A phase I dose-escalation study of pulsatile afatinib in patients with recurrent or progressive brain cancer.

Background: Afatinib (BIBW2992; Gilotrif®) is a selective and irreversible inhibitor of the epidermal growth factor receptor (ErbB; EGFR) family. It inhibits EGFR, HER2, and HER4 phosphorylation, resulting in tumor growth inhibition and regression. This phase I dose-escalation trial of pulsatile afatinib examined the safety, drug penetration into the central nervous system, preliminary antitumor activity, and recommended phase II dose in patients with progressive or recurrent brain cancers. Methods: Afatinib was taken orally once every 4 days or once every 7 days depending on dose cohort, until disease progression or unacceptable toxicity. Results: A total of 24 patients received the investigational agent and were evaluable for safety analyses, and 21 patients were evaluable for efficacy. Dosing was administered at 80 mg every 4 days, 120 mg every 4 days, 180 mg every 4 days, or 280 mg every 7 days. A recommended phase II dose of pulsatile afatinib was established at 280 mg every 7 days as there were no dose-limiting toxicities in any of the dosing cohorts and all toxicities were deemed manageable. The most common drug-related toxicities were diarrhea, rash, nausea, vomiting, fatigue, stomatitis, pruritus, and limb edema. Out of the 21 patients evaluable for efficacy, 2 patients (9.5%) exhibited partial response based on Response Assessment in Neuro-Oncology criteria and disease stabilization was seen in 3 patients (14.3%). Conclusions: Afatinib taken orally was safe and well-tolerated up to 280 mg every 7 days in brain cancer patients.

Clinical Course of Two Patients with COVID-19 Respiratory Failure After Administration of the Anticancer Small Molecule, RRx-001.

Two critically ill COVID-19 infected patients, who had exhausted all available treatment options, were treated with the small-molecule RRx-001 with subsequent improvement. RRx-001, a first-in-class small molecule with anti-inflammatory, vascular normalizing and macrophage-repolarizing properties, has been safely administered 300+ patients in clinical trials. This is the first report of RRx-001 treatment of COVID-19.

Correction to: Mesenchymal stem cells in the treatment of severe COVID-19.

[This corrects the article DOI: 10.1186/s41231-021-00095-0.].

Analysis of cell-free circulating tumor DNA in 419 patients with glioblastoma and other primary brain tumors.

Aim: Genomically matched trials in primary brain tumors (PBTs) require recent tumor sequencing. We evaluated whether circulating tumor DNA (ctDNA) could facilitate genomic interrogation in these patients. Methods: Data from 419 PBT patients tested clinically with a ctDNA NGS panel at a CLIA-certified laboratory were analyzed. Results: A total of 211 patients (50%) had ≥1 somatic alteration detected. Detection was highest in meningioma (59%) and gliobastoma (55%). Single nucleotide variants were detected in 61 genes, with amplifications detected in ERBB2, MET, EGFR and others. Conclusion: Contrary to previous studies with very low yields, we found half of PBT patients had detectable ctDNA with genomically targetable off-label or clinical trial options for almost 50%. For those PBT patients with detectable ctDNA, plasma cfDNA genomic analysis is a clinically viable option for identifying genomically driven therapy options.

The expanding role of the endonasal endoscopic approach in pituitary and skull base surgery: A 2014 perspective.

BACKGROUND: The past two decades have been the setting for remarkable advancement in endonasal endoscopic neurosurgery. Refinements in camera definition, surgical instrumentation, navigation, and surgical technique, including the dual surgeon team, have facilitated purely endonasal endoscopic approaches to the majority of the midline skull base that were previously difficult to access through the transsphenoidal microscopic approach. METHODS: This review article looks at many of the articles from 2011 to 2014 citing endonasal endoscopic surgery with regard to approaches and reconstructive techniques, pathologies treated and outcomes, and new technologies under consideration. RESULTS: Refinements in approach and closure techniques have reduced the risk of cerebrospinal fluid leak and infection. This has allowed surgeons to more aggressively treat a variety of pathologies. Four main pathologies with outcomes after treatment were identified for discussion: pituitary adenomas, craniopharyngiomas, anterior skull base meningiomas, and chordomas. Within all four of these tumor types, articles have demonstrated the efficacy, and in certain cases, the advantages over more traditional microscope-based techniques, of the endonasal endoscopic technique. CONCLUSIONS: The endonasal endoscopic approach is a necessary tool in the modern skull base surgeon's armamentarium. Its efficacy for treatment of a wide variety of skull base pathologies has been repeatedly demonstrated. In the experienced surgeon's hands, this technique may offer the advantage of greater tumor removal with reduced overall complications over traditional craniotomies for select tumor pathologies centered near the midline skull base.

Real-world impact of education: treating patients with ipilimumab in a community practice setting.

After decades without promising new treatments for advanced and metastatic melanoma, ipilimumab was the first systemic therapy approved for use in this patient population. A fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen 4 (CTLA-4) to augment antitumor T-cell responses, ipilimumab significantly extended overall survival in clinical trials. Because ipilimumab is associated with a set of immune-related adverse events that likely reflect the agent's mechanism of action, a management guide has been established. Nurses play a significant role in initially identifying these adverse reactions and assisting in patient education, treatment, and follow-up. Herein, we discuss commonly asked questions related to ipilimumab therapy and treatment of adverse events, and how nurses can be prepared to answer these questions as they arise from patients and caregivers.