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      Diagnostic Efficacy of Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Meta-Analysis of 66 Studies

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      PLoS ONE
      Public Library of Science

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          Abstract

          Objectives

          The diagnostic efficacy of sentinel lymph node biopsy(SLNB) in early oral squamous cell carcinoma(OSCC) still remains controversial. This meta-analysis was conducted to assess the diagnostic value of SLNB in clinically neck-negative T1-2 OSCC.

          Methods

          A systematic literature search for relevant literature published up to September 11, 2016 was conducted in PubMed, Embase, Web of Science, Cochrane Library and ClinicalTrials, and the reference lists of eligible studies were examined. Data from different studies were pooled to estimate the summary sentinel lymph node(SLN) identification rate, sensitivity, negative predictive value. Summary receiver operator characteristic curve(SROC) was plotted and area under the SROC curve (AUC) was calculated to evaluate the overall diagnostic efficacy. Threshold effect was assessed with use of the spearman correlation coefficient. Between-study heterogeneity was tested using the Q tests and the I 2 statistics. Subgroup analyses were conducted in view of the greater effect of different study characteristics on diagnostic efficacy of SLN. Deeks’ funnel plot asymmetry test was performed to evaluate publication bias. Sensitivity analysis was evaluated through omitting studies one by one and comparing the pooled results of random-effects model and fixed-effects model. All analyses were performed using Review Manager (version 5.3.5), Meta-DiSc (version 1.4), Comprehensive Meta Analysis (version 2.0) and STATA (version 12).

          Results

          66 studies comprising 3566 patients with cT1-2N0 OSCC were included in this meta-analysis. The pooled SLN identification rate was 96.3%(95% CI: 95.3%-97.0%). The pooled sensitivity was 0.87 (95% CI: 0.85–0.89), pooled negative predictive value was 0.94 (95% CI: 0.93–0.95), and AUC was 0.98 (95% CI: 0.97–0.99). Subgroup analyses indicated that SLN assessment with immunohistochemistry(IHC) achieved a significantly higher sensitivity than without IHC.

          Conclusions

          This meta-analysis suggests that SLNB has a high diagnostic accuracy in cT1-2N0 oral squamous cell carcinoma, and is an ideal alternative to elective neck dissection. Furthermore, the use of IHC can significantly improve SLNB diagnostic sensitivity for early OSCC.

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          Most cited references55

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          Sentinel European Node Trial (SENT): 3-year results of sentinel node biopsy in oral cancer.

          Optimum management of the N0 neck is unresolved in oral cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis. The object of this study was to establish whether the technique was both reliable in staging the N0 neck and a safe oncological procedure in patients with early-stage oral squamous cell carcinoma.
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            Sentinel lymph node biopsy accurately stages the regional lymph nodes for T1-T2 oral squamous cell carcinomas: results of a prospective multi-institutional trial.

            The validity of sentinel lymph node biopsy (SLNB) for T1 or T2, clinically N0, oral cancer was tested by correlation of sentinel node pathologic status with that of nodes within the completion neck dissection. This prospective, cooperative group trial involved 25 institutions over a 3-year period. One hundred forty patients with invasive oral cancers, stage T1 and T2, N0 including 95 cancers of the tongue, 26 of the floor of mouth, and 19 other oral cancers were studied. The study excluded lesions with diameter smaller than 6 mm or minimal invasion. Imaging was used to exclude nonpalpable gross nodal disease. Patients underwent injection of the lesion with (99m)Tc-sulfur colloid, nuclear imaging, narrow-exposure SLNB, and completion selective neck dissection. The major end point was the negative-predictive value (NPV) of SLNB. In the 106 SLNBs, which were found to be pathologically and clinically node-negative by routine hematoxylin and eosin stain, 100 patients were found to have no other pathologically positive nodes, corresponding to a NPV of 94%. With additional sectioning and immunohistochemistry, NPV was improved to 96%. In the forty patients with proven cervical metastases, the true-positive rate was 90.2% and was superior for tongue tumors relative to floor of mouth. For T1 lesions, metastases were correctly identified in 100%. For T1 or T2 N0 oral squamous cell carcinoma, SLNB with step sectioning and immunohistochemistry, performed by surgeons of mixed experience levels, correctly predicted a pathologically negative neck in 96% of patients (NPV, 96%).
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              Sentinel node biopsy for oral and oropharyngeal squamous cell carcinoma of the head and neck.

