CDH1 Genotype Exploration in Women With Hereditary Lobular Breast Cancer Phenotype.

Importance: Pathogenic or likely pathogenic (P/LP) germline CDH1 variants are associated with risk for diffuse gastric cancer and lobular breast cancer (LBC) in the so-called hereditary diffuse gastric cancer (HDGC) syndrome. However, in some circumstances, LBC can be the first manifestation of this syndrome in the absence of diffuse gastric cancer manifestation. Objectives: To evaluate the frequency of germline CDH1 variants in women with the hereditary LBC (HLBC) phenotype, somatic CDH1 gene inactivation in germline CDH1 variant carriers' tumor samples, and the association of genetic profiles with clinical-pathological data and survival. Design, Setting, and Participants: This single-center, longitudinal, prospective cohort study was conducted from January 1, 1997, to December 31, 2021, with follow-up until January 31, 2023. Women with LBC seen at the European Institute of Oncology were included. Testing for germline CDH1, BRCA1, and BRCA2 genes was performed. Somatic profiling was assessed for germline CDH1 carriers. Main Outcomes and Measures: Accurate estimates of prevalence of germline CDH1 variants among patients with HLBC and the association of somatic sequence alteration with HLBC syndrome. The Kaplan-Meier method and a multivariable Cox proportional hazards regression model were applied for overall and disease-free survival analysis. Results: Of 5429 cases of primary LBC, familial LBC phenotype accounted for 1867 (34.4%). A total of 394 women with LBC were tested, among whom 15 germline CDH1 variants in 15 unrelated families were identified. Among these variants, 6 (40.0%) were P/LP, with an overall frequency of 1.5% (6 of 394). Of the 6 probands with P/LP CDH1 LBC, 5 (83.3%) had a positive family history of BC and only 1 (16.7%) had sporadic juvenile early-onset LBC. No germline BRCA1 and BRCA2 variants were identified in CDH1 carriers. An inactivating CDH1 mechanism (second hit) was identified in 4 of 6 explored matched tumor samples (66.7%) in P/LP germline carriers. The P/LP CDH1 LBC variant carriers had a significantly lower age at diagnosis compared with the group carrying CDH1 variants of unknown significance or likely benign (42.5 [IQR, 38.3-43.0] vs 51.0 [IQR, 45.0-53.0] years; P = .03). Conclusions and Relevance: In this cohort study, P/LP germline CDH1 variants were identified in individuals not fulfilling the classic clinical criteria for HDGC screening, suggesting that identification of these variants may provide a novel method to test women with LBC with early age at diagnosis and/or positive family history of BC.

Body CT examinations in oncologic patients: the impact of subspecialty radiology on radiation exposure in the clinical practice. A quality care study.

PURPOSES: The primary objective of this retrospective study was to assess whether the CT dose delivered to oncologic patients was different in a subspecialty radiology department, compared to a general radiology department. The secondary explorative objective was to assess whether the objective image quality of CT examinations was different in the two settings. MATERIALS AND METHODS: Chest and abdomen CT scans performed for oncologic indications were selected from a general radiology department and a subspecialty radiology department. By using a radiation dose management platform, we extracted and compared CT dose index (CTDIvol) and dose length product (DLP) both for each phase and for the entire CT exams. For objective image quality evaluation, we calculated the signal-to-noise ratio (SNR) and the contrast-to-noise ratio (CNR) at the level of the liver and of the aorta. A P-value < 0.05 was considered significant. RESULTS: A total of 7098 CT examinations were included. CTDIvol was evaluated in 12,804 phases; DLP in 10,713 phases and in 6714 examinations. The CTDIvol and DLP overall were significantly lower in the subspecialty radiology department compared to the general radiology department CTDI median (IQR) 5.19 (3.91-7.00) and 5.51 (4.17-7.72), DLP median and IQR of 490.0 (342.4-710.6) and 503.4 (359.9-728.8), p < 0.001 and p = 0.01, respectively. The objective image quality showed no significant difference in the general and subspecialty radiology departments, with median and IQR of 4.03 (2.82-5.51) and 3.84 (3.09-4.94) for SNRLiv (p = 0.58); 4.81 (2.70-7.62) and 4.34 (3.05-6.25) for SNRAo (p = 0.30); 0.83 (0.20-1.89) and 1.00 (0.35-1.57) for CNRLiv (p = 0.99); 2.23 (0.09-3.83) and 1.01 (0.15-2.84) for CNRAo (p = 0.24) with SNRLiv (p = 0.58), SNRAo (p = 0.30), CNRLiv (p = 0.99) and CNRAo (p = 0.24). CONCLUSION: In a subspecialty radiology department, CT protocols are optimized compared to a general radiology department leading to lower doses to oncologic patients without significant objective image quality degradation.

