Solitary fibrous tumor of the prostate with accompanying low-grade prostate cancer.

We present the rare case of a 51-year-old male diagnosed with a solitary fibrous tumor (SFT) of the prostate, along with a concurrent low-grade prostate adenocarcinoma (Gleason score 3 + 3, Grade Group 1). The diagnosis was confirmed by positive immunohistochemical markers, including CD34, BCL2, and STAT6, and molecular analysis showing a NAB2-STAT6 fusion. Following successful surgical management and the simultaneous diagnosis of a pulmonary relapse from a prior thyroid carcinoma, the patient remains under clinical surveillance.

A diagnostic challenge of KIT p.V559D and BRAF p.G469A mutations in a paragastric mass.

A patient with gastrointestinal stroma tumor (GIST) and KIT p.V559D and BRAF p.G469A alterations was referred to our institutional molecular tumor board (MTB) to discuss therapeutic implications.

Renal Extramedullary Hematopoiesis in Mast Cell Leukemia with Bone Marrow Fibrosis.

Systemic mastocytosis is defined by the clonal proliferation of abnormal mast cells. The clinical course can range from indolent forms with normal life expectancy to advanced mast cell leukemia with dismal prognosis. An association with other diseases, including myeloproliferative neoplasia, has been described.

Evaluation of the effectiveness of a nationwide precision medicine program for patients with advanced non-small cell lung cancer in Germany: a historical cohort analysis.

Background: The national Network Genomic Medicine (nNGM) Lung Cancer provides comprehensive and high-quality multiplex molecular diagnostics and standardized personalized treatment recommendation for patients with advanced non-small cell lung cancer (aNSCLC) in Germany. The primary aim of this study was to investigate the effectiveness of the nNGM precision medicine program in terms of overall survival (OS) using real-world data (RWD).

Methods: A historical nationwide cohort analysis of patients with aNSCLC and initial diagnosis between 04/2019 and 06/2020 was conducted to compare treatment and OS of patients with and without nNGM-participation.

Leveraging Large Language Models for Decision Support in Personalized Oncology.

Importance: Clinical interpretation of complex biomarkers for precision oncology currently requires manual investigations of previous studies and databases. Conversational large language models (LLMs) might be beneficial as automated tools for assisting clinical decision-making.

Objective: To assess performance and define their role using 4 recent LLMs as support tools for precision oncology.

Tumour mutational burden and survival with molecularly matched therapy.

Background: The impact of tumour mutational burden (TMB) on outcome with molecularly matched therapy is unknown. Higher TMB could predict resistance to molecularly matched therapy through co-occurring driver mutations.

Methods: One hundred and four patients with advanced cancers underwent molecular profiling in the DKTK-MASTER program.

Targeted treatment in a case series of AR+, HRAS/PIK3CA co-mutated salivary duct carcinoma.

Background And Purpose: A subgroup of salivary duct carcinoma (SDC) harbor overexpression of the androgen receptor (AR), and co-occurring mutations in the - and -genes. The impact of genomic complexity on targeted treatment strategies in advanced cancer is unknown.

Materials And Methods: We analyzed molecular and clinical data from an institutional molecular tumor board (MTB) to identify AR+, / co-mutated SDC.

Prognostic factors in surgically treated malignant salivary gland tumors.

Objectives: To identify prognostic factors for evidence-based risk stratification in malignant salivary gland tumors.

Methods: This retrospective study identified 162 patients who presented with malignant salivary gland tumors between 2010 and 2020. Final analysis included 91 patients who underwent surgical treatment at our institution and were followed-up for ≥ 1 year.

Feasibility and outcome of reproducible clinical interpretation of high-dimensional molecular data: a comparison of two molecular tumor boards.

Background: Structured and harmonized implementation of molecular tumor boards (MTB) for the clinical interpretation of molecular data presents a current challenge for precision oncology. Heterogeneity in the interpretation of molecular data was shown for patients even with a limited number of molecular alterations. Integration of high-dimensional molecular data, including RNA- (RNA-Seq) and whole-exome sequencing (WES), is expected to further complicate clinical application.

A community approach to the cancer-variant-interpretation bottleneck.

As guidelines, therapies, and literature on cancer variants expand, the lack of consensus variant interpretations impedes clinical applications. CIViC is a public domain, crowd-sourced, and adaptable knowledgebase of evidence for the Clinical Interpretation of Variants in Cancer, designed to reduce barriers to knowledge sharing and alleviate the variant interpretation bottleneck.

Biomarker-driven therapies for metastatic uveal melanoma: A prospective precision oncology feasibility study.

Background: Targeted therapies for metastatic uveal melanoma have shown limited benefit in biomarker-unselected populations. The Treat20 Plus study prospectively evaluated the feasibility of a precision oncology strategy in routine clinical practice.

Patients And Methods: Fresh biopsies were analyzed by high-throughput genomics (whole-genome, whole-exome, and RNA sequencing).

Annotation and initial evaluation of a large annotated German oncological corpus.

