S852
Clinical - Lung
ESTRO 2026
Mini-Oral 5027
radiotherapy courses. Median age was 61 (range 36– 77). Eighty-three patients (81.4%) had adenocarcinoma and nineteen (18.6%) had squamous cell carcinoma. The median ECOG PS was 0. De novo brain metastases occurred in sixty-nine patients (67.6%), while thirty- three (32.4%) developed them during systemic therapy. Thirty-one patients (30.4%) harbored driver mutations (EGFR, ALK, or KRAS G12C), and seventy-one (69.6%) were mutation-negative. Radiotherapy included stereotactic radiosurgery (SRS), whole-brain irradiation (WBI), or combined WBI+SRS,performed in cases of intracranial progression. Systemic therapy consisted of chemotherapy, immunotherapy, targeted therapy or a combination of these. Survival was assessed by Kaplan–Meier and Cox regression models; intracranial control by Chi-square and Fisher’s exact tests. Results: Median OS was 37.6 months in patients with driver mutations and 23.9 months in wild-type cases (HR 1.69, 95% CI: 1.00–2.85, p=0.050). Radiotherapy modality had no significant OS impact (26-30 months, p=0.56) across SRS (including multiple sessions), WBI or WBI+SRS. Patients developing brain metastases during systemic therapy tended to live longer than those with de novo disease (33.1 vs. 24.1 months, p=0.15), suggesting that the timing of CNS involvement alone does not significantly affect survival when appropriate brain radiotherapy is administered. OS was unaffected by the number of irradiation courses (p=0.33), indicating sustained benefit from repeated courses of radiotherapy for intracranial control even in recurrent disease. Local (inside-field) control after SRS was similar across systemic regimens (75–80%) and systemic therapy did not significantly affect the development of new metastases outside irradiated areas (p=0.231). Conclusion: In NSCLC patients with brain metastases, radiotherapy serves as a key equalizer for intracranial outcomes. Consistently administering precise, and when indicated, repeated irradiation provides durable local control and yields comparable survival between patients treated with single or multiple courses of radiotherapy. Systemic therapy has a minimal impact on the intracranial progression. OS depends mainly on tumor biology and systemic disease status, underscoring the pivotal role of radiotherapy in maintaining the localcontrol of brain metastases. Keywords: SRS brain metastases
Sparing immune rich organs spare the expanding Ki-67+CD8+ and Ki-67+CD4+ T-cell fractions during lung SBRT- randomized clinical trial (NCT04273893) Krishni Wijesooriya 1,2 , Cam Nguyen 2 , James Larner 1 , Timothy Showalter 1 , Paul Read 1 , Lawrence Lum 3 , Archana Thakur 3 , Mark Conaway 4 1 Radiation Oncology, University of Virginia, Charlottesville, USA. 2 Physics, University of Virginia, Charlottesville, USA. 3 Hematology and oncology, University of Virginia, Charlottesville, USA. 4 Public health Sciences, University of Virginia, Charlottesville, USA Purpose/Objective: Stereotactic Body Radiation Therapy (SBRT) can stimulate anti-tumor T-cell generation but is limited by radiation-induced immunosuppression (RIIS), which destroys existing and newly formed lymphocytes. Considering circulating blood and lymphatics as organs at risk in treatment planning may reduce RIIS and preserve cytotoxic T-cells. We present results comparing immune cell profile changes between standard and optimized SBRT plans. Material/Methods: We conducted an NCI funded clinical trial for 48 early- stage lung cancer patients treated with SBRT alone, from 2020 to 2023, to investigate the ability to reduce RIIS by reducing dose to circulating blood and lymphatics. Patients were randomized to two arms: experimental optimization for RIIS (reduce dose to blood and lymphatic rich organs) versus standard SBRT planning. All plans adhered to treatment parameters from national protocols. Peripheral blood samples were collected at baseline, and at 4-weeks- post-Tx. Data acquired for lymphocyte sub populations CD3+, CD4+, CD8+, CD19+, CD56+, Tregs, MDSC. For 18 of the patients who had remaining peripheral blood samples, we examined the changes in Ki-67, a marker of cellular proliferation expressed by cycling or recently divided cells. Wilcoxon t-test was used to determine the statistical significance. Results: The absolute counts of circulating CD8+CTLs and CD4+CTLs post-SBRT compared to baseline increased for 50% (24/48 patients) and 44% (21/48 patients)of the patients respectively. However, the post-SBRT mean absolute counts of CD8+CTLs and CD4+CTLs compared to pre-treatment values decreased, but not significant. The mean proportion of expanding Ki- 67+CD4+ T-cells among peripheral blood lymphocytes (CD3+ cells) significantly decreased after SBRT for overall patient cohort as well as the standard arm patients (p=0.005, and p=0.008), while optimized-arm mean expanding Ki-67+CD4+ T-cells decrease is not significant. Total of 11/16 patients observed an
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