Response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation: A case report.

BACKGROUND: Although common in lung cancer, somatic epidermal growth factor receptor (EGFR) mutations are rarely found in colorectal cancer, occurring in approximately 3% of cases. Treatment with anti-EGFR antibodies is commonplace, but EGFR tyrosine kinase inhibitors are not standard treatments in colorectal cancer. Here we report a case of sustained response to osimertinib in a colorectal cancer patient with an EGFR T790M mutation on cell-free DNA analysis. CASE SUMMARY: A 72-year old woman with a past medical history of post-polio syndrome confined to a wheelchair, scoliosis and hypothyroidism presented with metastatic sigmoid colon adenocarcinoma with hepatic metastases. Next generation sequencing revealed a RAS/RAF wild-type, microsatellite stable, PD-L1 negative malignancy. Mutations in TP3 and APC were also identified, as well as EGFR amplification. Cell-free DNA analysis revealed an EGFR T790M mutation. She was unable to tolerate first-line treatment with panitumumab, 5-fluorouracil and leucovorin, progressed on second-line treatment with trifluridine/tipiracil plus bevacizumab, and was unable to tolerate third-line treatment with regorafenib. She was started on fourth-line treatment with off-label osimertinib, with clinical response - decrease in size of hepatic metastases and a pericardial effusion. She remained on treatment with osimertinib for seven months. CONCLUSION: This case shows the benefit of multi-gene sequencing assays to identify potential therapeutic options in patients with refractory disease.

Squamous cell carcinoma of the lung: improving the detection and management of immune-related adverse events.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for patients with non-small lung cancer (NSCLC). Currently approved ICIs are monoclonal antibodies that target programmed death receptor 1 (PD-1), its ligand PD-L1, or CTLA-4. With ICIs comes a novel collection of toxicities: immune-related adverse events (IRAEs). Management of IRAEs requires multidisciplinary expertise. We review the biology of IRAEs and their management in patients with squamous NSCLC. AREAS COVERED: We review the pathophysiology of ICIs and IRAEs. For IRAEs related to squamous NSCLC, Cochrane Central, EMBASE, and PubMed were queried for trials with patients with squamous cell carcinoma or adenocarcinoma histology, who were assessed for incidence rates of IRAEs. Thirteen trials met inclusion criteria. National guidelines are reviewed to outline management strategies for IRAEs. EXPERT OPINION: IRAEs are unique compared to standard chemotherapy. As the role of ICIs expand across all stages of squamous cell NSCLC and with different combinations of antineoplastics, management of IRAEs will become crucial. Optimal management of IRAEs requires multidisciplinary teamwork. Further investigation into the pathophysiology of IRAEs can enhance current management strategies.

Evaluation of an Initial Specimen Diversion Device (ISDD) on Rates of Blood Culture Contamination in the Emergency Department.

INTRODUCTION: Blood cultures are the gold standard for identifying bloodstream infections. The Clinical and Laboratory Standards Institute recommends a blood culture contamination rate of less than 3%. Contamination can lead to misdiagnosis, increased length of stay and hospital costs, unnecessary testing, and antibiotic use. These reasons led to the development of initial specimen diversion devices (ISDD). The purpose of this study was to evaluate the impact of an initial specimen diversion device on rates of blood culture contamination in the emergency department. METHODS: This was a retrospective, multi-site study including patients who had blood cultures drawn in an emergency department. February 2018 to April 2018, when an ISDD was not utilized, was compared with June 2019 to August 2019, when an ISDD was being used. The primary outcome was total blood culture contamination. Secondary outcomes were total hospital cost, hospital and intensive care unit length of stay, vancomycin duration of use, vancomycin serum concentrations obtained, and repeat blood cultures obtained. RESULTS: A statistically significant difference was found in blood culture contamination rates in the pre-ISDD group vs. the ISDD group (7.47% vs. 2.59%, p < 0.001). None of the secondary endpoints showed a statistically significant difference. CONCLUSIONS: Implementation of an ISDD reduced blood culture contamination. When implementing the ISDD to a healthcare system, compliance is important and will affect contamination rates dramatically.