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Abstract Background We compared computed tomography (CT) images and holograms (HG) to assess the number of arteries of the lung lobes undergoing lobectomy and assessed easiness in interpretation by radiologists and thoracic surgeons with both techniques. Methods Patients scheduled for lobectomy for lung cancer were prospectively included and underwent CT for staging. A patient-specific three-dimensional model was generated and visualized in an augmented reality setting. One radiologist and one thoracic surgeon evaluated CT images and holograms to count lobar arteries, having as reference standard the number of arteries recorded at surgery. The easiness of vessel identification was graded according to a Likert scale. Wilcoxon signed-rank test and κ statistics were used. Results Fifty-two patients were prospectively included. The two doctors detected the same number of arteries in 44/52 images (85%) and in 51/52 holograms (98%). The mean difference between the number of artery branches detected by surgery and CT images was 0.31 ± 0.98, whereas it was 0.09 ± 0.37 between surgery and HGs (p = 0.433). In particular, the mean difference in the number of arteries detected in the upper lobes was 0.67 ± 1.08 between surgery and CT images and 0.17 ± 0.46 between surgery and holograms (p = 0.029). Both radiologist and surgeon showed a higher agreement for holograms (κ = 0.99) than for CT (κ = 0.81) and found holograms easier to evaluate than CTs (p < 0.001). Conclusions Augmented reality by holograms is an effective tool for preoperative vascular anatomy assessment of lungs, especially when evaluating the upper lobes, more prone to anatomical variations. Trial registration ClinicalTrials.gov, NCT04227444 Relevance statement Preoperative evaluation of the lung lobe arteries through augmented reality may help the thoracic surgeons to carefully plan a lobectomy, thus contributing to optimize patients’ outcomes. Key points • Preoperative assessment of the lung arteries may help surgical planning. • Lung artery detection by augmented reality was more accurate than that by CT images, particularly for the upper lobes. • The assessment of the lung arterial vessels was easier by using holograms than CT images. Graphical Abstract

Purpose: Although younger age has been negatively associated with persistence to adjuvant endocrine therapy (ET), factors contributing to non-persistence remain poorly understood. We assessed factors associated with non-persistence to ET and described the 5-year trajectories of quality of life (QoL) and symptoms in young women (≤40 years) with hormone receptor-positive breast cancer (BC). Methods: We retrieved data on clinical characteristics and non-persistence from the medical annual records in the European cohort of the “Helping Ourselves, Helping Others: The Young Women's BC Study” (IBCSG 43-09 HOHO). Women completed surveys at baseline, biannually for three years, and annually for another seven years. Data collection included sociodemographic information, QoL aspects assessed by the Cancer Rehabilitation Evaluation System-Short Form and symptoms assessed by the Breast Cancer Prevention Trial symptom scales. Cox regression models were applied to identify factors associated with non-persistence. Results: The cumulative risk of interrupting ET within 5 years was 27.7 % (95 % CI, 21.5–35.2). The QoL subscale scores remained stable over 5 years, with slight improvements in the physical subscale. Hot flashes decreased (p

IntroductionSeveral studies have demonstrated that, following a breast cancer (BC) diagnosis, patients are eager to obtain information on cancer and nutrition, in order to ameliorate both their quality of life (QoL) and disease outcome. To avoid BC survivors to get wrong information from unreliable sources, healthcare providers need to be aware of patients’ needs, to guide them toward optimal nutrition recommendations, aimed at preventing tumor recurrence and increasing survival rates.Material and methodsThe cross-sectional web-based survey “Nutrition and breast cancer, what would you like to know?” has been conceived and conducted, in Italy, between the 2nd and the 25th of June 2023. The link to the 19-items questionnaire, structured in 6 sections, was distributed via social media (Facebook and Instagram), newsletter, institutional websites, and printed flyers. Patients’ responses were collected and analyzed, reporting absolute and relative frequencies.ResultsA total of 1616 participants (98.9% female and 1.1% male), with an average age of 47.5 years, answered the survey. Only subjects who declared having previously received a BC diagnosis (N=1159, 71.7%) were included in the present analysis. Overall, the respondents showed a wide interest in understanding whether nutrition might help to manage therapy side effects, as well as knowing how specific diets, foods, nutrients, and supplements could affect disease onset, progression and prognosis. Importantly, the need to receive evidence-based information from the “referring physician/specialist” and “nutritionist/dietitian” was expressed by 95.8% and 88.8% of them, respectively.DiscussionIn this study, we primarily aimed at intercepting nutrition information needs and sources of an Italian BC survivors’ group. Based on that, we first organized a proactive digital intervention, to respond via Instagram live broadcasts to patients’ “cancer and nutrition”-related questions. Secondly, we arranged a healthcare providers dedicated-workshop focused on the latest evidence-based knowledge on nutrition and BC. It is crucial, in fact, that once healthcare professionals capture patients’ information needs, they can respond with appropriate nutritional guidance, counseling and education programs, while counteracting misleading and incorrect messages.

