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Purpose: To investigate whether intermittent treatment after an induction phase of first-line schedule of fluorouracil, leucovorin, and irinotecan (FOLFIRI) plus panitumumab (PAN) prevents or delays the onset of resistance and improves safety and compliance with treatment in patients with unresectable RAS / BRAF wild-type (wt) metastatic colorectal cancer (mCRC)., Patients and Methods: IMPROVE (ClinicalTrials.gov identifier: NCT04425239) was an open-label, multicenter, randomized phase II noncomparative trial. Patients with unresectable RAS / BRAF wt mCRC were randomly assigned (1:1) to receive FOLFIRI plus PAN continuously until progression (arm A) or intermittently, with treatment-free intervals (arm B) until progression on treatment, toxicity, or death. The primary end point was progression-free survival on treatment (PFSot) at 12 months. Assuming a null hypothesis of median PFSot time ≤7 months and target PFSot ≥10 months, 65 patients per arm were needed to achieve 80% power and 10% type I error, according to the binomial test., Results: Between May 2018 and June 2021, 69 patients were randomly assigned to arm A and 68 to arm B. The median number of treatment cycles was 13 in arm A and 16 in arm B. At a median follow-up of 43.2 months (IQR, 35.0-50.5), median PFSot was 11.2 and 17.5 months with 12-month PFSot rates of 45.7% and 58.5%, for arms A and B, respectively. The overall response rates were 68.1% and 61.2%, and median overall survival rates were 36.3 and 35.1 months in arms A and B, respectively. The overall rate of grade >2 skin PAN-related adverse events was 30.3% in arm A and 17.9% in arm B., Conclusion: Intermittent FOLFIRI plus PAN after the induction phase was feasible, and the primary end point was met with reduced toxicity while allowing patients more time off treatment.

This manuscript evaluated the performance of silanes in cementitious matrices in the partial replacement of superplasticizers by silanes. For this, pastes with a water/cement ratio of 0.186 were produced and the superplasticizer admixture based on polycarboxylate esters was partially substituted by three types of silanes-vinyltriethoxysilane silanes (VTES), n-(2-aminoethyl)-3-aminopropyltrimethoxysilane (AEAPTMS), and methacryloxypropyltrimethox-ysilane (MCPTMS)-in two substitutions levels (20% and 40%), and then tested in Portland cement pastes. Specific gravity, trapped air, mini-slump, and hydration kinetics (evaluated by isothermal calorimetry up to 48 h) of the pastes were determined in the fresh state. Thus, in the hardened state, the compressive and flexural strength tests (7 and 28 days), specific gravity, and absorption by immersion of the pastes were carried out. The results showed that the substitution of 20% and 40% of VTES and AEAPTMS considerably reduced the workability and increased the air content of the pastes in comparison to the reference sample. In contrast, the incorporation of 20% and 40% of MCPTMS did not significantly affect these properties. The presence of silane, for all analyzed samples, had a delaying effect on the hydration process: the maximum delay verified had a hydration peak in approximately 36 h for the 40% MCPTMS sample and the minimum delay verified had a hydration peak in approximately 11 h for the 20% VTES sample. The replacement of 20% and 40% by any of the silanes progressively reduced the flexural strength at both 7 and 28 days. In the compressive strength, as well as in the tensile strength in flexion, there was a decrease in the results when compared to the reference, except for the MCPTMS, at 7 and 28 days. In immersion absorption, all samples showed high percentages of absorption and void index when compared to the reference.

