Background: Tumor-infiltrating immune cells have been correlated with prognosis for patients treated with immune checkpoint inhibitor (ICI) treatment of various cancers. However, no robust biomarker has been described to predict treatment response yet. We hypothesized that the activation potency of circulating T cells may predict response to ICI treatment. Methods: An exploratory analysis was conducted to investigate the association between the response to immune checkpoint inhibition (ICI) combined with stereotactic radiotherapy (SBRT) and the potency of circulating T cells to be activated. Blood-derived lymphocytes from 14 patients were stimulated ex vivo with, among others, Staphylococcal enterotoxin B (SEB) and compared to healthy controls (HCs). Patients were grouped into responders (>median progression free survival (PFS)) and non-responders (<median PFS). The expression of the T cell activation marker CD69 and intracellular cytokines (IL-2, IFNγ, TNFα) in both CD4+ and CD8+ T cells in response to stimulation was measured using flow cytometry. In addition, serum levels of BAFF, IFNγ, and IL-2 receptor (sIL-2R) were measured by Luminex. Results: At baseline, a higher percentage of activated CD8+ T cells (15.8% vs. 3.5% (p = <0.01)) and IL-2+CD69+CD8+ T cells (8.8% vs. 2.9% (p = 0.02)) was observed in responders compared to non-responders upon ex vivo stimulation with SEB. The concurrently measured serum cytokine levels were not different between responders and non-responders. Conclusion: Baseline blood CD8+ T cell activation potency, measured by intracellular cytokine production after ex vivo stimulation, is a potential biomarker to discriminate responders from non-responders to SBRT combined with ICI.
22 February 2025 in Clinical and Translational Radiation Oncology
Quality of life (QoL) of patients with inoperable lung cancer can be negatively affected by both the disease and its treatment, generally consisting of (chemo)radiotherapy. The aim of this study was to prospectively assess QoL in patients with inoperable lung cancer, treated with (chemo)radiotherapy and to assess whether patient- and/or treatment-related characteristics were associated with poorer QoL. This prospective cohort study evaluated QoL and patient-, tumor-, and treatment characteristics from inoperable lung cancer patients, treated with fractionated (≥40 Gy) (chemo)radiotherapy. Patients were evaluated at baseline, upon finishing radiotherapy, and 3 months, 6 months, 1 year, and yearly thereafter up to 5 years after radiotherapy. The QoL assessment consisted of questionnaires evaluating lung cancer-specific and treatment-related complaints using scale scores. Compliance rates of the 574 analyzed patients ranged from 87 to 97 % during follow-up. Complaints increased after radiotherapy, as the QoL scale scores increased from median 8 (interquartile range, IQR 4-14) to 17 (IQR 4-25) after completing radiotherapy (P < 0.0004), indicating more complaints. From 3 months to 24 months of follow-up, scale scores returned to a median of 13, but were significantly higher compared to baseline (P < 0.0004). However, no clinically relevant differences compared to baseline were observed. Patients with pulmonary comorbidity and WHO scores ≥ 2 generally reported more complaints. Patients experienced a temporary increase in complaints after finishing (chemo)radiotherapy, QoL returned to baseline level and remained stable up to five years of follow-up.
**Abstract text** Stereotactic body radiotherapy (SBRT) is the standard approach for patients with early stage lung cancer who are inoperable bec | POSTER
26 July 2024 in Physics and Imaging in Radiation Oncology
In non-small-cell lung cancer (NSCLC), improving local control through radiotherapy dose escalation might improve survival. However, a photon-based RCT showed increased organ at risk dose exposure and worse overall survival in the dose escalation arm. In this study, intensity-modulated proton therapy plans with dose escalation to the primary tumour were created for 20 NSCLC patients. The mediastinal envelope was delineated to spare structures around the heart. It was possible to increase primary tumour dose up to 74.0 Gy without a significant increase in organ at risk doses and predicted toxicity.