FLEX November 2023

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COSTANTINO ET AL .

performed to identify potential influential studies for SLN identification rate, SLNB positive rate, and RRR. In particular, a leave-one-out meta-analysis was performed to test the influence of each included study on the overall effect and I 2 heterogeneity. Scatter plots (Baujat plot) were created for each outcome. 42 The horizontal axis ( x -axis) shows the contribution of each study to the over all Q test statistic for heterogeneity. The standardized difference of the overall treatment effect is plotted on the vertical axis, showing the influence of each study on the pooled effect size. A meta-regression was performed using a mixed-effects model to explore the relationship between the SLNB technique and the SLN identification rate, SLNB positive rate, and RRR. Analysis of publication bias was performed by visual inspection of the funnel plot and using the Peters' linear regression test, 43 which statistically examines the asym metry of the funnel plot. All the analyses were performed using the R software for statistical computing (R version 4.0.1; “ meta ” and “ dmetar ” packages). Statistical significance was defined as p < 0.05. Figure 1 shows the flowchart of the study identification process. A total of 1324 potentially relevant publications was retrieved from the preliminary search on electronic databases. After automatic duplicates removal, both title and abstract of 987 articles were reviewed. Then, 93 full text manuscripts were assessed for eligibility. After apply ing the abovementioned inclusion and exclusion criteria, 20 studies 44 – 63 were included in the qualitative and quan titative synthesis. The reasons behind the exclusion of 73 studies are shown in Figure 1. Study's general characteristics are summarized in Table 1. A total of 705 patients (males: 77.5%, n = 340/439) with a median age of 71.5 years ( n = 455, 95%CI: 65 – 73) were included. All patients suffered from a clinically node nega tive sSCCHN, while the specific criteria for the definition of high-risk tumors are described in Table 1. The majority of included tumors were localized on the cheek, temple, or forehead ( n = 163, 23.1%), the scalp ( n = 110, 15.6%), the lip ( n = 109, 15.6%), and the ear ( n = 81, 11.5%). Less com mon tumor sites were the nose ( n = 34, 4.8%), the neck ( n = 17, 2.4%), the periorbital region ( n = 11, 1.6%), and 3.2 | Studies description 3 | RESULTS 3.1 | Literature search results

(SD = 19.1)

(range 7 – 44)

(%) FU (months)

lymphoscintigraphy + Gamma probe + Blue dye 5/5 (100%) 2/5 (40%) 1/3 (33%) Median 14

SPECT/CT and/or Planar lymphoscintigraphy + Gamma probe 83/88 (94%) 5/83 (6%) 4/78 (5%) Mean 19.9

84/84 (100%) 4/84 (5%) NA NA

lymphoscintigraphy + Gamma probe + Blue dye SPECT/CT + Gamma probe + Blue dye 7/7 (100%) 1/7 (14%) 0/6 (0%) NA Planar

RRR

SLNB

positive

rate (%)

SLN

identification (%)

SPECT/CT + Planar

Study N (male) Age (range) Criteria for high risk SLNB technique Tremblay-Abel et al. 60 84 (NA) NA Tumor size >2 cm; poor differentiation; PNI of nerves with a diameter >0.1 mm; tumor invasion beyond fat Vuthaluru et al. 61 7 (NA) NA Involving more than one third of the eyelid Wagner et al. 62 5 (NA) Median 81 (range 65 – 93) Wu et al. 63 84 (68) Mean 69 (range 17 – 89)

Tumor size >4 cm; invasive of deep connective skeletal or muscular

structures; recurrent tumor; tumor size >2 cm in immunosuppressed patients

At least 2 of: tumor size >2 cm; poor differentiation; PNI; tumor invasion beyond fat

TABLE 1 (Continued)

Abbreviations: ALI, angiolymphatic invasion; FU, follow-up; NA, not available; NCCN, National Comprehensive Cancer Network; PNI, perineural invasion; RRR, regional recurrence rate; SLN, sentinel lymph node; SLNB, sentinel lymph node biopsy.