Baseline Tumor Size as Prognostic Index in Patients With Advanced Solid Tumors Receiving Experimental Targeted Agents.

BACKGROUND: Baseline tumor size (BTS) has been associated with outcomes in patients with cancer treated with immunotherapy. However, the prognostic impact of BTS on patients receiving targeted therapies (TTs) remains undetermined. METHODS: We reviewed data of patients with advanced solid tumors consecutively treated within early-phase clinical trials at our institution from 01/2014 to 04/2021. Treatments were categorized as immunotherapy-based or TT-based (biomarker-matched or not). BTS was calculated as the sum of RECIST1.1 baseline target lesions. RESULTS: A total of 444 patients were eligible; the median BTS was 69 mm (IQR 40-100). OS was significantly longer for patients with BTS lower versus higher than the median (16.6 vs. 8.2 months, P < .001), including among those receiving immunotherapy (12 vs. 7.5 months, P = .005). Among patients receiving TT, lower BTS was associated with longer PFS (4.7 vs. 3.1 months, P = .002) and OS (20.5 vs. 9.9 months, P < .001) as compared to high BTS. However, such association was only significant among patients receiving biomarker-matched TT, with longer PFS (6.2 vs. 3.3 months, P < .001) and OS (21.2 vs. 6.7 months, P < .001) in the low-BTS subgroup, despite a similar ORR (28% vs. 22%, P = .57). BTS was not prognostic among patients receiving unmatched TT, with similar PFS (3.7 vs. 4.4 months, P = .30), OS (19.3 vs. 11.8 months, P = .20), and ORR (33% vs. 28%, P = .78) in the 2 BTS groups. Multivariate analysis confirmed that BTS was independently associated with PFS (P = .03) and OS (P < .001) but not with ORR (P = .11). CONCLUSIONS: Higher BTS is associated with worse survival outcomes among patients receiving biomarker-matched, but not biomarker-unmatched TT.

SARS-CoV-2 trends in Italy, Germany and Portugal and school opening during the period of Omicron variant dominance: A quasi experimental study in the EuCARE project.

OBJECTIVES: We investigated the impact of school reopening on SARS-CoV-2 transmission in Italy, Germany, and Portugal in autumn 2022 when the Omicron variant was prevalent. METHODS: A prospective international study was conducted using the case reproduction number (Rc) calculated with the time parametrization of Omicron. For Germany and Italy, staggered difference-in-differences analysis was employed to explore the causal relationship between school reopening and Rc changes, accounting for varying reopening dates. In Portugal, interrupted time series analysis was used due to simultaneous school reopenings. Multivariable models were adopted to adjust for confounders. RESULTS: In Italy and Germany, post-reopening Rc estimates were significantly lower compared to those from regions/states that had not yet reopened at the same time points, both in the student population (overall average treatment effect for the treated subpopulation [O-ATT]: -0.80 [95% CI: -0.94;-0.66] for Italy; O-ATT-0.30 [95% CI: -0.36;-0.23] for Germany) and the adult population (O-ATT: -0.04 [95% CI: -0.07;-0.01] for Italy; O-ATT: -0.07 [95% CI: -0.11;-0.03] for Germany). In Portugal, there was a significant decreasing trend in Rc following school reopenings compared to the pre-reopening period (sustained effect: -0.03 [95% CI: -0.04; -0.03] in students; -0.02 [95% CI: -0.03; -0.02] in adults). CONCLUSIONS: We found no evidence of a causal relationship between school reopenings in autumn 2022 and Omicron SARS-CoV-2 transmission.

Investigating Nutritional and Inflammatory Status as Predictive Biomarkers in Oligoreccurent Prostate Cancer-A RADIOSA Trial Preliminary Analysis.

