Biomarkers of Response to Immuno-chemotherapy & oliGometastatic Hypofractionated radioTherapy (BRIGHT) for Lung Cancer: Synergy of PET/CT Imaging and Peripheral Blood Assays

免疫化疗反应的生物标志物

• 批准号: 10363605
• 负责人: Stephen R. Bowen
• 金额: $ 62.23万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-20 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10363605
• 关键词: Biological Assay; Biological Markers; CD8-Positive T-Lymphocytes; Cancer Control; Cells; Cessation of life; Clinical; Clinical Trials; Combination Drug Therapy; Complex; Consensus; Data; Development; Disease; Early Intervention; Emission-Computed Tomography; Enrollment; External Beam Radiation Therapy; Financial Hardship; Future; Glycolysis; Image; Immune; Immune checkpoint inhibitor; Immune response; Immuno-Chemotherapy; Immunologic Markers; Immunophenotyping; Immunotherapy; Intervention; Lesion; Ligands; Link; Malignant neoplasm of lung; Metabolic; Monitor; Newly Diagnosed; Non-Small-Cell Lung Carcinoma; Nonmetastatic; Observational Study; Outcome; Patient Selection; Patient-Focused Outcomes; Patients; Pattern; Peripheral; Phenotype; Positron-Emission Tomography; Precision therapeutics; Progression-Free Survivals; Progressive Disease; Proteins; Radiation; Radiation therapy; Radio; Risk; Selection for Treatments; Site; Standardization; Systemic Therapy; Systemic disease; T-Cell Receptor; Therapeutic; Toxic effect; Treatment Efficacy; Treatment-related toxicity; Tumor Volume; United States National Institutes of Health; Validation; X-Ray Computed Tomography; anti-PD-1; base; biomarker signature; burden of illness; cancer survival; chemotherapy; circulating biomarkers; clinical imaging; cytokine; disorder control; fluorodeoxyglucose positron emission tomography; high risk; imaging biomarker; improved; improved outcome; individual patient; individual response; irradiation; learning strategy; monocyte; multidisciplinary; outcome prediction; patient stratification; peripheral blood; phase II trial; precision medicine; predictive marker; prognostic value; programmed cell death ligand 1; prospective; quantitative imaging; radiation response; radiomics; randomized trial; response; response biomarker; risk stratification; standard of care; support tools; survival outcome; synergism; treatment response; tumor; uptake

ABSTRACT Management of patients with metastatic non-small cell lung cancer (NSCLC) requires navigation of an increasingly diverse therapeutic landscape. Although immune checkpoint inhibitors (ICI) of anti-programmed cell death 1 (PD1) and its ligand PDL1, in combination with chemotherapy (chemoICI), are standard of care for metastatic NSCLC and have improved survival in some patients, the majority are subject to treatment-related toxicity at significant financial burden with little clinical benefit. Radiation therapy can prolong survival in patients with limited sites of metastatic disease (oligometastatic), or limited sites of progressive disease (oligoprogression) on systemic therapy, but no consensus exists on which patients and lesions would benefit from irradiation. Patient selection and treatment adaptation through early response assessment is an unmet need to increase the effective combination of chemotherapy, immunotherapy, and radiation therapy in metastatic NSCLC and improve outcomes. Biomarkers are critical to our understanding of complex response patterns to chemoICI and radiation. In patients with newly diagnosed metastatic NSCLC starting chemoICI per standard of care, we propose to assess and monitor treatment response by combining positron emission tomography (PET) imaging of macroscopic disease burden and circulating immunologic biomarkers of occult systemic disease burden in support of precision therapy through the following aims: (1) construct clinical PET imaging and circulating immunologic biomarker signatures of chemoICI response patterns to risk stratify patients into (a) early widespread progression, (b) oligoprogression, and (c) responsive disease; (2) construct clinical PET imaging and circulating immunologic biomarker signatures of oligoprogressive radiation therapy response patterns to identify patients and lesions that benefit from ablative radiation; and (3) correlate localized clinical PET imaging and global circulating immunologic biomarkers with survival outcomes. Fluorodeoxyglucose (FDG) PET scans and peripheral blood draws will be performed prior to chemoICI, 3 weeks into chemoICI, and 12 weeks into chemoICI. For patients who develop oligoprogressive disease, we will acquire FDG PET scans and peripheral blood prior to and 1-month post radiation therapy. We will develop combined quantitative PET imaging and circulating immunologic biomarker signatures of chemoICI and radiation response that stratify patients into the following groups: (i) high-risk patients predicted to develop rapid widespread progressive disease who require aggressive second-line systemic therapy, (ii) moderate-risk patients predicted to develop oligoprogressive disease who require consolidation radiation to high-risk lesion targets, (iii) low-risk patients predicted to have durable long-term response to first-line therapy. Successful completion of this project will support the launch of a clinical trial on biomarker response-adaptive chemoICI and radiation therapy in patients with metastatic non-small cell lung cancer, in order to improve cancer control and survival.

摘要