Summary: Background: The outcome of patients with metastatic tumors who discontinued immune checkpoint inhibitors (ICIs) not for progressive disease (PD) has been poorly explored. We performed a meta-analysis of all studies reporting the clinical outcome of patients who discontinued ICIs for reasons other than PD. Methods: We searched PubMed, Embase and Scopus databases, from the inception of each database to December 2023, for clinical trials (randomized or not) and observational studies assessing PD-(L)1 and CTLA-4 inhibitors in patients with metastatic solid tumors who discontinued treatment for reasons other than PD. Each study had to provide swimmer plots or Kaplan–Meier survival curves enabling the reconstruction of individual patient-level data on progression-free survival (PFS) following the discontinuation of immunotherapy. The primary endpoint was PFS from the date of treatment discontinuation overall and according to tumor histotype, type of treatment and reason of discontinuation. The Combersure’s method was used to estimate meta-analytical non-parametric summary survival curves assuming random effects at study level. Findings: Thirty-six studies (2180 patients) were included. The pooled median PFS (mPFS) was 24.7 months (95% CI, 18.8–30.6) and the PFS-rate at 12, 24, and 36 months was respectively 69.8% (95% CI, 63.1–77.3), 51.0% (95% CI, 43.4–59.8) and 34.0% (95% CI, 27.0–42.9). Univariable analysis showed that the mPFS was significantly longer for patients with melanoma (43.0 months), as compared with non-small cell lung cancer (NSCLC, 13.5 months) and renal cell carcinoma (RCC, 10.0 months; between-strata comparison test p-value < 0.001); for patients treated with anti-PD-(L)1 + anti-CTLA-4 as compared with anti-PD-(L)1 monotherapy (44.6 versus 19.9 months; p-value

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy. Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes. Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery. Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS). Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10–1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02–1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63–8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35–4.06, p = 0.79). Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.

Background: The possible association between cigarette smoking and breast cancer risk has been quite controversial. Methods: We conducted a systematic review and meta-analysis of all available observational studies published on the issue up to January 2020. Random-effects models were used to compute pooled relative risks (RRs) for cigarette smoking status and dose-risk relationships were evaluated using one-stage random-effects dose-response models. Results: A total of 169 studies were selected, providing a pooled RR for breast cancer of 1.07 (95% confidence interval [CI], 1.05–1.10) for current, 1.08 (95% CI, 1.06–1.10) for former, and 1.09 (95% CI, 1.07–1.11) for ever smokers, compared to never smokers. Results were consistent in case-control and cohort studies. No meaningful differences were observed across strata of most covariates considered, nor according to relevant genetic mutations and polymorphisms (ie, BRCA mutation, N-acetyltransferase and glutathione S-transferase genotypes, and P53). Breast cancer risk increased linearly with intensity of smoking (RR 1.12; 95% CI, 1.08–1.16 for 20 cigarettes/day and 1.26; 95% CI, 1.17–1.36 for 40 cigarettes/day), and with increasing duration of smoking (RR 1.05; 95% CI, 1.03–1.08 for 20 years of smoking and 1.11; 95% CI, 1.06–1.16 for 40 years of smoking). Conclusion: The present large and comprehensive meta-analysis—conducted using an innovative approach for study search—supports the evidence of a causal role of tobacco smoking on breast cancer risk.

Introduction: To provide evidence explaining the poor association between pCR and patients’ long-term outcome at trial-level in neoadjuvant RCTs for breast cancer (BC), we performed a systematic-review and meta-analysis of all RCTs testing neoadjuvant treatments for early-BC and reporting the hazard ratio of DFS (HRDFS) for the intervention versus control arm stratified by pathological response type (i.e., pCR yes versus no). Methods: The objective was to explore differences of treatment effects on DFS across patients with and without pCR.We calculated the pooled HRDFS in the two strata of pathological response (i.e., pCR yes versus no) using a random-effects model, and assessed the difference between these two estimates using an interaction test. Results: Ten RCTs and 8496 patients were included in the analysis.Patients obtaining pCR in the intervention-arm had a higher, although not statistically significant, risk of DFS-event as compared with patients obtaining pCR in the control-arm: the pooled HRDFS for the experimental versus control arm was 1.23 (95%CI, 0.91–1.65). On the opposite, the risk of DFS-event was higher for control as compared with the intervention-arm in the stratum of patients without pCR: the pooled HRDFS was 0.86 (95%CI, 0.78–0.95).Treatment effect on DFS was significantly different according to pathological response type (interaction test p: 0.014). Conclusion: We reported new evidence that contributes to explaining the poor surrogacy value of pCR at trial-level in neoadjuvant RCTs for early-BC.

