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HER2mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of HER2and EGFRmutations is extremely rare, and therefore, no data exist on the best treatment in these cases (Nagasaka et al., 2022).

Programmed death-ligand 1 expression currently represents the only validated predictive biomarker for immune checkpoint inhibition in metastatic NSCLC in the clinical routine, but it has limited value in distinguishing responses. Assessment of KRASand TP53mutations (mut) as surrogate for an immunosupportive tumor microenvironment (TME) might help to close this gap.

In contrast to other driver mutations, no targeted therapies have yet been approved in ERBB2mutated non-small cell lung cancer (HER2mu NSCLC). However, several compounds have shown promising early efficacy data, which need to be evaluated in the context of current standard approaches. While data on the efficacy of immune checkpoint inhibitors (ICI) in second or later lines of treatment remain limited and conflicting, there are virtually no data on patient outcome under ICI / platinum doublet combinations in the first-line setting.

Chronic hypoxia causes pulmonary vascular remodeling resulting in persistently increased pulmonary arterial pressures (PAP) even after return to normoxia. Recently, interest in chronic intermittent hypobaric hypoxia (CIHH) was raised because it occurs in subjects working at high altitude (HA) but living in lowland. However, effects of daily CIHH on PAP are unknown. In this pilot study, we included 8 healthy subjects working at (2650 m) each workday for 8-9 h while living and sleeping at LA and 8 matched control subjects living and working at LA. Cardiorespiratory measurements including echocardiography at rest and during exercise were performed at LA (Munich, 530 m) and HA (Zugspitze, 2650 m). Hemoglobin was higher in CIHH subjects. LA echocardiography showed normal right and left cardiac dimensions and function in all subjects. Systolic PAP (sPAP) and tricuspid annular plane systolic excursion (TAPSE) at rest were similar in both groups. Resting blood gas analysis (BGA) at HA revealed decreased pCO2 in CIHH compared to controls (HA: 28.4 versus 31.7 mmHg, p=0.01). During exercise, sPAP was lower in CIHH subjects compared to controls (LA: 28.7 versus 35.3 mmHg, p=0.02; HA: 26.3 versus 33.6 mmHg, p=0.04) and peripheral oxygen saturation (SpO2) was higher. In sum, subjects exposed to CIHH showed no signs of pulmonary vascular remodeling.