S818
Clinical - Lung
ESTRO 2026
response 3. We previously showed in the phase II Re- induction trial (NCT03406468) that adding radiotherapy to 1-4 metastases with ≥ 1 lesions left untreated to ICI, in metastatic NSCLC patients with progression on anti-PD(L)1 therapy, resulted in a 37.5% disease control rate at 6 months4. Hereby we present the final long-term analysis of the impact of hypo-RT on survival, including patients treated with chemo-ICI. We also evaluated the changes induced by radiotherapy on the expression of protein plasma levels (IFN- γ , IL-10, IL-12, IL-2, IL6, IL-8, TNF- α ). Material/Methods: Progression free survival (PFS) and overall survival (OS), considered as time after RT start, were calculated with the Kaplan-Meier method. Protein plasma levels were collected at baseline (RT start) and at the last day of RT in each patient. Data normality was assessed using the Shapiro–Wilk test (p>0.05 for all variables). Paired-sample t-tests were performed to evaluate differences between timepoints. Association between TNF- α and survival was evaluated with Univariate Cox regression analysis. P<0.05 was considered statistically significant. Results: 31 patients were prospectively enrolled (23 ICI-only, 8 chemo-ICI). Baseline patients’ characteristics are shown in Table 1. RT schedules were 24Gy/3 fractions or 20 Gy/5fractions. With a median PFS of 4.43 months (95% CI 1.7–7.2), the 6- and 12 months PFS were 45% and 25% respectively. The median OS was 8.27 months (95% CI NA–16.9) with 70% and 48% of patients still alive at 6 and 12 months. In an exploratory biomarker analysis (n=17), a significant post-RT increase in TNF- α was observed (p=0.035). However, in a Cox regression analysis, TNF- α changes were not statistically associated with PFS (p=0.78; HR 1.36 95%CI 0.16-11.33) or OS (p=0.68; HR 0.67 95%CI 0.1-4.42).Table1. Patients characteristics
Conclusion: Adding hypo-RT to ICI or chemo-ICI can re-sensitize metastatic NSCLC progressing on immunotherapy. At 6 and 12 months, 45% and 25% of patients respectively, showed no further progression, suggesting a survival benefit. Moreover, notably long PFS was observed with this strategy. TNF- α modulation supported an immune-activating effect of RT, although it was not associated with PFS or OS. These findings highlight the rationale for combining radiotherapy with immunotherapy and underscore the need for further translational research to identify potential
biomarkers. References:
1. Hendriks LE et al. Non-oncogene-addicted metastatic NSCLC: ESMO guideline. Ann Oncol. 2023;34:358–76. doi:10.1016/j.annonc.2023.01.0062. Remon J et al. ICIs in thoracic malignancies: IASLC review. J Thorac Oncol. 2020;15:914–47. doi:10.1016/j.jtho.2020.03.0063. Lyu S, Vaes RDW, Laven IEWG, Cortiula F, Hendriks LEL, Vooijs MA, et al. Peripheral immune proteins as biomarkers in lung cancer radiotherapy. Front Oncol. 2025;15:1625212. doi:10.3389/fonc.2025.16252124. Popp I, Vaes RDW, Wieten L, Adebahr S, Hendriks L, Haghighi EB, et al. Radiotherapy restoring immunotherapy after resistance in metastatic NSCLC:
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