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Principal Investigator: Stephen R. Bowen
Organization: UNIVERSITY OF WASHINGTON
Fiscal Year: 2024
Award: $577,989
Funding agency: National Cancer Institute
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.
Terms: <Assay><B7-H1><B7H1><Bioassay><Biological Assay><Biological Markers><Blood monocyte><CAT scan><CD274><CD8 Cell><CD8 T cells><CD8 lymphocyte><CD8+ T cell><CD8+ T-Lymphocyte><CD8-Positive Lymphocytes><CD8-Positive T-Lymphocytes><CT X Ray><CT Xray><CT imaging><CT scan><Cancer Control><Cancer Control Science><Cell Body><Cells><Cessation of life><Checkpoint inhibitor><Clinical><Clinical Trials><Combination Drug Therapy><Combined Modality Therapy><Complex><Computed Tomography><Consensus><Data><Death><Definitive Radiation Therapy><Development><Disease><Disorder><EBRT><Early Intervention><Enrollment><External Beam RT><External Beam Radiation Therapy><External Radiation><FDG PET><Financial Hardship><Future><Glycolysis><Image><Immune><Immune Markers><Immune checkpoint inhibitor><Immune mediated therapy><Immune response><Immunes><Immuno-Chemotherapy><Immunochemotherapy><Immunologic Markers><Immunologic Subtyping><Immunological response><Immunologically Directed Therapy><Immunophenotyping><Immunotherapy><Intervention><Intervention Strategies><Lesion><Ligands><Link><MHC Receptor><Major Histocompatibility Complex Receptor><Malignant Tumor of the Lung><Malignant neoplasm of lung><Marrow monocyte><Metabolic><Monitor><Multimodal Therapy><Multimodal Treatment><NIH><NSCLC><NSCLC - Non-Small Cell Lung Cancer><National Institutes of Health><Newly Diagnosed><Non-Small Cell Lung Cancer><Non-Small-Cell Lung Carcinoma><Observation research><Observation study><Observational Study><Observational research><Outcome><PD-L1><PDL-1><PDL1><PET><PET Scan><PET imaging><PETSCAN><PETT><Patient Selection><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Pattern><Peripheral><Phenotype><Polychemotherapy><Positron Emission Tomography Medical Imaging><Positron Emission Tomography Scan><Positron-Emission Tomography><Precision Medicine Initiative><Precision therapeutics><Programmed Cell Death 1 Ligand 1><Programmed Death Ligand 1><Progression-Free Survivals><Progressive Disease><Proteins><Pulmonary Cancer><Pulmonary malignant Neoplasm><Rad.-PET><Radiation><Radiation therapy><Radio><Radiotherapeutics><Radiotherapy><Randomization trial><Risk><SYS-TX><Site><Standardization><Systemic Therapy><Systemic disease><T-Cell Antigen Receptors><T-Cell Receptor><T8 Cells><T8 Lymphocytes><Therapeutic><Tomodensitometry><Toxic effect><Toxicities><Treatment Efficacy><Treatment-related toxicity><Tumor Volume><United States National Institutes of Health><Validation><X-Ray CAT Scan><X-Ray Computed Tomography><X-Ray Computerized Tomography><Xray CAT scan><Xray Computed Tomography><Xray computerized tomography><aPD-1><aPD1><anti programmed cell death 1><anti-PD-1><anti-PD1><anti-programmed cell death protein 1><antiPD-1><antiPD1><bio-markers><biologic marker><biomarker><biomarker identification><biomarker signature><burden of disease><burden of illness><cancer survival><catscan><chemo-immuno therapy><chemoimmunotherapy><chemotherapy><circulating biomarkers><circulating markers><clinical imaging><combination chemotherapy><combination pharmacotherapy><combination therapy><combined modality treatment><combined treatment><computed axial tomography><computer tomography><computerized axial tomography><computerized tomography><cytokine><developmental><disease burden><disease control><disorder control><enroll><external-beam radiation><financial adversity><financial burden><financial distress><financial insecurity><financial strain><financial stress><fluorodeoxyglucose PET><fluorodeoxyglucose positron emission tomography><high risk><host response><identification of biomarkers><identification of new biomarkers><imaging><imaging biomarker><imaging marker><imaging-based biological marker><imaging-based biomarker><imaging-based marker><immune check point inhibitor><immune system response><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based biomarkers><immune-based therapies><immune-based treatments><immuno therapy><immunological biomarkers><immunological markers><immunophenotype><immunoresponse><improved><improved outcome><individual patient><individual response><individualized response><intervention efficacy><interventional strategy><irradiation><irradiation response><learning activity><learning method><learning strategies><learning strategy><lung cancer><marker identification><monocyte><multi-modal therapy><multi-modal treatment><multidisciplinary><non-contrast CT><noncontrast CT><noncontrast computed tomography><outcome prediction><patient oriented outcomes><patient stratification><peripheral blood><phase 2 trial><phase II trial><positron emission tomographic (PET) imaging><positron emission tomographic imaging><positron emitting tomography><precision therapies><precision treatment><predictive biomarkers><predictive marker><predictive molecular biomarker><prognostic ability><prognostic power><prognostic utility><prognostic value><prognostication><programmed cell death ligand 1><programmed cell death protein ligand 1><prospective><protein death-ligand 1><quantitative imaging><radiation response><radiation treatment><radiomics><randomized trial><response><response biomarker><response markers><response to radiation><response to therapy><response to treatment><risk stratification><standard of care><stratified patient><stratify risk><support tools><survival outcome><synergism><therapeutic efficacy><therapeutic response><therapeutic toxicity><therapy associated toxicity><therapy efficacy><therapy related toxicity><therapy response><therapy toxicity><treatment response><treatment responsiveness><treatment toxicity><treatment with radiation><treatment-associated toxicity><tumor><uptake><validations><αPD-1><αPD1>