Patient recruitment into clinical studies of solid malignancies during the COVID-19 pandemic in a tertiary cancer center.

Background And Purpose: To analyze clinical trial activities and patient recruitment numbers into prospective clinical studies for solid malignancies during the COVID-19 pandemic in a tertiary cancer center.

Materials And Methods: Patient recruitment numbers in prospective clinical studies of solid malignancies were retrospectively analyzed for the years 2019 - 2021 at the Comprehensive Cancer Center Zurich (CCCZ). Changes in recruitment numbers were tested for association with organ-specific subunits, as well as organizational and treatment-related trial characteristics.

Molecular and functional landscape of malignant serous effusions for precision oncology.

Personalized treatment for patients with advanced solid tumors critically depends on the deep characterization of tumor cells from patient biopsies. Here, we comprehensively characterize a pan-cancer cohort of 150 malignant serous effusion (MSE) samples at the cellular, molecular, and functional level. We find that MSE-derived cancer cells retain the genomic and transcriptomic profiles of their corresponding primary tumors, validating their use as a patient-relevant model system for solid tumor biology.

ctDNA Dynamics and Mechanisms of Acquired Resistance in Patients Treated with Osimertinib with or without Bevacizumab from the Randomized Phase II ETOP-BOOSTER Trial.

Purpose: The ETOP 10-16 BOOSTER study was a randomized phase II trial of osimertinib and bevacizumab therapy versus osimertinib therapy in patients with an acquired EGFR T790M mutation. The mechanisms of acquired resistance to osimertinib and bevacizumab have not been described previously.

Experimental Design: Next-generation sequencing (Guardant360) was conducted in serial plasma samples.

Acquired NF2 mutation confers resistance to TRK inhibition in an ex vivo LMNA::NTRK1-rearranged soft-tissue sarcoma cell model.

Genomic rearrangements of the neurotrophic receptor tyrosine kinase genes (NTRK1, NTRK2, and NTRK3) are the most common mechanism of oncogenic activation for this family of receptors, resulting in sustained cancer cell proliferation. Several targeted therapies have been approved for tumours harbouring NTRK fusions and a new generation of TRK inhibitors has already been developed due to acquired resistance. We established a patient-derived LMNA::NTRK1-rearranged soft-tissue sarcoma cell model ex vivo with an acquired resistance to targeted TRK inhibition.

Insights into Orbital Symmetry: A Comprehensive Retrospective Study of 372 Computed Tomography Scans.

The operation planning and production of individualized implants with the help of AI-based software after orbital fractures have become increasingly important in recent years. This retrospective study aimed to investigate the healthy orbitae of 372 patients from CT images in the bone and soft tissue windows using the Disior™ Bonelogic™ CMF Orbital software. (version 2.

SAKK57/16 Nab-paclitaxel and Gemcitabine in Soft Tissue Sarcoma (NAPAGE): a phase I/II trial.

Background: To determine whether the combination of nab-paclitaxel with gemcitabine has activity in patients with pretreated soft tissue sarcoma (STS).

Patients And Methods: NAPAGE is a phase Ib/II clinical trial investigating the combination of nab-paclitaxel (nab-pc) with gemcitabine employing two cohorts. One of a dose-de-escalation phase and one of expansion.

Patterns of progression on first line osimertinib in patients with EGFR mutation-positive advanced non-small cell lung cancer (NSCLC): A Swiss cohort study.

Aim: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved for patients with EGFR mutated non-small cell lung cancer as first-line treatment. However, treatment resistance inevitably emerges and may present as oligo-progressive disease (OPD) or systemic progressive disease (SPD). The incidence of OPD on first-line osimertinib is unknown.

Improving the turnaround time of molecular profiling for advanced non-small cell lung cancer: Outcome of a new algorithm integrating multiple approaches.

Background: Molecular tumor profiling to identify oncogenic drivers and actionable mutations has a profound impact on how lung cancer is treated. Especially in the subgroup of non-small cell lung cancer (NSCLC), molecular testing for certain mutations is crucial in daily clinical practice and is recommended by international guidelines. To date, a standardized approach to identify druggable genetic alterations are lacking.

Unravelling homologous recombination repair deficiency and therapeutic opportunities in soft tissue and bone sarcoma.