(1) Background: In the RADIOSA phase II randomized clinical trial (NCT03940235), the biology task entails the identification of predictive and prognostic biomarkers in the context of oligorecurrent, castration-sensitive prostate cancer in order to distinguish polymetastatic from oligometastatic disease. This may lay the groundwork for personalized treatments for those patients who could really benefit from metastasis-directed therapies. (2) Methods: Oligorecurrent PCa pts with three or fewer bone or lymph nodal localizations were randomized 1:1 to receive SBRT alone (arm A) or SBRT + 6 months of ADT (arm B). Common serum-derived biomarkers were collected at baseline, and at 3 months after RT. The prognostic nutritional index, an immune and nutrition-based prognostic score, and the controlling nutritional status (CONUT) score, a scoring system for evaluating patient's nutritional status, were calculated in accordance with the body of available literature. As inflammatory indicators, neutrophil-lymphocyte ratio (NLR) and the NLR-albumin ratio (NLRAR) were assessed. Changes in these parameters between baseline and the 3-month timepoint were evaluated both in absolute and relative values. Changes in these parameters between baseline and the 3-month timepoint were evaluated. Significant differences in the trend of these parameters were assessed using the non-parametric Wilcoxon rank-sum test. A network analysis to analyze the relationships between different features stratifying patients according to the arm of study and site of metastases was performed. (3) Results: The current analysis comprised 88 patients (45 arm A, SBRT only, and 43 arm B, SBRT + ADT). When patients were stratified by ADT administration, cholesterol values showed an increasing trend in the group receiving ADT (p = 0.005) which was no longer significant at 1 year. When patients were stratified by site of metastases (52 lymph nodal, 29 bone localizations), the value of NLR was found to be increased in patients with bone localizations (p < 0.05). In addition, the network analysis showed that BMI and NRI are strongly and directly linked for patients at baseline and that this correlation is no longer found at three months. Finally, when patients were divided according to time from surgery to oligorecurrence (enrollment) the patients with a longer time (>6.7 years) showed an increase in CONUT score from baseline. All the other nutritional and inflammatory scores or parameters investigated in the present analysis showed no statistically significant differences at baseline, three months, 1 year, and in absolute change. (4) Conclusions: The nutritional and inflammatory parameters do not seem to represent valuable candidates for possible use in clinical decision making in our cohort of patients and a reliable biological characterization of the oligometastatic state in prostate cancer still seems far from being achieved. Ongoing molecular analysis will show if there is a role of mutational landscape in the definition of the oligometastatic state.

Are sex and gender considered in head and neck cancer clinical studies?

We analyzed the inclusion of sex and/or gender (S/G) in Head and Neck Cancer (HNC) clinical studies, through inspecting ClinicalTrials.gov (AACT) and the mention of Human Papilloma Virus (HPV) on a specific subgroup, namely oral cavity, larynx and oropharynx. Only 5% of HNC studies mention S/G as a planned analytical variable. Proportionally more observational studies treated S/G as an analytical variable than interventional studies (10% vs 5%, P-value ≤ 0.001), 8% of studies that mentioned S/G involved more than 100 subjects while 4% less than 100 (P-value ≤ 0.001). In randomized protocols, S/G was mentioned more in studies with a planned sample of more than 100 patients and including HPV status (P-value < 0.05). Small controlled studies have lower mention of S/G as an analytical variable than uncontrolled studies (4% and 10%, respectively among studies with less than 100 subjects). Significantly greater mention of S/G as an analytical variable is observed in controlled and randomized studies with a sample size greater than 100 subjects. HPV was mentioned in only 18% of oral cavity-larynx-oropharynx studies. Interventional studies do not regularly account for S/G during HNC study design. Thus, although fundamental, in studies concerning HNC the S/G variable is often not considered. In trials published in scientific journals (P-value = 0.01) and in more recent clinical trials (P-value = 0.002), S/G is taken more into account suggesting an increasing awareness on its importance. However, the need to systematically include S/G in study design clearly emerges, to better highlight sex-related differences in disease incidence and prognosis and best imbue science and medicine with the proper biological and cultural differences.

Inflammatory and Metabolic Biomarker Assessment in a Randomized Presurgical Trial of Curcumin and Anthocyanin Supplements in Patients with Colorectal Adenomas.

Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed (p = 0.02). The combined treatment of anthocyanins and curcumin did not result in the direct modulation of circulating biomarkers of inflammation and metabolism, but revealed a complex modulation of inflammatory and metabolic biomarkers of colon carcinogenesis.

