Evaluation of circulating tumor DNA as a prognostic and predictive biomarker in BRAF V600E mutated colorectal cancer-results from the FIRE-4.5 study.

The randomized FIRE-4.5 (AIO KRK0116) trial compared first-line therapy with FOLFOXIRI (folinic acid, fluorouracil, oxaliplatin, and irinotecan) plus either cetuximab or bevacizumab in B-Raf proto-oncogene, serine/threonine kinase (BRAF) V600E-mutant metastatic colorectal cancer (mCRC) patients. This study was accompanied by a prospective translational project analyzing cell-free circulating tumor DNA (ctDNA) in plasma to test whether ctDNA analysis may help to guide clinical treatment decision making.

Synthesis and Preclinical Evaluation of a Bispecific PSMA-617/RM2 Heterodimer Targeting Prostate Cancer.

Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRPR) have been used for diagnostic molecular imaging/therapy of prostate cancer (PCa). To address tumor heterogeneity, we synthesized and evaluated a bispecific PSMA/GRPR ligand () combining PSMA-617 () and the GRPR antagonist RM2 () with the radiometal chelator DOTA. was radiolabeled with Ga ([Ga]Ga-) and Lu ([Lu]Lu-).

Therapy adherence after interdisciplinary tumour board discussion is associated with improved outcome in soft tissue sarcoma: A Charité Comprehensive Cancer Centre analysis.

Centralising soft tissue sarcoma (STS) treatment in expert centres and implementing comprehensive therapy concepts through interdisciplinary tumour boards (ITB) has led to significant treatment progress. However, our knowledge on the implementation of the ITB recommendations and its impact on patient outcome is limited. In this retrospective analysis, we examined a cohort of 222 adult patients (pts) with primary STS who were presented to the ITB of the Charité Comprehensive Cancer Centre between 2015 and 2020.

Hyperlipasemia in the immediate postoperative period predicts postoperative pancreatic fistula after pancreatic resections.

Background: Postoperative pancreatic fistula is the most common severe complication after pancreatic surgery. It associated with increased morbidity and prolonged hospital stay. Identifying patients at low risk for postoperative pancreatic fistula is essential to enable timely removal of drains and facilitate early discharge.

Risk of bowel obstruction in patients with colon cancer responding to immunotherapy: an international case series.

Background: Immunotherapy is used routinely for treating deficient mismatch repair (dMMR) colon cancer (CC). This case series highlights an emerging safety issue, where patients develop bowel obstruction associated with immunotherapy response.

Patients And Methods: Patients with dMMR CC who developed bowel obstruction while responding to immunotherapy were retrospectively identified.

The sample locator: A federated search tool for biosamples and associated data in Europe using HL7 FHIR.

Background: This study outlines the development of a highly interoperable federated IT infrastructure for academic biobanks located at the major university hospital sites across Germany. High-quality biosamples linked to clinical data, stored in biobanks are essential for biomedical research. We aimed to facilitate the findability of these biosamples and their associated data.

Parameter optimization for proton density fat fraction quantification in skeletal muscle tissue at 7 T.

Objective: To establish an image acquisition and post-processing workflow for the determination of the proton density fat fraction (PDFF) in calf muscle tissue at 7 T.

Materials And Methods: Echo times (TEs) of the applied vendor-provided multi-echo gradient echo sequence were optimized based on simulations of the effective number of signal averages (NSA*). The resulting parameters were validated by measurements in phantom and in healthy calf muscle tissue (n = 12).

Dermatology-related quality-of-life outcomes in patients with RAS wild-type metastatic colorectal cancer treated with fluorouracil and folinic acid with or without panitumumab (Pmab) maintenance after FOLFOX + Pmab induction: a prespecified secondary analysis of the phase II randomized PanaMa (AIO KRK 0212) trial.

Background: The key endpoints for the assessment of the effect of maintenance therapy for metastatic colorectal cancer (mCRC) are survival and quality-of-life outcomes. We aimed to compare dermatology-related quality of life (DRQOL) in patients with RAS wild-type (wt) mCRC treated with fluorouracil and folinic acid (FU/FA) + panitumumab (Pmab) versus FU/FA alone as maintenance therapy after folinic acid, fluorouracil and oxaliplatin + Pmab induction.

Patients And Methods: The phase II randomized PanaMa (AIO KRK 0212; NCT01991873) trial included 387 patients at 70 community/academic sites in Germany.

Merkel cell polyomavirus pan-T antigen knockdown reduces cancer cell stemness and promotes neural differentiation independent of RB1.

Merkel cell carcinoma (MCC) is a highly aggressive skin cancer associated with integration of Merkel cell polyomavirus (MCPyV). MCPyV-encoded T-antigens (TAs) are pivotal for sustaining MCC's oncogenic phenotype, i.e.

An in-vivo treatment monitoring system for ion-beam radiotherapy based on 28 Timepix3 detectors.

Ion-beam radiotherapy is an advanced cancer treatment modality offering steep dose gradients and a high biological effectiveness. These gradients make the therapy vulnerable to patient-setup and anatomical changes between treatment fractions, which may go unnoticed. Charged fragments from nuclear interactions of the ion beam with the patient tissue may carry information about the treatment quality.

Sequential therapy of refractory metastatic pancreatic cancer with 5-FU/LV/irinotecan (FOLFIRI) vs. 5-FU/LV/oxaliplatin (OFF). The PANTHEON trial (AIO PAK 0116).

Purpose: In patients with metastatic pancreatic cancer, after failure of gemcitabine/nab-paclitaxel, this trial compares the efficacy of second-line therapy with FOLFIRI vs. OFF (1:1 randomisation) with cross-over to the vice-versa regimen as third-line therapy.