Background: In the TOPAZ-1, patients with biliary tract cancers (BTC) and recurrence within 6 months after surgery were excluded, even if this event is frequently observed in clinical practice. Our study aimed to assess if the efficacy of cisplatin-gemcitabine-durvalumab (CGD) in this population is comparable to that reported in the phase 3 trial., Methods: The study cohort included patients with BTC who underwent surgery on the primary tumor, experienced disease recurrence occurring ≤6 months or >6 months after surgery or after the end of adjuvant therapy and started CGD. The primary objectives were overall survival (OS) and progression free survival (PFS)., Results: A total of 178 patients were enrolled. No significant differences were observed between early and late relapse groups in OS (23.4 months vs not reached; HR 1.26; 95% CI, 0.67-2.37; P = .45) and PFS [7.0 months vs 9.8 months; HR 1.3(95% CI, 0.9-2.1) P = .13]. Overall response rate and disease control rate (P = .33 and P = .62) were comparable between the 2 groups, as the overall safety profile. In addition, we compared survival outcomes between the selected population and a historical cohort of patients with BTC treated with cisplatin-gemcitabine (CG) and found that despite the absence of statistical significance, CGD showed an outcome trend compared with CG regardless of the time of recurrence after surgery or adjuvant chemotherapy [(CG ≤ 6 vs CGD ≤ 6 months: HR 0.59, 95%CI, 0.35-1.01, P = .05; HR 0.70; 95%CI, 0.46-1.06, P = .09, OS and PFS, respectively) and (CG > 6 vs. CGD > 6 months: HR 0.50; 95%CI, 0.29-0.88, P = 0.0165; HR 0.54; 95%CI, 0.35-0.84, P = .0068, OS and PFS, respectively)]., Conclusion: Our analysis suggests that CGD retains its efficacy independently of the timing of relapse after surgery or completion of adjuvant treatment in patients with advanced BTC., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Metastatic pancreatic ductal adenocarcinoma (mPDAC) patients have very poor prognosis highlighting the urgent need of novel treatments. In this regard, repurposing non-oncology already-approved drugs might be an attractive strategy to offer more-effective treatment easily tested in clinical trials. Accumulating evidence suggests that epigenetic deregulation is a hallmark of cancer contributing to treatment resistance in several solid tumors, including PDAC. Histone deacetylase inhibitors (HDACi) are epigenetic drugs we have investigated preclinically and clinically as anticancer agents. Valproic acid (VPA) is a generic low-cost anticonvulsant and mood stabilizer with HDAC inhibitory activity, and anticancer properties also demonstrated in PDAC models. Statins use was reported to be associated with lower mortality risk in patients with pancreatic cancer and statins have been shown to have a direct antitumor effect when used alone or in combination therapy. We recently showed capability of VPA/Simvastatin (SIM) combination to potentiate the antitumor activity of gemcitabine/nab-paclitaxel in vitro and in vivo PDAC preclinical models., Methods/design: VESPA is a patient-centric open label randomized multicenter phase-II investigator-initiated trial, evaluating the feasibility, safety, and efficacy of VPA/SIM plus first line gemcitabine/nab-paclitaxel-based regimens (AG or PAXG) (experimental arm) versus chemotherapy alone (standard arm) in mPDAC patients. The study involves Italian and Spanish oncology centers and includes an initial 6-patients safety run-in-phase. A sample size of 240 patients (120 for each arm) was calculated under the hypothesis that the addition of VPA/SIM to gemcitabine and nab-paclitaxel-based regimens may extend progression free survival from 6 to 9 months in the experimental arm. Secondary endpoints are overall survival, response rate, disease control rate, duration of response, CA 19.9 reduction, toxicity, and quality of life. The study includes a patient engagement plan and complementary biomarkers studies on tumor and blood samples., Conclusions: VESPA is the first trial evaluating efficacy and safety of two repurposed drugs in oncology such as VPA and SIM, in combination with standard chemotherapy, with the aim of improving mPDAC survival. The study is ongoing. Enrollment started in June 2023 and a total of 63 patients have been enrolled as of June 2024., Trial Registration: EudraCT number: 2022-004154-63; ClinicalTrials.gov identifier NCT05821556, posted 2023/04/20., (© 2024. The Author(s).)

