Background/Objectives: ACEIs protect against radiation pneumonitis by reducing angiotensin II production, oxidative stress, and inflammation. This study highlights the significance of concurrent angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) use in radiotherapy by evaluating its impact on radiotherapy-related side effects and survival outcomes, addressing the gap in existing research and providing insights to guide clinical practice in oncology. Methods: The literature was retrieved from the MEDLINE, EMBASE, Web of Science, and Scopus databases from January 2000 to October 2024. Studies on adults (≥18 years) with histologically confirmed cancer, receiving ACEIs or ARBs during radiotherapy, were included. Radiotherapy-related side effects and clinical outcomes were analysed using odds ratios (ORs) and 95% confidence intervals (95%CIs), comparing ACEI/ARB users to non-users. Differences in the median survival time, recurrence, and death rates were also calculated. Results: Sixteen studies (14 cohort studies and two randomised trials) were included. ACEI users exhibited a 50% reduction in the risk of ≥grade 2 radiation pneumonitis (OR: 0.50, 95%CI: 0.32–0.77) in lung cancer and significant reductions in the odds of proctitis (80%, OR: 0.20, 95%CI: 0.12–0.33), haematuria (75%, OR: 0.25, 95%CI: 0.16–0.41), and rectal bleeding (61%, OR: 0.39, 95%CI: 0.30–0.51) in prostate cancer. ACEI/ARB users showed reduced symptomatic radiation necrosis in brain metastases and better 6-month functional independence in supratentorial glioblastoma. Among six studies reporting survival, ACEI/ARB users had longer median survival in early-stage non-small-cell lung cancer and glioblastoma but shorter survival in small cell lung cancer and brain metastases. ARB users had inconsistent survival rates for lung cancer. The varying survival outcomes suggest that ACEIs/ARBs have different effects depending on the cancer type and stage, potentially influenced by cancer-specific factors, treatment protocols, or disease progression. Conclusions: ACEI use is associated with a reduction in radiation pneumonitis, but evidence for other radiotherapy-related toxicity and survival outcomes remains inconsistent across cancer types and severities. Further research should carefully control for confounders.

Background: It remains unclear whether metformin, a widely used antidiabetic medication, has any influence on the survival outcomes or treatment-related toxicities of radiotherapy in cancer patients. Given metformin’s potential anti-cancer properties, including its ability to inhibit tumour growth through the modulation of cellular metabolism and enhancement of radiosensitivity, its impact on radiotherapy outcomes warrants thorough investigation. This study aimed to evaluate the impact of metformin on survival and adverse events among cancer patients receiving radiotherapy. Methods: Database searches were conducted in MEDLINE, EMBASE, Web of Science, Scopus, and PubMed (2000–2025) to retrieve studies of adults with cancer treated with radiotherapy and concurrent metformin. Metformin users were compared with non-users. The pooled overall survival rate was presented in terms of odds ratio (OR) and 95% confidence interval (95%CI). Diabetic subgroup analyses and meta-regression by cancer type were conducted. ORs and 95%CIs of radiotherapy-related adverse events were presented by cancer type. Results: This study identified 25 articles. The pooled overall survival rate showed no significant difference between metformin users and non-users across subgroups (ORs: 1.00–1.77). Conflicting survival trends were observed for prostate, oesophageal, and non-small cell lung cancer across diabetic conditions. Metformin users with breast cancer exhibited a significantly lower risk of heart failure (OR: 0.72; 95%CI: 0.56–0.94) and heart events (OR: 0.72; 95%CI: 0.59–0.88). Conclusions: Metformin did not significantly impact overall survival but may reduce heart-related adverse events in breast cancer patients based on limited data. Further research is needed on cancer types and diabetic conditions.

Introduction: Current treatments for patients with stage III non-small-cell lung cancer (NSCLC) are not sufficiently personalized, resulting in suboptimal outcomes and high mortality rates. The Developing Circulating and Imaging Biomarkers Towards Personalized Radiotherapy in Lung Cancer (VIGILANCE) study employs innovative health technologies to collect a range of clinical data and features. This includes longitudinal analyses of cell-free and circulating tumor DNA from blood samples and radiomic features extracted from standard-of-care imaging. Additionally, patient-reported outcome measures will be collected to capture patients’ symptoms and quality of life. This will provide invaluable insight into the patient experience during and after radiotherapy. We aim to evaluate whether the data, including patient-reported outcomes, can serve as biomarkers to refine treatment strategies, improve post-treatment follow-up and provide patients with realistic outcome predictions. Key endpoints include the following: (1) assessing whether baseline ctDNA status and its early on-treatment dynamics can identify patients with radioresistant disease who could benefit from treatment intensification; (2) determining whether post-radiotherapy ctDNA clearance can predict benefit from consolidation durvalumab, potentially sparing ctDNA-negative patients from unnecessary immunotherapy; and (3) developing integrated models combining novel ctDNA and radiomic biomarkers to distinguish between radiation fibrosis and tumor recurrence and to predict survival. We adopt a pragmatic approach by recruiting patients receiving standard-of-care treatments in a real-world setting. In addition, most of the clinical data is already routinely collected in our center, except for the blood tests for cell-free and circulating tumor DNA analysis. Methods and analysis: This is a single-center, prospective, exploratory, longitudinal, follow-up study, recruiting patients with stage III NSCLC undergoing standard-of-care curative-intent radiotherapy (with or without systemic therapy). Data collection spans from baseline to during radiotherapy and is extended up to 1 year following radiotherapy. The longitudinal analysis aims to describe and characterize dynamic changes in the collected features and assess their utility as prognostic and response biomarkers. Trial registration number: NCT06086574.