Cabozantinib use in second or subsequent line of treatment in renal cell carcinoma: an analysis of Italian administrative databases.

Background: Cabozantinib use in everyday clinical practice for advanced or metastatic renal cell carcinoma (RCC) is relatively recent, and real-world data on treatment persistence, adherence and sequencing are still limited. Methods: We conducted an analysis based on an integrated administrative database, covering around 6.9 million health-assisted Italian individuals, to explore the use of cabozantinib for RCC. Patients with at least one prescription for cabozantinib during 2017-2020 were searched. These were characterized during all available period (i.e. from 2010 onwards) before the index date and were observed after inclusion. Results: A total of 113 patients treated with cabozantinib in second or subsequent line were included, and their demographic, clinical and treatment characteristics were described. About half of these RCC patients were aged >65 years (47.8%). Sixty patients (53.1%) were highly adherent to cabozantinib therapy, and the median cabozantinib treatment duration of use was 8.7 months (95% confidence interval: 5.8-11.1). During the first year of follow-up, the average total cost per patient was €32,508. Conclusions: We described second or subsequent line cabozantinib treatment for RCC in a real-world setting and the economic burden of disease in Italy, taking advantage of large, integrated administrative databases.

Coupled Micromachined Magnetic Resonators for Microwave Signal Processing.

In this paper, the theory, micromachining technology, and experimental results of the coupling of integrated magnetic film-based resonators for microwave signal filtering are presented. This is an extended contribution to the field of magnetostatic wave coupled resonators, including details about the technological results, circuit theory, and perspective applications for tunable integrated coupled magnetic resonators. An analytical approach using the magnetostatic wave approximation is used to derive the coupling coefficient between adjacent resonators coupled by the electromagnetic field decaying outside the resonators. Then, micromachining employing hot phosphoric acid etching is presented to manufacture integrated coupled resonators. Finally, circuit modeling and experimental results obtained using the ferromagnetic resonance technique are discussed.

Triangular Sierpinski Microwave Band-Stop Resonators for K-Band Filtering.

Triangular resonators re-shaped with Sierpinski geometry were designed, manufactured, and tested for potential applications in the K-Band. Prototypes of band-stop filters working around 20 GHz and 26 GHz, interesting for RADAR and satellite communications, were studied in a coplanar waveguide (CPW) configuration. Single and coupled structures were analyzed to give evidence for: (i) the tuning of the resonance frequency by increasing the internal complexity of the triangle and (ii) resonance enhancement when coupled structures are considered. The exploited devices were part of the more extended family of metamaterial-inspired structures, and they were studied for their heuristic approach to the prediction of the spectrum using experimental results supported by electromagnetic simulations. As a result, a Sierpinski resonator, not only fed into but also fully embedded into a CPW environment, had a frequency response that was not easily determined by classical theoretical approaches.

MEMS-Switched Triangular and U-Shaped Band-Stop Resonators for K-Band Operation.

Triangular resonators re-shaped into Sierpinski geometry and U-shaped resonators were designed, linking them with single-pole-double-through (SPDT) RF MEMS switches to provide frequency tuning for potential applications in the K-Band. Prototypes of band-stop narrowband filters working around 20 GHz and 26 GHz, interesting for RADAR and satellite communications, were studied in a coplanar waveguide (CPW) configuration, and the tuning was obtained by switching between two paths of the devices loaded with different resonators. As a result, dual-band operation or fine-tuning could be obtained depending on the choice of the resonator, acting as a building block. The studied filters belong to the more general group of devices inspired by a metamaterial design.

Fabrication of Ultra-Sharp Tips by Dynamic Chemical Etching Process for Scanning Near-Field Microwave Microscopy.

This work details an effective dynamic chemical etching technique to fabricate ultra-sharp tips for Scanning Near-Field Microwave Microscopy (SNMM). The protruded cylindrical part of the inner conductor in a commercial SMA (Sub Miniature A) coaxial connector is tapered by a dynamic chemical etching process using ferric chloride. The technique is optimized to fabricate ultra-sharp probe tips with controllable shapes and tapered down to have a radius of tip apex around ∼1 µm. The detailed optimization facilitated the fabrication of reproducible high-quality probes suitable for non-contact SNMM operation. A simple analytical model is also presented to better describe the dynamics of the tip formation. The near-field characteristics of the tips are evaluated by finite element method (FEM) based electromagnetic simulations and the performance of the probes has been validated experimentally by means of imaging a metal-dielectric sample using the in-house scanning near-field microwave microscopy system.

