AI-guided Prognostication and Cranial Radiotherapy Optimization in EGFR-TKI-treated Non-small Cell Lung Cancer Patients With Baseline Brain Metastases

Artificial Intelligence-guided Prognostication and Cranial Radiotherapy Optimization in First-line Third-generation EGFR-TKI-treated EGFR-mutant Non-small Cell Lung Cancer With Baseline Brain Metastases: a Multicenter, Observational Study

The goal of this observational study is to extract the imaging features of brain lesions and primary lung lesions in NSCLC patients with brain metastases by deep learning, as well as common clinicopathological parameters, which are used to construct a multimode model that can accurately predict the treatment efficacy and survival of the third-generation EGFR-TKI treatment, and to use the model to assist in screening high-risk populations suitable for upfront cranial radiotherapy.

Participants receiving third-generation EGFR-TKI treatment will be enrolled in our study and we will collect their regular contrast-enhanced chest CT and contrast-enhanced brain MRI for model construction.

Study Overview

• Status: Not yet recruiting
• Conditions: NSCLC (Advanced Non-small Cell Lung Cancer); Brain Metastasases
• Intervention / Treatment: Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib)

• Study Type: Observational
• Enrollment (Estimated): 800

Contacts and Locations

• Study Contact: Name: Zhengfei Zhu; Phone Number: +86-18017312901; Email: fuscczzf@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients are collected all over china, diagnosed with EGFR-mutant NSCLC with brain metastases.

Description

Inclusion Criteria:

• Pathologically confirmed non-small cell lung cancer;
• clinical stage IV (AJCC, 8th edition, 2017);
• EGFR sensitive mutations: EGFR L858R, EGFR exon 19 deletion;
• age≥18 years old;
• KPS score≥70;
• brain metastases at diagnosis;
• complete systemic imaging (including brain MRI) before third-generation EGFR-TKI treatment;
• received standard third-generation EGFR-TKI therapy (monotherapy or combined with brain radiotherapy);
• willing to cooperate with the follow-up after third-generation EGFR-TKI treatment;
• informed consent of the patient.

Exclusion Criteria:

• Multiple primary or metastatic tumors (except early skin cancer, cervical carcinoma in situ that has been treated radically, with no recurrence or progression for more than 5 years);
• Pregnant or lactating women who, as judged by the investigator, were not candidates for brain MRI;
• EGFR sensitive mutations were negative or EGFR mutation status was not detected.
• Uncontrolled epilepsy, central nervous system disease, or history of mental disorders, judged by the researcher to potentially interfere with the signing of the informed consent form or affect patient compliance.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Construction of AI models (retrospective cohort)	Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); EGFR-mutated NSCLC patients with brain metastases who met the inclusion and exclusion criteria, would receive first-line third-generation EGFR-TKI treatment (monotherapy or combined with upfront cranial radiotherapy)
Validation of AI models (prospective cohort)	Drug: third-generation EGFR TKIs (Almonertinib/Furmonertinib/Osimertinib); EGFR-mutated NSCLC patients with brain metastases who met the inclusion and exclusion criteria, would receive first-line third-generation EGFR-TKI treatment (monotherapy or combined with upfront cranial radiotherapy)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS)	The time from the start of EGFR-TKI treatment until the documentation of disease progression or death from any cause, assessed according to the RECIST 1.1 criteria. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	The percentage of participants who achieve a Complete Response (CR) or Partial Response (PR) after treatment, assessed according to the RECIST 1.1 criteria.	1 year
Intracranial Objective Response Rate (iORR)	The percentage of participants in the analysis population whose brain lesions achieve CR or PR, assessed according to the modified RECIST 1.1 criteria.	1 year
Intracranial Progression-Free Survival (iPFS)	The time from the start of EGFR-TKI treatment until the documentation of intracranial disease progression or death from any cause. If the patients have extracranial disease progression (without intracranial disease progression), the cutoff date was the date of the first occurrence of extracranial disease progression. Patients who have not progressed at the time of analysis will have their last contact date used as the cutoff date.	1 year
Overall Survival (OS)	The time from the start of EGFR-TKI treatment until death from any cause. Patients who are still alive at the time of analysis will have their last contact date used as the cutoff date.	1 year

Collaborators and Investigators

• Sponsor: Fudan University

Study record dates

Study Major Dates

• Study Start (Estimated): September 30, 2024
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): October 1, 2025

Study Registration Dates

• First Submitted: September 18, 2024
• First Submitted That Met QC Criteria: September 18, 2024
• First Posted (Estimated): September 19, 2024

Study Record Updates

• Last Update Posted (Estimated): September 19, 2024
• Last Update Submitted That Met QC Criteria: September 18, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Central Nervous System Neoplasms; Nervous System Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Brain Neoplasms; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Tyrosine Kinase Inhibitors; Osimertinib; Aflutinib
• Other Study ID Numbers: BM-AI

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No