S2532
Radiobiology – Immuno-radiobiology
ESTRO 2026
Chongqing, China. 3 Oncology, Air Force Hospital of Southern Theater Command of the People's Liberation Army, Guangdong, China. 4 Thoracic Surgery, Sun Yat- sen University Cancer Center, Guangzhou, China Purpose/Objective: To evaluate the efficacy and safety of a neoadjuvant regimen featuring reduced-dose chemotherapy plus immunotherapy, followed by hypofractionated radiotherapy, concurrent chemotherapy (hypo-CCRT) and consolidative immunotherapy, in patients with unresectable locally advanced non-small cell lung This was a real-world observational study enrolled patients with newly diagnosed, unresectable stage III LA-NSCLC who received neoadjuvant chemoimmunotherapy followed by hypo-CCRT and consolidative immunotherapy between January 2020 and December 2023 from 2 prospective randomized studies. Participants were categorized into a reduced- dose or standard-dose chemotherapy group based on the neoadjuvant phase. Patients received either a neoadjuvant reduced-dose (Neo-RD-chemo) or standard-dose (Neo-SD-chemo) platinum-doublet chemotherapy regimen combined with standard-dose immunotherapy, followed by hypo-CCRT and subsequent consolidative immunotherapy. The primary efficacy outcomes were progression-free survival (PFS) and overall survival (OS). The primary safety outcomes were the incidence of grade(G) 3 or higher ( ≥ G3) lymphopenia, ≥ G2 esophagitis, and ≥ G2 pneumonitis. Results: cancer (LA-NSCLC). Material/Methods: A total of 304 patients were included (152 in the Neo- RD-chemo group, 152 in the Neo-SD-chemo group). Baseline characteristics were well-balanced between the two groups (Table 1). The Neo-RD-chemo group demonstrated comparable efficacy to the Neo-SD- chemo group, with no significant differences in median PFS (23.9 months vs 20.3 months; hazard ratio [HR], 0.88; 95% CI, 0.65-1.18) or median OS (35.2 months vs 32.7 months; HR, 0.85; 95% CI, 0.6-1.2). However, the Neo-RD-chemo regimen was associated with a significantly lower incidence of ≥ G3 lymphopenia (23.7% vs 35.5%; P= 0.03), an effect that persisted during both CCRT and consolidative immunotherapy. Furthermore, the Neo-RD- chemo group had significantly lower rates of ≥ G2 esophagitis during CCRT (4% vs 15.1%; P = 0.001) and ≥ G2 pneumonitis during consolidative immunotherapy (5.9% vs 17.5%; P = 0.03). Subgroup analyses suggested that patients with an Eastern Cooperative Oncology Group performance status (ECOG PS) of 1 and those with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1–2 airflow limitation may derive particular benefit from the Neo-RD-chemo
(LNI), and those with central nervous system tumours (CNS) patients who did not receive LNI. Material/Methods: Sixty-two patients undergoing radiotherapy were included (14 with CNS tumors, 48 with HNC). Demographic, clinical, and radiotherapy parameters were collected. Absolute lymphocyte counts (ALCs) were measured at baseline and periodically during treatment. Predictors of lymphocyte depletion were identified using least absolute shrinkage and selection operator regression. Mediation analysis assessed whether mean nodal dose mediated the relationship between nodal involvement and lymphocyte reduction. Results: Baseline ALCs were similar between CNS (2.01 × 10 ⁹ /L) and HNC patients (2.06 × 10 ⁹ /L, p = 0.835). Nadir ALCs were significantly lower in HNC patients (0.76 × 10 ⁹ /L vs. 1.17 × 10 ⁹ /L, p = 0.014), with faster reduction per week ( − 0.175 vs. − 0.082 × 10 ⁹ /L, p = 0.006). CNS patients received lower total radiation dose (56.1 Gy vs. 70.2 Gy, p < 0.001) and fewer fractions (30 vs. 34.8, p = 0.001). Lymphocyte depletion was strongly associated with the baseline lymphocyte count, chemotherapy, and treatment interruptions, with distinct temporal patterns observed between CNS and HNC patients (Figure 1). Conclusion: Lymphocyte depletion during radiotherapy is more pronounced in HNC patients and is primarily driven by chemotherapy, baseline lymphocyte levels, and treatment interruptions. Recognition of tumour- specific and treatment-related factors should be considered when interpreting the immune effects of radiotherapy. References: 1. Ellsworth SG. Field size effects on the risk and severity of treatment-induced lymphopenia in patients undergoing radiation therapy for solid tumors. Adv Radiat Oncol. 2018 Oct 23;3(4):512-519. doi: 10.1016/j.adro.2018.08.014. PMID: 30370350; PMCID: PMC6200885. Keywords: lymphopenia, immunomodulation Neoadjuvant reduced-dose chemotherapy plus standard dose immunotherapy in LA-NSCLC following CCRT and consolidative immunotherapy. Biao Xia 1 , Rui Zhou 2 , DaQuan Wang 1 , HongMei Zhang 3 , FangJie Liu 1 , PengXin Zhang 1 , HaoTing Zhang 1 , Yu SiTu 1 , MengRu Wang 1 , YuanYuan Zhao 1 , Yi Hu 4 , Bo Qiu 1 , Tao Zhang 2 , Hui Liu 1 1 Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China. 2 Oncology, The First Affiliated Hospital of Chongqing Medical University, Digital Poster 2605
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