Despite the progress of surgery, radiotherapy, and neoadjuvant chemotherapy, the prognosis for advanced sinonasal cancers (SNCs) remains poor. In the era of precision medicine, more research has been ...conducted on the molecular pathways and recurrent mutations of SNCs, with the aim of understanding carcinogenesis, helping with diagnosis, identifying prognostic factors, and finding potentially targetable mutations. In the treatment of SNC, immunotherapy is rarely used, and no targeted therapies have been approved, partly because these tumors are usually excluded from major clinical trials. Data on the efficacy of targeted agents and immune checkpoint inhibitors are scarce. Despite those issues, a tumor-agnostic treatment approach based on targeted drugs against a detected genetic mutation is growing in several settings and cancer subtypes, and could also be proposed for SNCs. Our work aims to provide an overview of the main molecular pathways altered in the different epithelial subtypes of sinonasal and skull base tumors, focusing on the possible actionable mutations for which potential target therapies are already approved in other cancer types.
•Cf-miRNA are stable in saliva collected from healthy and cancer patients.•Different saliva collection strategies reveal comparable levels of cf-miRNA.•Cf-miRNA level are stable in saliva supernatant ...for up to 48 h at 4 °C.•Long term storage of saliva supernatant at −20 °C affect miRNA stability remarkably.
Increasing evidence supports the practicability of salivary cell-free (cf) miRNA as liquid biopsy markers in cancers. Its successful translation in the clinical setting requires reproducible approaches for saliva manipulation, in order to control for pre-analytical variables influencing miRNA stability. This study aims to define the optimal conditions to maintain the integrity of saliva during collection, transport and processing with respect to cf-miRNA quantification.
Saliva was collected from 20 healthy subjects and 8 oral cancer patients. Two sampling methods were tested and different storage temperatures and times were evaluated. Salivary expression level of target miRNAs was quantified by qPCR. Comparison between group mean values at specific conditions were performed using paired t-tests. Agreement between measurements was evaluated using a Bland-Altman plot.
Different collection methods revealed comparable levels of salivary miR-484 and miR-106b-5p in both subject cohorts. MiRNAs were stable for up to 48 h at 4 °C in saliva supernatant, showing significant alteration after 96 h. Mid-term storage of supernatant at −20 °C decreased miRNA stability significantly compared to standard −80 °C.
Cf-miRNA in saliva were slightly altered by collection methods and storage conditions, both in healthy and in pathological contexts, and remained stable for a period of time compatible with main clinical routine needs.
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Background: Long-term cancer survivors (LTS) patients (pts) treated with immunotherapy (IT) represent a relatively new population whose characteristics, such as long-term toxicities, quality of ...life (QoL), and financial toxicities, need to be elucidated in a real-world setting. The aim of this study is to evaluate long-term toxicities in patients free of disease progression and treated with IT. Methods: This is a cross-sectional, multicentric study, involving ten Italian centres. Pts should have started IT (as monotherapy or combination, either in curative or adjuvant setting) more than 2 years before accrual and they needed to be progression free at last follow up (fup). Subjects who discontinued IT for disease progression or who started any subsequent line of systemic treatment were excluded. We retrieved baseline demographic and clinical characteristics of the pts, as well as haematological and biochemical exams at the start of IT (baseline) and at the last fup. We also assessed the patient's toxicities (according to CTCAE v5.0) at last fup and we submitted to each patient three questionnaires: PRO-CTCAE (selection of questions), EORTC QLQ C30, and FITALY (for financial toxicities), which were analysed according to subdomains. Results: We enrolled 141 LTS pts treated with IT from 2013 to 2022. Median age was 69 years (35-88), most were male (72%), and still receiving IT at time of last fup (72%). Primary tumour was in lung (43%), genito-urinary tract (26%), or melanoma (14%). IT included pembrolizumab and nivolumab in 40% and 32% of cases, respectively. The median global health status of QoL was 83 (IQR 25). Any toxicities > G2 negatively impacted on individual functional scales (physical, p=0.02; role, p= 0.06; and social p=0.08). A higher baseline Charlson Comorbidity Index was associated with worse global health status (p=0.02) at last fup. Most frequent low grade adverse events were fatigue, dyspnoea, and insomnia; younger age (< 65 years) was associated with higher pain (p=0.04). PRO-CTCAE questionnaires showed that the prevalent complained symptoms were rheumatological and cutaneous, regardless of tumor site. The most affected domain of financial toxicities was financial stress, including costs for out of pocket medications and transports. Pts with melanoma (p=0.01), with skin toxicities (p=0.04), and younger than 65 years (p=0.01) were at higher risk of financial toxicities (global score). Conclusions: Overall QoL is well preserved in LTS treated with IT. At long term fup, the pts complained mostly about rheumatological and skin adverse events. Financial stress due to out of pocket costs was the most affected financial toxicity domain. Baseline comorbidities predicted a worse long-term global health status, while young age, skin toxicities and melanoma predicted higher financial toxicities.
Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients ...receiving AIs and denosumab have not been explored to date.
To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM.
For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022.
Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy.
VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points.
Of the 237 patients enrolled (median range age, 61 28-84 years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio OR, 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression.
The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.