Patients And Methods: The primary endpoint was PFS (progression-free survival: time from randomization until progression or death) of second-line therapy.

The History of Chromosomal Instability in Genome-Doubled Tumors.

Tumors frequently display high chromosomal instability and contain multiple copies of genomic regions. Here, we describe Gain Route Identification and Timing In Cancer (GRITIC), a generic method for timing genomic gains leading to complex copy number states, using single-sample bulk whole-genome sequencing data. By applying GRITIC to 6,091 tumors, we found that non-parsimonious evolution is frequent in the formation of complex copy number states in genome-doubled tumors.

Likelihood of Post-COVID Condition in people with hybrid immunity; data from the German National Cohort (NAKO).

Objectives: The risk of Post-COVID-19 condition (PCC) under hybrid immunity remains unclear.

Methods: Using data from the German National Cohort (NAKO Gesundheitsstudie), we investigated risk factors for self-reported post-infection symptoms (any PCC is defined as having at least one symptom, and high symptom burden PCC as having nine or more symptoms).

Results: Sixty percent of 109,707 participants reported at least one previous SARS-CoV-2 infection; 35% reported having had any symptoms 4-12 months after infection; among them 23% reported nine or more symptoms.

Accelerated mapping and robust parallel transmit pulse design for heart and prostate imaging at 7 T.

Purpose: To investigate the impact of reduced k-space sampling on mapping and the resulting impact on phase shimming and dynamic/universal parallel transmit (pTx) RF pulse design.

Methods: Channel-wise 3D maps were measured at 7 T in 35 and 23 healthy subjects for the heart and prostate region, respectively. With these maps, universal phase shims optimizing homogeneity and efficiency were designed for heart and prostate imaging.

Disturbance in cerebral blood microcirculation and hypoxic-ischemic microenvironment are associated with the development of brain metastasis.

Background: Brain metastases (BM) constitute an increasing challenge in oncology due to their impact on neurological function, limited treatment options, and poor prognosis. BM occurs through extravasation of circulating tumor cells across the blood-brain barrier. However, the extravasation processes are still poorly understood.

Multi-cancer risk stratification based on national health data: a retrospective modelling and validation study.

Background: Health care is experiencing a drive towards digitisation, and many countries are implementing national health data resources. Although a range of cancer risk models exists, the utility on a population level for risk stratification across cancer types has not been fully explored. We aimed to close this gap by evaluating pan-cancer risk models built on electronic health records across the Danish population with validation in the UK Biobank.

Sodium quantification in skeletal muscle: comparison between Cartesian gradient-echo and radial ultra-short echo time Na MRI techniques.

Background: Clinical magnetic resonance imaging (MRI) studies often use Cartesian gradient-echo (GRE) sequences with ~2-ms echo times (TEs) to monitor apparent total sodium concentration (aTSC). We compared Cartesian GRE and ultra-short echo time three-dimensional (3D) radial-readout sequences for measuring skeletal muscle aTSC.

Methods: We retrospectively evaluated 211 datasets from 112 volunteers aged 62.

Evaluation of the inflammation-based modified Glasgow Prognostic Score (mGPS) as a prognostic and predictive biomarker in patients with metastatic colorectal cancer receiving first-line chemotherapy: a post hoc analysis of the randomized phase III XELAVIRI trial (AIO KRK0110).

Background: The inflammation-based modified Glasgow Prognostic Score (mGPS) combines serum levels of C-reactive protein and albumin and was shown to predict survival in advanced cancer. We aimed to elucidate the prognostic impact of mGPS on survival as well as its predictive value when combined with gender in unselected metastatic colorectal cancer (mCRC) patients receiving first-line chemotherapy in the randomized phase III XELAVIRI trial.

Patients And Methods: In XELAVIRI, mCRC patients were treated with either fluoropyrimidine/bevacizumab followed by additional irinotecan at first progression (sequential treatment arm; Arm A) or upfront combination of fluoropyrimidine/bevacizumab/irinotecan (intensive treatment arm; Arm B).

Incidences of colorectal adenomas and cancers under colonoscopy surveillance suggest an accelerated "Big Bang" pathway to CRC in three of the four Lynch syndromes.

Background: Colorectal cancers (CRCs) in the Lynch syndromes have been assumed to emerge through an accelerated adenoma-carcinoma pathway. In this model adenomas with deficient mismatch repair have an increased probability of acquiring additional cancer driver mutation(s) resulting in more rapid progression to malignancy. If this model was accurate, the success of colonoscopy in preventing CRC would be a function of the intervals between colonoscopies and mean sojourn time of detectable adenomas.

Modification of Dialysate Na Concentration but not Ultrafiltration or Dialysis Treatment Time Affects Tissue Na Deposition in Patients on Hemodialysis.

Introduction: Tissue Na overload is present in patients receiving hemodialysis (HD) and is associated with cardiovascular mortality. Strategies to actively modify tissue Na amount in these patients by adjusting the HD regimen have not been evaluated.

Methods: In several substudies, including cross-sectional analyses ( = 75 patients on HD), a cohort study and a cross-over interventional study ( = 10 patients each), we assessed the impact of ultrafiltration (UF) volume, prolongation of dialysis treatment time, and modification of dialysate Na concentration on tissue Na content using Na magnetic resonance imaging (Na-MRI).

Protocol for generating and analyzing organ-on-chip using human and mouse intestinal organoids.

Organ-on-chip technology is a powerful tool for in vitro modeling. Combining it with organoids overcomes lumen inaccessibility while preserving cellular diversity and function of the intestinal epithelium. Here, we present a protocol for generating and analyzing organ-on-chips using human and mouse intestinal organoids.