Project description:Measuring tumor response to treatment based on computed tomography (CT) and/or magnetic resonance imaging (MRI) has been a widely debated issue (response criteria in solid tumors [RECIST] and World Health Organization criteria). Furthermore, early identification of nonresponding patients is of great importance because the rates of response of common malignant solid tumors to chemotherapy are in the range of only 20-30%. Therefore, quantitative imaging of tumor metabolism with 18F-FDG PET/CT may provide important advantages and thus reduce side effects and costs of ineffective therapy. However, the evidence to date for the use of 18F-FDG-PET/CT with this indication is limited.
The purpose of the present trial is to determine the impact of 18F-FDG PET/CT in the management of advanced colorectal cancer. The aim is also to confirm whether a metabolic response can be used as a surrogate end point in monitoring treatment response in this cancer type.
The study consists of 40 patients with advanced colorectal cancer patients. All patients will be studied with 18F-FDG PET/CT combined with diagnostic contrast enhanced abdominal CT before the start of chemotherapy and re-evaluated 4-5 weeks after the initiation of therapy. Effect of this metabolic and anatomic change in therapy are evaluated and correlated to survival, morbidity, and treatment -related costs. Histopathologic confirmation of response is evaluated whenever possible. The data will be collected between 2008 and 2012.
Project description:Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous malignancy with limited predictive markers to guide personalized treatment, particularly in human papillomavirus (HPV)-negative cases, which exhibit poor outcomes. Identifying reliable biomarkers for prognosis and therapeutic response remains a critical challenge. In a retrospective cohort of 51 patients with primary HPV-negative HNSCC, we investigated the prognostic significance of the Hedgehog (HH) signaling pathway and its association with imaging biomarkers. Genomic and transcriptomic analysis revealed that HH pathway activation correlated with distinct [18F]FDG PET/CT radiomic features, notably the PET-derived “histogram:ih.max” - a surrogate for peak [18F]FDG uptake and was associated with inferior survival outcomes. Functionally, pharmacologic inhibition of HH signaling demonstrated anticancer efficacy across multiple models, including HNSCC cell lines, patient-derived tumoroids, and in vivo xenograft models. Importantly, HH inhibition altered imaging characteristics in HNSCC xenografts, leading to a measurable reduction in [18F]FDG uptake. This imaging phenotype closely mirrored our clinical findings, suggesting that [18F]FDG PET/CT radiomics may serve as a non-invasive biomarker to identify and monitor HH-driven HNSCC tumors. The integration of multi-level molecular profiling and functional imaging supports a potential precision oncology strategy, in which HH inhibition may offer a viable therapeutic approach for HPV-negative HNSCC. Our study underscores the value of [18F]FDG PET/CT multiomics in linking tumor biology with imaging features, paving the way for improved patient stratification and treatment monitoring. These findings provide a compelling rationale for further investigation into HH-targeted therapies in this aggressive subset of HNSCC and their clinical implications.
Project description:Circulating tumor DNA (ctDNA) as a biomarker of disease activity in classic Hodgkin lymphoma (cHL) patients are still not well-defined. By profiling primary tumors and ctDNA, we identified common variants between primary tumors and longitudinal plasma samples in most of the cases, confirming high PBatial and temporal heterogeneity. Though ctDNA analyses mirrored HRS cell genetics overall, the prevalence of variants shows that none of them can be used as a single biomarker. Conversely, the estimation of hGE/mL, based in total ctDNA quantification, reflects disease activity and is almost perfectly correlated with standard parameters such as PET/CT that are associated with refractoriness.