Defects in homologous recombination repair (HRR) in tumors correlate with poor prognosis and metastases development. Determining HRR deficiency (HRD) is of major clinical relevance as it is associated with therapeutic vulnerabilities and remains poorly investigated in sarcoma. Here, we show that specific sarcoma entities exhibit high levels of genomic instability signatures and molecular alterations in HRR genes, while harboring a complex pattern of chromosomal instability.

How to read a next-generation sequencing report-what oncologists need to know.

Next-generation sequencing (NGS) of tumor cell-derived DNA/RNA to screen for targetable genomic alterations is now widely available and has become part of routine practice in oncology. NGS testing strategies depend on cancer type, disease stage and the impact of results on treatment selection. The European Society for Medical Oncology (ESMO) has recently published recommendations for the use of NGS in patients with advanced cancer.

Mutational Landscape and Expression of PD-L1 in Patients with Non-Small Cell Lung Cancer Harboring Genomic Alterations of the MET gene.

Background: Mesenchymal-to-epithelial transition (MET) exon 14 skipping mutations and MET gene amplification occur in 3-5% of non-small cell lung cancer (NSCLC) patients. Tyrosine kinase inhibitors (TKIs) targeting MET alterations have shown promising results in these patients.

Objective: The aim of this study was to describe the genomic profile, PD-L1 expression and clinicopathological features of MET dysregulated NSCLC.

ROS1 genomic rearrangements are rare actionable drivers in microsatellite stable colorectal cancer.

c-Ros oncogene 1, receptor tyrosine kinase (ROS1) genomic rearrangements have been reported previously in rare cases of colorectal cancer (CRC), yet little is known about the frequency, molecular characteristics, and therapeutic vulnerabilities of ROS1-driven CRC. We analyzed a clinical dataset of 40 589 patients with CRC for ROS1 genomic rearrangements and their associated genomic characteristics (Foundation Medicine, Inc [FMI]). We moreover report the disease course and treatment response of an index patient with ROS1-rearranged metastatic CRC.

Alectinib for the treatment of pretreated RET-rearranged advanced NSCLC: Results of the ETOP ALERT-lung trial.

Background: Alectinib, a highly selective next generation ALK-inhibitor, has exhibited potent anti-tumour activity in RET-rearranged NSCLC in the preclinical stage.

Methods: ALERT-lung is a single-arm, phase II trial evaluating the activity of alectinib for the treatment of pretreated RET-rearranged advanced NSCLC. Alectinib was administered orally, 600 mg, twice per day until progression, refusal or unacceptable toxicity (treatment could continue beyond progression, if patient was deriving clinical benefit).

MTPpilot: An Interactive Software for Visualization of Next-Generation Sequencing Results in Molecular Tumor Boards.

Purpose: Comprehensive targeted next-generation sequencing (NGS) panels are routinely used in modern molecular cancer diagnostics. In molecular tumor boards, the detected genomic alterations are often discussed to decide the next treatment options for patients with cancer. With the increasing size and complexity of NGS panels, the discussion of these results becomes increasingly complex, especially if they are reported in a text-based form, as it is the standard in current molecular pathology.

Structure-based prediction of BRAF mutation classes using machine-learning approaches.

The BRAF kinase is attracting a lot of attention in oncology as alterations of its amino acid sequence can constitutively activate the MAP kinase signaling pathway, potentially contributing to the malignant transformation of the cell but at the same time rendering it sensitive to targeted therapy. Several pathologic BRAF variants were grouped in three different classes (I, II and III) based on their effects on the protein activity and pathway. Discerning the class of a BRAF mutation permits to adapt the treatment proposed to the patient.

Molecular and immunophenotypic characterization of SMARCB1 (INI1) - deficient intrathoracic Neoplasms.

The switch/sucrose-non-fermenting (SWI/SNF) complex is an ATP-dependent chromatin remodeling complex that plays important roles in DNA repair, transcription and cell differentiation. This complex consists of multiple subunits and is of particular interest in thoracic malignancies due to frequent subunit alteration of SMARCA4 (BRG1). Much less is known about SMARCB1 (INI1) deficient intrathoracic neoplasms, which are rare, often misclassified and understudied.

