FLEX November 2023

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COSTANTINO ET AL .

2.2 | Data source and study searching

Moreover, no clear benefit has been measured in terms of survival compared to clinical observation. 23 In this con text, an alternative surgical option in clinically node neg ative high-risk cSCCHN is sentinel lymph node biopsy (SLNB), which potentially reduces the risks and morbid ity associated with the more invasive END. SLNB has been validated as an accurate technique for the assess ment of regional nodal basins in several cancers, such as cutaneous melanoma 24,25 and mucosal oral cavity tumors. 26 – 28 Several papers have been published about the potential application of SLNB in the management of cSCCHN, 29 – 31 but current clinical guidelines have not clearly defined recommendations. 17 – 19 The aim of this study was to perform a systematic review and meta-analysis to better define the role of SLNB in cSCCHN. In particular, the primary aim was to define the SLNB positive rate in cSCCHN to clarify whether an elective regional treatment could be rec ommended. In addition, secondary purposes were to define the SLNB feasibility, and the regional disease con trol obtained with this procedure.

Scopus, PubMed/MEDLINE, Cochrane Library, and Goo gle Scholar databases were searched for relevant publica tions. Relevant keywords, phrases, and medical subject headings (MeSH) terms were used according to each database requirement. As an example, the following sea rch strategy was used for PubMed/MEDLINE: ((skin) OR (cutaneous)) AND ((squamous cell) OR (nonmelanoma)) AND ((cancer) OR (carcinoma) OR (tumor)) AND ((sen tinel node) OR (sentinel lymph node)). The other searches were adjusted to fit the specific requirements for each database. The reference lists of all papers selected for full-text assessment and all retrieved systematic and narrative reviews were examined for search completion. The “ cited by ” function on Google Scholar was used to minimize the risk of missing relevant data. The last research was performed on January 6th, 2022. Literature searches were conducted independently by two investigators (L.C. and B.M.F.). Records identified through database searching were merged and the dupli cates removed using the reference management software EndNote ® X9 (version X9.3.3). The two investigators (L.C. and B.M.F.) separately reviewed the abstract of each publication, and then performed a close reading of all papers to minimize selection bias and errors. A third author (A.C.) solved eventual conflict between reviewers. The most updated and inclusive data for each study were chosen for abstraction. Systematic data extraction from the included studies was made using a structured form, and data were archived in a customized Excel ® (Microsoft Corp, Seattle, Washington, USA) spreadsheet. In particu lar, two authors (L.C. and B.M.F.) extracted the following characteristics of the included studies: study design, num ber of patients, patient demographics, tumors characteris tics, criteria for high-risk tumors, SLNB technique, SLN identification rate, SLN basin, SLNB positive rate, RRR after negative SLNB, and patients' follow-up. Finally, another author (A.C.) checked for accuracy. 2.3 | Data collection process

2 | MATERIALS AND METHODS

This study adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) state ment. 32 Institutional review board approval and informed consents were not required for this study, since all the reported data were obtained from the available published literature. No review protocol was registered for this study.

2.1 | Eligibility criteria

This systematic review was conducted according to the PICOS tool 33 : Patients (P), adults suffering from cSCCHN; Intervention (I), SLNB; Comparator (C), none; Outcomes (O), SLNB positive rate (primary outcome), sentinel lymph node (SLN) identification rate, and regional recurrence rate (RRR) after negative SLNB (secondary outcomes); Study design (S), retrospective and prospective cohort studies, and randomized clinical trials (RCTs). Studies were excluded if they (a) were not in English, (b) were not available in full text form, (c) reported insufficient data or data were not extractable, (d) were ongoing projects, (e) included patients with other primary tumor sites, (f) included patients who underwent previous neck treatment, (g) included less than five patients, (h) were subgroup analyses of patients from a larger study, or (i) the article type was either a review, case report, conference abstract, letter to the editor, or book chapter. No publication date restriction was imposed, and articles had to be published in a peer-reviewed journal.

2.4 | Risk of bias and study quality assessment

Methodological quality of the included studies was assessed independently by two investigators (L.C. and B.M.F.) using the National Institute for Health and Clinical Excellence (NICE) quality assessment tool. 34 A funnel plot was created using the effect size for SLNB