Sports activity limitation during the COVID-19 pandemic in young Italian athletes: impact on mental health in children, adolescents, and young adults.

Introduction: The closure of sports centres was implemented as a preventive measure to mitigate the transmission of SARS-CoV-2. Given the observed global decline in physical activity and concurrent rise in sedentary behaviour, even among younger age groups, a retrospective cross-sectional study was undertaken to evaluate the effects of this measure on mental health in children, adolescents, and young adults during the initial phases of the COVID-19 pandemic. Methods: A total of 1,717 non-professional athletes (age range: 6-25; 53.9% males, 44.6% females) completed an online questionnaire including widely used and validated measures for mental health assessment (SDQ and PGWB-S) and questions regarding sociodemographic characteristics (such as gender), physical activity, and screen time. The association between mental health and sociodemographic characteristics, physical activity, and screen time was evaluated by using univariate and multivariable logistic regression models. Results: In children and adolescents, the incidence of psychological difficulties was associated with not being physically active (OR = 1.49; 95% CI: 1.09, 2.07; p = 0.015). Engaging in physical activity during the period of closures, particularly if more than twice a week, was significantly associated with less psychological difficulties for children/adolescents (OR = 0.54; 95% CI: 0.35, 0.82; p = 0.004) and psychological symptoms (i.e., psychological well-being lower than the median) for youth/young adults (OR = 0.25; 95% CI: 0.14, 0.45; p < 0.001). More psychological difficulties were also found in males for children and adolescents (OR = 1.37; 95% CI: 1.06, 1.79; p = 0.018). However, young adult males showed less psychological symptoms than females (OR = 0.35; 95% CI: 0.22, 0.55; p = 0.001). Additionally, a greater amount of screen time was associated with a higher incidence of psychological symptoms in the whole sample. Conclusions: Our results confirm the positive impact of physical activity on mental health during the COVID-19 pandemic among younger age groups. They also provide valuable insights into the risk-benefit relationship of interrupting sports activities as a preventive measure for infectious diseases.

Observational Study on Antibody Response to COVID-19 Vaccines in PAtients with Gastro-Entero-PanCreatic Cancers and NeuroendocrIne NeoplAsms on Systemic TreatmEnts (VACCINATE).

The coronavirus disease-19 (COVID-19) pandemic dramatically impacted oncological patients' care. Since the introduction of vaccines and the demonstration of their benefit on frail patients, COVID-19 vaccinations were indicated to also be beneficial to oncological population. However, data about the impact of anticancer-treatments and the timing between vaccinations and systemic therapy delivery were not available. We aimed to evaluate potential factors influencing the outcome of the COVID-19 vaccination in cancer patients. We prospectively collected data of patients undergoing the COVID-19 vaccination with gastro-entero-pancreatic and neuroendocrine neoplasms, treated at our institute, between 03/2021 and 12/2021. We enrolled 46 patients, 63.1% males; at the time of data collection, 86.9% had received two-doses of Pfizer-BioNTech and the rest had received the Moderna vaccine. All patients obtained a subsequent immune-response. Chemotherapy seems to determinate a significantly lower antibody response after vaccination compared to the other anti-cancer agents (p = 0.004). No significant effect on immune-response was reported for both vaccinations performed ≤7 vs. >7 days from the last systemic treatment (p = 0.77) and lymphocytes count (p = 0.11). The findings suggest that the optimal timing for COVID-19 vaccination and lymphocytes count are not the issue, but rather that the quality of the subset of lymphocytes before the vaccination determine the efficacy level of immune-response in this population.

Association between Alcohol Intake and Prostate Cancer Mortality and Survival.