Background and Aims: Cholangiocarcinoma (CCA), a rare and aggressive hepatobiliary malignancy, presents significant clinical management challenges. Despite rising incidence and evolving treatment options, prognosis remains poor, motivating the exploration of real-world data for enhanced understanding and patient care., Methods: This multicenter study analyzed data from 120 metastatic CCA patients at three institutions from 2016 to 2023. Kaplan-Meier curves assessed overall survival (OS), while univariate and multivariate analyses evaluated links between clinical variables (age, gender, tumor site, metastatic burden, ECOG performance status, response to first-line chemotherapy) and OS. Genetic profiling was conducted selectively., Results: Enrolled patients had a median age of 68.5 years, with intrahepatic tumors predominant in 79 cases (65.8%). Among 85 patients treated with first-line chemotherapy, cisplatin and gemcitabine (41.1%) was the most common regimen. Notably, one-third received no systemic treatment. After a median 14-month follow-up, 81 CCA-related deaths occurred, with a median survival of 13.1 months. Two clinical variables independently predicted survival: response to first-line chemotherapy (disease control vs. no disease control; HR: 0.27; 95% CI: 0.14-0.50; p < 0.0001) and metastatic involvement (>1 site vs. 1 site; HR: 1.99; 95% CI: 1.04-3.80; p = 0.0366). The three most common genetic alterations involved the ARID1A, tp53, and CDKN2A genes., Conclusions: Advanced CCA displays aggressive clinical behavior, emphasizing the need for treatments beyond chemotherapy. Genetic diversity supports potential personalized therapies. Collaborative research and deeper CCA biology understanding are crucial to enhance patient outcomes in this challenging malignancy., (© 2024 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Niobium oxide (Nb 2 O 5 ) is a semiconductor that exhibits photocatalytic properties, making it potentially valuable in addressing air pollution, self-cleaning, and self-disinfection in cement-based materials (CBMs). Therefore, this study aimed to evaluate the impact of different Nb 2 O 5 concentrations on various parameters, including rheological characteristics, hydration kinetics (measured using isothermal calorimetry), compressive strength, and photocatalytic activity, specifically in the degradation of Rhodamine B (RhB) in white Portland cement pastes. The incorporation of Nb 2 O 5 increased the yield stress and viscosity of the pastes by up to 88.9% and 33.5%, respectively, primarily due to the larger specific surface area (SSA) provided by Nb 2 O 5 . However, this addition did not significantly affect the hydration kinetics or the compressive strength of the cement pastes after 3 and 28 days. Tests focusing on the degradation of RhB in the cement pastes revealed that the inclusion of 2.0 wt.% of Nb 2 O 5 was insufficient to degrade the dye when exposed to 393 nm UV light. However, an interesting observation was made concerning RhB in the presence of CBMs, as it demonstrated a degradation mechanism that was not dependent on light. This phenomenon was attributed to the production of superoxide anion radicals resulting from the interaction between the alkaline medium and hydrogen peroxide.

This article introduces simulations of theoretical material with controlled properties for the evaluation of the effect of key parameters, as volumetric fractions, elastic properties of each phase and transition zone on the effective dynamic elastic modulus. The accuracy level of classical homogenization models was checked regarding the prediction of dynamic elastic modulus. Numerical simulations were performed with the finite element method for evaluations of the natural frequencies and their correlation with E d through frequency equations. An acoustic test validated the numerical results and obtained the elastic modulus of concretes and mortars at 0.3, 0.5 and 0.7 water-cement ratios. Hirsch calibrated according to the numerical simulation (x = 0.27) exhibited a realistic behavior for concretes of w/c = 0.3 and 0.5, with a 5% error. However, when the water-to-cement ratio (w/c) was set to 0.7, Young's modulus displayed a resemblance to the Reuss model, akin to the simulated theoretical triphasic materials, considering matrix, coarse aggregate and a transition zone. Hashin-Shtrikman bounds is not perfectly applied to theoretical biphasic materials under dynamic situations.

In this narrative review, we reported un up-to-date on the role of radiomics to assess prognostic features, which can impact on the liver metastases patient treatment choice. In the liver metastases patients, the possibility to assess mutational status (RAS or MSI), the tumor growth pattern and the histological subtype (NOS or mucinous) allows a better treatment selection to avoid unnecessary therapies. However, today, the detection of these features require an invasive approach. Recently, radiomics analysis application has improved rapidly, with a consequent growing interest in the oncological field. Radiomics analysis allows the textural characteristics assessment, which are correlated to biological data. This approach is captivating since it should allow to extract biological data from the radiological images, without invasive approach, so that to reduce costs and time, avoiding any risk for the patients. Several studies showed the ability of Radiomics to identify mutational status, tumor growth pattern and histological type in colorectal liver metastases. Although, radiomics analysis in a non-invasive and repeatable way, however features as the poor standardization and generalization of clinical studies results limit the translation of this analysis into clinical practice. Clear limits are data-quality control, reproducibility, repeatability, generalizability of results, and issues related to model overfitting., (© 2023. The Author(s).)

