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1.
Eur Phys J Spec Top ; : 1-9, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34490058

RESUMO

Containment measures have been applied throughout the world to halt the COVID-19 pandemic. In the United States, several forms of lockdown have been adopted in different parts of the country, leading to heterogeneous epidemiological, social, and economic effects. Here, we present a spatio-temporal analysis of a Twitter dataset comprising 1.3 million geo-localized Tweets about lockdown, from January to May 2020. Through sentiment analysis, we classified Tweets as expressing positive or negative emotions about lockdown, demonstrating a change in perception during the course of the pandemic modulated by socio-economic factors. A transfer entropy analysis of the time series of Tweets unveiled that the emotions in different parts of the country did not evolve independently. Rather, they were mediated by spatial interactions, which were also related to socio-ecomomic factors and, arguably, to political orientations. This study constitutes a first, necessary step toward isolating the mechanisms underlying the acceptance of public health interventions from highly resolved online datasets.

2.
Semin Cancer Biol ; 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34536504

RESUMO

Prostate cancer remains the most frequently diagnosed non-skin malignancy in male patients, still representing one of the main causes of cancer-related death worldwide. Evidence is mounting that suggests the putative role of microbiota in the carcinogenesis as well as in modulating the efficacy and activity of anticancer treatments (e.g., chemotherapy, immune checkpoint inhibitors, targeted therapies) in a large number of hematological and solid tumors. However, few data are available regarding the interactions between prostate cancer and microbiome so far, in particular in terms of the impact of microbiota on disease development, pathogenesis, and response to medical treatments in this genitourinary malignancy. Herein, we provide an overview of current knowledge, novel insights and emerging therapeutic approaches related to gastrointestinal and genitourinary microbiome in prostate cancer patients, especially focusing on available evidence and published trials on this topic.

3.
Adv Theory Simul ; : 2100157, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34514293

RESUMO

As COVID-19 vaccine is being rolled out in the US, public health authorities are gradually reopening the economy. To date, there is no consensus on a common approach among local authorities. Here, a high-resolution agent-based model is proposed to examine the interplay between the increased immunity afforded by the vaccine roll-out and the transmission risks associated with reopening efforts. The model faithfully reproduces the demographics, spatial layout, and mobility patterns of the town of New Rochelle, NY - representative of the urban fabric of the US. Model predictions warrant caution in the reopening under the current rate at which people are being vaccinated, whereby increasing access to social gatherings in leisure locations and households at a 1% daily rate can lead to a 28% increase in the fatality rate within the next three months. The vaccine roll-out plays a crucial role on the safety of reopening: doubling the current vaccination rate is predicted to be sufficient for safe, rapid reopening.

5.
Curr Oncol ; 28(5): 3393-3402, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34590592

RESUMO

Ampullary carcinomas (ACs) represent a rare entity, accounting for approximately 0.2% of all gastrointestinal solid tumors and 20% of all periampullary cancers (PACs). Unfortunately, few data are available regarding the optimal therapeutic strategy for ACs due to their rarity, and physicians frequently encounter significant difficulties in the management of these malignancies. In this review, we will provide an overview of current evidence on AC, especially focusing on biological features, histological characteristics, and available data guiding present and future therapeutic strategies for these rare, and still barely known, tumors.

7.
Tumori ; : 3008916211047888, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34585625

RESUMO

INTRODUCTION: Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) approved as first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Some osimertinib-related interstitial lung diseases (ILDs) were shown to be transient, called transient asymptomatic pulmonary opacities (TAPO)-clinically benign pulmonary opacities that resolve despite continued osimertinib treatment-and are not associated with the clinical manifestations of typical TKI-associated ILDs. METHODS: In this multicentric study, we retrospectively analyzed 92 patients with EGFR-mutated NSCLC treated with osimertinib. Computed tomography (CT) examinations were reviewed by two radiologists and TAPO were classified according to radiologic pattern. We also analyzed associations between TAPO and patients' clinical variables and compared clinical outcomes (time to treatment failure and overall survival) for TAPO-positive and TAPO-negative groups. RESULTS: TAPO were found in 18/92 patients (19.6%), with a median follow-up of 114 weeks. Median onset time was 16 weeks (range 6-80) and median duration time 14 weeks (range 8-37). The most common radiologic pattern was focal ground-glass opacity (54.5%). We did not find any individual clinical variable significantly associated with the onset of TAPO or significant difference in clinical outcomes between TAPO-positive and TAPO-negative groups. CONCLUSIONS: TAPO are benign pulmonary findings observed in patients treated with osimertinib. TAPO variability in terms of CT features can hinder the differential diagnosis with either osimertinib-related mild ILD or tumor progression. However, because TAPO are asymptomatic, it could be reasonable to continue therapy and verify the resolution of the CT findings at follow-up in selected cases.

