Correlation of psychological distress with quality of life and efficacy of immune checkpoint inhibitors in patients with newly diagnosed stage IIIB-IV NSCLC.

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12001 Background: Psychological distress is common among cancer patients and leads to activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) and continuous production of distress hormones, which may contribute to a highly immunosuppressive tumor microenvironment (TME). Meanwhile, preclinical studies have shown that psychological distress could undermine cancer therapies. Therefore, we investigate the prevalence of psychological distress in non-small-cell lung cancer (NSCLC) patients, identify its impact on quality of life (QoL) and efficacy of immune checkpoint inhibitors (ICIs), and explore the possible neuro-endocrinological mechanisms. Methods: Patients with newly diagnosed stage ⅢB-Ⅳ NSCLC received ICIs as first-line treatment were included. The assessments of psychological distress including depression and anxiety symptoms were measured using the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), respectively. The QoL was measured by Short Form Health Survey 36 (SF-36). Stress hormones including serum cortisol, adrenocorticotropic hormone (ACTH), plasma epinephrine (Epi), and norepinephrine (NE) were determined by ELISA kit before treatment. Objective response rates (ORR) and Median progression-free (PFS) were estimated using the Chi-square test, Kaplan-Meier, and Cox regression method. Results: 77 NSCLC patients with a mean age of 60.9 years were enrolled. Stage distribution included 50 (64.9%) stage ⅢB/C and 27 (35.1%) stage Ⅳ. 44(57.1%) patients were present psychological distress. Psychological distress was associated with poorer QoL (P<0.001). The median follow-up time was 16.2 months. Compared with non-psychological distress patients, psychological distress patients had a significant lower ORR (35.9% vs 63.64%; P=0.033) and shorter PFS (median 12.63 vs 14.60 months; 95% CI: 0.36 to 1.98; P=0.026). Moreover, psychological distress was the only independent predictor for PFS (HR:2.71, 95%CI: 1.06～6.90; P=0.037) in multivariate Cox regression analyses. The patients with psychological distress had higher levels of serum cortisol ( P=0.040) and plasma Epi ( P=0.023). Additionally, the serum cortisol ( P=0.043) and plasma Epi ( P=0.025) concentrations were associated with inferior ICIs response. Conclusions: Psychological distress is common within stage ⅢB-Ⅳ NSCLC patients. Patients with psychological distress are associated with worse QoL and inferior outcomes to ICIs and discover the potential mechanisms of neuro-endocrinological hormones in resistance to ICIs therapy.