Background: Maintaining angiogenesis inhibition and switching the chemotherapy backbone represent the current second-line therapy in patients with RAS-mutant metastatic colorectal cancer (mCRC). Regorafenib, an oral multikinase inhibitor, prolonged overall survival (OS) in the chemorefractory setting., Materials and Methods: STREAM was an academic, multicenter, single-arm phase II trial, evaluating the activity of regorafenib in RAS-mutant mCRC, in terms of the rate of patients who were progression-free after 6 months from study entry (6mo-PF). Patients were pretreated with fluoropyrimidine, oxaliplatin, and bevacizumab. According to Simon's two-stage design, ≥18 patients 6mo-PF were needed in the overall population (N = 46). Secondary endpoints were safety, objective response rate (ORR), progression-free survival (PFS), and OS. Early metabolic response by [ 18 F]2-fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography ([ 18 F]-FDG PET/CT) scan was an exploratory endpoint. EudraCT Number: 2015-001105-13., Results: The number of patients 6mo-PF was 8/22 at the first stage and 14/46 in the overall population. The ORR was 10.9%, disease control rate was 54.6%, median (m)PFS was 3.6 months [95% confidence interval (CI) 1.9-6.7 months], mOS was 18.9 months (95% CI 10.3-35.3 months), and mPFS2 (from study entry to subsequent-line progression) was 13.3 months (95% CI 8.4-19.7 months). Long benefiter patients (>6mo-PF) significantly more often had a single metastatic site and lung-limited disease. No unexpected toxicity was reported. Grade ≥3 events occurred in 39.1% of patients, with hand-foot syndrome (13%), fatigue, and hyperbilirubinemia (6.5%) occurring mostly. Baseline metabolic assessment was associated with OS in the multivariate analysis, while early metabolic response was not associated with clinical outcomes., Conclusions: The study did not meet its primary endpoint. However, regorafenib was well tolerated and did not preclude subsequent treatments. Patients with good prognostic features (single metastatic site and lung-limited disease) reported clinical benefit with regorafenib. The exploratory metabolic analysis suggests that baseline [ 18 F]-FDG PET/CT might be useful to select patients with a favorable outcome. A chemotherapy-free interval with regorafenib was associated with durable disease control in a selected group of patients with favorable clinical characteristics., Competing Interests: Disclosure CC declares personal honoraria for advisory board roles from Bayer. ADS declares personal honoraria for educational activities from Amgen. LA declares personal honoraria for educational activities from Pfizer. EM declares personal honoraria advisory board and speaker roles for Amgen, Bayer, Eisai, Merck Serono, Pierre Fabre, Roche, Servier, Incyte, ESMO; Travel grant: AstraZeneca, Pierre Fabre. FC declares personal honoraria advisor and speaker roles for Roche, Amgen, Merck Serono, Pfizer, Sanofi, Bayer, Servier, BMS, Cellgene, Lilly and institutional research grants from Bayer, Roche, Merck Serono, Amgen, AstraZeneca, Takeda. MCP declares personal honoraria for educational activities from Astellas, AstraZeneca, Pfizer, and institutional grants for support to research activities from AstraZeneca, Bayer, Roche. AA declares personal honoraria for advisory board roles from AstraZeneca, Amgen, MSD, Servier. All other authors have declared no conflicts of interest. Data sharing De-identified individual data might be available after publication upon reasonable request to the corresponding author by presenting a complete research proposal., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Pancreatic cancer (PC) is one of the deadliest cancers, and it is responsible for a number of deaths almost equal to its incidence. The high mortality rate is correlated with several explanations; the main one is the late disease stage at which the majority of patients are diagnosed. Since surgical resection has been recognised as the only curative treatment, a PC diagnosis at the initial stage is believed the main tool to improve survival. Therefore, patient stratification according to familial and genetic risk and the creation of screening protocol by using minimally invasive diagnostic tools would be appropriate. Pancreatic cystic neoplasms (PCNs) are subsets of lesions which deserve special management to avoid overtreatment. The current PC screening programs are based on the annual employment of magnetic resonance imaging with cholangiopancreatography sequences (MR/MRCP) and/or endoscopic ultrasonography (EUS). For patients unfit for MRI, computed tomography (CT) could be proposed, although CT results in lower detection rates, compared to MRI, for small lesions. The actual major limit is the incapacity to detect and characterize the pancreatic intraepithelial neoplasia (PanIN) by EUS and MR/MRCP. The possibility of utilizing artificial intelligence models to evaluate higher-risk patients could favour the diagnosis of these entities, although more data are needed to support the real utility of these applications in the field of screening. For these motives, it would be appropriate to realize screening programs in research settings.