Background: Controversy exists regarding the optimal duration of the extended adjuvant endocrine treatment (ET) in patients with early-stage breast-cancer (eBC).We performed a systematic review and trial-level meta-analysis of all randomized clinical trials (RCTs) comparing a “limited-extended” adjuvant ET (defined as more than 5 but less than 7.5 years of treatment overall) versus a “full-extended” adjuvant ET (defined as more than 7.5 years of treatment overall) in eBC. Methods: To be eligible, RCTs had to i) compare a “limited-extended” adjuvant ET versus a “full-extended” adjuvant ET in patients with eBC; and ii) report disease-free survival (DFS) hazard ratio (HR) according to the disease nodal-status [i.e., nodal-negative (N-ve) versus nodal-positive (N + ve)].The primary endpoint was to assess the difference in efficacy of full-versus limited-extended ET, measured in terms of the difference in DFS log-HR, according to the disease nodal-status. Secondary endpoint was the difference in efficacy of full-versus limited-extended ET according to tumor size (i.e., pT1 vs pT2/3/4), histological grade (i.e., G1/G2 vs G3), patients’ age (i.e., ≤60 vs > 60 years) and previous type of ET (i.e., aromatase inhibitors vs tamoxifen vs switch strategy). Results: Three phase III RCTs fulfilled the inclusion criteria. A total of 6689 patients were included in the analysis, of which 3506 (53%) had N + ve disease.The full-extended ET provided no DFS-benefit as compared with the limited-extended ET in patients with N-ve disease (pooled DFS-HR = 1.04, 95%CI: 0.89 to 1.22; I2 = 18%).Conversely, in patients with N + ve disease the full-extended ET significantly improved DFS, with a pooled DFS-HR of 0.85 (95%CI: 0.74 to 0.97; I2 = 0%).There was a significant interaction between the disease nodal-status and the efficacy of the full-versus limited-extended ET (p-heterogeneity = 0.048).The full-extended ET provided no significant DFS-benefit as compared with the limited-extended ET in all the other subgroups analyzed. Conclusions: Patients with eBC and N + ve disease can obtain a significant DFS-benefit from the full-extended as compared with the limited-extended adjuvant ET.

IntroductionThere is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs).MethodsWe systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients. We performed a meta-analysis of RCTs to compare the surrogacy value of PFS and modified-PFS (mPFS) for OS in RCTs testing ICIs, when the treatment effect is measured by the hazard ratio (HR) for OS, and by the HR and the ratio of restricted mean survival time (rRMST) for PFS and mPFS.Results61 RCTs (67 treatment comparisons and 36,034 patients) were included in the analysis. In comparisons testing ICI plus chemotherapy, HRPFS and HRmPFS both had a strong surrogacy value (R2 = 0.74 and R2 = 0.81, respectively). In comparisons testing ICI as monotherapy, HRPFS was the best surrogate, although having a moderate correlation (R2 = 0.58). In comparisons testing ICI plus other treatment(s), the associations were very weak for all the surrogate endpoints and treatment effect measures, with R2 ranging from 0.01 to 0.22.ConclusionIn RCTs testing ICIs, the value of potential surrogates for HROS was strongly affected by the type of treatment(s) tested. The evidence available supports HRPFS as the best surrogate, and disproves the use of alternative endpoints, such as the mPFS, or treatment effect measures, such as the RMST.

Renal Cell Carcinoma (RCC) is generally characterized by low-FDG avidity, and [18F]FDG-PET/CT is not recommended to stage the primary tumor. However, its role to assess metastases is still unclear. The aim of this study was to evaluate the diagnostic accuracy of [18F]FDG-PET/CT in correctly identifying RCC lung metastases using histology as the standard of truth. The records of 350 patients affected by RCC were retrospectively analyzed. The inclusion criteria were: (a) biopsy- or histologically proven RCC; (b) Computed Tomography (CT) evidence of at least one lung nodule; (c) [18F]FDG-PET/CT performed prior to lung surgery; (d) lung surgery with histological analysis of surgical specimens; (e) complete follow-up available. A per-lesion analysis was performed, and diagnostic accuracy was reported as sensitivity and specificity, using histology as the standard of truth. [18F]FDG-PET/CT semiquantitative parameters (Standardized Uptake Value [SUVmax], Metabolic Tumor Volume [MTV] and Total Lesion Glycolysis [TLG]) were collected for each lesion. Sixty-seven patients with a total of 107 lesions were included: lung metastases from RCC were detected in 57 cases (53.3%), while 50 lesions (46.7%) were related to other lung malignancies. Applying a cut-off of SUVmax ≥ 2, the sensitivity and the specificity of [18F]FDG-PET/CT in detecting RCC lung metastases were 33.3% (95% CI: 21.4–47.1%) and 26% (95%CI: 14.6–40.3%), respectively. Although the analysis demonstrated a suboptimal diagnostic accuracy of [18F]FDG-PET/CT in discriminating between lung metastases from RCC and other malignancies, a semiquantitative analysis that also includes volumetric parameters (MTV and TLG) could support the correct interpretation of [18F]FDG-PET/CT images.

