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Aim: To investigate whether methodological aspects may influence the performance of MRI-radiomic models to predict response to neoadjuvant treatment (NAT) in breast cancer (BC) patients., Materials and Methods: We conducted a systematic review until March 2023. A random-effects meta-analysis was performed to combine the area under the receiver operating characteristic curve (AUC) values. Publication bias was assessed using Egger's test and heterogeneity was estimated by I 2 . A meta-regression was conducted to investigate the impact of various factors, including scanner, features' number/transformation/type, pixel/voxel scaling, etc. RESULTS: Forty-two studies were included. The summary AUC was 0.77 (95% CI: 0.74-0.81). Substantial heterogeneity was observed (I 2  = 81%) with no publication bias (p = 0.35). Radiomic model accuracy was influenced by the scanner vendor, with lower AUCs in studies using mixed scanner vendors (AUC; 95% CI: 0.70; 0.61-0.78) compared to studies including images obtained from the same scanner (AUC (95% CI): 0.83 (0.77-0.88), 0.74 (0.67-0.82), 0.83 (0.78-0.89) for three different vendors; vendors 1, 2, and 3, respectively; p-value = 0.03 for comparison with vendor 1). Feature type also seemed to have an impact on the AUC, with higher prediction accuracy observed for studies using 3D than 2D/2.5D images (AUC; 95% CI: 0.81; 0.78-0.85 and 0.73; 0.65-0.81, respectively, p-value = 0.03). Non-significant between-study heterogeneity was observed in the studies including 3D images (I 2  = 33%) and Vendor 1 scanners (I 2  = 40%)., Conclusion: MRI-radiomics has emerged as a potential method for predicting the response to NAT in BC patients, showing promising outcomes. Nevertheless, it is important to acknowledge the diversity among the methodological choices applied. Further investigations should prioritize achieving standardized protocols, and enhancing methodological rigor in MRI-radiomics., Key Points: Question Do methodological aspects influence the performance of MRI-radiomic models in predicting response to NAT in BC patients? Findings Radiomic model accuracy was influenced by the scanner vendor and feature type. Clinical relevance Methodological discrepancies affect the performance of MRI-radiomic models. Developing standardized protocols and enhancing methodological rigor in these studies should be prioritized., Competing Interests: Compliance with ethical standards. Guarantor: The scientific guarantor of this publication is Sara Gandini. Conflict of interest: The authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article. Statistics and biometry: Sofia Netti, Sara Gandini, and Sara Raimondi have significant statistical expertise. Informed consent: Not applicable. Ethical approval: Institutional Review Board approval was obtained. Study subjects or cohorts overlap: No study subjects or cohorts have been previously reported. Methodology: Retrospective Observational Multicenter study/performed at one institution, (© 2024. The Author(s), under exclusive licence to European Society of Radiology.)

Objectives: This meta-analysis compares the efficacy, limitations, and clinical implications of abbreviated breast MRI (AB-MRI) and full protocol MRI (FP-MRI), focusing on diagnostic accuracy across diverse populations. It extends previous analyses by including studies conducted after 2019 in both screening and diagnostic contexts., Methods: We conducted a systematic review (November 2019 to December 2022), using a bivariate model to calculate summary estimates of sensitivity and specificity. Random effect models were applied for summary area under the curve (AUC), and probability distributions for negative and positive predictive values were obtained. Subgroup analyses explored differences in sensitivity, specificity, and AUC between AB-MRI and FP-MRI., Results: From 11 eligible studies (1 prospective, 10 retrospective), statistical analysis revealed a significant difference in sensitivity between FP-MRI (95%) and AB-MRI (86%, P = .005), with no significant difference in specificity (P = .50). AB-MRI's shorter acquisition time suggests potential for higher patient throughput, but challenges remain in detecting small lesions and nonmass enhancements. Some studies recommend additional sequences, like diffusion-weighted imaging, to improve diagnostic performance., Conclusions: While FP-MRI remains the gold standard in breast cancer detection, AB-MRI offers a quicker alternative, especially in high-risk screening. However, its lower sensitivity limits its use as a standalone diagnostic tool. Future research should optimize AB-MRI protocols and consider patient-specific factors to enhance breast cancer screening and diagnostic strategies., Advances in Knowledge: This meta-analysis expands understanding of AB-MRI's role in breast cancer detection, highlighting its benefits and limitations compared to FP-MRI, particularly in terms of sensitivity and screening efficiency., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology.)

