Sorafenib as a feasible therapeutic option in haemophiliacs with hepatocellular carcinoma

hepatocellular carcinoma, haemophilia, treatmen

Triplet schedule of weekly 5-Fluorouracil and alternating irinotecan or oxaliplatin in advanced colorectal cancer: A dose-finding and phase II study

A weekly administration of alternating irinotecan or oxaliplatin associated to 5-Fluorouracil in advanced colorectal cancer was planned in order to evaluate a new schedule maintaining dose intensities of each drug as in double combinations and tolerability of the triplet association. The following weekly schedule was administered: irinotecan, days 1 and 15; oxaliplatin, days 8 and 22; 5-fluorouracil (5-FU) over 12-h (from 10:00 p.m. to 10:00 a.m.) timed flat infusion, days 1-2, 8-9, 15-16 and 22-23, every 4 weeks. Dosefinding and phase II study were planned. Thirteen patients were enrolled in the dose-finding study and 23 in the phase II study. The recommended doses of our study are: irinotecan 160 mg/m2; oxaliplatin 80 mg/m2; 5-FU 900 mg/m2. The doselimiting toxicity was diarrhea (35% of patients) but no cases of febrile neutropenia were observed. In 30 patients assessable for response two complete (6.7%) and 18 partial (60%) responses were observed, for an overall response rate of 66.7% (α0.05, CI±7). The triplet association using this weekly alternating schedule is an active and well-tolerated outpatient regimen. Surgical removal of residual disease was considered in 5 patients and a radical resection was performed in 5 patients (14%)

SAFETY MONITORING by MEANS of SENSOR NETWORKS DISTRIBUTED within the FOSSA SITE PLAN

The seismic event of 6 April 2009 has inevitably left its mark on the history of the entire territory of L'Aquila (Italy), completely devastating the town and much of the province. Within such frantic and extensive reconstruction activity, the resulting construction works could not but draw attention to some issues of fundamental importance such as coordinated planning, safety, respect for the rules and above all the rebirth of the territory. This research is aimed at drawing up the site plan for Fossa, a municipality in the Province of L'Aquila and not far from the region capital of Abruzzo, Italy. The main objective is to create a monitoring standard by means of a dedicated sensors network and detailed strategies in order to coordinate, guide and support the single actions of intervention through design behaviours and highly technological tools. The Plan is configured as a tool for participatory planning, with the active involvement of planners, companies and citizens, whose common goal is the preservation of the identity of locations, the mitigation of seismic risk and the enhancement of the cultural heritage of the Municipality of Fossa. Implementation of this work is the application of technological systems for construction site monitoring: a concrete response to the growing demand for organized management of the construction process on site and safety in the workplace can be achieved through the use of systems and rational control and management procedures that include the use of innovative technologies

Managing wolf impacts on sheep husbandry: a collaborative implementation and assessment of damage prevention measures in an agricultural landscape

Wolves in Europe are expanding their range and significantly impacting farming livelihoods and landscapes. Damage prevention measures such as livestock guarding dogs and night-time enclosures have proven successful in mitigating losses. However, they are often implemented as top-down measures without a proper understanding of the farming dynamics they are meant to alter, making them unappealing and difficult to implement for farmers. Semi-extensive, small scale livestock farming systems are particularly vulnerable and diverse, requiring specific care and catered support when addressing issues related to wildlife management. In these contexts, it is crucial to employ adaptive management approaches that enable solutions to be collaboratively designed at the grassroots level. Here we propose a method for centring the experiences and knowledge of local farmers to co-produce damage prevention practices that better address their needs. We developed this approach in the course of the LIFE MEDWOLF project, which was implemented in the province of Grosseto, Italy, between 2012 and 2017. The project brought together local authorities, environmental associations, farming unions and individual farmers to develop tailor-made damage prevention measures and assess their technical and economic impact, through a stepwise process. Collaboration with 86 local farmers resulted in >50 modifications to the original project plan, and an overall 50% reduction of preyed livestock in farms that participated in the project. Our findings highlight the benefits of collaboratively designing, implementing, and monitoring damage prevention measures with farmers. Based on these results, we reflect on the importance of integrating local and scientific knowledge, on the implications this has had on stakeholder relations, and on the challenges that we faced in upscaling this management approach

clinical and psychometric validation of the bresas questionnaire for symptom assessment among breast cancer survivors

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Sodium Levels and Outcomes in Patients With Metastatic Renal Cell Carcinoma Receiving Nivolumab