The primary aim of our study was to assess the main mammographic and ultrasonographic features of invasive male breast malignancies. The secondary aim was to evaluate whether a specific radiological presentation would be associated with a worse receptor profile. Radiological images (mammography and/or ultrasound) of all patients who underwent surgery for male invasive breast cancer in our institution between 2008 and 2023 were retrospectively analyzed by two breast radiologists in consensus. All significant features of radiological presentation known in the literature were re-evaluated. Fifty-six patients were selected. The mean age at surgery of patients was 69 years (range: 35–81); in 82% of cases (46 patients), the histologic outcome was invasive ductal carcinoma. A total of 28 out of 56 (50%) patients had preoperative mammography; in 9/28 cases (32%), we found a mass with microcalcifications on mammography. The mass presented high density in 25 out of 28 patients (89%); the mass showed irregular margins in 15/28 (54%) cases. A total of 46 out of 56 patients had preoperative ultrasounds. The lesion showed a solid mass in 41/46 (89%) cases. In 5/46 patients (11%), the lesion was a mass with a mixed (partly liquid–partly solid) structure. We did not find any statistically significant correlation between major types of radiological presentation and tumor receptor arrangement. Knowledge of the main radiologic presentation patterns of malignant male breast neoplasm can help better manage this type of disease, which is rare but whose incidence is increasing.

Background: Adjuvant chemotherapy for Luminal B-like breast cancers usually includes anthracycline-based regimens. However, some patients are reluctant to receive chemotherapy because of side-effects, especially alopecia, and ask for a “less intensive” or personalized approach. Patients and methods: We conducted a phase II feasibility trial to evaluate pegylated liposomal doxorubicin (PLD, Caelyx®) as adjuvant chemotherapy. Patients who received surgery for pT1–3, any N, and luminal B-like early-stage breast cancer (EBC) candidates for adjuvant chemotherapy were included. PLD was administered intravenously at 20 mg/m2 biweekly for eight courses. Endocrine therapy was given according to menopausal status. Trastuzumab was administered in HER2-positive disease. The primary endpoint was to evaluate the feasibility of this regimen, defined as the ability of a patient to achieve a relative dose intensity (RDI) of at least 85% of the eight cycles of treatment. Secondary endpoints included adverse events (AEs), tolerability, breast cancer-free survival, disease-free survival, and overall survival. Results: From March 2016 to July 2018, 63 patients were included in the trial. Median age was 49 years (range: 33–76), with mostly pre- and peri-menopausal (65%) and stage I–II (94%). Only 5% of patients had HER2-positive EBC. Median RDI was 100% (range: 12.5–100%; interquartile range, IQR: 87.5–100%). The proportion of patients meeting the primary endpoint was 84% (95% confidence interval, CI: 73–92%). Overall, 55 out of 63 enrolled patients completed treatment (87%, 95% CI: 77–94%). Most common AEs were palmar-plantar erythrodysesthesia (12.2%), fatigue (10.4%), and mucositis (8.5%). Only 13% of patients had G3 AEs. None had alopecia. After a median follow-up of 3.9 years (range: 0.3–4.7) two distant events were observed, and all patients were alive at the date of last visit. Conclusions: The trial successfully met its primary endpoint: the regimen was feasible and well tolerated and could be considered for further evaluation as a treatment option for patients with contraindications to standard anthracyclines or requiring a personalized, less intensive approach.

Background: We report here for the first time, a comprehensive characterization of biological and clinical features of early-stage triple negative Invasive Lobular Carcinomas(TN-ILCs) Methods: We analyzed all consecutive patients with early-stage TN-ILC operated at two reference cancer-centers between 1994 and 2012.Primary objective was to assess the invasive disease-free survival(iDFS).Co-primary objective was to assess biological features of TN-ILCs, including molecular intrinsic subtypes based on PAM-50 assay, expression of androgen receptor (AR) and mutational status of ERBB2-gene.Additionally, DNA mutational status of an independent cohort of 45 TN-ILCs from three databases were analyzed, to confirm mutations in ERBB2-gene and to identify other recurrently mutated genes. Results: Among 4152 ILCs, 74(1.8%) were TN and were analyzed.The iDFS at 5 and 10 years of FUP were 50.4%(95%CI,38.0–61.6) and 37.2%(95%CI,25.5–48.8), respectively.The molecular subtype was defined through PAM50-classifier for 31 out of 74 TN-ILCs: 48% were Luminal-A(15/31), 3% luminal-B(1/31), 32% HER2-enriched (10/31), and only 16% basal-like(5/31).Luminal tumors expressed AR more frequently than non-luminal tumors (AR≥1% in 94% of luminal tumors versus 53% in non-luminal tumors; p-value = 0.001).20% of TN-ILCs analyzed(7/35), harbored a pathogenetic and actionable mutation in the ERBB2-gene. Analysis of the independent cohort of 45 TN-ILCs from three different databases, confirmed similar percentage of pathogenetic and actionable mutations in ERBB2-gene(20%; 9/45).Among the top 10 molecular pathways significantly enriched for recurrently mutated genes in TN-ILCs(FDR

