Risultati per: Linee guida per la gestione del carcinoma basocellulare

Domani ad Ancona congresso scientifico alla Politecnica Marche

Cardiologi, tante potenzialità diagnosi e gestione ma nodi etici

Objectives
Cutaneous squamous cell carcinoma (CSCC) represents a malignancy characterised by the aberrant proliferation of skin epithelial cells, and certain instances of squamous cell carcinoma (SCC) exhibit features indicative of a heightened proclivity for recurrence, metastasis, and mortality. Tracking the latest survival rates for CSCC is crucial for patient care and public health strategies.

Design
This was a retrospective study.

Setting
The Surveillance, Epidemiology, and End Results (SEER) Programme database was established by the National Cancer Institute in 1973. It is one of the commonly used cancer databases in the United States, covering a variety of tumour types including lung cancer, breast cancer, gastric cancer, colorectal cancer, prostate cancer, etc. It collects cancer diagnosis, treatment and survival data for approximately 50% of the US population, providing systematic evidence support and valuable first-hand information for clinicians’ evidence-based practice and clinical medical research. The data used in this study covers 20 years of information on patients with cutaneous squamous cell carcinoma from 2000 to 2019.

Participants
In this study, we identified a cohort of 2 04 055 patients, comprising 95 287 women and 1 08 768 men, who were diagnosed with CSCC between 2000 and 2019 in the SEER database. The inclusion criteria for this research encompassed individuals aged 15 years and older, availability of data spanning from 2000 to 2019, confirmation through microscopic examination, and the presence of a primary tumour classified as CSCC. Exclusion criteria involved cases solely validated through autopsy or a death certificate, those alive or with indeterminable survival times, and instances with incomplete data.

Outcome measures
The SEER database’s patient trends and relative survival rate for patients with CSCC were evaluated using period analysis method from 2000 to 2019. The anticipated 5 year relative survival rate among CSCC patients for the years 2020 to 2024 was projected using a generalised linear model.

Results
A total of 204,055 CSCC patients were identified, 95 287 women and 1 08 768 men. Most patients were male, white, lived in urban areas, presenting with localised metastases, aged 55–64 years, and had untyped CSCC. During the observation period, the 5 year relative survival rate of CSCC patients showed a slight improvement overall, while the 5 year relative survival rate of some subtypes showed obvious fluctuations. Particularly noteworthy was the substantial amelioration observed in the small cell nonkeratinizing SCC subtype, escalating from 60.4% in 2000 to 72.8% in 2019. The 5 year overall relative survival rates for CSCC patients during the intervals 2000–2004, 2005–2009, 2010–2014, and 2015–2019 documented rates of 62.4%, 63.4%, 64.3%, and 66.3%, respectively. Males had slightly lower survival rates than females, older patients had lower rates than younger patients, and white patients had better outcomes than non-white patients. Urban patients had higher survival rates than rural patients. Patients with distant metastases had significantly lower survival rates.

Conclusion
The temporal span from 2000 to 2019 witnessed a gradual yet delimited increase in survival rates among CSCC patients. This incremental trajectory persists, with a prognosticated survival rate of 67.1 anticipated between 2020 and 2024.

Aim
The objective of this research is to assess the cost-effectiveness of combining camrelizumab with rivoceranib in comparison to sorafenib as first-line therapeutic options for advanced hepatocellular carcinoma from the Chinese medical system perspective.

Methods
A partitioned survival model was employed to perform a comprehensive cost-effectiveness analysis. This analysis incorporated multiple factors, such as treatment effectiveness, adverse events and costs, all of which were derived from data obtained from the CARES-310 trial. Furthermore, sensitivity analyses were conducted to evaluate the robustness and reliability of the model.

Results
The comparison between the two groups demonstrated that the cohort receiving camrelizumab combined with rivoceranib exhibited a significant increase of 0.803 quality-adjusted life year (QALY), alongside an additional expenditure of US$7345.051. This computation resulted in an incremental cost-effectiveness ratio of US$9147.012 per QALY, which was lower than the willingness-to-pay threshold of US$39 855.785 per QALY in China. Sensitivity analyses conducted in this study further demonstrated the robustness of the results across various assumptions.

Conclusion
The adoption of camrelizumab plus rivoceranib as a treatment option is not only associated with improved health outcomes but also represents a cost-effective choice in China.