We conducted a systematic review and meta-analysis to investigate the role of alcohol consumption with the prognosis of prostate cancer (PCa). Published reports were gathered on 15 October 2022, from PUBMED/MEDLINE and EMBASE. We found 19 independent eligible studies on the association between consumption of alcoholic beverages and the risk of fatal PCa (n = 5), PCa mortality (n = 5) in healthy subjects, and PCa patients' survival (n = 7) or surrogates thereof (n = 2). We used random effects meta-analysis to obtain a summary risk estimate (SRE) and 95% confidence intervals (95%CI) for incidence of fatal PCa and PCa mortality. The meta-analysis revealed no association between alcohol consumption and fatal prostate cancer incidence risk in healthy subjects with an indication for publication bias, but omitting the study that mainly increased the between-study heterogeneity, the SRE becomes significant (SRE 1.33, 95%CI 1.12-1.58), and the heterogeneity disappeared (I2 = 0%) with no indication of publication bias. No association of alcohol consumption was found with mortality risk in PCa patients (SRE 0.97, 95%CI 0.92-1.03) and PCa mortality risk in healthy subjects (SRE 1.03, 95%CI 0.82-1.30). In conclusion, this study suggests that there is some evidence of an association between high alcohol consumption and an increased risk of incidence of fatal prostate cancer in healthy subjects. Given the inconsistencies this result warrants further confirmation.

Risk and incidence of breast cancer in transgender individuals: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The risk of developing breast cancer in transgender individuals [male-to-female (MtF) or female-to-male (FtM)] is still inadequately quantified. We aimed to evaluate the impact of breast cancer in this population. METHODS: We conducted a systematic literature search and review using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines through the PUBMED and SCOPUS databases. We identified six cohort studies (for both populations) plus 35 case reports. Incidence and breast cancer risk quantification were the main outcomes considered. RESULTS: FtM individuals had a higher risk of developing breast cancer in comparison to cisgender men [standardized incidence ratio (SIR) = 63.4; 95% confidence interval (CI), 32.2-124.9] but a lower risk than cisgender women (SIR = 0.42; 95% CI, 0.07-2.41). Similarly, MtF individuals were at higher risk of developing breast cancer in comparison to cisgender men (SIR = 22.5; 95% CI, 5.54-91.8) and at lower risk than cisgender women (SIR = 0.30; 95% CI, 0.22-0.42). CONCLUSION: In this systematic study and meta-analysis, we identified that FtM and MtF individuals are at substantially higher risk of developing breast cancer in comparison to cisgender men, though at lower risk than cisgender women. These individuals, in the absence of defined guidelines for breast cancer prevention, should periodically undergo breast or chest examinations.

Prognostic Impact of Sarcopenia's Occurrence during Radiotherapy in Oropharyngeal Cancer Patients.

The current study aims to profile sarcopenic condition (both at baseline and developed during treatment) in oropharyngeal carcinoma (OPC) patients treated with curative radiotherapy (RT) +/- chemotherapy and to evaluate its impact on oncological outcomes and toxicity. A total of 116 patients were included in this retrospective single-center study. Sarcopenia assessment at baseline and at 50 Gy re-evaluation CT was obtained from two different methodologies: (i) the L3-skeletal muscle index (SMI) derived from the contouring of the cross-sectional area (CSA) of the masticatory muscles (CSA-MM); and (ii) the paravertebral and sternocleidomastoid muscles at the level of the third cervical vertebra (CSA-C3). Based on L3-SMI from CSA-MM, developing sarcopenic condition during RT (on-RT sarcopenia) was associated with worse progression-free survival (PFS) (p = 0.03) on multivariable analysis and a trend of correlation with overall survival (OS) was also evident (p = 0.05). According to L3-SMI derived from CSA-C3, on-RT sarcopenia was associated with worse PFS (p = 0.0096) and OS (p = 0.013) on univariate analysis; these associations were not confirmed on multivariable analysis. A significant association was reported between becoming on-RT sarcopenia and low baseline haemoglobin (p = 0.03) and the activation of nutritional counselling (p = 0.02). No significant associations were found between sarcopenia and worse RT toxicity. Our data suggest that the implementation of prompt nutritional support to prevent the onset of sarcopenia during RT could improve oncological outcomes in OPC setting.

European Cohorts of patients and schools to Advance Response to Epidemics (EuCARE): a cluster randomised interventional and observational study protocol to investigate the relationship between schools and SARS-CoV-2 infection.

