Supplementary materials

Efficacy and prognostic factors of postoperative radiotherapy for high-risk cutaneous squamous cell carcinoma: a systematic review and meta-analysis

eFigure1. Adjusted analysis of overall survival and disease-free survival:
Overall survival analysis exclude study by Kyrgidis 2010 using the random effects model

eFigure2. Forest plots for prognostic factors relevant to disease-free survival:
Concerning the deleterious impact of PNI demonstrated by our analysis, the AJCC staging system for cSCC also regards PNI as a high risk factor. Besides, our analysis of PNI also was determined robustly since the presence of PNI increases T stage of cSCC in the NCCN guidelines. Surprisingly, immunosuppression in this study showed a high heterogeneity indicating the uncertainty of its influence, whereas the recent AJCC Cancer Staging Manual recommanded this risk factor as additional aspect for clinical care in patients with cSCC of the head and neck region. We included IS as a general category without specific stratification and most selected articles also had not defined the IS. Although Estall et al1 presented IS associated with an increased risk of metastases on the basis of well-defined patients with coexisting hematological malignancy, immunosuppressant use, and end stage renal failure requiring dialysis, it is difficult for a meta-analysis to anlyze all cohorts with vague definition of IS. In this situation, the data suggested that clarification of the types of IS is essential for the comprehension of the factors influencing DFS.
A high heterogeneity was observed among included studies concerning the treatment of adjuvant radiotherapy. Some reporters implied that adjuvant radiotherapy showed significant benefit in DFS, while Harris et al and Trosman et al found little association between adjuvant radiotherapy and DFS. It is consistent with the 2018 NCCN guidelines, in which the diversity of study populations was addressed to complicate the comparison of treatment outcomes. Nonetheless, the more accurate N-stage information is crucial for further analysis to identify whether patients with regional metastases would benefit from adjuvant radiotherapy with increased DFS.

eFigure3. Funnel plot of recurrence analyses
eTable1. Prognostic hazard ratio summarize
eTable2. New-castle Ottawa Scale scoring of included studies