Outcome and Prognostic Factors of COVID-19 Infection in Swiss Cancer Patients: Final Results of SAKK 80/20 (CaSA).

Purpose: These are the final results of a national registry on cancer patients with COVID-19 in Switzerland. Methods: We collected data on symptomatic COVID-19-infected cancer patients from 23 Swiss sites over a one-year period starting on 1 March 2020. The main objective was to assess the outcome (i.

Safety of Tepotinib in Patients With MET Exon 14 Skipping NSCLC and Recommendations for Management.

Introduction: The MET inhibitor tepotinib demonstrated durable clinical activity in patients with advanced MET exon 14 (METex14) skipping NSCLC. We report detailed analyses of adverse events of clinical interest (AECIs) in VISION, including edema, a class effect of MET inhibitors.

Patients And Methods: Incidence, management, and time to first onset/resolution were analyzed for all-cause AECIs, according to composite categories (edema, hypoalbuminemia, creatinine increase, and ALT/AST increase) or individual preferred terms (pleural effusion, nausea, diarrhea, and vomiting), for patients with METex14 skipping NSCLC in the phase II VISION trial.

Comprehensive Statistical Exploration of Prognostic (Bio-)Markers for Responses to Immune Checkpoint Inhibitor in Patients with Non-Small Cell Lung Cancer.

Metastatic non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) may suffer from heavy side effects and not all patients benefit from the treatment. We conducted a comprehensive statistical analysis to identify promising (bio-)markers for treatment response. We analyzed retrospective data from NSCLC patients treated with ICIs in first- or further-line therapy settings at the University Hospital Zurich.

A randomised phase II study of osimertinib and bevacizumab versus osimertinib alone as second-line targeted treatment in advanced NSCLC with confirmed EGFR and acquired T790M mutations: the European Thoracic Oncology Platform (ETOP 10-16) BOOSTER trial.

Background: While osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) is the standard treatment in patients with advanced non-small-cell lung cancer (NSCLC) with sensitising EGFR and acquired T790M mutations, progression inevitably occurs. The angiogenic pathway is implicated in EGFR TKI resistance.

Patients And Methods: BOOSTER is an open-label randomised phase II trial investigating the efficacy and safety of combined osimertinib 80 mg daily and bevacizumab 15 mg/kg every 3 weeks, versus osimertinib alone, in patients with EGFR-mutant advanced NSCLC and acquired T790M mutations after failure on previous EGFR TKI therapy.

Tepotinib Efficacy and Safety in Patients with MET Exon 14 Skipping NSCLC: Outcomes in Patient Subgroups from the VISION Study with Relevance for Clinical Practice.

Purpose: Primary analysis of VISION showed tepotinib had durable clinical activity in patients with MET exon 14 (METex14) skipping non-small cell lung cancer (NSCLC). We present updated outcomes for clinically relevant subgroups.

Patients And Methods: This phase II, open-label, multi-cohort study of 500 mg (450 mg active moiety) tepotinib in patients with METex14 skipping NSCLC assessed efficacy and safety in predefined subgroups according to age, prior therapies (chemotherapy and immune checkpoint inhibitors), and brain metastases.

Setting a diagnostic benchmark for tumor BRCA testing: detection of BRCA1 and BRCA2 large genomic rearrangements in FFPE tissue - A pilot study.

PARP inhibitors are used for treatment of tumors lacking function of the double-strand DNA break repair proteins BRCA1 or BRCA2 and are already approved for several cancer types. Thus, it is clinically crucial to determine germline as well as somatic BRCA1/2 mutations in those patients. The amplicon-based Oncomine BRCA1 and BRCA2 Assay is a test routinely used in diagnostics with FFPE specimens.

When SUV Matters: FDG PET/CT at Baseline Correlates with Survival in Soft Tissue and Ewing Sarcoma.

Introduction: The role of positron-emission tomography/computed-tomography (PET/CT) in the management of sarcomas and as a prognostic tool has been studied. However, it remains unclear which metric is the most useful. We aimed to investigate if volume-based PET metrics (Tumor volume (TV) and total lesions glycolysis (TLG)) are superior to maximal standardized uptake value (SUVmax) and other metrics in predicting survival of patients with soft tissue and bone sarcomas.