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The advent of personalized therapy for non-small-cell lung carcinoma (nsclc) has improved patient outcomes. Selection of appropriate targeted therapy for patients with nsclc now involves testing for multiple biomarkers, including EGFR. EGFR mutation status is required to optimally treat patients with NSCLC, and thus timely and accurate biomarker testing is necessary. However, in Canada, there are currently no standardized processes or methods in place to ensure consistent testing implementation. That lack creates challenges in ensuring that all appropriate biomarkers are tested for each patient and that the medical oncologist receives the results for making informed treatment decisions in a timely way. An expert multidisciplinary working group was convened to create consensus recommendations about biomarker testing in advanced NSCLC in Canada, with a primary focus on EGFR testing. Recognizing that there are biomarkers beyond EGFR that require timely identification, the expert multidisciplinary working group considered EGFR testing in the broader context of integration into complex lung biomarker testing. Primarily, the panel of experts recommends that all patients with nonsquamous nsclc, regardless of stage, should undergo comprehensive reflex biomarker testing at diagnosis with targeted next-generation sequencing. The panel also considered the EGFR testing algorithm and the challenges associated with the pre-analytic, analytic, and post-analytic elements of testing. Strategies for funding testing by reducing silos of single biomarker testing for EGFR and for optimally implementing the recommendations presented here and educating oncology professionals about them are also discussed. [ABSTRACT FROM AUTHOR]

Rapid advancements in next-generation sequencing (ngs) technology have created an unprecedented opportunity to decipher the molecular profile of tumours to more effectively prevent, diagnose, and treat cancer. Oncologists now have the option to order molecular tests that can guide treatment decisions. However, to date, most oncologists have received limited training in genomics, and they are now faced with the challenge of understanding how such tests and their interpretation align with patient management. Guidance on how to effectively use ngs technology is therefore needed to aid oncologists in applying the results of genomic tests. The Canadian guideline presented here describes best practices and unmet needs related to ngs-based testing for somatic variants in oncology, including clinical application, assay and sample selection, bioinformatics and interpretation of reports performed by laboratories, patient communication, and clinical trials. [ABSTRACT FROM AUTHOR]

Lung cancer is the leading cause of cancer-specific death among Canadians, with non-small-cell lung cancer (NSCLC) being the most common histologic variant. Despite advances in the understanding of the molecular biology of NSCLC, the survival rate for this malignancy is still poor. It is now understood that, to evade detection and immune clearance, NSCLC tumours overexpress the immunosuppressive checkpoint protein programmed death ligand 1 (PD-L1). Inhibiting the PD-1/PD-L1 axis with monoclonal antibodies has significantly changed the treatment landscape in NSCLC during the last 5 years. Despite evidence of clinical response in some patients, only approximately 20% of patients obtain any durable benefit, and many of the patients who do respond ultimately relapse with drug-resistant disease. The identification of patients who are most likely to benefit from such therapy is therefore important. In the present review, we cover the basics of the PD-1/PD-L1 axis and its clinical significance in NSCLC, biomarkers that are predictive of treatment response, relevant clinical trials of PD-1/PD-L1 blockade completed to date, and proposed mechanisms of acquired therapeutic resistance. [ABSTRACT FROM AUTHOR]

The ROS1 kinase is an oncogenic driver in non-small-cell lung cancer (NSCLC). Fusion events involving the ROS1 gene are found in 1%–2% of NSCLC patients and lead to deregulation of a tyrosine kinase–mediated multi-use intracellular signalling pathway, which then promotes the growth, proliferation, and progression of tumour cells. ROS1 fusion is a distinct molecular subtype of NSCLC, found independently of other recognized driver mutations, and it is predominantly identified in younger patients (<50 years of age), women, never-smokers, and patients with adenocarcinoma histology. Targeted inhibition of the aberrant ROS1 kinase with crizotinib is associated with increased progression-free survival (PFS) and improved quality-of-life measures. As the sole approved treatment for ROS1-rearranged NSCLC, crizotinib has been demonstrated, through a variety of clinical trials and retrospective analyses, to be a safe, effective, well-tolerated, and appropriate treatment for patients having the ROS1 rearrangement. Canadian physicians endorse current guidelines which recommend that all patients with nonsquamous advanced NSCLC, regardless of clinical characteristics, be tested for ROS1 rearrangement. Future integration of multigene testing panels into the standard of care could allow for efficient and cost-effective comprehensive testing of all patients with advanced NSCLC. If a ROS1 rearrangement is found, treatment with crizotinib, preferably in the first-line setting, constitutes the standard of care, with other treatment options being investigated, as appropriate, should resistance to crizotinib develop. [ABSTRACT FROM AUTHOR]

