The Associations of Psychological Stress With Therapy Efficacy and Prognosis of Lung Cancer (STRESS-LUNG)

Cohort Studies of Associations of Psychological Stress With Therapy Efficacy and Prognosis of Lung Cancer, Including Non-small-cell Lung Cancer and Small-cell Lung Cancer With Early and Advanced Staging (STRESS-LUNG)

This is the prospective, observational cohort study (STRESS-LUNG) to explore the associations of psychological stress with progression, efficacy of immune checkpoint inhibitors (ICIs) and prognosis of Lung Cancer. The participants including the patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who received the first-line therapy or neoadjuvant therapy of ICIs; patients diagnosed with advanced small-cell lung cancer (SCLC) receiving the first-line therapy ICIs; patients diagnosed with early small-cell lung cancer (SCLC) receiving surgery.

Study Overview

• Status: Recruiting
• Conditions: Lung Cancer; Cancer, Treatment-Related; Psychological Stress; Immune Checkpoint Inhibitors
• Intervention / Treatment: Other: Exposure: psychological stress status

Detailed Description

This is the prospective, observational cohort study (STRESS-LUNG) to explore the associations of psychological stress with progression, efficacy of ICIs and prognosis of Lung Cancer. This study will have 4 cohorts

• Cohort 1 (STRESS-LUNG-1): A prospective, observational cohort study to explore the association between psychological stress and the efficacy of first-line treatment of ICIs in advanced NSCLC.
• Cohort 2 (STRESS-LUNG-2): A prospective, observational cohort study to explore the association between psychological stress and the efficacy of first-line treatment of limited-stage and extensive-stage SCLC.
• Cohort 3 (STRESS-LUNG-3): A prospective, observational cohort study to explore the association between psychological stress and the efficacy of neoadjuvant therapy of ICIs in resectable NSCLC.
• Cohort 4 (STRESS-LUNG-4): A prospective, observational cohort study to explore the association of psychological stress with cancer progression, and Prognosis in early-stage NSCLC receiving radical surgery.

• Study Type: Observational
• Enrollment (Estimated): 750

Contacts and Locations

• Study Contact: Name: Fang Wu, MD. PhD; Phone Number: +86 13574858332; Email: wufang4461@csu.edu.cn

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410011
      • Recruiting
      • Department of Oncology, The Second Xiangya Hospital, Central South University
      • Contact: Fang Wu, MD, PhD; Phone Number: +86 13574858332; Email: wufang4461@csu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

The participants including the patients diagnosed with advanced non-small-cell lung cancer (NSCLC) who received the first-line therapy or neoadjuvant therapy of ICIs; patients diagnosed with advanced small-cell lung cancer (SCLC) receiving the first-line therapy ICIs; patients diagnosed with early small-cell lung cancer (SCLC) receiving surgery.

Description

Cohort 1 (STRESS-LUNG-1):

Inclusion Criteria:

1. Age ≥ 18 years;
2. Histologically confirmed diagnosis of NSCLC;
3. Unresectable locally advanced, metastatic, or recurrent stage ⅢB-Ⅳ based on AJCC TNM staging 8th edition;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
5. Systematic treatments naive ( e. g., chemotherapy, anti-angiogenic drugs, targeted drugs, and immunotherapy );
6. Presence of at least one measurable lesion according to the Response Evaluation Criteria in Advanced Solid Tumors version 1.1 (RECIST v1.1) ;
7. Receiving PD-1/PD-L1 inhibitors monotherapy or combination with chemotherapy;
8. Informed and agreed to participate in the study;

Exclusion Criteria:

1. Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) gene and/or ROS proto-oncogene 1 (ROS1) fusion-positive;
2. Combined with other malignant tumors in the past 3 years;
3. Concurrent acute or chronic psychiatric disorders;
4. Current receiving anti-depressive or anti-anxiety therapy;
5. Previous treatment with other clinical drug trials;
6. Patients with symptomatic brain metastasis;
7. Can't cooperate with psychological scale assessment;

Cohort 2 (STRESS-LUNG-2):

1. Age ≥ 18 years；
2. Pathologically diagnosed as small cell lung cancer；
3. Unresectable locally advanced, metastatic, or recurrent stage Ⅲ-Ⅳ based on AJCC TNM staging 8th edition;
4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
5. Systematic treatments naive ( e. g., chemotherapy, anti-angiogenic drugs, targeted drugs, and immunotherapy );
6. Presence of at least one measurable lesion according to the Response Evaluation Criteria in Advanced Solid Tumors version 1.1 (RECIST v1.1) ;
7. Receiving PD-1/PD-L1 inhibitors monotherapy or combination with chemotherapy;
8. Informed and agreed to participate in the study;

Exclusion Criteria:

1. Combined with other malignant tumors in the past 3 years;
2. Concurrent acute or chronic psychiatric disorders;
3. Current receiving anti-depressive or anti-anxiety therapy;
4. Previous treatment with other clinical drug trials;
5. Patients with symptomatic brain metastasis;
6. Can't cooperate with psychological scale assessment;

Cohort 3 (STRESS-LUNG-3):

1. Age ≥18 years ；
2. Pathologically diagnosed as non-small cell lung cancer;
3. Resectable clinical stage IB-IIIB based on AJCC TNM staging 8th edition;
4. At least one measurable lesion can be evaluated according to the RECIST 1.1 standard；
5. Systematic treatments naive ( e. g., chemotherapy, anti-angiogenic drugs, targeted drugs, and immunotherapy );
6. Receiving PD-1/PD-L1 inhibitors combined with chemotherapy as neoadjuvant therapy.