Purpose: Incomplete response to neoadjuvant chemotherapy (NACT) in triple negative breast cancer (TNBC) patients is correlated to high risk of relapse. This study aimed to evaluate the role of adjuvant chemotherapy in TNBC with residual tumor after NACT. Methods: We retrospectively reviewed the outcome of patients with TNBC with residual tumor at surgery after a neoadjuvant treatment, followed by either adjuvant chemotherapy or observation. Primary endpoints were Disease Free Survival (DFS) and Overall Survival (OS). Results: Between January 2000 and December 2016, 223 patients with early TNBC operated at the European Institute of Oncology were eligible. A total of 83.4 % of patients received adjuvant chemotherapy after surgery. 90 patients received standard dose infusional regimens, while 96 patients (51.6 %) received oral metronomic chemotherapy. Adjusting the analysis by surgical stage and Ki67 value there was a benefit for DFS and OS in favor of the group that received postoperative chemotherapy (DFS-HR 0.58 p = 0.04; OS-HR 0.54, p = 0.02). At a subgroup analysis according to the different adjuvant treatments received, a benefit for metronomic chemotherapy versus no chemotherapy both for DFS (HR 0.46, p = 0.008) and OS (HR 0.45, p = 0.009) was reported. Conclusion: Our retrospective analysis in a large cohort of TNBC patients with residual disease after NACT confirms the benefit of adding a postoperative treatment to reduce risk of relapse and death. Based on these results, we suggest that the adjuvant therapy based on metronomic cyclophosphamide and methotrexate deserves further investigation in this patients population.

BackgroundRisk stratification in long QT syndrome (LQTS) patients is important for optimizing patient care and informing clinical decision making. We developed a risk prediction algorithm with prediction of 5-year absolute risk of the first life-threatening arrhythmic event [defined as aborted cardiac arrest, sudden cardiac death, or appropriate implantable cardioverter defibrillator (ICD) shock] in LQTS patients, accounting for individual risk factors and their changes over time.MethodsRochester-based LQTS Registry included the phenotypic cohort consisting of 1,509 LQTS patients with a QTc ≥ 470 ms, and the genotypic cohort including 1,288 patients with single LQT1, LQT2, or LQT3 mutation. We developed two separate risk prediction models which included pre-specified time-dependent covariates of beta-blocker use, syncope (never, syncope while off beta blockers, and syncope while on beta blockers), and sex by age < and ≥13 years, baseline QTc, and genotype (for the genotypic cohort only). Follow-up started from enrollment in the registry and was censored at patients’ 50s birthday, date of death due to reasons other than sudden cardiac death, or last contact, whichever occurred first. The predictive models were externally validated in an independent cohort of 1,481 LQTS patients from Pavia, Italy.ResultsIn Rochester dataset, there were 77 endpoints in the phenotypic cohort during a median follow-up of 9.0 years, and 47 endpoints in the genotypic cohort during a median follow-up of 9.8 years. The time-dependent extension of Harrell’s generalized C-statistics for the phenotypic model and genotypic model were 0.784 (95% CI: 0.740–0.827) and 0.785 (95% CI: 0.721–0.849), respectively, in the Rochester cohort. The C-statistics obtained from external validation in the Pavia cohort were 0.700 (95% CI: 0.610–0.790) and 0.711 (95% CI: 0.631–0.792) for the two models, respectively. Based on the above models, an online risk calculator estimating a 5-year risk of life-threatening arrhythmic events was developed.ConclusionThis study developed two risk prediction algorithms for phenotype and genotype positive LQTS patients separately. The estimated 5-year absolute risk can be used to quantify a LQTS patient’s risk of developing life-threatening arrhythmic events and thus assisting in clinical decision making regarding prophylactic ICD therapy.

The aim of this study was to evaluate the diagnostic performance of contrast-enhanced spectral mammography (CESM) in predicting breast lesion malignancy due to microcalcifications compared to lesions that present with other radiological findings. Three hundred and twenty-one patients with 377 breast lesions that underwent CESM and histological assessment were included. All the lesions were scored using a 4-point qualitative scale according to the degree of contrast enhancement at the CESM examination. The histological results were considered the gold standard. In the first analysis, enhancement degree scores of 2 and 3 were considered predictive of malignity. The sensitivity (SE) and positive predictive value (PPV) were significative lower for patients with lesions with microcalcifications without other radiological findings (SE = 53.3% vs. 82.2%, p-value < 0.001 and PPV = 84.2% vs. 95.2%, p-value = 0.049, respectively). On the contrary, the specificity (SP) and negative predictive value (NPV) were significative higher among lesions with microcalcifications without other radiological findings (SP = 95.8% vs. 84.2%, p-value = 0.026 and NPV = 82.9% vs. 55.2%, p-value < 0.001, respectively). In a second analysis, degree scores of 1, 2, and 3 were considered predictive of malignity. The SE (80.0% vs. 96.8%, p-value < 0.001) and PPV (70.6% vs. 88.3%, p-value: 0.005) were significantly lower among lesions with microcalcifications without other radiological findings, while the SP (85.9% vs. 50.9%, p-value < 0.001) was higher. The enhancement of microcalcifications has low sensitivity in predicting malignancy. However, in certain controversial cases, the absence of CESM enhancement due to its high negative predictive value can help to reduce the number of biopsies for benign lesions

