Prognostic Impact of Inflammatory Profiling During and after Multimodal Treatment for Stage III NSCLC.

e20559 Background: Immune cells have a broad impact on tumor initiation, growth, and progression, and many of these effects are mediated by proinflammatory cytokines. The prognostic impact of dynamic changes of inflammatory cytokines in non-operable stage III NSCLC patients treated with (chemo)-radiotherapy ± immune checkpoint inhibition is unknown. In a prospective analysis, pro-inflammatory cytokines including interleukin 2, 6, and 8 from peripheral blood samples were evaluated 5-10 days before treatment start (T1), on the last day of thoracic radiotherapy (T2), and 3 weeks after radiation (T3) for their impact on overall survival (OS) and progression-free survival (PFS). Methods: Twenty patients, 85% male, at a median age of 65.5 (range 33-77) years were prospectively enrolled in this study. Eighteen (90%) patients received platinum-based concurrent chemoradiotherapy (CRT); seven (35%) patients additional concurrent and/or sequential immune checkpoint inhibition (four patients nivolumab and three durvalumab); patients treated with nivolumab received induction chemotherapy. Thoracic irradiation (TRT) was applied in all patients with a median cumulative dose in equivalent 2Gy fractions (EQD2) of 64Gy (range: 52-65Gy). Results: Median follow-up achieved 25 (range 14-30) months, median OS was not reached and median PFS was 11.8 (95%CI 5.2-18.4) months. To analyze pre-treatment data, median values were used as cut-off for dichotomization. Higher IL6 levels (≥9.75pg/ml) before irradiation (T1) were associated with impaired OS (median 11 months vs. not reached; p < 0.001) and PFS (median 7.0 months vs. not reached; p = 0.041). Higher IL8 levels (≥4.62pg/ml) were also associated with shorter OS (median 16 months vs. not reached; p = 0.009) and PFS (median 7 months vs. not reached p = 0.040). Patients with a decline of ≥10% of IL8 level between T1 and T2 had a significantly shorter PFS (11.8 months vs. not reached; p = 0.028). Conclusions: High proinflammatory cytokine levels were significantly associated with deterioration of outcome regarding OS and PFS in patients enrolled in multimodal treatment for stage III NSCLC. A decline of ≥10% of IL8 level during TRT was associated with impaired PFS.