Case report: Single gene testing and comprehensive genomic profiling in non-small cell lung cancer-a case series of divergent results from a large reference laboratory.

Clinical management of non-small cell lung cancer (NSCLC) requires accurate identification of tumor-specific genetic alterations to inform treatment options. Historically, providers have relied on single-gene testing (SGT) for actionable variants due to a perception of cost-effectiveness and/or efficient turnaround time compared to next-generation sequencing (NGS). However, not all actionable variants may be evaluated through SGT modalities, and an SGT approach can exhaust valuable tissue needed for more comprehensive analyses.

Biomarkers in head and neck squamous cell carcinoma: unraveling the path to precision immunotherapy.

Recent strides in understanding the molecular underpinnings of head and neck cancers have sparked considerable interest in identifying precise biomarkers that can enhance prognostication and enable personalized treatment strategies. Immunotherapy has particularly revolutionized the therapeutic landscape for head and neck squamous cell carcinoma, offering new avenues for treatment. This review comprehensively examines the application and limitations of the established and emerging/novel biomarkers for head and neck squamous cell carcinoma.

Real-world comprehensive genomic and immune profiling reveals distinct age- and sex-based genomic and immune landscapes in tumors of patients with non-small cell lung cancer.

Introduction: Younger patients with non-small cell lung cancer (NSCLC) (<50 years) represent a significant patient population with distinct clinicopathological features and enriched targetable genomic alterations compared to older patients. However, previous studies of younger NSCLC suffer from inconsistent findings, few studies have incorporated sex into their analyses, and studies targeting age-related differences in the tumor immune microenvironment are lacking.

Methods: We performed a retrospective analysis of 8,230 patients with NSCLC, comparing genomic alterations and immunogenic markers of younger and older patients while also considering differences between male and female patients.

Cancer Trials Ecosystem in India-Ready for Prime Time?

Executing global clinical trials for cancer is a long, expensive, and complex undertaking. While selecting countries global studies, sponsors must consider several aspects including patient pool, quality of trained investigators, competing trials, availability of infrastructure, and financial investment versus returns. With a large, often treatment-naïve, and diverse patient pool, relatively low cost, good quality health care facilities in urban areas, and a robust and well-trained workforce, India offers several advantages for conducting oncology clinical trials.

The Convergence of Radiology and Genomics: Advancing Breast Cancer Diagnosis with Radiogenomics.

Despite significant progress in the prevention, screening, diagnosis, prognosis, and therapy of breast cancer (BC), it remains a highly prevalent and life-threatening disease affecting millions worldwide. Molecular subtyping of BC is crucial for predictive and prognostic purposes due to the diverse clinical behaviors observed across various types. The molecular heterogeneity of BC poses uncertainties in its impact on diagnosis, prognosis, and treatment.

Bladder Cancer, Loss of Y Chromosome, and New Opportunities for Immunotherapy.

Immune checkpoint inhibitors (ICI) have emerged as an important therapeutic approach for patients with cancers including bladder cancer (BC). This commentary describes a recent study that demonstrated that the loss of Y chromosome (LOY) and/or loss of specific genes on Y chromosome confers an aggressive phenotype to BC because of T cell dysfunction resulting in CD8T cell exhaustion. Loss of expression of Y chromosome genes KDM5D and UTY was similarly associated with an unfavorable prognosis in patients with BC as these genes were partially responsible for the impaired anti-tumor immunity in LOY tumors.

Neoadjuvant therapy in hormone Receptor-Positive/HER2-Negative breast cancer.

Neoadjuvant therapy is commonly used in patients with locally advanced or inoperable breast cancer (BC). Neoadjuvant chemotherapy (NACT) represents an established treatment modality able to downstage tumours, facilitate breast-conserving surgery, yet also achieve considerable pathologic complete response (pCR) rates in HER2-positive and triple-negative BC. For patients with HR+/HER2- BC, the choice between NACT and neoadjuvant endocrine therapy (NET) is still based on clinical and pathological features and not guided by biomarkers of defined clinical utility, differently from the adjuvant setting where gene-expression signatures have been widely adopted to drive decision-making.

CAR-T-Cell Therapy in Multiple Myeloma: B-Cell Maturation Antigen (BCMA) and Beyond.

Significant progress has been achieved in the realm of therapeutic interventions for multiple myeloma (MM), leading to transformative shifts in its clinical management. While conventional modalities such as surgery, radiotherapy, and chemotherapy have improved the clinical outcomes, the overarching challenge of effecting a comprehensive cure for patients afflicted with relapsed and refractory MM (RRMM) endures. Notably, adoptive cellular therapy, especially chimeric antigen receptor T-cell (CAR-T) therapy, has exhibited efficacy in patients with refractory or resistant B-cell malignancies and is now also being tested in patients with MM.

From Incidence to Intervention: A Comprehensive Look at Breast Cancer in South Africa.

The formidable impact of breast cancer extends globally, with South Africa facing pronounced challenges, including significant disparities in breast cancer screening, treatment and survival along ethnic and socioeconomic lines. Over the last two decades, breast cancer incidence has increased and now accounts for a substantial portion of cancers in women. Ethnic disparities in terms of screening, incidence and survival exacerbate the issue, leading to delayed diagnosis among Black patients and highlighting healthcare inequities.

Intracellular DNA sensing by neutrophils and amplification of the innate immune response.