Background: Triple negative breast cancer encompasses several biological entities with different outcomes and is a priority to identify which patients require more treatment to reduce the risk of recurrence and which patients need less treatment. Patients and methods: Among the 210 women with first primary invasive apocrine non metastatic breast cancer operated on between January 1998 and December 2016 at the European Institute Oncology, Milan, we identified 24 patients with a pT1-pT2, node-negative, triple negative subtype and Ki-67 ≤ 20% who did not receive adjuvant chemotherapy (CT). We compared the outcome of this cohort with a similar group of 24 patients with ductal tumors who received adjuvant chemotherapy, matched by pathological stage and biological features and also with a similar group of 12 patients with apocrine tumors who received adjuvant chemotherapy. Results: The median age was 64 and 61 years in the apocrine (w/o CT) and ductal group, respectively. The median value of Ki-67 expression was 12% in the apocrine group (w/o CT) and 16% in the ductal group (p

Objectives: Tumor-associated antigens (TAAs) are frequently overexpressed in several cancer types. The aim of this study was to investigate the expression of TAAs in breast cancer. Material and methods: A total of 250 selected invasive breast cancers including 50 estrogen receptor (ER)-positive (Luminal B like), 50 triple-negative (TN), 50 ER-positive lobular type, 50 ER- and progesterone receptor (PgR)-positive (Luminal A like) and 50 cerbB2-positive breast cancers, were assessed for New York esophageal squamous cell carcinoma-1 (NY-ESO-1), Wilms tumor antigen (WT-1) and PReferentially expressed Antigen of MElanoma (PRAME) antigen expression by immunohistochemistry (IHC). Results: A significantly higher expression of cancer testis (CT)-antigens NY-ESO-1 and WT-1 antigen was detected in TN breast cancers compared with ER-positive tumors. NY-ESO-1 overexpression (score 2 + and 3+) assessed by monoclonal and polyclonal antibodies was detected in 9 (18%) TN cancers as compared to 2 (4%) ER-positive tumors (p = 0.002). WT1 over-expression (score 2 + and 3+) was confirmed in 27 (54%) TN tumor samples as compared to 6 (12%) ER-positive (p

Abstract Background Although lifestyle factors have been studied in relation to individual non-communicable diseases (NCDs), their association with development of a subsequent NCD, defined as multimorbidity, has been scarcely investigated. The aim of this study was to investigate associations between five lifestyle factors and incident multimorbidity of cancer and cardiometabolic diseases. Methods In this prospective cohort study, 291,778 participants (64% women) from seven European countries, mostly aged 43 to 58 years and free of cancer, cardiovascular disease (CVD), and type 2 diabetes (T2D) at recruitment, were included. Incident multimorbidity of cancer and cardiometabolic diseases was defined as developing subsequently two diseases including first cancer at any site, CVD, and T2D in an individual. Multi-state modelling based on Cox regression was used to compute hazard ratios (HR) and 95% confidence intervals (95% CI) of developing cancer, CVD, or T2D, and subsequent transitions to multimorbidity, in relation to body mass index (BMI), smoking status, alcohol intake, physical activity, adherence to the Mediterranean diet, and their combination as a healthy lifestyle index (HLI) score. Cumulative incidence functions (CIFs) were estimated to compute 10-year absolute risks for transitions from healthy to cancer at any site, CVD (both fatal and non-fatal), or T2D, and to subsequent multimorbidity after each of the three NCDs. Results During a median follow-up of 11 years, 1910 men and 1334 women developed multimorbidity of cancer and cardiometabolic diseases. A higher HLI, reflecting healthy lifestyles, was strongly inversely associated with multimorbidity, with hazard ratios per 3-unit increment of 0.75 (95% CI, 0.71 to 0.81), 0.84 (0.79 to 0.90), and 0.82 (0.77 to 0.88) after cancer, CVD, and T2D, respectively. After T2D, the 10-year absolute risks of multimorbidity were 40% and 25% for men and women, respectively, with unhealthy lifestyle, and 30% and 18% for men and women with healthy lifestyles. Conclusion Pre-diagnostic healthy lifestyle behaviours were strongly inversely associated with the risk of cancer and cardiometabolic diseases, and with the prognosis of these diseases by reducing risk of multimorbidity.

Cervico-vaginal (CV) localization of extra-mammary Paget’s disease (EMPD) of the vulva is extremely rare. In order to investigate the incidence risk and the pathognomonic clinical and pathological features of this condition, a retrospective analysis was conducted including 94 women treated for vulvar EMPD at the European Institute of Oncology, Milan, Italy, from October 1997 to May 2020. Overall nine patients developed CV involvement from EMPD, with a cumulative incidence of 2.5% (95% CI: 0.5–8.0%) at 5 years, 6.5% (95% CI: 1.9–15.1%) at 10 years and 14.0% (95% CI: 4.8–27.8%) at 15 years, respectively. All cases except one were firstly detected by abnormal glandular cytology. None reported vaginal bleeding or other suspicious symptoms. The colposcopic findings were heterogeneous and could sometimes be misdiagnosed. Cervical and/or vaginal biopsies were always performed for histopathological diagnosis by identification of Paget cells in the epithelium or stroma. Most patients developed invasive EMPD (5/9) of the cervix and/or vagina and underwent hysterectomy with partial or total colpectomy. CV involvement from EMPD should not be underestimated in women with a long-standing history of vulvar Paget’s disease. Liquid-based cytology with immunocytochemistry represents a valuable tool for early diagnosis and should be routinely performed during the required lifelong follow-up.

