ESMO Recommendations on clinical reporting of genomic test results for solid cancers.

Background: Genomic tumour profiling has a crucial role in the management of patients with solid cancers, as it helps selecting and prioritising therapeutic interventions based on prognostic and predictive biomarkers, as well as identifying markers of hereditary cancers. Harmonised approaches to interpret the results of genomic testing are needed to support physicians in their decision making, prevent inequalities in precision medicine and maximise patient benefit from available cancer management options.

Methods: The European Society for Medical Oncology (ESMO) Translational Research and Precision Medicine Working Group assembled a group of international experts to propose recommendations for preparing clinical genomic reports for solid cancers.

The Innate Immune Landscape of dMMR/MSI Cancers Predicts the Outcome of Nivolumab Treatment: Results from the Drug Rediscovery Protocol.

Purpose: The treatment efficacy of nivolumab was evaluated in patients with advanced, treatment-refractory solid mismatch repair deficiency/microsatellite-instable (dMMR/MSI) tumors, and in-depth biomarker analyses were performed to inform precision immunotherapy approaches.

Patients And Methods: Patients with dMMR/MSI tumors who exhausted standard-of-care treatment options were enrolled in the Drug Rediscovery Protocol, a pan-cancer clinical trial that treats patients with cancer based on their tumor molecular profile with off-label anticancer drugs (NCT02925234). Patients received nivolumab (four cycles of 240 mg every 2 weeks, thereafter 480 mg every 4 weeks).

Multi-omic analysis identifies hypoalbuminemia as independent biomarker of poor outcome upon PD-1 blockade in metastatic melanoma.

We evaluated the prognostic value of hypoalbuminemia in context of various biomarkers at baseline, including clinical, genomic, transcriptomic, and blood-based markers, in patients with metastatic melanoma treated with anti-PD-1 monotherapy or anti-PD-1/anti-CTLA-4 combination therapy (n = 178). An independent validation cohort (n = 79) was used to validate the performance of hypoalbuminemia compared to serum LDH (lactate dehydrogenase) levels. Pre-treatment hypoalbuminemia emerged as the strongest predictor of poor outcome for both OS (HR = 4.

Efficacy of Pembrolizumab and Biomarker Analysis in Patients with WGS-Based Intermediate to High Tumor Mutational Load: Results from the Drug Rediscovery Protocol.

Purpose: To evaluate the efficacy of pembrolizumab across multiple cancer types harboring different levels of whole-genome sequencing-based tumor mutational load (TML; total of nonsynonymous mutations across the genome) in patients included in the Drug Rediscovery Protocol (NCT02925234).

Patients And Methods: Patients with solid, treatment-refractory, microsatellite-stable tumors were enrolled in cohort A: breast cancer cohort harboring a TML of 140 to 290, cohort B: tumor-agnostic cohort harboring a TML of 140 to 290, and cohort C: tumor-agnostic cohort harboring a TML >290. Patients received pembrolizumab 200 mg every 3 weeks.

Combining Genomic Biomarkers to Guide Immunotherapy in Non-Small Cell Lung Cancer.

Purpose: The clinical value of STK11, KEAP1, and EGFR alterations for guiding immune checkpoint blockade (ICB) therapy in non-small cell lung cancer (NSCLC) remains controversial, as some patients with these proposed resistance biomarkers show durable ICB responses. More specific combinatorial biomarker approaches are urgently needed for this disease.

Experimental Design: To develop a combinatorial biomarker strategy with increased specificity for ICB unresponsiveness in NSCLC, we performed a comprehensive analysis of 254 patients with NSCLC treated with ligand programmed death-ligand 1 (PD-L1) blockade monotherapy, including a discovery cohort of 75 patients subjected to whole-genome sequencing (WGS), and an independent validation cohort of 169 patients subjected to tumor-normal large panel sequencing.

Neoadjuvant atezolizumab plus chemotherapy in gastric and gastroesophageal junction adenocarcinoma: the phase 2 PANDA trial.

Gastric and gastroesophageal junction (G/GEJ) cancers carry a poor prognosis, and despite recent advancements, most patients die of their disease. Although immune checkpoint blockade became part of the standard-of-care for patients with metastatic G/GEJ cancers, its efficacy and impact on the tumor microenvironment (TME) in early disease remain largely unknown. We hypothesized higher efficacy of neoadjuvant immunotherapy plus chemotherapy in patients with nonmetastatic G/GEJ cancer.

Comparing technology and regulatory landscape of probiotics as food, dietary supplements and live biotherapeutics.

Application of beneficial microorganisms as probiotics targets a broad range of intended uses, from maintaining health and supporting normal bodily functions to curing and preventing diseases. Currently, three main regulatory fields of probiotic products can be defined depending on their intended use: the more similar probiotic foods and probiotic dietary supplements, and live biotherapeutic products. However, it is not always straightforward to classify a probiotic product into one of these categories.

Is the dark triad always detrimental to firm performance? Testing different performance outcomes and the moderating effects of competitive rivalry.

There is growing evidence that CEOs who have the 'dark triad' of personality traits (Machiavellianism, narcissism, and psychopathy) detrimentally influence firm performance. However, there is still much we do not know. The present study suggests that the CEO dark triad might directly influence typical performance indicators in different ways: positively affecting external performance indicators (breakthrough sales), but negatively affecting internal performance indicators (organizational performance).

Functional precision oncology using patient-derived assays: bridging genotype and phenotype.

