BRIEF RESEARCH REPORT article
Front. Oncol.
Sec. Radiation Oncology
Outcomes and Toxicity of Concomitant Radioimmunotherapy following PD-1 blockade for Locally Advanced and Metastatic Cutaneous Squamous Cell Carcinoma
Provisionally accepted
Ari Azad Kassardjian1*
Colton Ladbury1
Andrew Tam1
Sean Maroongroge1Yan Xing2Ramya Muddasani2Badri Modi2
Arya Amini1- 1City of Hope Department of Radiation Oncology, Duarte, United States
- 2City of Hope Duarte Main Campus, Duarte, United States
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
Introduction Immune checkpoint inhibitors (ICI) effectively treat advanced cutaneous squamous cell carcinoma (cSCC), yet some patients continue to have disease progression. Combining radiation therapy (RT) with ICI represents a potential therapeutic option, yet limited data exist regarding oncologic outcomes and safety profile. Methods This retrospective cohort study examined patients treated with concurrent ICI and RT between April 2019 and November 2022 and stratified by locally advanced or metastatic status. Outcomes included locoregional control (LRC), freedom from distant metastases (FFDM), progression-free survival (PFS), overall survival (OS), and toxicity. Statistical analysis was performed using Kaplan-Meier or Fine-Gray competing risk survival analyses. Results Thirteen patients (median age 77 years) with locally advanced (53.8%) or metastatic (46.2%) cSCC on cemiplimab (84.6%) or pembrolizumab (15.4%) received concomitant RT using intensity-modulated radiotherapy (69.2%) or stereotactic body radiotherapy (30.8%). With median follow-up of 15.4 months, overall 1-year and 2-year outcomes were OS: 75.2% and 62.7%; PFS: 59.8% and 25.6%; FFDM: 83.8% and 62.4%; LRC 100% and 84.3%, respectively. Locally advanced patients had significantly greater LRC than metastatic patients (100% vs. 56.3%; p<0.001), but no significant difference in PFS, FFDM, or OS. Only one patient experienced grade 3 radiation dermatitis, with no grade 4+ toxicities. Conclusion Radioimmunotherapy demonstrated favorable oncologic outcomes with minimal toxicity. Addition of consolidative RT to ICI therapy may represent a safe and effective approach for this challenging patient population, warranting further prospective investigation.
Keywords: Cutaneous squamous cell carcinoma (cSCC), Immune checkpoint inhibitor (ICI), Stereotactic body radiation therapy (SBRT), Intensity modulated radiation therapy (IMRT), Immunotherapy, Concurrent radiation therapy
Received: 05 Aug 2025; Accepted: 04 Nov 2025.
Copyright: © 2025 Kassardjian, Ladbury, Tam, Maroongroge, Xing, Muddasani, Modi and Amini. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Ari Azad Kassardjian, akassardjian@gmail.com
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.