No abstract

An increasing number of tyrosine kinase inhibitors (TKIs) are available for the treatment of non-small cell lung cancer (NSCLC). QT prolongation is one of the known, but relatively rare, adverse events of several TKIs (e.g. osimertinib, crizotinib, ceritinib). Screening for QT prolongation in (high risk) patients is advised for these TKIs. When a QT prolongation develops, the physician is challenged with the question whether to (permanently) discontinue the TKI. In this perspective, we report on a patient who developed a grade III QT prolongation during osimertinib (a third-generation epidermal growth factor receptor [EGFR]-TKI) treatment. On discontinuation of osimertinib, she developed a symptomatic disease flare, not responding to subsequent systemic treatment. The main aim of this perspective is to describe the management of QT prolongation in stage IV EGFR driver mutation NSCLC patients. We also discuss the ethical question of how to weigh the risk of a disease flare due to therapy cessation against the risk of sudden cardiac death. A family history of sudden death and a prolonged QT interval might indicate a familiar long QT syndrome. We have summarised the current monitoring advice for TKIs used in the treatment of lung cancer and the most common drug-TKI interactions to consider and to optimise TKI treatment in lung cancer patients.

BACKGROUND: Dynamic hyperinflation is a major cause of dyspnea in patients with COPD. Dynamic hyperinflation is usually measured with cardiopulmonary exercise testing, but this test requires maximal effort from the patient, and inspiratory capacity (IC) measurements may influence test results. This study investigated another approach by measuring dynamic hyperinflation during the more natural and better-tolerated 6-min walk test (6MWT), using a mobile system for IC measurements. METHODS: Twenty subjects were studied, including 10 healthy subjects and 10 subjects with COPD. Each subject performed a pair of 6MWTs. RESULTS: The study showed that test-retest reliability in healthy subjects was excellent (intraclass correlation coefficient 0.995). In addition, mean resting IC in healthy subjects (3.27 ؎ 0.77 L) was not affected at the end of the 6MWT, whereas mean resting IC in subjects with COPD (2.45 ؎ 0.90 L) decreased to 1.93 L ؎ 0.68 L at the end of the 6MWT (P ‫؍‬ .004). The tolerability of the device for subjects with COPD appeared to be only slightly hampered by an increased sense of dyspnea attributed to wearing a mask. CONCLUSIONS: This study provides a proof of principle for mobile IC measurements during the 6MWT, demonstrating good test performance, reasonable tolerability, and a power to differentiate normal from pathologic conditions.