Phase II study of cabazitaxel as second-third line treatment in patients with metastatic adrenocortical carcinoma.

BACKGROUND: Adrenocortical carcinoma (ACC) is a rare and aggressive malignancy with a poor prognosis. No efficacious treatment options are currently available for patients with advanced metastatic disease with disease progression to standard etoposide, doxorubicin, cisplatin and mitotane (EDP-M) therapy. We assessed the activity and tolerability of cabazitaxel as a second/third-line approach in metastatic ACC. PATIENTS AND METHODS: Patients included in this single-center, phase II study (ClinicalTrials.gov identifier NCT03257891) had disease progression to a cisplatin-containing regimen (such as EDP) plus mitotane, plus/minus a further chemotherapy line. Cabazitaxel was administered intravenously at 25 mg/m2 on day 1 of a 21-day cycle, for a maximum of six cycles. The primary endpoint was a disease control rate after 4 months. RESULTS: From March 2018 to September 2019, 25 eligible patients were enrolled. A disease control rate after 4 months was obtained in six patients (24%). No patients attained a disease response according to RECIST 1.1, 9 patients (36%) had stable disease and 16 patients (64%) progressive disease. Median progression-free survival and overall survival were 1.5 months (range 0.3-7 months) and 6 months (range 1-22.2 months), respectively. Cabazitaxel therapy was well tolerated and only three (12%) patients developed grade 3 toxicity which were nausea in one patient (4%) and anemia in two patients (8%). CONCLUSIONS: Cabazitaxel has a manageable toxicity profile but is poorly active as second/third-line treatment in advanced ACC patients. These results do not support further evaluation of cabazitaxel in this setting.

RalGPS2 is involved in tunneling nanotubes formation in 5637 bladder cancer cells.

RalGPS2 is a Ras-independent Guanine Nucleotide Exchange Factor (GEF) for RalA containing a PH domain and an SH3-binding region and it is involved in several cellular processes, such as cytokinesis, control of cell cycle progression, differentiation, cytoskeleton organization and rearrangement. Up to now, few data have been published regarding RalGPS2 role in cancer cells, and its involvement in bladder cancer is yet to be established. In this paper we demonstrated that RalGPS2 is expressed in urothelial carcinoma-derived 5637 cancer cells and is essential for cellular growth. These cells produces thin membrane protrusions that displayed the characteristics of actin rich tunneling nanotubes (TNTs) and here we show that RalGPS2 is involved in the formation of these cellular protrusions. In fact the overexpression of RalGPS2 or of its PH-domain increased markedly the number and the length of nanotubes, while the knock-down of RalGPS2 caused a strong reduction of these structures. Moreover, using a series of RalA mutants impaired in the interaction with different downstream components (Sec5, Exo84, RalBP1) we demonstrated that the interaction of RalA with Sec5 is required for TNTs formation. Furthermore, we found that RalGPS2 interacts with the transmembrane MHC class III protein leukocyte specific transcript 1 (LST1) and RalA, leading to the formation of a complex which promotes TNTs generation. These findings allow us to add novel elements to molecular models that have been previously proposed regarding TNTs formation.

MRI post-vertebroplasty.

PURPOSE: Percutaneous vertebroplasty (PVP), first described by Hervè Deramond in 1984, is an interventional procedure for the treatment of aggressive vertebral angioma. The aim of this study was to evaluate magnetic resonance imaging (MRI) patterns in the affected vertebrae before and after vertebroplasty by determining changes in signal intensity and size and distribution of bone cement within the vertebra at follow-up carried out at 1 week, 6 months and 12 months. MATERIALS AND METHODS: Fourteen patients were examined using MRI, for a total of 41 treated vertebrae; MRI was performed with a 0.5-Tesla (T) superconductive magnet (SIGNA GE). RESULTS: MRI patterns following vertebroplasty are mainly characterised by the signal produced by the areas surrounding the cement and by the cement itself. There is little effect on the size of the treated vertebra. Acrylic cement appears as an intraspongy focal area of T1 and T2 hypointensity that is mostly oval (34%) or rounded (26.8%); this appearance tends to become stable 6 months after treatment. The area surrounding the cement appears hypointense on T1 and hyperintense on T2, a likely expression of bone marrow oedema; this signal alteration tends to disappear gradually. CONCLUSIONS: In pre- and post-vertebroplasty imaging, MRI is regarded as the reference standard for correct evaluation of both container and content. Awareness of cement changes over time and of the reaction of the surrounding bone tissue is crucial for correct assessment of post-vertebroplasty images.

Magnetic resonance angiography and colour-Doppler sonography in the evaluation of abdominal aortic aneurysms.

This prospective study was aimed at comparing the diagnostic accuracy of magnetic resonance angiography (MRA) with colour-Doppler ultrasonography (colour-Doppler US) in the assessment of abdominal aortic aneurysms (AAA). Twenty patients with abdominal aortic aneurysms underwent MRA, colour-Doppler US, digital subtraction angiography (DSA) and CT. The MRA technique and colour-Doppler findings were compared with DSA as well as surgical and pathological findings, which were considered as the gold standard. In 6 patients who refused surgery, CT and DSA were considered as the gold standard. The MRA technique always correctly assessed the size and site of the aneurysms, the involvement of the renal and common iliac arteries, the course of the left renal vein, the thrombotic component and the calcifications. Colour-Doppler US always correctly assessed the size and site of the aneurysms, the thrombotic component and calcifications and the involvement of the iliac arteries. Our preliminary results suggest that MRA together with colour-Doppler US represents a valid alternative to invasive imaging in the assessment of AAA.