              The aims were to assess the technical feasibility of sentinel node biopsy (SNB), to validate SNB against elective neck dissection, and to report the results of the clinical application of the SNB concept for early oral and oropharyngeal squamous cell carcinoma. Prospective consecutive cohort analysis. Between 2000 and 2006, a total of 79 patients were included. Lymphatic mapping consisted of preoperative lymphoscintigraphy and intraoperative use of a hand-held gammaprobe. Twenty-eight patients were assessed for feasibility and validation; the SNB was done in context with an elective neck dissection. Fifty-one patients were evaluated in an observational trial; elective neck dissection was performed only in case of positive SNB. Validation revealed a sentinel node detection rate by lymphoscintigraphy of 93%, with the gammaprobe of 100%. The negative predictive value of a negative SNB was 100%. During the observational trial 40% of the patients were upstaged as a result of a positive SNB. Intraoperative frozen section analysis showed a negative predictive value of 83%. Two patients (6%) with negative SNB experienced a neck recurrence, the negative predictive value of SNB was therefore 94%. Patients with positive SNB were treated successfully with elective neck dissection. SNB is technically feasible and reproducible with a high sentinel node detection rate. Validation against elective neck dissection revealed a negative predictive value of 100%. Application of the SNB concept in clinical practice was very successful. The recurrence rate within the neck was very low and the morbidity and cost of an elective neck dissection could be spared to 60% of the patients.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                20 January 2017
                2017
                : 12
                : 1
                : e0170322
                Affiliations
                [1 ]Department of Head and Neck, Cancer Hospital of Shantou University Medical College, Shantou, China
                [2 ]Department of Otolaryngology-Head and Neck Surgery, University of Arizona College of Medicine, Tucson, Arizona, United States of America
                Texas A&M University, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                • Conceptualization: MYL SJW HWP.

                • Data curation: MYL SJW YXH.

                • Formal analysis: MYL SJW YXH.

                • Investigation: MYL SJW YXH.

                • Methodology: MYL SJW HWP.

                • Project administration: HWP.

                • Supervision: HWP.

                • Visualization: MYL SJW.

                • Writing – original draft: MYL.

                • Writing – review & editing: SJW HWP.

                Author information
                http://orcid.org/0000-0002-6754-2627
                Article
                PONE-D-16-44971
                10.1371/journal.pone.0170322
                5249063
                28107500
                5a3905d5-124a-4468-8e46-d196b03a5fc4
                © 2017 Liu et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 12 November 2016
                : 3 January 2017
                Page count
                Figures: 6, Tables: 2, Pages: 18
                Funding
                The authors received no specific funding for this work.
                Categories
                Research Article
                Research and Analysis Methods
                Mathematical and Statistical Techniques
                Statistical Methods
                Meta-Analysis
                Physical Sciences
                Mathematics
                Statistics (Mathematics)
                Statistical Methods
                Meta-Analysis
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Biology and Life Sciences
                Anatomy
                Lymphatic System
                Lymph Nodes
                Medicine and Health Sciences
                Anatomy
                Lymphatic System
                Lymph Nodes
                Medicine and Health Sciences
                Diagnostic Medicine
                Cancer Detection and Diagnosis
                Lymphatic Mapping
                Medicine and Health Sciences
                Oncology
                Cancer Detection and Diagnosis
                Lymphatic Mapping
                Research and Analysis Methods
                Specimen Preparation and Treatment
                Specimen Sectioning
                Medicine and Health Sciences
                Oncology
                Cancers and Neoplasms
                Carcinomas
                Squamous Cell Carcinomas
                Research and Analysis Methods
                Histochemistry and Cytochemistry Techniques
                Immunohistochemistry Techniques
                Research and Analysis Methods
                Immunologic Techniques
                Immunohistochemistry Techniques
                Medicine and Health Sciences
                Oncology
                Metastasis
                Medicine and Health Sciences
                Oncology
                Basic Cancer Research
                Metastasis
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

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