Anaplastic lymphoma kinase (ALK) is an oncogenic driver in non-small-cell lung cancer (NSCLC). Chromosomal rearrangements involving the ALK gene occur in up to 4% of nonsquamous NSCLC patients and lead to constitutive activation of the ALK signalling pathway. ALK-positive NSCLC is found in relatively young patients, with a median age of 50 years. Patients frequently have brain metastasis. Targeted inhibition of the ALK pathway prolongs progression-free survival in patients with ALK-positive advanced NSCLC. The results of several recent clinical trials confirm the efficacy and safety benefit of crizotinib and ceritinib in this population. Canadian oncologists support the following consensus statement: All patients with advanced nonsquamous NSCLC (excluding pure neuroendocrine carcinoma) should be tested for the presence of an ALK rearrangement. If an ALK rearrangement is present, treatment with a targeted ALK inhibitor in the first-line setting is recommended. As patients become resistant to first-generation ALK inhibitors, other treatments, including second-generation ALK inhibitors can be considered. [ABSTRACT FROM AUTHOR]

Aims:  To compare the disinfection ability of two widely used electrolytic generation systems (ClorTec and MIOX) and the conventional chlorine disinfectant (sodium hypochlorite) using three strains of Bacillus subtilis spores and MS2 bacteriophage. Methods and Results:  Three B. subtilis aerobic spore strains (ATCC1A1, 35021 and 35946) and the bacteriophage MS2 (ATCC 15597-B1) were propagated and sporulated. Four indicator organisms were exposed to four disinfectant treatments for comparing the effectiveness of inactivation: hypochlorite, ClorTec, MIOX and MIOX-anode. The results indicated that the two electrolytic generation systems were as effective as the conventional chlorination for the inactivation of micro-organisms used. Some data points showed the variation usinganova analysis, in which the inactivation of MIOX and ClorTec was higher than that of hypochlorite. Conclusions:  The ClorTec and MIOX systems are quite similar to hypochlorite in the inactivation-effectiveness for aerobic spores and bacteriophage in drinking water. Significance and Impact of the Study:  Laboratory-scale investigation proved that gaseous chlorine could be replaced by either ClorTec or MIOX systems for the drinking water treatment utilities, which still could maintain the same disinfection efficiency. [ABSTRACT FROM AUTHOR]

Biodegradation of 14C-tagged hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) was studied in aerobic, anaerobic, and anaerobic/aerobic slurries to identify the conditions maximizing RDX-mineralization in Cornhusker Army Ammunition Plant (CAAP, NE) groundwater. Supplementation with phosphate and adequate quantities of acetate caused 25% mineralization of RDX in 3 weeks by microorganisms native to CAAP. Under anaerobic conditions, the same supplementation resulted in 20% mineralization in 3 weeks and 30% mineralization in 6 weeks. The highest degree of mineralization (50%) was obtained under aerobic conditions when the contaminated groundwater was augmented with a consortium of three microbes isolated from another RDX contaminated soil (Hastings, NE) in addition to supplemented with phosphate and acetic acid. Use of complex organic sources (potato or corn starch) slowed down the rates of mineralization under anaerobic conditions, but rapid mineralization ensued as soon as the aerobic conditions were created. Final RDX concentrations in aqueous phase were below detection limit under most conditions. Assimilation of RDX by the cells was negligible. [Copyright &y& Elsevier]