Background/objectives: Our previous study of 291 cancer patients, we showed that 20% did not respond to two doses of COVID-19 vaccine administered six weeks apart., Methods: Here, we investigated if psychological factors (distress, anxiety, and depressive symptoms) affected antibody response and markers of vaccine activation (D-dimer) after 6 months from initial vaccination., Results: Overall, 31 subjects (14.2%) had no antibody response at 6 months. Our analysis revealed significant predictors of vaccine failure, including the stage of metastatic disease and high-stress levels (OR = 2.46, 95% CI, 1.05-5.77, p = 0.04). Notably, nonresponders showed twice the prevalence of distress than responders (21% vs. 10%, p = 0.04). Longitudinal measurements of IgG levels indicated that participants with high depressive symptoms at baseline maintained lower antibody levels over six months ( p = 0.003). In addition, women with high anxiety showed reduced levels of D-dimer at 6 months ( p = 0.03). These data also showed that smokers and former smokers had significantly lower antibody levels than their nonsmoking counterparts ( p = 0.0004). At baseline, the high discomfort rate (≥5) was 34.4% in women and 23.8% in men; only men experienced an increase in median discomfort during the observation period. Moreover, a higher educational level was related to increased distress among women ( p = 0.046)., Conclusions: These findings underscore a critical association between elevated psychological distress and reduced immune responses to the COVID-19 vaccine, emphasizing the urgent need for targeted psychological and behavioral support within this vulnerable population.

Background: Elderly patients are underrepresented in clinical trials, particularly in early-phase studies. Our study assessed the safety and efficacy of novel anti-cancer treatments investigated in early-phase clinical trials, comparing outcomes between younger and elderly patients., Methods: This retrospective study analyzed data from patients enrolled in phase I/II trials at our center between January 2014 and April 2021. We evaluated clinicopathologic characteristics, toxicity, and clinical efficacy, categorizing patients into younger (≤ 65 years) and elderly (> 65 years) groups., Results: 419 patients were included with a median age of 56 years. Among these, 107 (26 %) were older than 65 years. Predominant cancers included breast (48 %), lung (10 %), and melanoma (5 %). Patients were treated in 64 trials, predominantly receiving immunotherapy-based (47 %) or targeted therapy-based (45 %) treatment. Elderly presented with poorer ECOG performance status (P = 0.001) and had fewer prior therapy lines (P = 0.01) than younger patients. Grade ≥ 3 adverse events (AEs) were similar across age groups (31 % younger vs 33 % elderly; P = 0.7), including in combination therapy scenarios. However, elderly patients experienced more AEs with antibody-drug conjugates compared to younger counterparts (56 % vs 14 %, P = 0.036) and were more likely to discontinue treatment due to toxicity (15 % vs 7 %; P = 0.011). No significant age-related differences in response rates and survival outcomes were observed across treatment modalities, except for immunotherapy-based regimens for which elderly patients exhibited higher response rates, disease control rates, and prolonged progression-free survival., Conclusions: Our findings suggest that elderly exhibit comparable safety and efficacy outcomes to younger patients in early-phase clinical trials for new cancer drugs. This underscores the importance of including elderly patients in phase I/II trials to ensure the generalizability of study results and mitigate age-related disparities in cancer treatment access., Competing Interests: Declaration of Competing Interest Disclosures: SM reports expenses reimbursement from Menarini/Stemline and AstraZeneca. PT discloses research funding (to institution) from AstraZeneca and consultancy/advisory role for AstraZeneca, Daiichi Sankyo, Gilead, Novartis and Lilly. MC reports personal fees from Lilly, Sermonix, Data Genomics, Foundation Medicine, Guardant Health, Celcuity, Iylon, and Ellipses and grants and personal fees from Pfizer, AZ and Menarini, all outside the submitted work. CC reports consultancy/advisory role/speaker bureau: AstraZeneca, Daiichi Sankyo, MSD, Gilead, Lilly, Roche, Pfizer, Novartis and Seagen, all outside the submitted work. AM has received honoraria as a consultant, advisor or speaker from Roche and Menarini/Stemline, and has received support for accommodation and travel from AstraZeneca, all outside the submitted work. AE reports speaker bureau: Daiichi Sankyo, Novartis, all outside the submitted work. GC reports payment or honoraria for lectures, presentations, speaker bureaus, manuscript writing or educational events: Lilly, Pfizer, Relay, Gilead, Novartis; Consulting fees: BMS, Roche, Pfizer, Novartis, Lilly, Astra Zeneca, Daichii Sankyo, Merck, Seagen, Ellipsis, Gilead, Menarini; Grants or contracts: Merck; Support for attending meetings and/or travel: Daichii Sankyo. Institutional research funding for conducting Phase 1 and 2 clinical trials: Pfizer, Roche, Novartis, Sanofi, Celgene, Servier, Orion, AstraZeneca, Seattle Genetics, AbbVie, Tesaro, BMS, Merck Serono, Merck Sharp Dohme, Janssen-Cilag, Philogen, Bayer, Medivation, Medimmune. All outside the submitted work. No other potential conflicts of interest are reported., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