Design of U-Shaped Frequency Tunable Microwave Filters in MEMS Technology.

U-shaped microwave resonators implemented by RF MEMS switches can be considered the result of a novel design approach for obtaining small-footprint tunable resonators, owing to the bent shape of the resonator and the microsystem solution for changing the frequency of resonance. In this paper, we discuss the design approach for potential configurations of U-shaped structures combined with ohmic RF MEMS switches. Owing to their prospective application in RADAR and satellite systems, the devices were assessed for K-Band operation, specifically for 15 GHz, 20 GHz, and 26 GHz. The ON-OFF states determined by an electrostatic actuation of metal beams composing the RF MEMS ohmic switches allow for selecting different path lengths corresponding to different frequencies. In this contribution, initial configurations were designed and manufactured as a proof-of-concept. The advantages and critical aspects of the designs are discussed in detail.

ATTRv in Lazio-Italy: A High-Prevalence Region in a Non-Endemic Country.

Hereditary transthyretin amyloidosis (ATTRv, v for variant) prevalence in Italy, a non-endemic region, has been established by ATTRv amyloidosis Italian Registry. However, values of prevalence were extremely heterogeneous, considering different regions. To properly establish the prevalence of the disease in the Lazio region, a survey was sent to university regional hospitals and to main regional hospitals, in order to collect all affected patients regularly followed. We identified 100 ATTRv patients and, considering a Lazio population of 5.8/million, we estimated a ATTRv prevalence of 17.2/million. The ATTRv amyloidosis Italian Registry reported a prevalence of 8.0/million in Lazio, while our survey showed a value of double this. Our survey documented a high-prevalence for a non-endemic country. The increased awareness of the disease among general practitioners and medical specialists is a fundamental step to reduce the diagnostic delay and start an effective treatment of this disease.

Discontinuation of first-line bevacizumab in metastatic colorectal cancer: the BEAWARE Italian Observational Study.

AIMS: BEAWARE investigated the pattern of first-line bevacizumab early interruption in the Italian real-world setting of metastatic colorectal cancer. METHODS: A total of 386 patients were followed for 15 months after first-line chemotherapy + bevacizumab start. The rate of bevacizumab interruption for progression or adverse drug reactions (ADRs) constituted the primary endpoint. RESULTS: A total of 78.2% of patients interrupted bevacizumab: 56.6% for progression, 7.3% for ADRs, and 36.1% for other reasons. Median treatment duration was 6.7, 2.5, and 4.6 months, respectively. Median progression-free survival was 10.3 months; however, 35.8% of patients were not progressed and were thus censored at the data cutoff of 15 months, while 21.8% were still receiving bevacizumab. Patients discontinuing for progression/ADRs more frequently had metastases in >1 site (p = .0001), and a shorter median progression-free survival (6.9 vs 13.9 months, p < .0001). CONCLUSIONS: In Italy, first-line bevacizumab is interrupted mainly for progression, only 7.3% due to adverse events, and about one third of cases for other reasons. In clinical practice, the attitude to treat until progression as per guidelines might be implemented. ClinicalTrials.gov Identifier: NCT01609075.

A broadband toolbox for scanning microwave microscopy transmission measurements.

In this paper, we present in detail the design, both electromagnetic and mechanical, the fabrication, and the test of the first prototype of a Scanning Microwave Microscope (SMM) suitable for a two-port transmission measurement, recording, and processing the high frequency transmission scattering parameter S21 passing through the investigated sample. The S21 toolbox is composed by a microwave emitter, placed below the sample, which excites an electromagnetic wave passing through the sample under test, and is collected by the cantilever used as the detector, electrically matched for high frequency measurements. This prototype enhances the actual capability of the instrument for a sub-surface imaging at the nanoscale. Moreover, it allows the study of the electromagnetic properties of the material under test obtained through the measurement of the reflection (S11) and transmission (S21) parameters at the same time. The SMM operates between 1 GHz and 20 GHz, current limit for the microwave matching of the cantilever, and the high frequency signal is recorded by means of a two-port Vector Network Analyzer, using both contact and no-contact modes of operation, the latter, especially minded for a fully nondestructive and topography-free characterization. This tool is an upgrade of the already established setup for the reflection mode S11 measurement. Actually, the proposed setup is able to give richer information in terms of scattering parameters, including amplitude and phase measurements, by means of the two-port arrangement.

AVAREG: a phase II, randomized, noncomparative study of fotemustine or bevacizumab for patients with recurrent glioblastoma.