9.
Anticancer Drugs ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34407053

RESUMO

The administration of approved systemic treatments for advanced hepatocellular carcinoma (HCC) is limited to patients with preserved liver function (Child-Pugh A/B7) and performance status. Conversely, metronomic chemotherapy can be safely administered to patients with poor clinical conditions and severe liver impairment. The metronomic schedule demonstrated to exert different anticancer mechanisms compared to that of the same agent administered at its standard schedule, including immune stimulation and the inhibition of angiogenesis and vasculogenesis. Nevertheless, metronomic chemotherapy is a nearly neglected option for the treatment of advanced HCC patients, even among those who cannot afford standard treatments. Herein, we report the case of a 40-year-old patient affected by HBV-HDV-related cirrhosis who was diagnosed with advanced HCC. The severe liver impairment (Child-Pugh B9) did not allow to administer first-line treatment with tyrosine kinase inhibitors so that the patient received metronomic capecitabine as upfront therapy. Due to the suspect of progressive disease at the first radiologic assessment, metronomic cyclophosphamide was added to capecitabine aiming to enhance its efficacy. After 4 months of treatment, complete tumor response, alpha-fetoprotein (AFP) normalization and the recovery of a Child-Pugh A were achieved. The patient was then able to undergo liver transplantation, and, after 18 months from the diagnosis, he is still free of disease recurrence. This experience emphasizes the reliability of metronomic capecitabine as a well-tolerated and effective treatment when patient's conditions prevent the administration of standard first-line treatments. In fact, metronomic capecitabine demonstrated its effectiveness in advanced HCC in retrospective and prospective analyses, leading to median progression-free survival and overall survival of, respectively, 6.03 and 14.47 months in phase II single-arm trial. Moreover, in consideration of the raising interest in immune-checkpoint inhibition in HCC, we believe that the immunomodulating effects of metronomic chemotherapy, either capecitabine or cyclophosphamide, warrant future trials exploring its combination with immunotherapy.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34431725

RESUMO

INTRODUCTION: Immunotherapy has recently taken on an extremely important role in medical oncology, as first- or later-line treatment in several tumor types, and recent years have seen the emerging of clinical trials assessing immune checkpoint inhibitors (ICIs) in unresectable hepatocellular carcinoma (HCC). AREAS COVERED: Herein, we provide an overview of recently published studies exploring the dual immune checkpoint blockade or the combination of ICIs plus biological treatments as first-line treatment in HCC patients with advanced disease, especially focusing on the biological rationale behind these therapeutic strategies, and ongoing active and recruiting clinical trials. EXPERT OPINION: Results of studies on monotherapy with ICIs have suggested that this strategy could be beneficial only in a minority of patients; conversely, the recently published IMbrave150 study has reported an overall survival benefit in HCC receiving the combination of atezolizumab plus bevacizumab compared to sorafenib as first-line treatment. A wide number of clinical trials is evaluating ICI-based combinations in advanced HCC, a strategy which is supported by robust preclinical and early-phase clinical data, and results of these studies are highly awaited.

11.
Expert Opin Drug Metab Toxicol ; : 1-7, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34407702

RESUMO

Background: With hormonal agents quickly expanding as novel therapeutic options in nonmetastatic castration-resistant prostate cancer (nmCRPC), the toxicity profile of enzalutamide, apalutamide, and darolutamide should be kept in mind.Methods: We performed an updated meta-analysis with the aim to analyze the risk of treatment-related cardiovascular (CV) events, any grade, and grade 3-4 (G3-4) hypertension in nmCRPC patients treated with enzalutamide, apalutamide, and darolutamide plus androgen deprivation therapy (ADT) versus ADT plus placebo in randomized controlled trials (RCTs). Results were compared by calculating Relative Risk (RR) with 95% confidence intervals (CIs); RRs were combined with Mantel-Haenszel method.Results: Three RCTs involving 4110 patients were available for the meta-analysis. According to our results, the addition of novel hormonal agents was associated with a significantly increased risk of CV events (RR = 1.71; 95% CI 1.29-2.27) and G3-4 hypertension (RR = 1.53; 95% CI 1.19-1.97). In addition, a trend toward a higher risk of any grade hypertension was reported in the experimental arm.Conclusions: The use of enzalutamide, apalutamide, and darolutamide in nmCRPC patients implies a careful benefit-risk assessment. Real-world, large-cohort studies are warranted to confirm the findings of our meta-analysis.