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.

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 (CTDI vol ) 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. CTDI vol was evaluated in 12,804 phases; DLP in 10,713 phases and in 6714 examinations. The CTDI vol 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 SNR Liv (p = 0.58); 4.81 (2.70-7.62) and 4.34 (3.05-6.25) for SNR Ao (p = 0.30); 0.83 (0.20-1.89) and 1.00 (0.35-1.57) for CNR Liv (p = 0.99); 2.23 (0.09-3.83) and 1.01 (0.15-2.84) for CNR Ao (p = 0.24) with SNR Liv (p = 0.58), SNR Ao (p = 0.30), CNR Liv (p = 0.99) and CNR Ao (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., (© 2024. The Author(s).)

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., (© The Author(s) 2023. Published by Oxford University Press.)

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 (R c ) 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 R c 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 R c 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 R c 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., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

(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.

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.

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., (© 2023. Nature Publishing Group UK.)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tomezzoli, D'Ecclesiis, Raimondi, Pravettoni, Cammarata, Testa, Bellerba, Gnagnarella, Iannuzzo, Sartorio, Sasso, Ricci, Marazzi, Galli and Gandini.)

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., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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 ( I 2 = 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.

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.

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.

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., (© 2022. The Author(s).)

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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tagliabue, D’Ecclesiis, De Berardinis, Gaeta, Martinoli, Piana, Maffini, Gandini, Ansarin and Chiocca.)

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., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

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 I 2 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., Competing Interests: Conflict of Interest All the authors of this manuscript declare no relationships with any companies, whose products or services may be related to the subject matter of the article., (Copyright © 2022. Published by Elsevier Inc.)

Background and Aims: Metaplastic breast cancer (MBC) and triple-negative (TN) BC of no special type are often confounded with each other in terms of survival and prognosis. In this systematic study and meta-analysis, we evaluated the prognosis of each of these two different diagnoses., Methods: We conducted a systematic literature search and review using the MOOSE guidelines, through PUBMED database, the Ovid MEDLINE database, and the ISI Web of Science Citation Index Expanded (SCI Expanded). Overall survival (OS) and disease-free survival (DFS) were the main outcomes considered., Results: Our review eventually selected six independent studies, with a total of more than 59 519 patients. MBC was found to associate with worse OS compared to TNBC of no special type, with a significant 40% increased risk of death [summary hazard ratio (SHR) = 1.40, 95% confidence interval (CI): 1.30-1.50]. We found neither heterogeneity ( I2 = 0%) nor evidence of publication bias ( P = 0.82 and P = 0.49 by Begg's and Egger's test, respectively) between studies. No statistically significant difference was found between MBC and TNBC of no special type in terms of DFS (SHR = 1.17, 95% CI: 0.80-1.71)., Conclusion: This study demonstrates that TNBC of no special type and MBC have comparable DFS, although the latter presents a significantly worse prognosis in terms of OS. Despite DFS being similar in both subtypes, this did not result in significant OS benefits, with MBC score being the worse of the two diseases., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., Competing Interests: The authors have declared that no competing interests exist.

