Pre-treatment risk factors to predict early cisplatin-related nephrotoxicity in locally advanced head and neck cancer patients treated with chemoradiation: A single Institution experience

Objectives: Cisplatin is essential in the curative treatment of locally advanced head and neck squamous cell carcinoma (LA-HNSCC) patients. The assessment of risk factors to predict an early cisplatin-induced nephrotoxicity could help in better managing one of the most relevant cisplatin-related dose-limiting factors. Material and methods: We retrospectively collected data of LA-HNSCC patients treated at our Institution from 2008 to 2019. Patients received cisplatin in a curative setting concurrently with radiation. Acute Kidney Injury (AKI) was assessed as a dichotomous variable (CreaIncr) based on pre-treatment values, and values recorded at days 6-20 post-first cycle of cisplatin. Univariable logistic regression models were performed to investigate associations between CreaIncr and clinical characteristics. A multivariable logistic model on a priori selected putative covariates was performed. Results: Of the 350 LA-HNSCC treated patients, 204 were analyzed. Ninety (44 %) suffered from any grade AKI (grade I 51.1 %): out of them, 84.4 % received high-dose cisplatin (100 mg/m2 q21). On the univariable logistic regression model, male sex, age, serum uric acid, creatinine, concomitant drugs, and cisplatin schedule were significantly associated with a higher rate of AKI. At multivariable model, age (p = 0.034), baseline creatinine (p = 0.027), concomitant drugs (p = 0.043), and cisplatin schedule (one-day bolus or fractionated high-dose vs. weekly; p = 0.001) maintained their significant association. Conclusions: Identifying pre-treatment risk factors in LA-HNSCC patients may improve decision-making in a setting where cisplatin has a curative significance. A strict monitoring of AKI could avoid cisplatin dose adjustments, interruptions, and treatment delays, thus limiting a negative impact on outcomes

HER2 status in recurrent/metastatic androgen receptor overexpressing salivary gland carcinoma patients

BackgroundOverexpression of human epidermal growth factor receptor type 2 (HER2) occurs in almost 25-30% of androgen receptor (AR)-positive salivary gland carcinomas (SGCs), notably salivary duct carcinoma (SDC) and adenocarcinoma not otherwise specified (NOS). In the last years, several studies have reported the clinical benefit of HER2 directed therapies in this setting. This work aims at describing the natural history of AR-positive recurrent/metastatic (R/M) SGC patients, based on HER2 amplification status.MethodsConsecutive R/M AR-positive SGC patients accessing our Institution from 2010 to 2021 were analyzed. Descriptive statistics and survival analyses were performed to present the clinical characteristics of the selected patients and the outcomes, based on HER2 status. A specific focus was dedicated to patients developing metastases to the central nervous system (CNS).ResultsSeventy-four R/M AR-positive SGC patients (72 men) were analyzed. Median follow-up was 36.18 months (95% CI 30.19-42.66). HER2 status was available in 62 cases (84%) and in 42% the protein was overexpressed (HER2+). Compared with patients with HER2- SGCs, in patients with HER2+ disease, HR for disease recurrence was 2.97 (95% CI 1.44-6.1, p=0.003), and HR for death from R/M disease was 3.22 (95% CI 1.39-7.49, p=0.007). Moreover, the HER2+ group showed a non-significant trend towards a higher prevalence of CNS metastases (40% vs. 24%, p=0.263). Patients developing CNS metastases had shorter survival than those who did not; at bivariate analysis (covariates: CNS disease and HER2 status), HER2 status demonstrated its independent prognostic significance.DiscussionIn our patient population, HER2 amplification was a negative prognostic factor, and it was associated with a non-statistically significant higher risk of developing CNS metastasis. Further studies are needed to explore the potential clinical benefit of tackling the two biological pathways (AR and HER2) in patients affected by this rare and aggressive malignancy

Circulating pre-treatment Epstein-Barr virus DNA as prognostic factor in locally-advanced nasopharyngeal cancer in a nonendemic area

The prognostic value of pre-treatment Epstein-Barr Virus (EBV) DNA viral load for non-endemic, locally-advanced, EBV-related nasopharyngeal cancer (NPC) patients is yet to be defined. All patients with EBV encoded RNA (EBER)-positive NPC treated at our Institution from 2005 to 2014 with chemotherapy (CT) concurrent with radiation (RT) +/- induction chemotherapy (ICT) were retrospectively reviewed. Pre-treatment baseline plasma EBV DNA (b-EBV DNA) viral load was detected and quantified by PCR. Median b-EBV DNA value was correlated to potential influencing factors by univariate analysis. Significant variables were then extrapolated and included in a multivariate linear regression model. The same variables, including b-EBV DNA, were correlated with Disease Free Survival (DFS) and Overall Survival (OS) by univariate and multivariate analysis. A total of 130 locally-advanced EBER positive NPC patients were evaluated. Overall, b-EBV DNA was detected in 103 patients (79.2%). Median viral load was 554 copies/mL (range 50-151075), and was positively correlated with T stage (p= 0.002), N3a-b vs N0-1-2 stage (p= 0.048), type of treatment (ICT followed by CTRT, p= 0.006) and locoregional and/or distant disease recurrence (p= 0.034). In the overall population, DFS and OS were significantly longer in patients with pre-treatment negative EBV DNA than in positive subjects at the multivariate analysis. Negative b-EBV DNA can be considered as prognostic biomarker of longer DFS and OS in NPC in non-endemic areas. This finding needs confirmation in larger prospective series, with standardized and inter-laboratory harmonized method of plasma EBV DNA quantificatio