13.
Expert Opin Pharmacother ; : 1-14, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34405738

RESUMO

Introduction: In the evolving treatment scenario of metastatic renal cell carcinoma, cabozantinib is gaining increasing attention, presenting as a cornerstone therapy, both as a monotherapy and in combination with immune-checkpoint inhibitors.Areas covered: In this review, the authors explore the role of cabozantinib in the treatment of metastatic clear cell and non-clear cell renal cell carcinoma, presenting data from the most recent clinical trials and investigating ongoing studies. They, furthermore, evaluate the pharmacokinetic, pharmacodynamic, and immunomodulatory effect of cabozantinib, as well as underlining the tolerability profile and patients' quality of life.Expert opinion: Cabozantinib's administration as a single agent is restricted to intermediate- and poor-risk patients (according to IMDC criteria). The further advent of anti-VEGF-receptor tyrosine kinase inhibitors combined with immune checkpoint inhibitor regimens (such as pembrolizumab + axitinib) has allowed to expand the use of cabozantinib, leading to its combination with nivolumab. In the next few years, more information is required to look for the application of cabozantinib-based combinations as a later-line approach in metastatic RCC patients, beside their use in the first-line setting.

14.
Pharmaceuticals (Basel) ; 14(7)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358103

RESUMO

Pancreatic cancer (PC) is a recalcitrant disease characterized by high incidence and poor prognosis. The extremely complex genomic landscape of PC has a deep influence on cultivating a tumor microenvironment, resulting in the promotion of tumor growth, drug resistance, and immune escape mechanisms. Despite outstanding progress in personalized medicine achieved for many types of cancer, chemotherapy still represents the mainstay of treatment for PC. Olaparib was the first agent to demonstrate a significant benefit in a biomarker-selected population, opening the doors for a personalized approach. Despite the failure of a large number of studies testing targeted agents or immunotherapy to demonstrate benefits over standard chemotherapy regimens, some interesting agents, alone or in combination with other drugs, have achieved promising results. A wide spectrum of therapeutic strategies, including immune-checkpoint inhibitors tyrosine kinase inhibitors and agents targeting metabolic pathways or the tumor microenvironment, is currently under investigation. In this review, we aim to provide a comprehensive overview of the current landscape and future directions of personalized medicine for patients affected by PC.

15.
Target Oncol ; 16(5): 625-632, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34338966

RESUMO

BACKGROUND: Renal cell carcinoma with sarcomatoid differentiation is a highly aggressive form of kidney cancer. OBJECTIVE: We aimed to analyze the outcomes of patients treated with cabozantinib for metastatic renal cell carcinoma with sarcomatoid features. METHODS: We retrospectively collected data from 16 worldwide centers. Overall survival and progression-free survival were analyzed using Kaplan-Meier curves. Cox proportional models were used for univariate and multivariate analyses. RESULTS: We collected data from 66 patients with metastatic sarcomatoid renal cell carcinoma receiving cabozantinib as second-line (51%) or third-line (49%) therapy. The median progression-free survival from the start of cabozantinib was 7.59 months (95% confidence interval [CI] 5.75-17.49) and was longer in male patients (8.81 vs 5.95 months, p = 0.042) and in patients without bone metastases (7.59 vs 5.11 months, p = 0.010); the median overall survival was 9.11 months (95% CI 7.13-23.80). At the multivariate analysis, female sex (hazard ratio = 1.81; 95% CI 1.02-3.37, p = 0.046), bone metastases (hazard ratio = 2.62; 95% CI 1.34-5.10, p = 0.005), and International Metastatic Renal Cell Carcinoma Database Consortium criteria (hazard ratio = 3.04; 95% CI 1.54-5.99, p = 0.001) were significant predictors of worse overall survival. CONCLUSIONS: Our data show that cabozantinib is active in pretreated patients with sarcomatoid renal cell carcinoma. Biomarkers are needed in this field to select patients for multi-kinase inhibitors or other options.

