NCCN Guidelines ® Insights: Non-Small Cell Lung Cancer, Version 4.2016 Featured Updates to the NCCN Guidelines

TL;DR: Functional studies report that BMSC-Exo shuffle miR-193a to suppress the colony formation, invasion, migration, and proliferation as well as advance apoptosis of NSCLC DDP-resistant cells via downregulating LRRC1.

TL;DR: The overall results are highly concordant suggesting diagnostic equivalence of tested assays, and a significant subset of 56/235 urothelial carcinomas stained positive for PD-L1 with high concordance between all four antibodies and RNA ISH assay.

TL;DR: The use of agents able to modulate the immune system to induce or potentiate its anti-tumour activity is not a new strategy in oncology, but the development of new agents has achieved unprecedented efficacy results in a wide variety of tumours, dramatically changing the landscape of cancer treatment in recent years.

Abstract: BACKGROUND Genomic fusions of the anaplastic lymphoma kinase gene (ALK) are a well-established therapy target in non-small cell lung cancer (NSCLC). From a survey of 114,200 clinical cases, we determined the prevalence of ALK rearrangements (rALK) in non-NSCLC tumors and report their responsiveness to therapies targeting ALK. MATERIALS AND METHODS Comprehensive genomic profiling of 114,200 relapsed and metastatic malignancies, including both solid tumors and hematolymphoid cancers, was performed using a hybrid-capture, adaptor ligation-based next-generation sequencing assay. RESULTS Of 114,200 clinical samples, 21,522 (18.8%) were NSCLC and 92,678 (81.2%) were other tumor types. Of the 876 (0.8%) cases with ALK fusions (fALK) or rALK, 675 (77.1%) were NSCLC and 201 (22.9%) were other tumor types. ALK fusions were significantly more frequent in NSCLC (3.1%) than non-NSCLC (0.2%; p < .0001). Patients with non-NSCLC tumors harboring fALK were significantly younger (p < .0001) and more often female (p < .0001) than patients with fALK-positive NSCLC. EML4 was more often the fusion partner in NSCLC (83.5%) versus non-NSCLC tumors (30.9%; p < .0001). CONCLUSION ALK rearrangements can be identified in a wide variety of epithelial and mesenchymal malignancies beyond NSCLC. Anti-ALK therapies can be effective in non-NSCLC tumors driven by fALK, and further study of therapies targeting ALK in clinical trials involving a wider variety of cancer types appears warranted. IMPLICATIONS FOR PRACTICE Rearrangements involving the ALK gene have been detected in dozens of cancer types using next-generation sequencing. Patients whose tumors harbor ALK rearrangements or fusions respond to treatment with crizotinib and alectinib, including tumors not normally associated with ALK mutations, such as non-Langerhans cell histiocytosis or renal cell carcinoma. Comprehensive genomic profiling using next-generation sequencing can detect targetable ALK fusions irrespective of tumor type or fusions partner.

TL;DR: Overall cancer incidence trends are stable in women, but declining by 3.1% per year in men, much of which is because of recent rapid declines in prostate cancer diagnoses, and brain cancer has surpassed leukemia as the leading cause of cancer death among children and adolescents.

TL;DR: Although initially thought to be rare, the incidence rates of renal toxicities might be higher as identified by recent studies, Steroids appear to be effective in treating the immune-related adverse effects noted with these agents.

TL;DR: Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression (≥1, ≥5%, and ≥10%) of the PD-1 ligand.