BACKGROUND: Few prospective studies have assessed the role of bevacizumab and included a control arm with standard treatments for recurrent glioblastoma. We conducted a noncomparative phase II trial (AVAREG) to examine the efficacy of bevacizumab or fotemustine in this setting. METHODS: Eligible patients were randomized 2:1 to receive bevacizumab (10 mg/kg every 2 weeks) or fotemustine (75 mg/m(2) on days 1, 8, and 15, then 100 mg/m(2) every 3 weeks after a 35-day interval). The primary endpoint was 6-month overall survival (OS) rate (OS-6). No formal efficacy comparison was made between the treatment arms. RESULTS: Ninety-one patients were enrolled (bevacizumab n = 59; fotemustine n = 32). Median age was 57 years (range, 28-78 y), and patients had Eastern Cooperative Oncology Group performance status of 0 (n = 42), 1 (n = 35), or 2 (n = 14). OS-6 rate was 62.1% (95% confidence interval [CI], 48.4-74.5) with bevacizumab and 73.3% (95% CI, 54.1-87.7) with fotemustine. OS-6 rates were lower in bevacizumab-treated patients with MGMT promoter methylated tumors than in those with unmethylated tumors (50% and 85%, respectively), but higher in fotemustine-treated patients (87.5% and 50%, respectively). OS rates at 9 months were 37.9% (95% CI, 25.5-51.6) and 46.7% (95% CI, 28.3-65.7) with bevacizumab and fotemustine, respectively, and median OS was 7.3 months (95% CI, 5.8-9.2) and 8.7 months (95% CI, 6.3-15.4), respectively. Toxicity was as expected with the 2 agents. CONCLUSION: Single-agent bevacizumab may have a role in patients with recurrent glioblastoma.

Morphometric X-ray absorptiometry in the assessment of vertebral fractures in renal transplant patients.

BACKGROUND: Bone mineral density (BMD) is widely employed to evaluate the risk of fractures, but more than mineral content is bone quality that accounts for bone strength. In fact, occasionally, subjects with normal or only mildly reduced BMD also experience pathologic fractures. In metabolic bone disease, like renal transplantation, the agreement between fractures and BMD is less predictable. We assessed the prevalence of vertebral fractures by means of a new, DEXA-based method (morphometric absorptiometry, MXA) and compared its concordance with the two mostly employed radiological techniques (Visual semi-quantitative, SQ, and morphometric radiography, MRX) in an asymptomatic population of transplanted patients. Moreover, the association of bone fractures with low BMD values was examined. METHODS: Fifty-three renal transplant patients underwent spinal radiographs and BMD measurements by DEXA. In order to obtain a morphometric assessment, a lateral DEXA scan was performed. RESULTS: Patients with vertebral fracture were 17/53 (32%) with both SQ and MRX, and 12/53 (23%) with MXA (chi(2) = n.s.). A single fracture was detected in 9/53 patients (17%) with SQ and MRX, and in 4/53 (7.5%) with MXA; multiple fractures were 8/53 (15%) with any technique. With SQ as the standard reference, predictive indexes were excellent with MRX (invariably 100%) and quite good with MXA (sensitivity 70.6%; specificity 100%). Of the total of 689 vertebrae, 49 were fractured with SQ, 54 with MRX and 41 with MXA. Mild deformities were present in 21 (SQ), 26 (MRX) and 13 (MXA) vertebral bodies, respectively, while moderate-severe deformities were 28 with any technique. Again, with SQ as standard reference, predictive indexes were good (MRX: sensitivity 100%, specificity 99.2%; MXA: sensitivity 83.7%, specificity 100%). When we classified patients according to BMD T-score values, SQ and MRX recognized fractures in 4/18 normal (22%), 10/22 osteopenic (45%) and 3/13 osteoporotic (23%). With MXA 3/18 (17%) normal, 6/22 (27%) osteopenic and 3/13 (23%) osteoporotic were fractured. The lower performance of MXA was very likely due to the poor quality of images from the upper thoracic spine of obese subjects. CONCLUSIONS: Prevalence of vertebral fractures in renal transplant patients is quite high and randomly associated with reduced BMD. A surveillance of the spine by Rx, implemented with vertebral morphometry, is therefore warranted to recognize the disease. (MXA is a reliable alternative technique, especially in more severely affected individuals.) MXA, although less sensitive than the conventional techniques because of possible technical biases, is very specific, and can be proposed for follow-up purposes in this population of patients.