BACKGROUND: Contradictory results were reported on the role of school closure/reopening on the overall SARS-CoV-2 transmission rate, as well as on which kind and level of mitigation measures implemented in schools may be effective in limiting its diffusion. Some recent studies were reassuring, showing that opening did not increase the community spread, although teachers and families are worried about the high class density. On the other hand, distance learning was associated with a negative impact on learning, sociability and psychological health, especially in vulnerable children. As it becomes clear that the SARS-CoV-2 pandemic will last for a long time, there is a high need for studies and solutions to support safe schools opening based on scientific evidence of harms and benefits. The Lolli-Methode (LM) is a strategy for epidemiological surveillance and early intervention aiming at SARS-CoV-2 outbreaks' reduction in schools, relying on polymerase chain reaction analysis of saliva samples. METHODS: In this cluster randomised trial protocol, we aim to determine whether the LM is useful to support schools opening and to reduce clusters and attack rates in schools, compared with the standard of care (SoC) surveillance by public health departments. This multicenter study will enrol 440 classes (around 8800 students, teachers and other personnel) from two countries, cluster randomised to LM or SoC. The samples from the pools will be collected and tested using PCR-based techniques. Test results will be combined with questionnaires filled in by children, parents, schoolteachers, and principals, concerning ongoing mitigation measures, their perceived psychological impact and other health and socio-economic information. An ancillary observational study will be carried out to study the prevalence of SARS-CoV-2 in schools, frequencies and size of clusters and attack rates, to compare the effectiveness of the different preventive measures adopted and to evaluate psychological issues in students and teachers in relation to the pandemic's containment measures. DISCUSSION: By the end of this study, we will have defined and characterised the applicability of the LM for SARS-CoV-2 surveillance, as well as the impact of pandemic preventive measures on children and teachers. Trial registration International Standard Randomised Controlled Trial Number: NCT05396040, 27.05.2022.

The prognostic role of sex and hemoglobin levels in patients with oral tongue squamous cell carcinoma.

Background: Women and men differ genetically, biologically (sex) and by social construct (gender), possibly impacting on prognostic factors in predicting cancer survival. Hemoglobin levels and immune system activation are players acting in this scenario which could play a role in partly determining prognosis between patients of different sex/gender (S/G). Here, we investigate these factors in patients affected by tongue squamous cell carcinoma. Methods: This is an observational retrospective cohort study. We collected tongue cancer patients' clinical data, including hemoglobin levels and neutrophil lymphocyte ratio (NLR). Overall survival (OS) and disease-free survival (DFS) were compared between women and men considering confounding and prognostic factors in multivariate Cox proportional hazard models. Stratified analyses were also conducted by sex and tumor stage. Result: 576 patients, 39.9% women and 60.1% men, were found eligible for the analysis. Men were more often smokers (p<0.001), alcohol consumers (p<0.001), overweight or obese (p<0.001) and undergoing radiotherapy (p=0.002). In multivariate models for stage I-II, men showed half risk of death and relapse compared to women (HR=0.44; 95%CI 0.24-0.81, p=0.009; HR=0.55; 95%CI 0.34-0.87, p=0.01, for OS and DFS respectively). Moreover, low hemoglobin levels appeared to be an independent prognostic factor for women but not for men in terms of both OS and DFS. Specifically, women with low hemoglobin levels showed a worse tumor outcome (HR=2.66; 95%CI 1.50-4.70; HR=2.09; 95%CI 1.24-3.53, for OS and DFS respectively). Low hemoglobin levels appeared to be a poor OS prognostic factor for women at stage I-II (p<0.004) but not for men (p=0.10). Women with advanced stage tumors, NLR>2.37, who did not performed Radiotherapy and with depth of invasion (DOI)> 10 were associated with a significant increase in relapse and death (all p<0.05). Conclusion: In our cohort of patients with oral tongue squamous cell carcinoma, men present better OS and DFS than women with early stages tumors. Low hemoglobin level was an independent prognostic factor for women, especially at early-stage tumors. For advanced stages (III-IV), sex is not a significant factor related to patients' prognosis.

Prediction of the Pathological Response to Neoadjuvant Chemotherapy in Breast Cancer Patients With MRI-Radiomics: A Systematic Review and Meta-analysis.