\ua9 2023 American Medical Association. All rights reserved.IMPORTANCE Low sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs). OBJECTIVE To investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy. DESIGN, SETTING, AND PARTICIPANTS In this retrospective cohort study, the clinical and biochemical data of patients with mRCC receiving nivolumab were collected from October 2015 to November 2019 as part of a multicenter Italian study. Data analysis was performed from February to March 2023. EXPOSURE Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks and, since May 2018, at a fixed dose of 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were divided into 2 groups according to their median serum sodium value (<140 or ≥140 mEq/L). MAIN OUTCOMES AND MEASURES The primary outcomes were the associations of pre-ICI and post-ICI sodium levels with overall survival (OS), progression-free survival (PFS), objective response rate, and disease control rate (DCR). The Kaplan-Meier method was used to estimate PFS and OS, and differences between groups were compared using the log-rank test. RESULTS A total of 401 patients with mRCC receiving nivolumab as second-line therapy were evaluated, and 355 eligible patients (median [range] age, 76 [44-84] years; 258 male patients [72.7%]) were included in the final cohort. Among patients with pre-ICI sodium greater than or equal to 140 mEq/L compared with those with sodium less than 140 mEq/L, the median PFS was 9.3 months (95% CI, 6.5-11.5 months) vs 7.4 months (95% CI, 4.6-10.1 months; P = .90), and the median OS was 29.2 months (95% CI, 21.8-35.9 months) vs 20.0 months (95% CI, 14.1-26.8 months; P = .03). Patients with post-ICI sodium values greater than or equal to 140 mEq/L had longer PFS (11.1 months [95% CI, 8.5-1.5 months] vs 5.1 months [95% CI, 4.1-7.5 months]; P = .01) and OS (32.9 months [95% CI, 25.1-42.6 months] vs 17.1 months [95% CI, 12.6-24.5 months]; P = .006) compared with patients with sodium values less than 140 mEq/L. Patients with both pre-ICI and post-ICI sodium values greater than or equal to 140 mEq/L exhibited a significant improvement in clinical outcomes compared with those with a value less than 140 mEq/L (PFS, 11.5 months [95% CI, 8.8-16.4 months] vs 5.8 months [95% CI, 4.4-8.3 months]; P = .008); OS, 37.6 months [95% CI, 29.0-49.9 months] vs 19.4 months [95% CI, 14.1-24.5 months]; P = .01). Moreover, sodium levels greater than or equal to 140 mEq/L were associated with significantly better DCR than lower sodium levels. CONCLUSIONS AND RELEVANCE In this retrospective cohort study of patients with mRCC receiving nivolumab, sodium values greater than or equal to 140 mEq/L, both before and/or after ICI, were associated with better OS and PFS, as well as a higher DCR, compared with levels less than 140 mEq/L. These findings suggest that sodium levels may be associated with survival outcomes in patients with mRCC and may have potential use as variables to consider in patients’ risk scores

Sodium levels and immunotherapy efficacy in mRCC patients with bone metastases: sub analysis of Meet-Uro 15 study

Copyright \ua9 2024 Catalano, Rebuzzi, Maruzzo, De Giorgi, Buti, Galli, Fornarini, Zucali, Claps, Chiellino, Zampiva, Pipitone, Ricotta, Sorar\uf9, Mollica, Tudini, Fratino, Prati, Caffo, Atzori, Morelli, Prati, Nol\ue8, Vignani, Cavo, Di Napoli, Malgeri, Naglieri, Signori, Banna, Rescigno, Cerbone, Antonuzzo and Roviello.Background: Immune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy. Materials and methods: This retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed. Results: Among 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels <140 mE/L (18.7 vs. 12.0, p=0.04). Post-treatment sodium levels ≥140 mEq/L were associated with improved PFS (9.6 vs. 3.2 months) and OS (25.1 vs. 8.8 months) (p=0.05 and p<0.01, respectively). Patients with consistent sodium levels ≥140 mEq/L at both time points exhibited the best outcomes compared to those with lower values (PFS 11.5 vs. 3.3 months and OS 42.2 vs. 9.0 months, respectively, p<0.01). Disease control rate was significantly higher in the latter group (p<0.01). Multivariate analysis confirmed the prognostic significance of sodium levels. Conclusion: Elevated sodium levels (≥140 mEq/L) pre- and post-ICI treatment correlate with better survival outcomes in mRCC patients with BMs. This finding suggests sodium level assessment as a potential prognostic factor in these patients and warrants further investigation, particularly in combination immunotherapy settings

Time to strategy failure and treatment beyond progression in pretreated metastatic renal cell carcinoma patients receiving nivolumab: <em>post-hoc</em> analysis of the Meet-URO 15 study

Copyright \ua9 2024 Murianni, Signori, Buti, Rebuzzi, Bimbatti, De Giorgi, Chiellino, Galli, Zucali, Masini, Naglieri, Procopio, Milella, Fratino, Baldessari, Ricotta, Mollica, Sorar\uf9, Tudini, Prati, Malgeri, Atzori, Di Napoli, Caffo, Spada, Morelli, Prati, Nol\ue8, Vignani, Cavo, Lipari, Roviello, Catalano, Damassi, Cremante, Rescigno, Fornarini and Banna.Background: Immunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy. Methods: The Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS. Results: Overall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p &lt; 0.001) and overall survival (OS) (34.8 vs 17.9 months; p &lt; 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59). Conclusion: We found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS

Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report.

The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility

Long-term responders to nivolumab in previously treated advanced renal cell carcinoma: a sub-analysis of meet-URO15 study

\ua9 The Author(s) 2024. Background: Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment. Materials and methods: A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses. Results: A total of 571 patients with a median age of 61 years (range 17–85) were included in the analysis. With a median follow-up of 22.1 (1.0–89.0) months, 23.1% of patients were 2-year progression-free on treatment with nivolumab, hence they were categorized as long-term responders. Baseline characteristics, including age, gender, and histology, were similar between long- and short-term responders. Karnofsky Performance Status ≥ 80% was significantly associated with long-term response (p = 0.02), while bone metastases (p = 0.03), International mRCC Database Consortium intermediate-poor risk (p &lt; 0.01) and Neutrophil-to-Lymphocyte Ratio ≥ 3.2 (p = 0.02) were associate with short-term responses. Long-term responders exhibited a median progression-free survival of 55.0 months versus 4.0 months of the short-term responders. The median OS was not reached in long-term responders while it was 17.0 months for short*term responders. Conclusion: This retrospective analysis sheds light on factors associated with long-term response to nivolumab in mRCC. Understanding these clinical features will be essential for selecting patients who may mostly benefit from immunotherapy