FLEX November 2023

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COSTANTINO ET AL .

further studies should be encouraged to define high-risk features able to better select patients that may benefit from a SLNB. Finally, we found a pooled RRR of 2.9%, due to regional recurrence after a negative SLNB. Even if only a minority of patients with cSCCHN suffered from a regional failure, this data should be weighed with the low rate of lymph node metastases found through SLNB. In particular, almost one-third of patients that may arbor occult regional diseases were not diagnosed with a SLNB, and a regional metastasis occurred later during follow up. However, the regional recurrence could not be always considered a direct consequence of an occult node metas tasis at the time of diagnosis, and the time to regional relapse after SLNB could not be extracted from the included studies. Moreover, it was argued that true SLNB false-negatives should be differentiated from regional recurrences due to local recurrences or metachronous lesions. 20 This meta-analysis is subjected to some limitations. First, high heterogeneity was measured between stud ies in all the analyzed outcomes. As already stated above, this may be a consequence of different high-risk criteria used to indicate SLNB. Given the wide range of SLNB positive rate found in the included studies, further efforts should be conducted to better define potential indications to SLNB. Second, a not negligible proportion of patients were recruited in retrospective studies, that are prone to various biases especially regarding patient selection, vari ability in execution and evaluation of the SLNB, and assessment of disease recurrence during patients' follow up. Third, no individual patients' data have been pro vided in the included studies, and no stratified analysis could be performed to better define predictors of positive SLNB and regional recurrence. Only specifically designed prospective multicenter studies may found the adequate combination of high-risk features that can select those few patients that might benefit from SLNB. Finally, there are no data in the current literature suggesting a real sur vival benefit of SLNB in cSCCHN. Further RCTs compar ing patients who undergo SLNB versus observation should be conducted to better define this aspect.

of SLN identification are that: radioactive tracer does not migrate in the lymphatics; low radioactivity counts are measured during the surgical procedure; or no nodal tis sue is identified during the histological examination. As already stated above, several papers demonstrated the feasibility of SLNB in head and neck cutaneous mela noma and mucosal oral cavity tumors. 24 – 28 On the other hand, some aspects should be considered when dealing with a cSCCHN in terms of lymph node basins. In fact, the lymphatic network of the head and neck area is extremely complex if compared to other regions. How ever, regional lymphatic drainage occurs to specific regional lymph nodes in a sequential and predictable manner. 69 – 71 In particular, even if the head and neck skin usually drains to cervical lymph nodes, the primary drainage in intra-parotid lymph nodes should not be underestimated. 72,73 In fact, our analysis performed on more than 500 SLNs showed a parotid location in 18% of lymph nodes. Moreover, if the primary tumor is located on the temple or in the periocular region the risk of intraparotid SLN is up to approximately 40%. This aspect should be taken into account in planning a SLNB. In fact, when the SLN is located into the parotid gland, a lim ited/superficial parotidectomy with facial nerve identifi cation or with facial nerve monitoring is needed to reduce the risk of facial nerve palsy. The surgical proce dure is indeed more complex and its risk – benefit ratio may be revised. Hence, these data raise some concerns about the role of parotid surgery in the management of cSCCHN. In fact, some authors proposed elective parotidectomy for the management of advanced cSCCHN due to the high rate of occult parotid metastases (up to 37%). 74,75 However, few reports have been published, and no survival benefit was measured in clinically node negative cSCCHN. 76 As a con sequence, elective parotidectomy may be recommended only if an involvement of the neck nodes is suspected, according to current evidences. 19 We measured a pooled SLNB positive rate of 5.6%, demonstrating an overall low incidence of lymph node metastases. According to these data, an elective treatment of the neck cannot be recommended in high-risk cSCCHN. However, few aspects should be considered in the evaluation of this result. As already stated above, dif ferent tumor-related and patient-related factors have been proposed as predictors of lymph node metastases. 13 – 16,68 However, various indications to SNLB may be used in different centers. Even if the criteria used in the included studies regarding the definition of high-risk tumors usually adhered to the NCCN guidelines, some differences may be found among different studies. Accordingly, a high degree of between-study heteroge neity was measured, introducing some doubts about the validity of the criteria used. From this perspective,

5 | CONCLUSIONS

SLNB is feasible in cSCCHN given the high SLN identifi cation rate. However, this procedure showed a low inci dence of lymph node metastases, and a relatively high RRR in negative SLNB, raising some doubts concerning its clinical utility. Further studies are mandatory to define predictors of lymph node metastases able to better select patients that may benefit from a SLNB.