As the first responders, neutrophils lead the innate immune response to infectious pathogens and inflammation inducing agents. The well-established pathogen neutralizing strategies employed by neutrophils are phagocytosis, the action of microbicide granules, the production of ROS, and the secretion of neutrophil extracellular traps (NETs). Only recently, the ability of neutrophils to sense and respond to pathogen-associated molecular patterns is being appreciated.

Mechanisms of immune modulation in the tumor microenvironment and implications for targeted therapy.

The efficacy of cancer therapies is limited to a great extent by immunosuppressive mechanisms within the tumor microenvironment (TME). Numerous immune escape mechanisms have been identified. These include not only processes associated with tumor, immune or stromal cells, but also humoral, metabolic, genetic and epigenetic factors within the TME.

Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in advanced non-small cell lung cancer.

Introduction: Advanced non-small cell lung cancer (aNSCLC) is an incurable disease. The effort to develop treatments with more effective systemic agents continues. This has led to the FDA approval of one antibody-drug conjugate (ADC) and eight immune checkpoint inhibitors (ICIs) for patients with aNSCLC.

RNA Sequencing Identifies Novel NRG1 Fusions in Solid Tumors that Lack Co-Occurring Oncogenic Drivers.

NRG1 gene fusions are rare, therapeutically relevant, oncogenic drivers that occur across solid tumor types. To understand the landscape of NRG1 gene fusions, 4397 solid tumor formalin-fixed, paraffin-embedded samples consecutively tested by comprehensive genomic and immune profiling during standard care were analyzed. Nineteen NRG1 fusions were found in 17 unique patients, across multiple tumor types, including non-small-cell lung (n = 7), breast (n = 2), colorectal (n = 3), esophageal (n = 2), ovarian (n = 1), pancreatic (n = 1), and unknown primary (n = 1) carcinomas, with a cumulative incidence of 0.

Quantifying the impact of the COVID-19 pandemic on clinical trial screening rates over time in 37 countries.

The COVID-19 pandemic has had an unprecedented and disruptive impact on people's health and lives worldwide. In addition to burdening people's health in the short-term in the form of infection, illness, and mortality, there has been an enormous negative impact on clinical research. Clinical trials experienced challenges in ensuring patient safety and enrolling new patients throughout the pandemic.

Role of decentralized clinical trials in cancer drug development: Results from a survey of oncologists and patients.

As a result of the unprecedented challenges imposed by the COVID-19 pandemic on enrollment to cancer clinical trials, there has been an urgency to identify and incorporate new solutions to mitigate these difficulties. The concept of decentralized or hybrid clinical trials has rapidly gained currency, given that it aims to reduce patient burden, increase patient enrollment and retention, and preserve quality of life, while also increasing the efficiency of trial logistics. Therefore, the clinical trial environment is moving toward remote collection and assessment of data, transitioning from the classic site-centric model to one that is more patient-centric.

Immuno-oncology trends: preclinical models, biomarkers, and clinical development.

The landscape in immuno-oncology (I-O) has undergone profound changes since its early beginnings up through the rapid advances happening today. The current drug development pipeline consists of thousands of potential I-O therapies and therapy combinations, many of which are being evaluated in clinical trials. The efficient and successful development of these assets requires the investment in and utilization of appropriate tools and technologies that can facilitate the rapid transitions from preclinical evaluation through clinical development.

Emerging issues related to COVID-19 vaccination in patients with cancer.

Coronavirus disease 2019 (COVID-19) has resulted in millions of deaths globally. The pandemic has had a severe impact on oncology care and research. Patients with underlying cancer are more vulnerable to contracting COVID-19, and also have a more severe clinical course following the infection.

Mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection with a specific focus on lung and breast cancers: A systematic review and meta-analysis.

Background: A systematic review and meta-analysis was performed to estimate mortality in adult patients with solid or hematological malignancies and SARS-CoV-2 infection.

Methods: A systematic search of PubMed, up to 31 January 2021, identified publications reporting the case-fatality rate (CFR) among adult patients with solid or hematological malignancies and SARS-CoV-2 infection. The CFR, defined as the rate of death in this population, was assessed with a random effect model; 95% confidence intervals (CI) were calculated.

Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics.

Introduction: Advanced breast cancer (aBC) remains incurable and the quest for more effective systemic anticancer agents continues. Promising results have led to the FDA approval of three antibody-drug conjugates (ADCs) and two immune checkpoint inhibitors (ICIs) to date for patients with aBC.

Areas Covered: With the anticipated emergence of newer ADCs and ICIs for patients with several subtypes of breast cancer, and given their potential synergy, their use in combination is of clinical interest.

Determining lines of therapy in patients with solid cancers: a proposed new systematic and comprehensive framework.

The complexity of neoplasia and its treatment are a challenge to the formulation of general criteria that are applicable across solid cancers. Determining the number of prior lines of therapy (LoT) is critically important for optimising future treatment, conducting medication audits, and assessing eligibility for clinical trial enrolment. Currently, however, no accepted set of criteria or definitions exists to enumerate LoT.

Mortality in patients with cancer and coronavirus disease 2019: A systematic review and pooled analysis of 52 studies.

Background: Patients with coronavirus disease 2019 (COVID-19) who have underlying malignancy have a higher mortality rate compared with those without cancer, although the magnitude of such excess risk is not clearly defined. We performed a systematic review and pooled analysis to provide precise estimates of the mortality rate among patients with both cancer and COVID-19.

Methods: A systematic literature search involving peer-reviewed publications, preprints and conference proceedings up to July 16, 2020, was performed.