AIM To analyze the clinicopathological characteristics of patients with both node-negative gastric carcinoma and diagnosis of recurrence during follow-up. METHODS We enrolled 41 patients treated with ...curative gastrectomy for p T2-4 a N0 gastric carcinoma between 1992 and 2010,who developed recurrence(Group 1). We retrospectively selected this group from the prospectively collected database of 4 centers belonging to the Italian Research Group for Gastric Cancer,and compared them with 437 p T2-4 a N0 patients without recurrence(Group 2). We analyzed lymphatic embolization,microvascular infiltration,perineural infiltration,and immunohistochemical determination of p53,Ki67,and HER2 in Group 1 and in a subgroup of Group 2(Group 2 bis) of 41 cases matched with Group 1 according to demographic and pathological characteristics. RESULTS T4 a stage and diffuse histotype were associated with recurrence in the group of p N0 patients. In-depth pathological analysis of two homogenous groups of p N0 patients,with and without recurrence during longterm follow-up(groups 1 and 2 bis),revealed two striking patterns: lymphatic embolization and perineural infiltration(two parameters that pathologists can easily report),and p53 and Ki67,represent significant factors for recurrence.CONCLUSION The reported pathological features should be considered predictive factors for recurrence and could be useful to stratify node-negative gastric cancer patients for adjuvant treatment and tailored follow-up.
Machine learning and AI-assisted trading have attracted growing interest for the past few years. Here, we use this approach to test the hypothesis that the inefficiency of the cryptocurrency market ...can be exploited to generate abnormal profits. We analyse daily data for 1,681 cryptocurrencies for the period between Nov. 2015 and Apr. 2018. We show that simple trading strategies assisted by state-of-the-art machine learning algorithms outperform standard benchmarks. Our results show that nontrivial, but ultimately simple, algorithmic mechanisms can help anticipate the short-term evolution of the cryptocurrency market.
In January 2021, retail investors coordinated on Reddit to target short-selling activity by hedge funds on GameStop shares, causing a surge in the share price and triggering significant losses for ...the funds involved. Such an effective collective action was unprecedented in finance, and its dynamics remain unclear. Here, we analyse Reddit and financial data and rationalize the events based on recent findings describing how a small fraction of committed individuals may trigger behavioural cascades. First, we operationalize the concept of individual commitment in financial discussions. Second, we show that the increase of commitment within Reddit pre-dated the initial surge in price. Third, we reveal that initial committed users occupied a central position in the network of Reddit conversations. Finally, we show that the social identity of the broader Reddit community grew as the collective action unfolded. These findings shed light on financial collective action, as several observers anticipate it will grow in importance.
Personalized therapeutic strategies in HER2-driven gastric cancer Ughetto, Stefano; Migliore, Cristina; Pietrantonio, Filippo ...
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association,
07/2021, Letnik:
24, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Background
Trastuzumab is the only approved targeted therapy in patients with
HER2
-amplified metastatic gastric cancer (GC). Regrettably, in clinical practice, only a fraction of them achieves ...long-term benefit from trastuzumab-based upfront strategy. To advance precision oncology, we investigated the therapeutic efficacy of different HER2-targeted strategies, in
HER2
“hyper”-amplified (≥ 8 copies) tumors.
Methods
We undertook a prospective evaluation of HER2 targeting with monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates, in a selected subgroup of
HER2
“hyper”-amplified gastric patient-derived xenografts (PDXs), through the design of ad hoc preclinical trials.
Results
Despite the high level of
HER2
amplification, trastuzumab elicited a partial response only in 2 out of 8 PDX models. The dual-HER2 blockade with trastuzumab plus either pertuzumab or lapatinib led to complete and durable responses in 5 (62.5%) out of 8 models, including one tumor bearing a concomitant
HER2
mutation. In a resistant PDX harboring
KRAS
amplification, the novel antibody–drug conjugate trastuzumab deruxtecan (but not trastuzumab emtansine) overcame
KRAS
-mediated resistance. We also identified a HGF-mediated non-cell-autonomous mechanism of secondary resistance to anti-HER2 drugs, responsive to MET co-targeting.
Conclusion
These preclinical randomized trials clearly indicate that in HER2-driven gastric tumors, a boosted HER2 therapeutic blockade is required for optimal efficacy, leading to complete and durable responses in most of the cases. Our results suggest that a selected subpopulation of
HER2
-“hyper”-amplified GC patients could strongly benefit from this strategy. Despite the negative results of clinical trials, the dual blockade should be reconsidered for patients with clearly HER2-addicted cancers.
In December 2019 in Wuhan, China, an outbreak related to a new Coronavirus (Covid-19) rapidly spread to other countries, including Italy, emerged. On 11 March 2020, the WHO declared a state of ...pandemic. During the ensuing health crisis, the media exposure of Italian nurses increased. The aim of this research was to investigate whether and how, during the pandemic, citizens' perceptions of nurses have changed, and if this change were related to the public image of health professionals provided by the mass media. Method: A multi-centric quantitative exploratory study has been conducted. 2114 online questionnaires were analysed for residents of Italy, including health working but excluding the nurses themselves. The results obtained were compared with the results of the scientific literature.
Positive perceptions on the part of the citizens towards the nurses are evident, coming to define them "heroes", while discriminatory attitudes are rare. According to the participants, the mass media have conveyed a positive image of the nurses and in relation to this, a percentage of respondents have changed their opinion favourably regarding nurses. Conclusions: The Covid19-related health emergency has helped raise awareness of the nursing role among both citizens and other health workers, even if a lack of knowledge has been highlighted in the training and care role of nurses. The opportunity should be taken by nurses to make well-know their role, promoting public communication, in order to make their image clearer and more truthful.
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