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

术后放疗对高风险皮肤鳞状细胞癌疗效及预后因素的系统性综述与荟萃分析：eFigure1. 调整分析总体生存率和无病生存率：排除2010年Kyrgidis研究，采用随机效应模型进行总体生存率分析
eFigure2. 与无病生存率相关的预后因素森林图：本分析揭示了PNI（周围神经侵犯）的恶性影响，AJCC分期系统亦将PNI视为高风险因素之一。此外，根据NCCN指南，PNI的存在可增加cSCC（皮肤鳞状细胞癌）的T分期。令人惊讶的是，本研究中免疫抑制的异质性较高，表明其影响的不确定性，而最新的AJCC癌症分期手册建议将此风险因素作为临床护理患者头颈部cSCC的额外考虑方面。我们将IS（免疫抑制）作为一个总体类别，未进行具体分层，且大部分入选文章也未定义IS。尽管Estall等根据并存血液恶性肿瘤、免疫抑制药物使用和终末期肾病需要透析的患者，确定了IS与转移风险增加的相关性，但荟萃分析难以分析所有具有模糊定义的IS队列。在这种情况下，数据表明，阐明IS的类型对于理解影响DFS（无病生存期）的因素至关重要。
在包括的研究中，辅助放疗的治疗存在高度异质性。一些报道暗示辅助放疗在DFS方面显示出显著的益处，而Harris等和Trosman等发现辅助放疗与DFS之间几乎没有关联。这与2018年NCCN指南一致，其中指出研究人群的多样性复杂化了治疗结果的比较。尽管如此，更准确的N期信息对于进一步分析以确定具有区域性转移的患者是否能够从增加DFS的辅助放疗中受益至关重要。
eFigure3. 复发分析漏斗图
eTable1. 预后风险比总结
eTable2. 包含研究的Newcastle-Ottawa量表评分