Objectives
This study delineates the global nasopharyngeal carcinoma’s (NPC) incidence and mortality across 185 countries in 2020 and projects the disease’s burden by 2040.

Design
A prediction study.

Setting
Countries within the 20 world regions.

Participants
Global NPC population.

Primary and secondary outcome measures
The estimated counts of NPC cases and deaths were retrieved from the GLOBOCAN 2020 database. Age-standardised incidence rates (ASIR) and age-standardised death rates (ASDR) were computed. Projections for NPC by 2040 were derived from global population forecasts.

Results
In the year 2020, East Asia emerged as the epicentre of both NPC incidences and mortalities, encompassing 49.39% (65 866 of the total 133 354 cases) and 45.56% (36 453 of the total 80 008 deaths), respectively, with China’s contribution being the most substantial (46.82% of cases and 43.50% of deaths). The disparity between genders was notable, as the ASIR and ASDR for males were approximately triple those observed in females. The incidence exhibited regional diversity, with South-Eastern Asia and East Asia recording the highest ASIR for males and females (7.7 and 2.5, and 3.9 and 1.5 per 100 000 person-years, respectively). Similarly, South-Eastern Asia also reported the highest ASDR for both genders (5.4 and 1.5 per 100 000 person-years, respectively). Projections for 2040 anticipate a rise in annual cases and deaths to 179 476 (indicating a 34.58% increase from 2020) and 113 851 (reflecting a 42.29% increase), respectively. Further analysis revealed a correlation between the Human Development Index and disease burden.

Conclusions
NPC, primarily impacting East Asia and predominantly affecting men, is poised for a significant increase in incidence and mortality by 2040, especially in Asia.

Objective
Fat mass and obesity-associated protein (FTO), an eraser of N 6-methyadenosine (m6A), plays oncogenic roles in various cancers. However, its role in hepatocellular carcinoma (HCC) is unclear. Furthermore, small extracellular vesicles (sEVs, or exosomes) are critical mediators of tumourigenesis and metastasis, but the relationship between FTO-mediated m6A modification and sEVs in HCC is unknown.

Design
The functions and mechanisms of FTO and glycoprotein non-metastatic melanoma protein B (GPNMB) in HCC progression were investigated in vitro and in vivo. Neutralising antibody of syndecan-4 (SDC4) was used to assess the significance of sEV-GPNMB. FTO inhibitor CS2 was used to examine the effects on anti-PD-1 and sorafenib treatment.

Results
FTO expression was upregulated in patient HCC tumours. Functionally, FTO promoted HCC cell proliferation, migration and invasion in vitro, and tumour growth and metastasis in vivo. FTO knockdown enhanced the activation and recruitment of tumour-infiltrating CD8+ T cells. Furthermore, we identified GPNMB to be a downstream target of FTO, which reduced the m6A abundance of GPNMB, hence, stabilising it from degradation by YTH N 6-methyladenosine RNA binding protein F2. Of note, GPNMB was packaged into sEVs derived from HCC cells and bound to the surface receptor SDC4 of CD8+ T cells, resulting in the inhibition of CD8+ T cell activation. A potential FTO inhibitor, CS2, suppresses the oncogenic functions of HCC cells and enhances the sensitivity of anti-PD-1 and sorafenib treatment.

Conclusion
Targeting the FTO/m6A/GPNMB axis could significantly suppress tumour growth and metastasis, and enhance immune activation, highlighting the potential of targeting FTO signalling with effective inhibitors for HCC therapy.

Several studies have highlighted the significance of targeting fat mass and obesity-associated protein (FTO) in gastrointestinal cancers including hepatocellular carcinoma (HCC) .1 The recent study from the group of Irene Oi-Lin Ng presented in Gut by Chen et al2 introduces new insights into the molecular dynamics of HCC, focusing on the pivotal role of FTO in the disease’s pathophysiology. Functioning as an eraser of N6-methyladenosine (m6A), FTO modulates RNA stability and translation. In the context of HCC, FTO’s activity leads to the stabilisation of oncogenic transcripts, thereby promoting cancer cell proliferation and survival.3 The study identifies glycoprotein non-metastatic melanoma protein B (GPNMB) as a downstream effector of FTO (figure 1). By diminishing the m6A modification on GPNMB, FTO enhances its stability, thereby protecting it from YTHDF2-mediated degradation. This stabilisation facilitates the incorporation of GPNMB into small extracellular vesicles (sEVs), which are…

Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses a wide spectrum of liver injuries, ranging from hepatic steatosis, metabolic dysfunction-associated steatohepatitis (MASH), fibrosis, cirrhosis to MASLD-associated hepatocellular carcinoma (MASLD-HCC). Recent studies have highlighted the bidirectional impacts between host genetics/epigenetics and the gut microbial community. Host genetics influence the composition of gut microbiome, while the gut microbiota and their derived metabolites can induce host epigenetic modifications to affect the development of MASLD. The exploration of the intricate relationship between the gut microbiome and the genetic/epigenetic makeup of the host is anticipated to yield promising avenues for therapeutic interventions targeting MASLD and its associated conditions. In this review, we summarise the effects of gut microbiome, host genetics and epigenetic alterations in MASLD and MASLD-HCC. We further discuss research findings demonstrating the bidirectional impacts between gut microbiome and host genetics/epigenetics, emphasising the significance of this interconnection in MASLD prevention and treatment.

Introduction
The exact role of hepatic arterial infusion chemotherapy (HAIC) in advanced hepatocellular carcinoma (aHCC) is still unknown. The combination of HAIC and sorafenib has been proven to be more effective than sorafenib alone in the first-line treatment of aHCC. The aim of the study is to evaluate the efficacy and safety of HAIC plus regorafenib in the second-line treatment of aHCC.

Methods and analysis
This is a multicenter, open-label, randomised controlled phase III trial. A total of 294 patients with aHCC, who are unable to tolerate the first-line systemic therapy or progress after the first-line systemic therapy, will be enrolled in the study. The patients will be randomly (2:1) assigned into the combination treatment group (HAIC plus regorafenib, n=196) and the control group (regorafenib alone, n=98). HAIC and regorafenib (160 mg/day) will be given in a 4-week cycle. The primary endpoint is overall survival in the intention-to-treat population. The second endpoints include progression-free survival, overall response rate, time to progression, etc. The radiological assessments will be based on the criteria of Response Evaluation Criteria in Solid Tumors 1.1.

Ethics and dissemination
This study is approved by the ethics committee of Cancer Hospital, Chinese Academy of Medical Sciences. All participants are required to provide written informed consent. The results of this study will be disseminated through peer-reviewed publications and esteemed academic conferences.

Trial registration number
Chinese Clinical Trial Registry (ChiCTR2300073075).

Introduction
Treatment combination of pembrolizumab plus platinum and 5-fluorouracil (PF) has increased the survival of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). The combination of platinum and gemcitabine (PG) has been shown to be superior to PF in the treatment of R/M nasopharyngeal carcinoma patients. Therefore, we hypothesise that the combination of pembrolizumab with PG would be comparable to pembrolizumab with PF as a first-line treatment in R/M HNSCC.

Methods and analysis
This is an open-label, multicentre, single-arm, phase 2 study of pembrolizumab plus PG for first-line treatment in subjects with R/M HNSCC in Malaysia. The study is conducted using the Optional Simon optimal 2-stage design. At the initial stage, 26 subjects will be enrolled and if seven or more patients achieve an objective response rate (ORR), then 63 patients will be enrolled. Subjects will be given pembrolizumab 200 mg3 every 3 weeks up to 35 cycles in combination with chemotherapy for up to six cycles of platinum (either cisplatin at 35 mg/m2 intravenous on day 1 and day 8 or carboplatin at area under the curve 5 intravenous on day 1 of each 3-week cycle) and gemcitabine at 1250 mg/m2 intravenous on days 1 and 8 of a 3-week cycle. The primary end point is the ORR as per Response Evaluation Criteria in Solid Tumors 1.1. Secondary end points include the overall survival, progression free survival, response duration and safety. The exploratory objectives include relationships of microbiome profiles, prognostic and predictive biomarkers with the clinical responses.

Ethics and dissemination
The study was approved by the ethics committee of the University Malaya Medical Centre (202213–10884). Findings will be disseminated through conference presentations and peer review publications.

Trial registration number
ClinicalTrials.gov (www.clinicaltrial.gov); NCT05286619.

This phase 2 nonrandomized clinical trial assesses the efficacy and safety of dual immune checkpoint inhibition in patients with aggressive thyroid carcinoma.