The Effect of Chronic Stress on Efficacy of ICIs in Esophageal Cancer Patients (STRESS-ESCA Study)

The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

Time from the beginning of first-line immunotherapy to the first progression(PD) in patients with advanced esophageal cancer

The chronic stress status including depression and anxiety symptoms.We will use two types of questionnaires, Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), as a whole to conduct a comprehensive psychological assessment of patients. And then evaluate the impact of chronic stress status on the efficacy of immune checkpoint inhibitors, including ORR, PFS, and OS.

PHQ-9 has 9 items, each on a scale of 0 to 3. The sum score (range 0 to 27) indicates the degree of depression, with scores of 5, 10, 15, and 20 represent mild, moderate, moderate to severe and severe levels of depression.

GAD-7 has 7 items, each on a scale of 0 to 3. Higher total scores (ranging from 0 to 21) indicate higher anxious symptoms with 5 to 9 classified as mild, 10 to 14 classified as moderate, and 15 to 21 classified as moderate-severe.

Overall survival (OS) is defined as the duration from the beginning of first-line immunotherapy until death due to any cause. Subjects who are still alive at the end of the study observation period will be censored at the time of last known vital status.

Chronic stress status including depression and anxiety symptoms.We will use Short Form Health Survey 36 (SF-36) and EORTC QLQ-C30 (version. 3) questionnaires as a whole to evaluate the quality of life of patients.

SF-36 includes 36 items and assesses the functional status and well-being on eight multi-item subscales. The total score on each SF-36 subscale ranges between 0 and 100. A greater score indicates better QoL.

The EORTC QLQ-C30 is composed of 9 multi-item scales: 5 functioning scales (physical, role, cognitive, emotional, and social), a global QOL scale, and 3 symptom scales (fatigue, pain, and nausea/vomiting). All scales and single items are linearly transformed to an 0-100 scale. A higher score represents a better level of functioning.

The baseline fetal is collected and assessed by 16S rRNA sequencing. We will measure the abundance of gut microbiota such as Bacteroides, Lactobacillus, and Ackermann's bacteria through 16s RNA sequencing. And expose the association between gut microbiota and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.

The baseline paraffin-embedded tissue is collected and assessed by multiplex immunohistochemistry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between tumor microenvironment signature and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.

The baseline peripheral venous blood is collected and assessed by flow cytometry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells. And explore the association between peripheral immune cells signature signature and chronic stress (PHQ-9 and GAD-7) and the efficacy of ICIs (ORR, PFS, and OS) during the enrolled observation process through correlation analysis.