Abstract Background Invasive lobular carcinomas (ILCs) account for 10–15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs. Patients and methods We retrospectively analyzed all consecutive patients with hormone receptor–positive ILC operated at the European Institute of Oncology (EIO) between June 1994 and December 2010 and scheduled to receive at least 5 years of endocrine treatment. The aim was to identify clinical and pathological variables that provide prognostic information in the period beginning 5 years after definitive surgery. The cumulative incidence of distant metastases (CI-DM) from 5 years after surgery was the prospectively defined primary endpoint. Results One thousand eight hundred seventy-two patients fulfilled the inclusion criteria. The median follow-up was 8.7 years. Increased tumor size and positive nodal status were significantly associated with higher risk of late distant recurrence, but nodal status had a significant lower prognostic value in late follow-up period (DM-HR, 3.21; 95% CI, 2.06–5.01) as compared with the first 5 years of follow-up (DM-HR, 9.55; 95% CI, 5.64–16.2; heterogeneity p value 0.002). Elevated Ki-67 labeling index (LI) retained a significant and independent prognostic value even after the first 5 years from surgery (DM-HR, 1.81; 95% CI 1.19–2.75), and it also stratified the prognosis of ILC patients subgrouped according to lymph node status. A combined score, obtained integrating the previously validated Clinical Treatment Score post 5 years (CTS5) and Ki-67 LI, had a strong association with the risk of late distant recurrence of ILCs. Conclusion We identified factors associated with the risk of late distant recurrence in ER-positive ILCs and developed a simple prognostic score, based on data that are readily available, which warrants further validation.

Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced resectable gastric cancer but, despite important progresses, relapse-related death remains a major challenge. Therefore, it appears crucial to understand which patients will benefit from peri-operative treatment. Biomarkers such as human epidermal growth factor receptor-2 (HER2), microsatellite instability (MSI), and Epstein-Barr Virus (EBV) have been widely studied; however, they do not yet guide the choice of perioperative treatment in clinical practice. We performed a narrative review, including 23 studies, addressing the value of tissue- or blood-based biomarkers in the neoadjuvant setting. Ten studies (43.5%) were prospective, and more than half were conducted in East-Asia. Biomarkers were evaluated only post-NAC (on surgical samples or blood) in seven studies (30.4%), only pre-NAC (on endoscopic specimens or blood) in 10 studies (43.5%), and both pre- and post-NAC (26.1%) in six studies. Among the high variety of investigated biomarkers, some of these including MSI-H or enzymatic profile (as TS, UGT1A1, MTHFR, ERCC or XRCC) showed promising results and deserve to be assessed in methodologically sound clinical trials. The identification of molecular biomarkers in patients treated with NAC for locally advanced resectable gastric or EGJ cancer remains crucial.

Background and Aims: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1–2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). Patients and Methods: We carried out a retrospective study on 67 patients affected by stage I–III ASCC, treated with CDDP (60–70 mg/m 2 every 21 days for two courses) plus C (825 mg/m 2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. Results: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively. Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3–4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). Conclusion: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

Obesity correlates with hematologic malignancies including leukemias, but risk of specific leukemia subtypes like acute promyelocytic leukemia and underlying molecular mechanisms are poorly understood. We explored multiple datasets for correlation between leukemia, body mass index (BMI) and molecular features. In a population-based study (n=5.2 million), we correlated BMI with promyelocytic leukemia, and other acute myeloid, lymphoid or other leukemias. In cross-sectional studies, we tested BMI deviation in promyelocytic leukemia trial cohorts from that expected based on national surveys. We explored The Cancer Genome Atlas for transcriptional signatures and mutations enriched in promyelocytic leukemia and/or obesity, and confirmed a correlation between body mass and FLT3 mutations in promyelocytic leukemia cohorts by logistic regression. In the population-based study, hazard ratio per 5 kg/m2 increase was: promyelocytic leukemia 1.44 (95%CI: 1.0-2.08), non-promyelocytic acute myeloid leukemias 1.17 (95%CI: 1.10-1.26), lymphoid leukemias 1.04 (95%CI: 1.0-1.09), other 1.10 (95%CI: 1.04-1.15). In cross-sectional studies, body mass deviated significantly from that expected (Italy: P

The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions—Mediterranean (M) and high protein (HP)—improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M–HP or HP–M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = −6.98 (−12.30, −1.65) µIU/mL, p = 0.01; HOMA-IR: −1.78 (95% CI: −3.03, −0.52), p = 9 × 10−3); and (ii) improving glycemic variability (−3.13 (−4.60, −1.67) mg/dL, p = 4 × 10−4), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera Coprococcus and Lachnoclostridium, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.