Genomics-based precision medicine has revolutionized oncology but also has inherent limitations. Functional precision oncology is emerging as a complementary approach that aims to bridge the gap between genotype and phenotype by modelling individual tumours in vitro. These patient-derived ex vivo models largely preserve several tumour characteristics that are not captured by genomics approaches and enable the functional dissection of tumour vulnerabilities in a personalized manner.

Understanding New Zealand firm innovation: exploring human resource factors by firm size and strength.

Firm innovation is of vital importance to New Zealand's economy, but we understand little about how different human resource (workforce) factors influence innovation approaches (product/services innovation, process innovation, and innovation speed). We explore three human resource (HR) factors: workforce knowledge, skills, and abilities (KSAs), workforce attraction, and workforce retention, using a sample of New Zealand private sector firms ( = 402). Regression analysis shows all HR factors are significant predictors of all innovation approaches.

γδ T cells are effectors of immunotherapy in cancers with HLA class I defects.

DNA mismatch repair-deficient (MMR-d) cancers present an abundance of neoantigens that is thought to explain their exceptional responsiveness to immune checkpoint blockade (ICB). Here, in contrast to other cancer types, we observed that 20 out of 21 (95%) MMR-d cancers with genomic inactivation of β2-microglobulin (encoded by B2M) retained responsiveness to ICB, suggesting the involvement of immune effector cells other than CD8 T cells in this context. We next identified a strong association between B2M inactivation and increased infiltration by γδ T cells in MMR-d cancers.

How scientists interpret and address funding criteria: value creation and undesirable side effects.

Scientists and funding bodies are interdependent actors involved in an ongoing two-way signalling interaction; however, we lack insight on the social mechanisms underpinning this interaction. To address this issue, we examine how successfully funded scientists interpret and address criteria set by the funding body to maximise their chances of funding success. We also consider the possible adverse side effects that can arise from scientists' competitive efforts to address these criteria.

A post-lockdown study of burnout risk amongst New Zealand essential workers.

Background And Rationale: Job burnout is an essential topic for researchers and a pressing issue for employers and employees. However, the most popular tool has become widely critiqued, and a new measure of burnout - the Burnout Assessment Tool (BAT) - is used here. The BAT is helpful because it provides a cut-off threshold score representing high burnout risk.

Deliberating Upon the Living Wage to Alleviate In-Work Poverty: A Rhetorical Inquiry Into Key Stakeholder Accounts.

Most developed nations have a statutory minimum wage set at levels insufficient to alleviate poverty. Increased calls for a living wage have generated considerable public controversy. This article draws on 25 interviews and four focus groups with employers, low-pay industry representatives, representatives of chambers of commerce, pay consultants, and unions.

Pandemic or Not, Worker Subjective Wellbeing Pivots About the Living Wage Point: A Replication, Extension, and Policy Challenge in Aotearoa New Zealand.

Recent pre-pandemic research suggests that living wages can be pivotal for enhancing employee attitudes and subjective wellbeing. This article explores whether or not the present COVID-19 pandemic is impacting pivotal links between living wages and employee attitudes and subjective wellbeing, with replication indicating robustness. Twin cohorts each of 1,000 low-waged workers across New Zealand (NZ), one pre- (2018), and one present-pandemic (2020) were sample surveyed on hourly wage, job attitudes, and subjective wellbeing as linked to changes in the world of work associated with the pandemic (e.

MSD-based assays facilitate a rapid and quantitative serostatus profiling for the presence of anti-AAV antibodies.

Adeno-associated virus (AAV) vector applications are often limited by capsid-directed humoral immune responses, mainly through neutralizing antibodies (NAbs), which are present throughout the human population due to natural AAV infections. Currently, antibody levels are often quantified via ELISA-based protocols or by cellular NAb assays and less frequently by NAb assays in mice. These methods need optimization for each serotype and are often not applicable to AAV variants with poor transduction.

Patients with Rare Cancers in the Drug Rediscovery Protocol (DRUP) Benefit from Genomics-Guided Treatment.

Purpose: Patients with rare cancers (incidence less than 6 cases per 100,000 persons per year) commonly have less treatment opportunities and are understudied at the level of genomic targets. We hypothesized that patients with rare cancer benefit from approved anticancer drugs outside their label similar to common cancers.

Experimental Design: In the Drug Rediscovery Protocol (DRUP), patients with therapy-refractory metastatic cancers harboring an actionable molecular profile are matched to FDA/European Medicines Agency-approved targeted therapy or immunotherapy.

Are human resource practices the key to managing job burnout in New Zealand nurses? Testing a path model.

Aim: To explore if human resource practices are the key to manage job burnout in nurses.

Objective: To determine if human resource practices provide more meaningful work to nurses, subsequently leading to enhanced work-life balance and lower job burnout (emotional exhaustion and cynicism).

Background: Job burnout is a global phenomenon, particularly relevant in the nursing profession due to pressures within the health sector.

Limited evolution of the actionable metastatic cancer genome under therapeutic pressure.

Genomic profiling is critical for the identification of treatment options for patients with metastatic cancer, but it remains unclear how frequently this procedure should be repeated during the course of the disease. To address this, we analyzed whole-genome sequencing (WGS) data of 250 biopsy pairs, longitudinally collected over the treatment course of 231 adult patients with a representative variety of metastatic solid malignancies. Within the biopsy interval (median, 6.