We performed a systematic review and a meta-analysis of studies using MRI-radiomics for predicting the pathological complete response in breast cancer patients undergoing neoadjuvant therapy , and we evaluated their methodological quality using the radiomics-quality-score (RQS). Random effects meta-analysis was performed pooling area under the receiver operating characteristics curves. Publication-bias was assessed using the Egger's test and visually inspecting the funnel plot. Forty-three studies were included in the qualitative review and 34 in the meta-analysis. Summary area under the receiver operating characteristics curve was 0,78 (95%CI:0,74-0,81). Heterogeneity according to the I2 statistic was substantial (71%) and there was no evidence of publication bias (P-value = 0,2). The average RQS was 12,7 (range:-1-26), with an intra-class correlation coefficient of 0.93 (95%CI:0.61-0.97). Year of publication, field intensity and synthetic RQS score do not appear to be moderators of the effect (P-value = 0.36, P-value = 0.28 and P-value = 0.92, respectively). MRI-radiomics may predict response to neoadjuvant therapy in breast cancer patients but the heterogeneity of the current studies is still substantial.

Post-diagnosis smoking cessation and survival of patients with head and neck cancer: a systematic review and meta-analysis.

Cigarette smoking is the main risk factor for head and neck cancer (HNC) and many HNC patients are active smokers at diagnosis. We conducted a systematic literature review and meta-analysis to quantify the survival impact of smoking cessation at or around the time of HNC diagnosis. We searched studies published until December 31, 2021, and used random-effects meta-analysis to pool study-specific estimates into summary hazard ratio (SHR) and corresponding 95% confidence intervals (CI). Sixteen studies were published between 1983 and 2021, and over 2300 HNC patients were included. Studies were diverse in terms of design, patients, tumours and treatment characteristics, and criteria used to discriminate quitters from continued smokers. HNC patients who quit smoking at or around diagnosis had significantly better overall survival than continued smokers (SHR 0.80, 95% CI 0.70-0.91, n studies = 10). A beneficial effect of post-diagnosis smoking cessation was suggested for other survival endpoints as well, but the results were based on fewer studies (n = 5) and affected by publication bias. Cessation counselling should be offered to all smokers who start a diagnostic workup for HNC and should be considered standard multidisciplinary oncological care for HNC patients. PROSPERO registration number CRD42021245560.

Prognostic Impact of Post-Diagnosis Smoking Cessation among Bladder Cancer Patients: A Systematic Literature Review and Meta-Analysis.

We reviewed the studies examining whether quitting smoking at or around diagnosis favourably affects the prognosis of bladder cancer (BC) patients, who are often active smokers at diagnosis. We found only nine eligible articles published until 31 January 2022, which encompassed around 5500 BC in total, the majority of which were nonmuscle invasive BC (only one paper included muscle-invasive BC). We used random effects meta-analysis to obtain a summary hazard ratio (SHR) and 95% confidence intervals (CI). The median proportion of smokers who quit at or around diagnosis was 29.8% (range 8.4-43.1%). For the overall, BC-specific, and progression-free survival, the studies were limited in number (n = 3) and provided conflicting results. At the same time, quitters did not appear to have a lower risk of recurrence than continued smokers (SHR 0.99, 95% CI 0.61-1.61). In conclusion, while the evidence is currently not sufficient to draw firm conclusions (especially for patients with muscle-invasive BC), physicians should not refrain from educating smoking BC patients about the benefits of smoking cessation and provide the necessary support.

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis.

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

SARS-CoV-2 Circulation in the School Setting: A Systematic Review and Meta-Analysis.

The contribution of children to viral spread in schools is still debated. We conducted a systematic review and meta-analysis of studies to investigate SARS-CoV-2 transmission in the school setting. Literature searches on 15 May 2021 yielded a total of 1088 publications, including screening, contact tracing, and seroprevalence studies. MOOSE guidelines were followed, and data were analyzed using random-effects models. From screening studies involving more than 120,000 subjects, we estimated 0.31% (95% confidence interval (CI) 0.05-0.81) SARS-CoV-2 point prevalence in schools. Contact tracing studies, involving a total of 112,622 contacts of children and adults, showed that onward viral transmission was limited (2.54%, 95% CI 0.76-5.31). Young index cases were found to be 74% significantly less likely than adults to favor viral spread (odds ratio (OR) 0.26, 95% CI 0.11-0.63) and less susceptible to infection (OR 0.60; 95% CI 0.25-1.47). Lastly, from seroprevalence studies, with a total of 17,879 subjects involved, we estimated that children were 43% significantly less likely than adults to test positive for antibodies (OR 0.57, 95% CI 0.49-0.68). These findings may not applied to the Omicron phase, we further planned a randomized controlled trial to verify these results.