKIs (OR:1.64, 95% CI: 0.35–7.78). Finally, patients on TKIs were at higher risk for new-onset or exacerbation of pre-existing hypertension (OR:3.31, 95% CI: 1.87–5.86). In conclusion, SSAs and TPH inhibitors appear to be safer as compared to mTOR inhibitors and TKIs with regards to their overall toxicity profile, and cardiovascular toxicities in particular. Special consideration should be given to a patient-tailored approach with anticipated toxicities of targeted NEN treatments together with assessment of cardiovascular comorbidities, assisting clinicians in treatment selection and early recognition/management of cardiovascular toxicities. This approach could improve patient compliance and preserve cardiovascular health and overall quality of life.

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Prognostic factors for relapse in resected gastroenteropancreatic neuroendocrine neoplasms: A systematic review and meta-analysis

Cancer Treatment Reviews ◽

10.1016/j.ctrv.2021.102299 ◽

2021 ◽

pp. 102299

Author(s):

Rachel Broadbent ◽

Roseanna Wheatley ◽

Sabrina Stajer ◽

Timothy Jacobs ◽

Angela Lamarca ◽

...

Keyword(s):

Systematic Review ◽

Prognostic Factors ◽

Meta Analysis ◽

Neuroendocrine Neoplasms ◽

Gastroenteropancreatic Neuroendocrine Neoplasms

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The risk of lymph node metastases and their impact on survival in patients with appendiceal neuroendocrine neoplasms: a systematic review and meta-analysis of adult and paediatric patients

Endocrine ◽

10.1007/s12020-019-02072-y ◽

2019 ◽

Vol 67 (1) ◽

pp. 20-34 ◽

Cited By ~ 4

Author(s):

Kosmas Daskalakis ◽

Krystallenia Alexandraki ◽

Evanthia Kassi ◽

Marina Tsoli ◽

Anna Angelousi ◽

...

Keyword(s):

Systematic Review ◽

Lymph Node ◽

Lymph Node Metastases ◽

Meta Analysis ◽

Neuroendocrine Neoplasms ◽

Paediatric Patients ◽

Impact On Survival ◽

Node Metastases

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Intracorporeal vs extracorporeal anastomosis following neoplastic right hemicolectomy resection: a systematic review and meta-analysis of randomized control trials

International Journal of Colorectal Disease ◽

10.1007/s00384-020-03807-4 ◽

2020 ◽

Cited By ~ 1

Author(s):

B. Creavin ◽

I. Balasubramanian ◽

M. Common ◽

C. McCarrick ◽

S. El Masry ◽

...

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Right Hemicolectomy ◽

Randomized Control Trials ◽

Extracorporeal Anastomosis ◽

Randomized Control

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Calcitonin-secreting neuroendocrine neoplasms of the lung: a systematic review and narrative synthesis

Endocrine Connections ◽

10.1530/ec-21-0071 ◽

2021 ◽

Vol 10 (4) ◽

pp. 447-461

Author(s):

David C Llewellyn ◽

Rajaventhan Srirajaskanthan ◽

Royce P Vincent ◽

Catherine Guy ◽

Eftychia E Drakou ◽

...

Keyword(s):

Systematic Review ◽

Thyroid Carcinoma ◽

Medullary Thyroid Carcinoma ◽

Meta Analysis ◽

A Priori ◽

Neuroendocrine Neoplasm ◽

Neuroendocrine Neoplasms ◽

Cochrane Central Register ◽

Medullary Thyroid ◽

Stimulation Tests

Calcitonin-secreting neuroendocrine neoplasms of the lung are rare, with few cases reported in the literature. Differentiating between medullary thyroid carcinoma and an ectopic source of calcitonin secretion can represent a complex diagnostic conundrum for managing physicians, with cases of unnecessary thyroidectomy reported in the literature. This manuscript reports a case of ectopic hypercalcitonaemia from a metastatic neuroendocrine neoplasm of the lung with concurrent thyroid pathology and summarises the results of a systematic review of the literature. Medical Literature Analysis and Retrieval System Online, Excerpta Medica, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and SCOPUS databases were systematically and critically appraised for all peer reviewed manuscripts that suitably fulfilled the inclusion criteria established a priori. The protocol for this systematic review was developed according to the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols, and followed methods outlined in The Cochrane Handbook for Systematic Reviews of Interventions. This systematic review is registered with PROSPERO. It is vital to consider diagnoses other than medullary thyroid carcinoma when presented with a patient with raised calcitonin, as it is not pathognomonic of medullary thyroid carcinoma. Lung neuroendocrine neoplasms can appear similar to medullary thyroid carcinoma histologically, they can secrete calcitonin and metastasize to the thyroid. Patients with medullary thyroid carcinoma may show stimulated calcitonin values over two or more times above the basal values, whereas calcitonin-secreting neuroendocrine neoplasms may or may not show response to stimulation tests. The present review summarises existing evidence from cases of ectopic hypercalcitonaemia to lung neuroendocrine neoplasms.

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Performance of machine learning-augmented analysis of radiomics for the head and neck cancer histopathological diagnosis: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e18526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e18526-e18526

Author(s):

Sotirios Bisdas ◽

Jade Seguin ◽

Diana Roettger ◽

Daisuke Yoneoka ◽

Faiq Shaikh

Keyword(s):

Machine Learning ◽

Systematic Review ◽

Head And Neck ◽

Meta Analysis ◽

Superior Performance ◽

Support Vector ◽

Histopathological Diagnosis ◽

Weighted Mean ◽

Number Of Patients ◽

Testing Set

e18526 Background: The imaging criteria used for head and neck cancers (HNC) staging are mostly anatomical with basic quantitative measures, such as size, and admittedly radiologists’ reading of images is dependent on their expertise level. Radiomics, a term referring to extracting and investigating higher dimensional data from images, has been suggested to address these shortcomings. Assisted by machine learning (ML), highly efficient prediction models could revolutionise our diagnostic practices. Our goal was to study the role of ML in the histopathological diagnosis of HNC based on radiomics. Methods: A systematic review and meta-analysis was conducted using electronic databases (PubMed, Scopus, EMBASE, Google Scholar) and including MRI, PET, and CT studies in patients with HNC. Our study was aimed only at diagnosis utilising radiomics and artificial intelligence (ML). A PRISMA diagram retracing the steps of this search process was completed. QUADAS-2 and EQUATOR checklists were completed. A weighted mean, a mean and a median of the performance indicators were recorded. Results: 7 studies were found eligible for meta-analysis. Patient sample sizes ranged between 2-107 patients (median: 18). CT was the most common modality used (4/7 studies). All but one studies were retrospective. Support vector machine and random forest techniques were the main ML techniques used but how the model was built was rarely described. Furthermore, studies did not make clear the exact number of patients in the testing set. Other issues included the reporting of the final model performance with few studies reporting confidence intervals and 2 studies not reporting the exact performance metrics. The accuracy values for the testing set ranged from 58% -94.1%. The meta-analysis showed an overall weighted-mean accuracy of 78.53%, a mean of 82.9% and a median of 84.4%. The weighted mean of the sensitivity was 76.5%, the mean was 83.3%, and for specificity was 83.9% and 88.5%., respectively. The AUC was 0.8. The neuroradiologists’ overall accuracy was 50.4% if weighted, and 54.5% if not, and the corresponding accuracy of the ML classifiers were 78.4% and 79.6%. The ML scored an accuracy of 20% higher than the radiologists. Conclusions: The results are overall encouraging, keeping in perspective the possible calculation biases and small number of studies. There is need for better documentation and standardisation of the applied ML models, which show initially superior performance compared to radiologists.

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