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.

In phase I testing, alisertib tablets with irinotecan and temozolomide showed significant antitumor activity in patients with neuroblastoma. This study sought to confirm activity of this regimen; evaluate an alisertib oral solution; and evaluate biomarkers of clinical outcomes. We conducted a two-stage phase II trial of alisertib tablets (60 mg/m/dose × 7 days), irinotecan (50 mg/m/dose i.v. × 5 days), and temozolomide (100 mg/m/dose orally × 5 days) in patients with relapsed or refractory neuroblastoma. The primary endpoint was best objective response. A separate cohort was treated with alisertib at 45 mg/m using oral solution instead of tablets. Exploratory analyses sought to identify predictors of toxicity, response, and progression-free survival (PFS) using pooled data from phase I, phase II, and oral solution cohorts. Twenty and 12 eligible patients were treated in the phase II and oral solution cohorts, respectively. Hematologic toxicities were the most common adverse events. In phase II, partial responses were observed in 19 evaluable patients (21%). The estimated PFS at 1 year was 34%. In the oral solution cohort, 3 patients (25%) had first cycle dose-limiting toxicity (DLT). Alisertib oral solution at 45 mg/m had significantly higher median and exposure compared with tablets at 60 mg/m Higher alisertib trough concentration was associated with first cycle DLT, whereas amplification was associated with inferior PFS. This combination shows antitumor activity, particularly in patients with nonamplified tumors. Data on an alisertib oral solution expand the population able to be treated with this agent.

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Objective: The purpose of this review is to show the present state of art on breath sounds and lung auscultation, including normal and adventitious lung sounds, especially how they originate, and to which of the most common diseases they are related. Methods: The history of auscultation and the first stethoscope is presented, followed by the classification and description of physiologic lung sounds with regard to the lung regions where they should be heard and the sound characteristics. Added lung sounds, including their classification, distinction between continuous and discontinuous sound, as well as the presentation of the diseases most commonly associated with them are presented. Results: Since it may be found that breath sounds are difficult to understand it is reasonable to present a simple method of lung auscultation that may be helpful in the education of medical students. The usefulness of lung auscultation in diagnosing the most common diseases, with special regard to lung disorders, is of great importance. Discussion/Conclusion: The short and simple presentation of lung sound, auscultation methods and their application in clinical practice has been presented, and may be helpful for medical staff.

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