16.
Expert Opin Investig Drugs ; : 1-9, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34429006

RESUMO

INTRODUCTION: Hepatocellular carcinoma (HCC) represents the sixth most commonly diagnosed malignancy worldwide, accounting for millions of deaths annually. Despite immune checkpoint inhibitors (ICIs) reported important results, only a minority of HCC patients benefit from these treatments, and the identification of predictive biomarkers of response still remains a highly unmet need. AREAS COVERED: Herein, we provide a timely overview of available evidence on biochemical predictors of response to immunotherapy in advanced HCC patients; we speculate on how PD-L1, TMB, and other emerging biomarkers could assist drug clinical trials in the near future. A literature search was conducted in June 2021 using Pubmed/Medline, Cochrane library, and Scopus databases. EXPERT OPINION: Reliable predictors of response to ICIs are of pivotal importance to allow a proper stratification and selection of HCC patients that could derive more benefit from immunotherapy. Well-designed, multicenter clinical trials specifically focused on predictive biomarkers are warranted in this setting, where most of evidence currently derives from retrospective, single-center studies with small sample size.

18.
Anticancer Drugs ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34387593

RESUMO

Several novel androgen receptor (AR)-inhibitors have been introduced for nonmetastatic castration-resistant prostate cancer (nmCRPC) treatment, with the improvement of survival outcomes which need to be balanced against the risk of adverse events. We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating enzalutamide, apalutamide and darolutamide in nmCRPC patients, to assess overall survival (OS), incidence and risk of adverse drug events, adverse-events-related death and adverse-events-related treatment discontinuation. We selected three RCTs (SPARTAN, PROSPER and ARAMIS). New hormonal agents administration resulted in better OS, despite the increased risk of several any grade and grade 3-4 adverse events. In the decision-making process, careful evaluation of expected adverse events, patients' comorbidities and maintenance of quality of life are mandatory.

19.
Anticancer Drugs ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34387596

RESUMO

AIM: We performed a systematic review and meta-analysis to evaluate the role of platinum-based adjuvant chemotherapy (AC) in upper tract urothelial carcinoma. MATERIALS METHODS: Eligible studies were identified using Pubmed/Medline, Cochrane library, Embase and meeting abstracts. Outcomes of interest included: overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS). RESULTS: Platinum-based AC was associated with improved DFS, while the benefit in OS and CSS was not statistically significant compared to observation. Conversely, platinum-based AC showed a modest OS benefit in an analysis combing multivariable HRs with estimated HRs from Kaplan-Meier curves. CONCLUSION: Our results suggest that platinum-based AC is associated with improved DFS and a modest OS benefit in patients with locally advanced urothelial carcinomas.

20.
Eur J Cancer ; 154: 120-127, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34265504

RESUMO

BACKGROUND: Recent years have witnessed the advent of novel treatment options for metastatic renal cell carcinoma (mRCC), including combination therapies with immune checkpoint inhibitors. Herein, we conducted an up-to-date and comprehensive meta-analysis including recently published data of phase III clinical trials evaluating immune-based combinations in mRCC. METHODS: We retrieved all the relevant trials published from 15th June 2008 to 24th February 2021, evaluating immune-based combinations in treatment-naïve mRCC through PubMed/MEDLINE, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Outcomes of interest included overall survival (OS), progression-free survival (PFS), complete response (CR) rate, and overall response rate (ORR). Hazard ratios (HRs) and their 95% confidence intervals (CIs) for OS and PFS, and odds ratios (ORs) and 95% CIs for CR rate and ORR, were extracted. RESULTS: Overall, 6 phase III studies involving 5175 treatment-naïve mRCC patients were available for the meta-analysis (immune-based combinations, n = 2576; sunitinib, n = 2597). According to our results, the use of immune-based combinations decreased the risk of death by 26% (HR 0.74, 95% CI 0.67-0.81, P < 0.001); similarly, a PFS benefit was observed (HR 0.68, 95% CI 0.54-0.85, P = 0.001). In addition, immune-based combinations showed better CR rate and ORR, with ORs of 3.04 (95% CI 2.31-3.99, P = 0.001) and 2.53 (95% CI 1.77-3.62, P < 0.03), respectively. CONCLUSIONS: The results of our meta-analysis confirm the clinical benefit provided by immunotherapy combinations, with CR rate more than tripled in mRCCs receiving immune-based combinations. Further studies in real-world setting are warranted to validate the findings of our meta-analysis, the most updated to systematically evaluate immune-based combinations in mRCC.

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