The aim of the study was to analyse papers describing the use of Electrochemotherapy (ECT) in local treatment of primary and secondary liver tumours located at different sites and with different histologies. Other Local Ablative Therapies (LAT) are also discussed. Analyses of these papers demonstrate that ECT use is safe and effective in lesions of large size, independently of the histology of the treated lesions. ECT performed better than other thermal ablation techniques in lesions > 6 cm in size and can be safely used to treat lesions distant, close, or adjacent to vital structures. ECT spares vessel and bile ducts, is repeatable, and can be performed between chemotherapeutic cycles. ECT can fill the gap in local ablative therapies due to being lesions too large or localized in highly challenging anatomical sites.

Despite geopolymers having emerged as a more sustainable alternative to Portland cement, their rheological properties still need to be thoroughly investigated, aiming at the material's applicability. Additionally, studies that evaluated the fresh state of geopolymer composites with nanomaterials are scarce. Thus, two metakaolin-based geopolymer systems were reinforced with nanomaterials with a similar geometry: carbon nanotubes (CNT) and silicon carbide whiskers (SCW). The nanomaterials incorporation was assessed by rotational rheometry (conducted up to 110 min), isothermal calorimetry, compressive strength after 7 and 28 days, and the microstructure was investigated using X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FTIR). CNT and SCW incorporation (0.20 wt.%) did not significantly affect the yield stress and viscosity of the R2-group (based on metakaolin type 2), while increasing the rheological parameters up to 56.0% for the R1-group (based on metakaolin type 1). Both additions modified the reaction kinetics. Increments of up to 40.7% were observed in the compressive strength of geopolymer pastes with the incorporation of a SCW content of 0.2 wt.%. XRD and FTIR results suggest similar structural modifications between precursors. Nevertheless, R2 showed substantial transformations while the R1 group exhibited anhydrous material that can react over time. Overall, incorporating CNT and SCW contributed to higher mechanical increments on systems with average mechanical strength (R1) compared to systems with higher potential mechanical performance (R2).

Purpose: The purpose of this study is to evaluate the Radiomics and Machine Learning Analysis based on MRI in the assessment of Liver Mucinous Colorectal Metastases.Query METHODS: The cohort of patients included a training set (121 cases) and an external validation set (30 cases) with colorectal liver metastases with pathological proof and MRI study enrolled in this approved study retrospectively. About 851 radiomics features were extracted as median values by means of the PyRadiomics tool on volume on interest segmented manually by two expert radiologists. Univariate analysis, linear regression modelling and pattern recognition methods were used as statistical and classification procedures., Results: The best results at univariate analysis were reached by the wavelet&#95;LLH&#95;glcm&#95;JointEntropy extracted by T2W SPACE sequence with accuracy of 92%. Linear regression model increased the performance obtained respect to the univariate analysis. The best results were obtained by a linear regression model of 15 significant features extracted by the T2W SPACE sequence with accuracy of 94%, a sensitivity of 92% and a specificity of 95%. The best classifier among the tested pattern recognition approaches was k-nearest neighbours (KNN); however, KNN achieved lower precision than the best linear regression model., Conclusions: Radiomics metrics allow the mucinous subtype lesion characterization, in order to obtain a more personalized approach. We demonstrated that the best performance was obtained by T2-W extracted textural metrics., (© 2022. Italian Society of Medical Radiology.)

The ornamental stone industry generates large amounts of waste thus creating environmental and human health hazards. Thus, pastes with 0-30 wt.% ornamental stone waste (OSW) incorporated into ordinary Portland cement (OPC) were produced and their rheological properties, hydration kinetics, and mechanical properties were evaluated. The CO 2 equivalent emissions related to the pastes production were estimated for each composition. The results showed that the paste with 10 wt.% of OSW exhibited similar yield stress compared to the plain OPC paste, while pastes with 20 and 30 wt.% displayed reduced yield stresses up to 15%. OSW slightly enhanced the hydration kinetics compared to plain OPC, increasing the main heat flow peak and 90-h cumulative heat values. The incorporation of OSW reduced the 1-, 3-, and 28-days compressive strength of the pastes. Water absorption results agreed with the 28 days compressive strength results, indicating that OSW increased the volume of permeable voids. Finally, OSW incorporation progressively reduced the CO 2 emission per m 3 of OPC paste, reaching a 31% reduction for the highest 30 wt.% OSW content. Overall, incorporating up to 10 wt.% with OSW led to pastes with comparable fresh and hardened properties as comported to plain OPC paste.