Clinical Research Directory

Timely Ordering of Pharmacogenetic Testing

The goal of this trial is to learn if a machine learning (ML) model can help optimize drug therapy in the pediatric population. The main question\[s\] it aims to answer are whether a machine learning model predicting receipt of a targeted medication within the next three months: * Increases the offering of pharmacogenetic testing prior to receipt of a targeted medication * Increases the number of patients with pharmacogenetic results prior to receipt of a targeted medication * Increases the number of patients who have alteration in medication choice or dose based on pharmacogenetic results This trial only focuses on the prediction and provision of participants with a high-risk of receiving a medication with a pharmacogenetic indication in the next three months.

The Liver BIoBank Lombardia of Fatty Liver

NAFLD is most frequently linked to excess adiposity, insulin resistance and cardiometabolic risk factors, it has become the leading cause of liver disease worldwide, and is associated with increased mortality due to multiple causes. HFC has a strong genetic component and the investigators recently showed that it plays a causal role in determining progressive liver disease and insulin resistance. The genetic risk score predicting liver fat content (HFC-GRS) improves the stratification of liver related events, and the investigators have preliminary data on new common and rare variants that contribute to NAFLD susceptibility, and on a new non-invasive circulating biomarker associated with hepatic fat and lipotoxicity (Interleukin-32). However, no data are yet available on the causal role of hepatic fat on the procoagulant state associated with NAFLD, which could participate to liver damage and is a causal factor in atherothrombotic complications. The aim of the study is to examine the potential application of a precision medicine approach to the improvement of stratification of the risk of liver-related and cardiovascular thrombotic complications of hepatic fat accumulation (HFC) and non-alcoholic fatty liver disease (NAFLD), with a special focus on the role of procoagulant imbalance in mediating the at-risk phenotypes.

Evaluating a Clinical Decision Support Tool for Antiretroviral Therapy Optimization

This study is testing software designed to help healthcare providers choose the best HIV treatment combinations for their patients. HIV medicines, known as antiretroviral therapy (ART), can be complex to manage because the right regimen depends on many factors-such as drug resistance, other health conditions, and medication schedules. Many people with HIV are cared for by general clinicians who may not have access to HIV specialists, which can make treatment decisions more challenging. In this study, healthcare providers will use patient cases to compare standard HIV treatment resources with a new clinical decision support tool that gives evidence-based ART recommendations at the point of care. The investigators hypothesize that using the tool will help providers select treatment plans that better match clinical guidelines, make decisions faster, reduce mental effort, and increase overall satisfaction with the prescribing process.

Study of Pazopanib Combined With Palbociclib for Refractory Solid Tumors With Co-amplified in the 11q13(FGF3/4/19/CCND1)

The efficacy and safety of Pazopanib combined with Palbociclib in the third line and above treatment of refractory solid tumors co amplified in the 11q13 region (FGF3/4/19/CCND1).

Precision Therapy Based on Immune Microenvironment by Transcriptome Sequencing of Osteosarcoma, a Prospective, Multi-cohort Exploratory Clinical Study

Bagaev et al. have identified four tumor microenvironment (TME) subtypes that are conserved across diverse cancers and correlated with immunotherapy response in melanoma, bladder, and gastric cancers. They provided a visual tool revealing the TME subtypes integrated with targetable genomic alterations, which provided a planetary view of each tumor that can aid in oncology clinical decision making. We aim to use this tool to prospectively analyse the biopsy specimens of osteosarcomas to identify their TME subtypes so as to deliver appropriate treatment strategy if these osteosarcomas experience disease progression afterwards. We will compare the past sequencing date stored in PKUPH bank so as to compare the event-free survival(EFS) of these patients to check the Superiority of this method later.

Precision Medicine Trial Based on Molecular Matching Therapy for Patients With Standard Treatment Exhaustion

The main purpose of this study is to explore the feasibility of selecting treatment plans based on genomic variations guided by MTB in patients with advanced refractory solid tumors.

Oncometabolome and MALDI-MSI in Upper GI Carcinomas - Chemosensitivity in Esophageal Carcinoma

Locally advanced adenocarcinoma of the esophagus is a leading cause of death from malignant disease in Germany and has been characterized on a molecular level in recent years. This retrospective observational study deals with patients after esophagectomy with different risk constellations of esophageal carcinoma. An early and individualized therapy of this tumor in an approach of precision oncology significantly improves the prognosis. The metabolomic profile plays a central role in tumor plasticity and oncological outcome. At the same time, these factors affect the efficacy of chemotherapy and need to be investigated in more detail at the molecular level. A central element of this study is the investigation of phospholipid metabolism locally in tumor tissue, in adjacent normal tissue in terms of the tumor microenvironment and systemically in blood plasma. The focus lies on the validation of known oncometabolites that significantly influence tumor sensitivity to chemotherapy. By combining mass spectrometry imaging using matrix-assisted laser desorption ionization - mass spectrometry imaging (MALDI-MSI) with metabolomics using liquid chromatography tandem mass spectrometry (LC-MS/MS), the metabolic profile of tumors can be analyzed in detail, allowing conclusions to be drawn about chemo-insensitive and therapeutically challenging tumors. Both mass spectrometric methods are used to understand the heterogeneous metabolism of the tumors and to describe possible constellations that are associated with increasing chemoresistance. For precise investigation, the cohort under investigation is divided into two patient collectives. Patients with a regression grade 1 after four sessions of FLOT chemotherapy are compared with a regression grade 3 according to Becker in the postoperative pathological assessment. This facilitates the development of personalized therapeutic approaches tailored to the individual oncological profiles of the tumors. The study is complemented by conventional HE microscopic examinations of the tumor itself and the tumor microenvironment, which allow to analyze the morphology and its correlation with metabolic alterations in the tissue. We hypothesize that adenocarcinoma of the esophagus with regression grade 1 encompasses a fundamentally distinct metabolic profile than adenocarcinoma of the esophagus with regression grade 3. Consequently, a stratification parameter within the local tumor metabolism and the tumor microenvironment exists, which correlates with the systemic response to neoadjuvant chemotherapy in blood plasma. The primary aim of the study is to create a comprehensive metabolic profile that clearly identifies tumors with a regression grade 1 versus a regression grade 3 according to Becker. This will be used to improve diagnostics and develop personalized treatment strategies that increase treatment efficiency and patients' chances of survival. This is ultimately carried out with the intention of achieving an improved survival rate and a higher quality of life for patients with locally advanced esophageal cancer. The comprehensive analysis of the tumor microenvironment and the morphological and metabolic profiles should provide new insights into the mechanisms of tumor progression and resistance, which in turn will form the basis for future translational research and treatment approaches. The findings from this study have the potential to change the way esophageal cancer is treated by contributing to the development of stratified therapeutic approaches tailored to the molecular subtype of esophageal cancer.