6. Cardiopulmonary function can withstand surgery; 7. Informed and agreed to participate in the study;

Exclusion Criteria:

1. Epidermal growth factor receptor (EGFR)-sensitizing mutation and/or anaplastic lymphoma kinase (ALK) gene and/or ROS proto-oncogene 1 (ROS1) fusion-positive;
2. Combined with other malignant tumors in the past 3 years;
3. Concurrent acute or chronic psychiatric disorders;
4. Current receiving anti-depressive or anti-anxiety therapy;
5. Previous treatment with other clinical drug trials;
6. Can't cooperate with psychological scale assessment;

Cohort 4 (STRESS-LUNG-4):

1. Age ≥18 years;
2. Pathologically diagnosed as non-small-cell lung cancer；
3. Pathologically stage conformed as early stage of IA-IIIA
4. Available for tumor tissue samples；
5. Systematic treatments naive ( e. g., chemotherapy, anti-angiogenic drugs, targeted drugs, and immunotherapy );
6. Receiving radical surgery;
7. Informed and agreed to participate in the study;

Exclusion Criteria:

1. Combined with other malignant tumors in the past 3 years;
2. Concurrent acute or chronic psychiatric disorders;
3. Current receiving anti-depressive or anti-anxiety therapy;
4. Previous treatment with other clinical drug trials;
5. Can't cooperate with psychological scale assessment;

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort 1: advanced NSCLC patients receiving first-line ICIs (STRESS-LUNG-1 study); For stage IIIB-IV patients with NSCLC who have received immune checkpoint inhibitors as first-line therapy.	Other: Exposure: psychological stress status; The assessment of depressive and anxiety symptoms was conducted using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment 7 (GAD-7). Patients with a PHQ-9 score ≥ 5 or a GAD-7 score ≥ 5 were categorized as the stressed group.
Cohort 2: limited-stage and extensive-stage SCLC patients receiving ICIs (STRESS-LUNG-2 study); For limited-stage and extensive-stage SCLC patients who have received immune checkpoint inhibitors	Other: Exposure: psychological stress status; The assessment of depressive and anxiety symptoms was conducted using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment 7 (GAD-7). Patients with a PHQ-9 score ≥ 5 or a GAD-7 score ≥ 5 were categorized as the stressed group.
Cohort 3: NSCLC patients receive neoadjuvant therapy of ICIs（STRESS-LUNG-3 study）; For stage IB-IIIB patients with non-small cell lung cancer who have received neoadjuvant therapy of immune checkpoint inhibitors.	Other: Exposure: psychological stress status; The assessment of depressive and anxiety symptoms was conducted using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment 7 (GAD-7). Patients with a PHQ-9 score ≥ 5 or a GAD-7 score ≥ 5 were categorized as the stressed group.
Cohort 4: NSCLC patients receive radical resection (STRESS-LUNG-4 study)); For early-stage patients with non-small cell lung cancer who have received radical resection.	Other: Exposure: psychological stress status; The assessment of depressive and anxiety symptoms was conducted using Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder Assessment 7 (GAD-7). Patients with a PHQ-9 score ≥ 5 or a GAD-7 score ≥ 5 were categorized as the stressed group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort 1 & 2: Progression-free survival (PFS)	Time from the beginning of first-line immunotherapy to the first progression (PD) in patients with lung cancer	3 years
Cohort 3: Pathologic complete response (pCR) rate	pCR is no viable tumor cells in tumor bed and lymph nodes. The pCR rate is the proportion of patients with a pathologic complete response.	3 years
Cohort 4: Disease-free survival (DFS)	The duration between the date after surgery to the date of any recurrence or death firstly	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The proportion of patients with a complete response or partial response to treatment according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1)	2 years
Overall survival (OS)	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.	5 years
Quality of life	Quality of life (QoL) is assessed longitude by Short Form Health Survey 36 (SF-36) and EORTC QLQ-C30 (version.3). 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.	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The correlation between gut microbiota and chronic stress and the efficacy of ICIs	The baseline fetal is collected and assessed by 16S rRNA sequencing. And explore the association between gut microbiota and chronic stress and the efficacy of ICIs during the enrolled observation process.	5 years
The correlation between tumor microenvironment signature and chronic stress and the efficacy of ICIs	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 and the efficacy of ICIs during the enrolled observation process.	5 years
The correlation between peripheral stress biomarker and immune cells signature and chronic stress and the efficacy of ICIs	The baseline peripheral venous blood is collected. The stress biomarkers including epinephrine, norepinephrine, cortisol and ACTH. The peripheral immune cells signature and assessed by flow cytometry, including T lymphocytes, B lymphocytes, NK lymphocytes, macrophagocyte, and DC cells.	5 years

Collaborators and Investigators

• Sponsor: Second Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: July 23, 2022
• First Submitted That Met QC Criteria: July 26, 2022
• First Posted (Actual): July 28, 2022

Study Record Updates

• Last Update Posted (Estimated): December 8, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Biomarker; Prognosis; Lung cancer; Immune checkpoint inhibitors; Psychological stress; Cancer progression
• Additional Relevant MeSH Terms: Behavioral Symptoms; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Stress, Psychological; Neoplasms, Second Primary
• Other Study ID Numbers: XYEYY20220704

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No