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.

Purpose: Initial findings in patients with cancer suggest a lower seroconversion to SARS-CoV-2 vaccination possibly related to myelo-immunosuppressive therapies. We conducted a prospective study to assess factors predicting poor seroconversion and adverse events following immunisation (AEFI) to the BNT162b2 vaccine in patients on active treatment., Patients and Methods: Cancer patients, candidates to two doses of BNT162b2 SARS-CoV-2 vaccination, were enrolled. Patients on active surveillance served as controls. The primary endpoint was poor seroconversion (anti S1/S2 IgG < 25 AU/mL) after 21 days from the second dose., Results: Between March and July 2021, 320 subjects were recruited, and 291 were assessable. The lack of seroconversion at 21 days from the second dose was 1.6% (95% CI, 0.4-8.7) on active surveillance, 13.9% (8.2-21.6) on chemotherapy, 11.4% (5.1-21.3) on hormone therapy, 21.7% (7.5-43.7) on targeted therapy and 4.8% (0.12-23.8) on immune-checkpoint-inhibitors (ICI). Compared to controls, the risk of no IgG response was greater for chemotherapy (p = 0.033), targeted therapy (0.005) and hormonotherapy (p = 0.051). Lymphocyte count < 1 × 10 9 /L (p = 0.04) and older age (p = 0.03) also significantly predicted poor seroconversion. Overall, 43 patients (14.8%) complained of AEFI, mostly of mild grade. Risk of AEFI was greater in females (p = 0.001) and younger patients (p = 0.009)., Conclusion: Chemotherapy, targeted therapy, hormone therapy, lymphocyte count < 1 × 10 9 /L, and increasing age predict poor seroconversion after two doses of BNT162b2 in up to 20% of patients, indicating the need for a third dose and long-term serological testing in non-responders. AEFI occur much more frequently in women and younger subjects who may benefit from preventive medications. CLINICALTRIALS., Gov Identifier: NCT04932863., Competing Interests: Conflict of interest statement We declare no competing interests., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Aim: Over the last decades, the incidence of melanoma has been steadily growing, with 4.2% of the population worldwide affected by cutaneous melanoma (CM) in 2020 and with a higher incidence and mortality in men than in women. We investigated both the risk factors for CM development and the prognostic and predictive factors for survival, stratifying for both sex and gender., Methods: We conducted a systematic review of studies indexed in PUB-MED, EMBASE, and Scopus until 4 February 2021. We included reviews, meta-analyses, and pooled analyses investigating differences between women and men in CM risk factors and in prognostic and predictive factors for CM survival., Data Synthesis: Twenty-four studies were included, and relevant data extracted. Of these, 13 studies concerned potential risk factors, six concerned predictive factors, and five addressed prognostic factors of melanoma., Discussion: The systematic review revealed no significant differences in genetic predisposition to CM between males and females, while there appear to be several gender disparities regarding CM risk factors, partly attributable to different lifestyles and behavioral habits between men and women. There is currently no clear evidence of whether the mutational landscapes of CM differ by sex/gender. Prognosis is justified by a complex combination of phenotypes and immune functions, while reported differences between genders in predicting the effectiveness of new treatments are inconsistent. Overall, the results emerging from the literature reveal the importance of considering the sex/gender variable in all studies and pave the way for including it towards precision medicine., Conclusions: Men and women differ genetically, biologically, and by social construct. Our systematic review shows that, although fundamental, the variable sex/gender is not among the ones collected and analyzed.