Systematic assessment of COVID-19 host genetics using whole genome sequencing data.

Courses of SARS-CoV-2 infections are highly variable, ranging from asymptomatic to lethal COVID-19. Though research has shown that host genetic factors contribute to this variability, cohort-based joint analyses of variants from the entire allelic spectrum in individuals with confirmed SARS-CoV-2 infections are still lacking. Here, we present the results of whole genome sequencing in 1,220 mainly vaccine-naïve individuals with confirmed SARS-CoV-2 infection, including 827 hospitalized COVID-19 cases.

App-based assessment of patient-reported outcomes in the Molecular Tumor Board in the Center for Personalized Medicine-(TRACE).

Background: Biomarker-based therapies are increasingly used in cancer patients outside clinical trials. Systematic assessment of patient-reported outcomes (PRO) is warranted to take patients' perspectives during biomarker-based therapies into consideration. We assessed the feasibility of an electronic PRO assessment via a smartphone application.

Protocol of a first-in-human clinical trial to evaluate the safety, tolerability, and preliminary efficacy of the bispecific CD276xCD3 antibody CC-3 in patients with colorectal cancer (CoRe_CC-3).

Introduction: Colorectal cancer (CRC) is the third most common cancer worldwide in men and women. In the metastasized stage, treatment options and prognosis are limited. To address the high medical need of this patient population, we generated a CD276xCD3 bispecific antibody termed CC-3.

Global Expanded Access Program for Pemigatinib in Patients with Previously Treated Locally Advanced or Metastatic Cholangiocarcinoma and Fibroblast Growth Factor Receptor Gene Alterations.

Purpose: Pemigatinib is a fibroblast growth factor receptor-2 (FGFR2) inhibitor approved for use in patients with previously treated cholangiocarcinoma (CCA) and FGFR2 fusions or rearrangements. This ongoing global Expanded Access Program (EAP) allows physicians in regions where pemigatinib is not commercially available to request pemigatinib for patients with locally advanced or metastatic CCA who, in the physician's opinion, could benefit from pemigatinib treatment.

Materials And Methods: Eighty-nine patients from Europe, North America, and Israel were treated from January 2020 through September 2021.

The molecular interaction pattern of lenvatinib enables inhibition of wild-type or kinase-mutated FGFR2-driven cholangiocarcinoma.

Fibroblast growth factor receptor (FGFR)-2 can be inhibited by FGFR-selective or non-selective tyrosine kinase inhibitors (TKIs). Selective TKIs are approved for cholangiocarcinoma (CCA) with FGFR2 fusions; however, their application is limited by a characteristic pattern of adverse events or evocation of kinase domain mutations. A comprehensive characterization of a patient cohort treated with the non-selective TKI lenvatinib reveals promising efficacy in FGFR2-driven CCA.

Long-term efficacy of the peptide-based COVID-19 T cell activator CoVac-1 in healthy adults.

Objectives: T cell immunity is key for the control of viral infections including SARS-CoV-2, in particular with regard to immune memory and protection against arising genetic variants.

Methods: We recently evaluated a peptide-based SARS-CoV-2 T cell activator termed CoVac-1 in a first-in-human trial in healthy adults. Here, we report on long-term safety and efficacy data of CoVac-1 until month 12.

Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial.

Cancer of unknown primary has a dismal prognosis, especially following failure of platinum-based chemotherapy. 10-20% of patients have a high tumor mutational burden (TMB), which predicts response to immunotherapy in many cancer types. In this prospective, non-randomized, open-label, multicenter Phase II trial (EudraCT 2018-004562-33; NCT04131621), patients relapsed or refractory after platinum-based chemotherapy received nivolumab and ipilimumab following TMB vs.

BRAF in-frame deletion mutants differ in their dimerization propensity, HSP90 dependence, and druggability.

In-frame exon 12 deletions are increasingly identified in various tumor types. The resultant BRAF oncoproteins usually lack five amino acids in the β3-αC helix linker and sometimes contain de novo insertions. The dimerization status of BRAF oncoproteins, their precise pathomechanism, and their direct druggability by RAF inhibitors (RAFi) has been under debate.

Maintained imbalance of triglycerides, apolipoproteins, energy metabolites and cytokines in long-term COVID-19 syndrome patients.

Background: Deep metabolomic, proteomic and immunologic phenotyping of patients suffering from an infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have matched a wide diversity of clinical symptoms with potential biomarkers for coronavirus disease 2019 (COVID-19). Several studies have described the role of small as well as complex molecules such as metabolites, cytokines, chemokines and lipoproteins during infection and in recovered patients. In fact, after an acute SARS-CoV-2 viral infection almost 10-20% of patients experience persistent symptoms post 12 weeks of recovery defined as long-term COVID-19 syndrome (LTCS) or long post-acute COVID-19 syndrome (PACS).

Clinical outcome of biomarker-guided therapies in adult patients with tumors of the nervous system.

Background: The clinical utility of molecular profiling and targeted therapies for neuro-oncology patients outside of clinical trials is not established. We aimed at investigating feasibility and clinical utility of molecular profiling and targeted therapy in adult patients with advanced tumors in the nervous system within a prospective observational study.

Methods: molecular tumor board (MTB)@ZPM (NCT03503149) is a prospective observational precision medicine study for patients with advanced tumors.

Local control and patient reported outcomes after online MR guided stereotactic body radiotherapy of liver metastases.

Introduction: Stereotactic body radiotherapy (SBRT) is used to treat liver metastases with the intention of ablation. High local control rates were shown. Magnetic resonance imaging guided radiotherapy (MRgRT) provides the opportunity of a marker-less liver SBRT treatment due to the high soft tissue contrast.

Regional hyperthermia with cisplatin added to gemcitabine versus gemcitabine in patients with resected pancreatic ductal adenocarcinoma: The HEAT randomised clinical trial.

Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adenocarcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma.

Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m on day 1, 15 and cisplatin 25 mg/m with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m on day 1,8,15), four-weekly over six cycles.

External Validation of COVID-19 Risk Scores during Three Waves of Pandemic in a German Cohort-A Retrospective Study.

Several risk scores were developed during the COVID-19 pandemic to identify patients at risk for critical illness as a basic step to personalizing medicine even in pandemic circumstances. However, the generalizability of these scores with regard to different populations, clinical settings, healthcare systems, and new epidemiological circumstances is unknown. The aim of our study was to compare the predictive validity of qSOFA, CRB65, NEWS, COVID-GRAM, and 4C-Mortality score.