# Chemotherapy-Free Treatment with Radiotherapy and Immunotherapy for Locally Advanced Non-Small Cell Lung Cancer

## TL;DR

This paper investigates combining radiotherapy and immunotherapy as a chemotherapy-free treatment for advanced lung cancer, showing early promise with fewer side effects.

## Contribution

The paper proposes and reviews chemotherapy-free regimens combining radiotherapy and immunotherapy for locally advanced non-small cell lung cancer.

## Key findings

- Phase I/II trials showed one-year progression-free survival rates ranging from 39% to 76%.
- Toxicity was generally acceptable, though higher-grade adverse events occurred in older, frail patients.
- Biomarkers like PD-L1 and TMB may help identify patients who benefit most from this treatment.

## Abstract

This article explores new treatment strategies for patients with advanced non-small cell lung cancer that has not spread. Traditionally, these patients receive a combination of chemotherapy and radiation, but many cannot tolerate chemotherapy due to age or health conditions. We review studies investigating whether radiation combined with therapies which help the immune system fight cancer could be a safer and effective alternative. Early results show that this approach may work well and cause fewer side effects; however, more large-scale studies are needed to confirm these early results.

Background: Concurrent chemoradiotherapy (CRT) followed by immunotherapy is a standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), yet many patients are ineligible due to treatment-related toxicity or poor functional status. Chemotherapy-free approaches using radiotherapy (RT) and immunotherapy may offer a safer and equally effective alternative in select patient populations. Methods: A comprehensive literature review was conducted using PubMed, Google Scholar, and relevant conference proceedings focusing on trials between 2000 and 2024. Studies investigating chemotherapy-free regimens combining RT and immunotherapy in LA-NSCLC were analyzed, with emphasis on clinical outcomes, biomarker use, treatment sequencing, radiation dose/fractionation, and safety. Results: Multiple Phase I/II trials reported promising efficacy with one-year progression-free survival (PFS) ranging from 39% to 76%. Toxicity was generally acceptable, though higher-grade adverse events were more frequent in older, frail populations. Trials integrating PD-L1 expression, tumor mutational burden (TMB), and circulating tumor DNA (ctDNA) showed potential for improved patient stratification. Variation in immunotherapy timing (induction, concurrent, or consolidation) and radiation schedules highlight the need for optimization. Conclusions: Chemotherapy-free regimens represent a promising treatment strategy for patients with LA-NSCLC, especially those that are ineligible for standard CRT. Biomarker-driven patient selection and the rational integration of RT and immunotherapy are critical to improving outcomes. Randomized trials are warranted to establish the efficacy and safety of these emerging approaches.