Publications by authors named "S Markar"

234 Publications

Clinical utility and applicability of circulating tumor DNA testing in esophageal cancer: a systematic review and meta-analysis.

Dis Esophagus 2021 Jul 21. Epub 2021 Jul 21.

Department of Surgery and Cancer, Imperial College London, London, UK.

Esophageal cancer is an aggressive malignancy with a relatively poor prognosis even after multimodality therapy. Currently, patients undergo a series of investigations that can be invasive and costly or pose secondary risks to their health. In other malignancies, liquid biopsies of circulating tumor DNA (ctDNA) are used in clinical practice for diagnostic and surveillance purposes. This systematic review summarizes the latest evidence for the clinical applicability of ctDNA technology in esophageal cancer. A systematic review of the literature was performed using MEDLINE, EMBASE, the Cochrane Review and Scopus databases. Articles were evaluated for the use of ctDNA for diagnosis and monitoring of patients with esophageal cancer. Quality assessment of studies was performed using the QUADAS-2 tool. A meta-analysis was performed to assess the diagnostic accuracy of sequencing methodologies. We included 15 studies that described the use of ctDNA technology in the qualitative synthesis and eight studies involving 414 patients in the quantitative analysis. Of these, four studies assessed its utility in cancer diagnosis, while four studies evaluated its use for prognosis and monitoring. The pooled sensitivity and specificity for diagnostic studies were 71.0% (55.7-82.6%) and 98.6% (33.9-99.9%), while the pooled sensitivity and specificity for surveillance purposes were 48.9% (29.4-68.8%) and 95.5% (90.6-97.9%). ctDNA technology is an acceptable method for diagnosis and monitoring with a moderate sensitivity and high specificity that is enhanced in combination with current imaging methods. Further work should demonstrate the practical integration of ctDNA in the diagnostic and surveillance clinical pathway.
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http://dx.doi.org/10.1093/dote/doab046DOI Listing
July 2021

Esophagectomy or Total Gastrectomy for Siewert 2 Gastroesophageal Junction (GEJ) Adenocarcinoma? A Registry-Based Analysis.

Ann Surg Oncol 2021 Jul 13. Epub 2021 Jul 13.

Department of Surgery & Cancer, Imperial College London, London, UK.

Backgrounds: Due to a lack of randomized and large studies, the optimal surgical approach for Siewert 2 gastroesophageal junctional (GEJ) adenocarcinoma remains unknown. This population-based cohort study aimed to compare survival between esophagectomy and total gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma.

Methods: Data from the National Cancer Database (NCDB) from 2010 to 2016 was used to identify patients with non-metastatic Siewert 2 GEJ adenocarcinoma who received either esophagectomy (n = 999) or total gastrectomy (n = 8595). Propensity score-matching (PSM) and multivariable analyses were used to account for treatment selection bias.

Results: Comparison of the unmatched cohort's baseline demographics showed that the patients who received esophagectomy were younger, had a lower burden of medical comorbidities, and had fewer clinical positive lymph nodes. The patients in the unmatched cohort who received gastrectomy had a significantly shorter overall survival than those who received esophagectomy (median, 47 vs. 68 months [p < 0.001]; 5-year survival, 45 % vs. 53 %). After matching, gastrectomy was associated with significantly reduced survival compared with esophagectomy (median, 51 vs. 68 months [p < 0.001]; 5-year survival, 47 % vs. 53 %), which remained in the adjusted analyses (hazard ratio [HR], 1.22; 95 % confidence interval [CI], 1.09-1.35; p < 0.001).

Conclusions: In this large-scale population study with propensity-matching to adjust for confounders, esophagectomy was prognostically superior to gastrectomy for the treatment of Siewert 2 GEJ adenocarcinoma despite comparable lymph node harvest, length of stay, and 90-day mortality. Adequately powered randomized controlled trials with robust surgical quality assurance are the next step in evaluating the prognostic outcomes of these surgical strategies for GEJ cancer.
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http://dx.doi.org/10.1245/s10434-021-10346-xDOI Listing
July 2021

Developing a reporting guideline for artificial intelligence-centred diagnostic test accuracy studies: the STARD-AI protocol.

BMJ Open 2021 Jun 28;11(6):e047709. Epub 2021 Jun 28.

Division of Health Policy and Management, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.

Introduction: Standards for Reporting of Diagnostic Accuracy Study (STARD) was developed to improve the completeness and transparency of reporting in studies investigating diagnostic test accuracy. However, its current form, STARD 2015 does not address the issues and challenges raised by artificial intelligence (AI)-centred interventions. As such, we propose an AI-specific version of the STARD checklist (STARD-AI), which focuses on the reporting of AI diagnostic test accuracy studies. This paper describes the methods that will be used to develop STARD-AI.

Methods And Analysis: The development of the STARD-AI checklist can be distilled into six stages. (1) A project organisation phase has been undertaken, during which a Project Team and a Steering Committee were established; (2) An item generation process has been completed following a literature review, a patient and public involvement and engagement exercise and an online scoping survey of international experts; (3) A three-round modified Delphi consensus methodology is underway, which will culminate in a teleconference consensus meeting of experts; (4) Thereafter, the Project Team will draft the initial STARD-AI checklist and the accompanying documents; (5) A piloting phase among expert users will be undertaken to identify items which are either unclear or missing. This process, consisting of surveys and semistructured interviews, will contribute towards the explanation and elaboration document and (6) On finalisation of the manuscripts, the group's efforts turn towards an organised dissemination and implementation strategy to maximise end-user adoption.

Ethics And Dissemination: Ethical approval has been granted by the Joint Research Compliance Office at Imperial College London (reference number: 19IC5679). A dissemination strategy will be aimed towards five groups of stakeholders: (1) academia, (2) policy, (3) guidelines and regulation, (4) industry and (5) public and non-specific stakeholders. We anticipate that dissemination will take place in Q3 of 2021.
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http://dx.doi.org/10.1136/bmjopen-2020-047709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240576PMC
June 2021

Guideline Assessment Project II: statistical calibration informed the development of an AGREE II extension for surgical guidelines.

Surg Endosc 2021 Aug 22;35(8):4061-4068. Epub 2021 Jun 22.

Department of Primary Education, School of Education, University of Ioannina, 451 10, Ioannina, Greece.

Objective: To inform the development of an AGREE II extension specifically tailored for surgical guidelines. AGREE II was designed to inform the development, reporting, and appraisal of clinical practice guidelines. Previous research has suggested substantial room for improvement of the quality of surgical guidelines.

Methods: A previously published search in MEDLINE for clinical practice guidelines published by surgical scientific organizations with an international scope between 2008 and 2017, resulted in a total of 67 guidelines. The quality of these guidelines was assessed using AGREE II. We performed a series of statistical analyses (reliability, correlation and Factor Analysis, Item Response Theory) with the objective to calibrate AGREE II for use specifically in surgical guidelines.

Results: Reliability/correlation/factor analysis and Item Response Theory produced similar results and suggested that a structure of 5 domains, instead of 6 domains of the original instrument, might be more appropriate. Furthermore, exclusion and re-arrangement of items to other domains was found to increase the reliability of AGREE II when applied in surgical guidelines.

Conclusions: The findings of this study suggest that statistical calibration of AGREE II might improve the development, reporting, and appraisal of surgical guidelines.
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http://dx.doi.org/10.1007/s00464-021-08604-wDOI Listing
August 2021