Does Dose Modification Affect Efficacy of First-Line Pazopanib in Metastatic Renal Cell Carcinoma?

BACKGROUND: Pazopanib is a standard treatment for metastatic renal cell carcinoma (mRCC), and 800 mg/daily is considered the optimal dose. However, some patients require dose modification because of toxicity. Whether a reduced dose of pazopanib is as effective as the standard dose in achieving clinical benefit remains unclear. OBJECTIVES: Our objective was to conduct a retrospective analysis to investigate the clinical effect of different therapeutic doses of first-line pazopanib in patients with mRCC. METHODS: Consecutive patients with mRCC treated with first-line pazopanib between 2011 and 2016 at the Istituto Nazionale Tumori of Milan were retrospectively analysed for demographics, response, outcomes, and toxicity. Three patient groups were compared: group 1 received the standard dose of 800 mg/day; group 2 started with 800 mg/day and then reduced the dose to 400 or 600 mg/day because of toxicity; and group 3 received a reduced starting dose of 400 or 600 mg/day because they had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 2 and/or comorbidities. RESULTS: In total, 69 patients were evaluated: 34 in group 1, 19 in group 2, and 16 in group 3. After a median follow-up of 13.9 months (range 0.3-43.8), 27 (39.1%) patients had progressive disease (PD) and three (4.3%) patients had died. The incidence rate of PD or death per 100 person-months was 2.5 [95% confidence interval (CI) 0.6-4.4; hazard ratio (HR) 1] in group 1 and 3.9 (95% CI 0-14.3; HR 1.43) in the combined group (2 + 3). The discontinuation rate due to PD was 28% in group 1, 42% in group 2, and 44% in group 3. The objective response rate was 44, 11, and 19% in groups 1, 2, and 3, respectively. CONCLUSIONS: Our results may suggest that patients with mRCC receiving a lower dose of first-line pazopanib might not have a meaningful progression-free survival advantage compared with those receiving a standard dose. These data highlight that proper management of treatment-related side effects may lead to optimal drug exposure

1053pdgenomics features gf and integration with mri radiomics features rf to develop a prognostic model in oral cavity squamous cell carcinoma oscc

n/

A Prospectively Validated Prognostic Model for Patients with Locally Advanced Squamous Cell Carcinoma of the Head and Neck Based on Radiomics of Computed Tomography Images

Background: Locoregionally advanced head and neck squamous cell carcinoma (HNSCC) patients have high relapse and mortality rates. Imaging-based decision support may improve out-comes by optimising personalised treatment, and support patient risk stratification. We propose a multifactorial prognostic model including radiomics features to improve risk stratification for advanced HNSCC, compared to TNM eighth edition, the gold standard. Patient and methods: Data of 666 retrospective-and 143 prospective-stage III-IVA/B HNSCC patients were collected. A multivar-iable Cox proportional-hazards model was trained to predict overall survival (OS) using diagnostic CT-based radiomics features extracted from the primary tumour. Separate analyses were performed using TNM8, tumour volume, clinical and biological variables, and combinations thereof with radi-omics features. Patient risk stratification in three groups was assessed through Kaplan–Meier (KM) curves. A log-rank test was performed for significance (p-value < 0.05). The prognostic accuracy was reported through the concordance index (CI). Results: A model combining an 11-feature radiomics signature, clinical and biological variables, TNM8, and volume could significantly stratify the validation cohort into three risk groups (p < 0∙01, CI of 0.79 as validation). Conclusion: A combination of radiomics features with other predictors can predict OS very accurately for advanced HNSCC patients and improves on the current gold standard of TNM8

Proprietà di trasporto elettrico del tiofosfato di ferro intercalato con il litio

We have carried out $dc$ conductivity measurements on the lithium intercalation complexes $Li_xFePS_3$ both during the intercalation process and after the intercalation was ceased. Prelirninary results for equilibrated samples are presented as a function of both the temperature and the intercalation time. As in the $Li_xNiPS_3$ case, an increase in the electrical conductivity and a contemporary decrease in the activation energy are observed, These features seem to indicate that, with respect to the pure $FePS_3$, a new conduction mechanism takes piace at a different energy levei since the very beginning of the intercaiation process. In the eariy intercalation times, the empirical model, proposed for the $Li_xNiPS_3$ complexes, was used to correlate the data as a function of the intercalation time and as a function of temperature. For the investigated intercalation times a possibie nature of the reduction sites is also provided

The Prognostic Role of TNM Staging Compared With Tumor Volume and Number of Pleural Sites in Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is an aggressive disease with a unique morphology and distribution. Because of its peculiar growth pattern, clinical staging is difficult. Quantitative assessment such as tumor volume (TV) was suggested as an alternative prognostic evaluation. In this study we aimed to compare the prognostic role of Tumor, Node, Metastases (TNM) clinical staging with that of alternative staging approaches on the basis of the use of 2 quantitative clinical parameters, TV and number of pleural sites (NPS), in MPM patients (pts). Our data confirmed the prognostic role of TNM, tumor size, TV, and NPS. However, the TV and NPS combination performed better than TV, NPS, and TNM alone as prognostic classifier. Considering different quantitative parameters and translating such an approach from research level to clinical practice could increase prognostic accuracy for MPM pts, and help clinicians choose the best therapeutic strategy

Effects of lithium intercalation on the electronic properties of FePS3 single crystals

The reaction of FePS3 single crystals with a 1.6M n-butyl lithium solution in n-hexane has been followed through de electrical conductivity measurements as a function of the intercalation time. In order to investigate the influence of lithium insertion on the FePS3 electronic properties we have also measured as a function of both temperature and intercalation time the de conductivity of equilibrated LixFePS3 single crystals. Upon lithium intercalation we have observed the following main effects: (i) an increase in the electrical conductivity, (ii) a simultaneous decrease in the activation energy, and (iii) a degenerate semiconductor behavior at the highest lithium content. In analogy to the LixNiPS3 systems, these results, discussed in terms of both the rigid band model and the so-called transition-metal weakly interacting one, seem to indicate that in the LixFePS3 complexes a new conduction mechanism appears at a different energy level from the beginning of the intercalation process with respect to the pure FePS3. Aiming at a better understanding of the still uncertain nature of reduction sites in the FePS3 lattice during lithium intercalation, we have also carried out Fourier transform infrared absorption measurements on single crystals of FePS3 and their lithium intercalation compounds at room temperature and in the frequency region from 800 to 3000 cm(-1). The results agree well with both the literature and the above conductivity data allowing a better identification of the lithium 2s electron accepting levels

Use of apparent diffusion coefficient images to predict response to induction chemotherapy in sinonasal cancer

The purpose of this study is to identify a set of radiomic features extracted from apparent diffusion coefficient (ADC) maps, obtained using baseline diffusion weighted magnetic resonance imaging (DW-MRI), which are able to predict the outcome of induction chemotherapy (IC) in sinonasal cancers. Such prediction could help the clinician defining the better treatment for a particular patient. Eighty-eight radiomic features were extracted from the ADC maps of 15 patients that underwent IC. A preliminary filtering of the features was made by assessing their stability to geometrical transformations of the region of interest (ROI). Mann-Whitney tests corrected for control of false discoveries were performed to identify the features that could discriminate between responsive and nonresponsive patients (4 and 11 respectively). Twenty features were found to be able to discriminate the two groups and they can potentially be used for prediction of response to treatment