Statistical Assessment of New Methods to Optimize the Power Flux Distribution in TV-sat Broadcasting at 20 GHz

In this paper we present the results of a statistical performance assessment of a new advanced TV-sat system operating in the ka band. The on-board transmission system is based on the idea of reconfigurable antenna, i.e. the antenna directivity can be modified so as to irradiate more power to the regions affected by bad weather. The core is a power flux distribution optimizer based on the “derivative slicing” method, whose mathematical basis is described in the companion paper [1] presented at this Conference. Here, the above technique is assessed by verifying the system performance through a statistical analysis over six-months. The simulations make use of a meteorological database provided by the European Centre for Medium-range Weather Forecasts (ECMWF). The constraints unavoidably posed by the usage of a physically realizable Beam-Forming Network (BFN) are taken into account as well. The results presented allow a preliminary assessment of the predicted advantage (in terms of availability) of an adaptive system over non-adaptive systems currently implemented, which are based on long-term climatological data. The BFN used to distribute the signal power across the service area (Europe) is constituted by a set of 8x8 multiport amplifiers, each driven by a Butler-Like Matrix (BLM), covering the area with 64 beams. The BFN excitation coefficients are refreshed every 3-6 hours, in accordance with the update rate of the input meteorological data. Our analysis shows that the number of users lost due to atmospheric effects is reduced by a factor of about 5 with respect to the case of a non-reconfigurable system fed by the same transmitted power. Morevoer, the theoretical reduction factor achievable by the "derivative slicing” method removing the system constraints (i.e. the BLM elements) would increase to 10

Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial

The activity of androgen-deprivation therapy (ADT) in androgen receptor-positive (AR+) salivary gland carcinomas (SGCs) has been established in the past few years. Second-line treatment in castration-resistant patients is still unknown. We investigated the activity of abiraterone acetate as second-line treatment in ADT-resistant, AR+ patients with SGC

A Clutter Loss Model for Satellite Communication Systems

Buildings and vegetation in the proximity of a terrestrial base station induce a significant additional loss, typically referred to as “clutter loss”, which sums up to free space loss and atmospheric attenuation. Clutter loss is essentially due to the radiowave reflection and diffraction caused by buildings and vegetation, and tends to reduce the interference between terrestrial systems, such as upper 6 GHz (U6G), and satellite systems operating in the same frequency bands. In fact, for example, at low elevation angles, the clutter loss could reach some tens of dB in the U6G band. A novel clutter loss model in urban and suburban environments for frequencies up to 10 GHz is proposed. The model relies on the Monte Carlo simulation approach presented in Report ITU-R P.2402-0, but some limitations have been removed to extend its applicability to more complex scenarios and possibly increase its accuracy for U6G systems. An analytical approach is also proposed to model the clutter loss statistics obtained by properly fitting the obtained statistics for the cities of London and Melbourne. Finally, the proposed model is validated by comparing its results to those obtained by a commercial ray tracer

Refining Tumor Treatment in Sinonasal Cancer Using Delta Radiomics of Multi-Parametric MRI after the First Cycle of Induction Chemotherapy

Background: Response to induction chemotherapy (IC) has been predicted in patients with sinonasal cancer using early delta radiomics obtained from T1- and T2-weighted images and apparent diffusion coefficient (ADC) maps, comparing results with early radiological evaluation by RECIST. Methods: Fifty patients were included in the study. For each image (at baseline and after the first IC cycle), 536 radiomic features were extracted as follows: semi-supervised principal component analysis components, explaining 97% of the variance, were used together with a support vector machine (SVM) to develop a radiomic signature. One signature was developed for each sequence (T1-, T2-weighted and ADC). A multiagent decision-making algorithm was used to merge multiple signatures into one score. Results: The area under the curve (AUC) for mono-modality signatures was 0.79 (CI: 0.65–0.88), 0.76 (CI: 0.62–0.87) and 0.93 (CI: 0.75–1) using T1-, T2-weighted and ADC images, respectively. The fuse signature improved the AUC when an ADC-based signature was added. Radiological prediction using RECIST criteria reached an accuracy of 0.78. Conclusions: These results suggest the importance of early delta radiomics and of ADC maps to predict the response to IC in sinonasal cancers