Efficacy of tyrosine kinase inhibitors in patients with non-small-cell lung cancer with performance status 4: a case series and review of the literature

Abstract Background Current guidelines for non-small-cell lung cancer (NSCLC) recommend that each tyrosine kinase inhibitor (TKI) is indicated even for driver mutation-positive patients with a poor performance status (PS). In previous studies, most patients had a PS of 2–3, but those with a PS of 4 were very few. Therefore, the efficacy of TKIs in patients with NSCLC with a PS of 4 remains unclear. Case presentation We retrospectively reviewed the clinical records of four patients with NSCLC with PS 4 treated with TKIs: an 89-year-old Japanese woman (Case 1), a 80-year-old Japanese woman (Case 2), an 50-year-old Japanese man (Case 3), and a 81-year-old Japanese woman (Case 4). Genetic alterations were epidermal growth factor receptor (EGFR), MET exon 14 skipping, BRAFV600E, and ROS1 proto-oncogene receptor tyrosine kinase (ROS1). One case with ROS1 fusion showed a significant response with the recovery of PS. However, in the remaining three cases (i.e., EGFR, MET exon 14 skipping, and BRAFV600E mutations), patients died despite the administration of TKIs. These three patients had to be hospitalized at the end of their life to receive treatment. Conclusions This is the first case series to summarize the efficacy of TKIs in patients with NSCLC with a PS of 4. Additionally, this case series poses a question concerning the indication of TKIs for older patients with a PS of 4

Disproportionate subarachnoid space hydrocephalus-outcome and perivascular space

OBJECTIVE: We sought to identify the prevalence of MRI features of disproportionately enlarged subarachnoid space hydrocephalus in possible idiopathic normal pressure hydrocephalus (DESH-iNPH) and to describe the clinico-radiological features and outcomes of a community-based investigation (The Vienna Trans-Danube Aging study). METHODS: Of the 697 inhabitants (all 75 years old), 503 completed extensive neurological examinations at baseline and were followed up every 30 months thereafter with MRIs, mini-mental state examination (MMSE), and the Unified Parkinson Disease Rating Scale-Motor Section (UPDRSM). The DESH-iNPH participant data were compared with the data from participants with Evans index ratios >0.3 (ex vacuo hydrocephalus), cerebral small-vessel diseases, and normal MRIs. The widening of perivascular space was also evaluated by MRI in these groups. RESULTS: Eight participants with DESH-iNPH (1.6%) and 76 with ex vacuo hydrocephalus (16.1%) at baseline were identified. The mean MMSE in DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs was 26.4, 27.9, and 28.3, respectively, and the mean UPDRSM was 9.75, 2.96, and 1.87, respectively. After a 90-month follow-up, the mortality rates for DESH-iNPH, ex vacuo hydrocephalus, and normal MRIs were 25.0%, 21.3%, and 10.9%, respectively. The perivascular-space widening scores were significantly smaller in the DESH-iNPH cases, particularly at the centrum semiovale, compared to cerebral small-vessel disease and ex vacuo hydrocephalus cases. INTERPRETATION: The prevalence of DESH-iNPH was 1.6% for participants aged 75 years and revealed significantly lower MMSE and higher UPDRSM scores compared to the ex vacuo hydrocephalus and controls. Moreover, it is suggested that perivascular-space narrowing is a morphological and pathophysiological marker of DESH-iNPH

Thermochronology of hydrothermal alteration zones in the Kii Peninsula, southwest Japan: an attempt for detecting the thermal anomalies and implications to the regional exhumation history

Abstract Fluid-inclusion and thermochronometric analyses have been applied to hydrothermal alteration zones and their host rocks outcropping in the Hongu area of the Kii Peninsula, southwestern Japan in an attempt to detect thermal anomalies related to hydrothermal events and quantify the thermal effects on the host rocks. Hydrothermal events at ~ 150 °C and ~ 200 °C were identified by fluid-inclusion microthermometry of quartz veins in the alteration zones. For the host rocks and alteration zones, in the youngest population zircon yielded U–Pb dates ranging between ~ 74.7–59.2 Ma, fission-track dates of ~ 27.2–16.6 Ma, and (U–Th)/He single-grain dates of ~ 23.6–8.7 Ma. Apatite yielded pooled fission-track ages of ~ 14.9–9.0 Ma. The zircon U–Pb dates constrain the maximum depositional ages of the sedimentary samples. However, the fission-track and (U–Th)/He dates show no clear trend as a function of distance from the alteration zones. Hence, no thermal anomaly was detected in the surrounding host rocks based on the thermochronometric data patterns. The fission-track and (U–Th)/He dates are rather thought to record regional thermal and exhumation histories rather than a direct thermal imprint of fluid flow, probably because the duration of such activity was too short or because fluid flow occurred before regional cooling events and were later thermally overprinted. Apatite fission-track ages of ~ 10 Ma may reflect regional mountain uplift and exhumation related to the obduction of the SW Japan lithospheric sliver onto the Shikoku Basin, or the rapid subduction of the Philippine Sea slab associated with the clockwise rotation of the Southwest Japan Arc. Graphical Abstrac