Objective: We present the Berlin-Tübingen-Oncology corpus (BRONCO), a large and freely available corpus of shuffled sentences from German oncological discharge summaries annotated with diagnosis, treatments, medications, and further attributes including negation and speculation. The aim of BRONCO is to foster reproducible and openly available research on Information Extraction from German medical texts.

Materials And Methods: BRONCO consists of 200 manually deidentified discharge summaries of cancer patients.

Distinct immune evasion in APOBEC-enriched, HPV-negative HNSCC.

Immune checkpoint inhibition leads to response in some patients with head and neck squamous cell carcinoma (HNSCC). Robust biomarkers are lacking to date. We analyzed viral status, gene expression signatures, mutational load and mutational signatures in whole exome and RNA-sequencing data of the HNSCC TCGA dataset (n = 496) and a validation set (DKTK MASTER cohort, n = 10).

A harmonized meta-knowledgebase of clinical interpretations of somatic genomic variants in cancer.

Precision oncology relies on accurate discovery and interpretation of genomic variants, enabling individualized diagnosis, prognosis and therapy selection. We found that six prominent somatic cancer variant knowledgebases were highly disparate in content, structure and supporting primary literature, impeding consensus when evaluating variants and their relevance in a clinical setting. We developed a framework for harmonizing variant interpretations to produce a meta-knowledgebase of 12,856 aggregate interpretations.

Support of a molecular tumour board by an evidence-based decision management system for precision oncology.

Background: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow for the interpretation of molecular analyses.

Validating Comprehensive Next-Generation Sequencing Results for Precision Oncology: The NCT/DKTK Molecularly Aided Stratification for Tumor Eradication Research Experience.

Purpose: Rapidly evolving genomics technologies, in particular comprehensive next-generation sequencing (NGS), have led to exponential growth in the understanding of cancer biology, shifting oncology toward personalized treatment strategies. However, comprehensive NGS approaches, such as whole-exome sequencing, have limitations that are related to the technology itself as well as to the input source. Hence, clinical implementation of comprehensive NGS in a quality-controlled diagnostic workflow requires both the standardization of sequencing procedures and continuous validation of sequencing results by orthogonal methods in an ongoing program to enable the determination of key test parameters and continuous improvement of NGS and bioinformatics pipelines.

Comparison of Treatment Recommendations by Molecular Tumor Boards Worldwide.

Purpose: Precision oncology holds the promise of improving patient outcome. It is based on the idea that the testing of genomic biomarkers can lead to the recommendation of a treatment option tailored to the specific patient. To derive treatment recommendations from molecular profiles, interdisciplinary molecular tumor boards (MTBs) have been established recently in many academic institutions.

Cancer Precision Medicine: Why More Is More and DNA Is Not Enough.

Every tumour is different. They arise in patients with different genomes, from cells with different epigenetic modifications, and by random processes affecting the genome and/or epigenome of a somatic cell, allowing it to escape the usual controls on its growth. Tumours and patients therefore often respond very differently to the drugs they receive.

CIViC is a community knowledgebase for expert crowdsourcing the clinical interpretation of variants in cancer.

CIViC is an expert-crowdsourced knowledgebase for Clinical Interpretation of Variants in Cancer describing the therapeutic, prognostic, diagnostic and predisposing relevance of inherited and somatic variants of all types. CIViC is committed to open-source code, open-access content, public application programming interfaces (APIs) and provenance of supporting evidence to allow for the transparent creation of current and accurate variant interpretations for use in cancer precision medicine.

Targeted Therapy of Head and Neck Cancer.

Head and neck squamous cell carcinoma (HNSCC) is one of the most common solid cancers worldwide. It is mainly caused by exposure to tobacco smoke and alcohol as well as infection with the human papilloma virus (HPV). The prognosis is poor, especially once it recurs or metastasizes.

Systemic Treatment in HPV-Induced Recurrent or Metastatic HNSCC.

Recurrent or metastatic head and neck cancer describes tumor deposits that arise locally, regionally, or at distant sites after treatment or distant metastases at the time of primary diagnosis. Prognosis for R/M squamous cell carcinomas of the head and neck (HNSCC) is poor and treatment options are limited in this situation. Human papillomavirus (HPV) is an important risk factor for HNSCC.

Methylation of RAD51B, XRCC3 and other homologous recombination genes is associated with expression of immune checkpoints and an inflammatory signature in squamous cell carcinoma of the head and neck, lung and cervix.

Immune checkpoints are emerging treatment targets, but mechanisms underlying checkpoint expression are poorly understood. Since alterations in DNA repair genes have been connected to the efficacy of checkpoint inhibitors, we investigated associations between methylation of DNA repair genes and CTLA4 and CD274 (PD-L1) expression.A list of DNA repair genes (179 genes) was selected from the literature, methylation status and expression of inflammation-associated genes (The Cancer Genome Atlas data) was correlated in head and neck squamous cell carcinoma (HNSCC), cervical and lung squamous cell carcinoma.