Local Control Comparison of Early-Stage Epidermal Skin Cancers Treated With and Without Dermal Image Guidance: A Meta-Analysis

Background Various treatments exist for non-melanoma skin cancer (NMSC), but the mainstay is surgical removal. Superficial radiotherapy (SRT) is one non-surgical technique that has been used for over a century but fell out of favor due to the advent of Mohs micrographic surgery (MMS). A new technology that combines a 22 megahertz (MHz) dermal ultrasound with SRT (US-SRT) enables tumor visualization before, during, and after treatment, and demonstrates increased cure rates and reduced recurrences. Methods We conducted a meta-analysis comparing the local control (LC) of four studies using traditional non-image-guided forms of radiotherapy for NMSC treatment to two seminal studies utilizing high-resolution dermal ultrasound-guided SRT (HRUS-SRT). The four traditional radiotherapy studies were obtained from a comprehensive literature search used in an article published by the American Society of Radiation Oncology (ASTRO) on curative radiation treatment of basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and squamous cell carcinoma in-situ (SCCIS) lesions. The meta-analysis employed a logit as the effect size indicator with Q-statistic to test the null hypothesis. Results LC rates for the 2 US-SRT studies were statistically superior to the 4 traditional therapies individually and collectively. When stratified by histology, statistically superior outcomes for US-SRT were observed in all subtypes with p-values ranging from p < 0.0001 to p = 0.0438. These results validated an earlier analysis using a logistic regression statistical method showing the same results. Conclusion US-SRT is statistically superior to non-image-guided radiotherapies for NMSC treatment. This modality may represent the future standard of non-surgical treatment for early-stage NMSC. ### Competing Interest Statement Dr. Lio Yu is the National Radiation Oncologist for SkinCure Oncology and has received research, speaking and/or consulting support from SkinCure Oncology. He has served on an advisory board for Bayer Pharmaceuticals previously. Mairead Moloney has no conflicts of interest to disclose. Dr. Alison Tran has no conflicts of interest to disclose. Songzhu Zheng has no conflicts of interest to disclose. Dr. James Rogers is a managing member of Summit Analytical, LLC, which was contracted to provide statistical analysis for this study. Dr. James Rogers received payment for the statistical analysis services he performed from, and thereby has a financial relationship with Next Step Business Services, LLC (a closely-held company owned by Dr. Lio Yu). The payment to Dr. Rogers was made to his own closely-held company known as Summit Analytical LLC). ### Funding Statement SkinCure Oncology provided funding for Dr. Lio Yu as an independent contractor for independent researching and writing of this paper. This included reimbursement of professional statistical service fees paid. The sponsor of the study (SkinCure Oncology) was not involved in the study design, collection, analysis, interpretation of data, or writing of the manuscript. Writing of this paper and the submission process was solely that of Dr. Lio Yu and co-authors. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was reviewed by an IRB committee (WIRB-Copernicus Group) and determined to be exempt from IRB approval under 45 CFR 46.104 (d)(4) as it fulfilled one or more of the exemption categories. Specifically, the information obtained is recorded by the investigator in such a manner that the identity of the human subject cannot readily be ascertained directly or through identifiers linked to the subjects, the investigator does not contact the subjects, and the investigator will not re-identify subjects. Any health information used in this study has been de-identified for use in this study. This study was performed in compliance with the pertinent sections of the Helsinki Declaration and its amendments. All methods were carried out in accordance with relevant guidelines and regulations. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Deidentified data are available on request from the corresponding author: Dr. Lio Yu at lio.yu@protonmail.com. Data will be available for request with publication for period of at least 1 year. Additional analyses may be available upon request, including but not limited to all odds and probabilities using logistic regression, conversion of some of the odds to probabilities with asymmetric confidence limits, raw percentages, and raw odds