Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Treatment monitoring by longitudinal circulating tumor DNA measurements and Quality of Life assessments

Treatment monitoring by longitudinal CT scans (standard) and Quality of Life Assessments

A comparison of treatment monitoring by circulating tumor DNA and CT scans (standard) in patients with newly diagnosed advanced Non-Small Cell Lung Cancer (NSCLC)

Circulating tumor DNA treatment monitoring

Malene Støchkel Frank, MD, PhD

Michael Elmkvist Andersen, MD

Weronika Maria Szejniuk, MD, PhD

Christa Haugaard Nyhus, MD

Torben Frøstrup Hansen, Professor

The study is a prospective randomized interventional study including patients with advanced non-small cell lung cancer, receiving immunotherapy, with the aim of optimizing treatment monitoring. The study aims to investigate the clinical utility of liquid biopsy monitoring in order to reduce the numbers of inefficient treatments and needless toxicity - and to explore the cost-effectiveness and cost-utility of introducing liquid biopsy monitoring in daily clinical practice.

Lung cancer is the leading cause of cancer-related death worldwide with Non-Small Cell Lung Cancer (NSCLC) being the most common subtype. Performance status deterioration due to progressive symptoms and toxicity by treatments are major challenges in managing advanced NSCLC patients. Moreover, standard treatment monitoring by radiologic scans is often imprecise. This technology has limited sensitivity as only a visible increase or decrease in tumor mass can be evaluated, making interpretation challenging and conclusions of whether patients benefit from treatment indefinite. Interpretation of radiologic scans has been further challenged after implementation of immunotherapy, causing immunotherapy-induced recruitment of immune cells resembling increment in tumor size, called "pseudo-progression." More sensitive methods are highly needed to reduce ineffective treatments and needless toxicity. Liquid biopsy has the potential to overcome these challenges by measuring molecular changes with high precision in a dynamic manner. Recent studies have demonstrated its promising potential as a biomarker predictive of treatment efficacy and overall survival. In a recent real-life study, investigators found that ctDNA measurements could reduce 33% of likely inefficient treatments and clarify 79% of non-conclusive CT-scans, highlighting the clinical potential. A randomized interventional multicenter study will be performed, investigating the true clinical potenial of liquid biopsy compared to standard monitoring by radiological scans. A total of 350 patients with advanced NSCLC will be included in the study from three Departments of Clinical Oncology. In the interventional arm, liquid biopsy monitoring will be the basis for treatment discontinuation before the standard two years of immunotherapy in patients reaching a complete molecular response in plasma. Thus clarifying the question if treatment duration can be reduced for the benefit of patients and health cost.

Circulating Tumor DNA Guided Treatment Monitoring in Advanced Lung Cancer

Circulating Tumor DNA Guided Treatment Monitoring in Advanced Lung Cancer - a Randomized Interventional Study

Physicians Global Assessment to measure quality of life

Common Terminology Criteria for Adverse Events

Zealand University Hospital

Medical Oncologist, PhD

Heart and Blood Diseases

Rare Diseases

Glioma

Mitral Valve Insufficiency

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Marc Sanson, MD, PhD

Francesca Branzoli, PhD

In France, about 5000 new people with a primary malignant brain tumor are diagnosed each year. The most common primary tumors are gliomas, originating from glial cells (astrocytomas and oligodendrogliomas). Low-grade gliomas are mildly aggressive, but they often evolve into a more malignant form.

Mutations in the genes encoding isocitrate dehydrogenase (IDH) are found in about 80% of low-grade gliomas and are associated with a favorable prognosis. Remarkably, IDH-mutated gliomas are characterized by a specific cellular metabolism causing the accumulation of D-2-hydroxyglutarate (2HG) in tumor cells. 2HG can be detected in vivo using 1H magnetic resonance spectroscopy (MRS) and is recognized as a unique, noninvasive biomarker of IDH-mutated gliomas. Noninvasive detection of IDH mutations via 2HG MRS represents a crucial step for decision-making and patient care.

A subset of IDH-mutated tumors also presents a complete deletion of 1p and 19q chromosome arms (1p/19q codeletion). The 1p/19q codeletion is specifically linked to the oligodendroglial histologic subtype and it has been associated with a better patient outcome. However, the biological effects of this genetic alteration are still unclear and in vivo markers are lacking. Recently, we reported the first in vivo detection of the cystathionine molecule in human brain gliomas using MRS and explored the association between cystathionine accumulation and 1p/19q codeletion in gliomas.

In this project, the investigation team will combine cutting edge MRI and MRS techniques for metabolic and microstructural characterization of brain tumors with the aim of providing novel reliable noninvasive biomarkers of tumor genetic subtypes. These methods will enable noninvasive identification of IDH-mutated gliomas and, potentially, 1p/19q codeleted gliomas. In addition, the researchers will investigate the utility of 2HG, cystathionine and MRI microstructural markers to monitor tumor response to anti-cancer treatments and tumor progression.

The outputs of this project, altogether, may open new avenues to a better understanding of the pathophysiological mechanisms of oncogenesis and the design of new treatments for gliomas.

MRS of Glioma Genomics

Magnetic Resonance Spectroscopy Markers of Glioma Genomics

Concentrations of 2-hydroxyglutarate and cystahionine measured by MRS will be correlated with IDH mutational status and 1p19q codeletion derived from ex vivo analyses in tumor tissue samples

Diffusion MRI metrics will be correlated with the 1p19q codeletion status derived from ex vivo analyses in tumor tissue samples

The changes in concentration of 2-hydroxyglutarate, cystathionine and choline will be compared to the changes in tumor volumes and to the clinical response

Diffusion MRI and amide proton transfer signal changes will be compared to the changes in metabolism, tumor volumes and to the clinical response

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Circulating Tumor DNA Guided Treatment Monitoring in Advanced Lung Cancer	NCT05889247	Non-small Cell ...	Circulating tum...	-	Zealand University Hospital
MRS of Glioma Genomics	NCT05700071	Glioma	MRI	18 Years -	Institut National de la Santé Et de la Recherche Médicale, France

Spots Global Cancer Trial Database for treatment monitoring