Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation). Several phase III studies have demonstrated the superiority of gefitinib, erlotinib (first generation of TKIs) or afatinib (second generation) to chemotherapy in progression-free survival and response rates. Drug-related toxicities, such as diarrhoea, acneiform skin rash, mucositis, and paronychia, are frequently encountered in patients who receive EGFR TKIs. Other rare side-effects, such as hepatic impairment and interstitial lung disease, should be identified early and managed carefully. Patients with uncommon EGFR mutations, such as G719X, S768I, and L861Q, may require special selection of EGFR TKIs. The combination of erlotinib plus bevacizumab has been accepted in certain parts of the world as an alternative front-line treatment. This review article summarizes the studies leading to the establishment of EGFR TKIs in EGFR-mutant lung cancer patients. The side-effect profiles of the current EGFR TKIs in these large trials are listed, and the management of uncommon EGFR mutations is discussed. Finally, the potential role of combination front-line treatment is discussed.

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Two-dimensional simulations of the 11 January 1972 Boulder, Colorado, windstorm, obtained from 11 diverse nonhydrostatic models, are intercompared with special emphasis on the turbulent breakdown of topographically forced gravity waves, as part of the preparation for the Mesoscale Alpine Programme field phase. The sounding used to initialize the models is more representative of the actual lower stratosphere than those applied in previous simulations. Upper-level breaking is predicted by all models in comparable horizontal locations and vertical layers, which suggests that gravity wave breaking may be quite predictable in some circumstances. Characteristics of the breaking include the following: pronounced turbulence in the 13-16-km and 18-20-km layers positioned beneath a critical level near 21-km, a well-defined upstream tilt with height, and enhancement of upper-level breaking superpositioned above the low-level hydraulic jump. Sensitivity experiments indicate that the structure of the wave breaking was impacted by the numerical dissipation, numerical representation of the horizontal advection, and lateral boundary conditions. Small vertical wavelength variations in the shear and stability above 10 km contributed to significant changes in the structures associated with wave breaking. Simulation of this case is ideal for testing and evaluation of mesoscale numerical models and numerical algorithms because of the complex wave-breaking response.

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