Grade 3 (G3) neuroendocrine tumors (NETs) are a novel category among digestive neuroendocrine neoplasms, characterized by Ki-67 >20% and a well-differentiated morphology, presenting high intra-tumor heterogeneity. We aimed to explore the role of dual-tracer PET imaging (68Gallium (Ga)-DOTATOC and 18Fluorodeoxyglucose (FDG)) as overall survival (OS) predictor in NET G3 patients. We performed a retrospective analysis in NET G3 patients treated at our institution between 2003 and 2021. Accordingly, 30 NET G3 patients were analyzed. 68Ga-DOTA-TOC and 18F-FDG uptake were assessed by tumor/non-tumor (T-nonT) ratio. We reported a slightly better OS for patients with ≥75% concordance between 68Ga-DOTA-TOC and 18F-FDG PET/CT (p = 0.42). Among patients with discordant functional imaging, we reported a better 5-y OS rate for patients with a prevalent 68Ga-DOTATOC vs. 18F-FDG PET/CT (p = 0.016). In positive 18F-FDG PET/CT cases, we reported a better OS for p = 0.021). Among upfront-NET G3 patients with concordant exams, 5-y OS rate was 83.3% (95% CI: 27.3–97.5). Among patients with discordant exams, 5-y OS rate was 81.3% (52.5–93.5), 100% for those with prevalent receptor expression, and 50% (11.1–80.4) for those with prevalent 18F-FDG uptake. Our findings suggest that dual-tracer PET/CT can be considered as a predictor of patient outcome, able to stratify NET G3 patients with poorer prognosis.

(1) Background: to evaluate which factors can reduce the upgrade rate of atypical ductal hyperplasia (ADH) to in situ or invasive carcinoma in patients who underwent vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. (2) Methods: 2955 VABBs were reviewed; 141 patients with a diagnosis of ADH were selected for subsequent surgical excision. The association between patients’ characteristics and the upgrade rate to breast cancer was evaluated in both univariate and multivariate analyses. (3) Results: the upgrade rates to ductal carcinoma in situ (DCIS) and invasive carcinoma (IC) were, respectively, 29.1% and 7.8%. The pooled upgrade rate to DCIS or IC was statistically lower at univariate analysis, considering the following parameters: complete removal of the lesion (p-value < 0.001); BIRADS ≤ 4a (p-value < 0.001); size of the lesion ≤15 mm (p-value: 0.002); age of the patients p-value: 0.035). (4) Conclusions: the overall upgrade rate of ADH to DCIS or IC is high and, as already known, surgery should be recommended. However, ADH cases should always be discussed in multidisciplinary meetings: some parameters appear to be related to a lower upgrade rate. Patients presenting these parameters could be strictly followed up to avoid overtreatment.

Background: The management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in medical oncology, surgical oncology, radiation oncology and radiology. It is crucial for highly specialized centers to collaborate via networks that aim to maintain uniformity in every aspect of treatment and rigorously gather patients’ data, from the first clinical evaluation to the last follow-up visit. The Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network aims to create a rectal cancer registry. This will prospectively collect the data of patients operated on for non-metastatic rectal cancer in high volume colorectal surgical units through a well design pre-fashioned database for non-metastatic rectal cancer, in order to take all multidisciplinary aspects into consideration. Methods/Design: The protocol describes a multicenter prospective observational cohort study, investigating demographics, frailty, cancer-related features, surgical and radiological parameters, and oncological outcomes among patients with non-metastatic rectal cancer who are candidates for surgery with curative intent. Patients enrolled in the present registry will be followed up for 5 years after surgery. Discussion: Standardization and centralization of data collection for neoplastic diseases is a virtuous process for patient care. The creation of a register will allow the control of the quality of treatments provided and permit prospective and retrospective studies to be carried out on complete and reliable high quality data. Establishing data collection in a prospective and systematic fashion is the only possibility to preserve the enormous resource that each patient represents.

Background: The management of rectal cancer is multimodal and involves a multidisciplinary team of cancer specialists with expertise in medical oncology, surgical oncology, radiation oncology and radiology. It is crucial for highly specialized centers to collaborate via networks that aim to maintain uniformity in every aspect of treatment and rigorously gather patients’ data, from the first clinical evaluation to the last follow-up visit. The Advanced International Mini-Invasive Surgery (AIMS) academy clinical research network aims to create a rectal cancer registry. This will prospectively collect the data of patients operated on for non-metastatic rectal cancer in high volume colorectal surgical units through a well design pre-fashioned database for non-metastatic rectal cancer, in order to take all multidisciplinary aspects into consideration. Methods/Design: The protocol describes a multicenter prospective observational cohort study, investigating demographics, frailty, cancer-related features, surgical and radiological parameters, and oncological outcomes among patients with non-metastatic rectal cancer who are candidates for surgery with curative intent. Patients enrolled in the present registry will be followed up for 5 years after surgery. Discussion: Standardization and centralization of data collection for neoplastic diseases is a virtuous process for patient care. The creation of a register will allow the control of the quality of treatments provided and permit prospective and retrospective studies to be carried out on complete and reliable high quality data. Establishing data collection in a prospective and systematic fashion is the only possibility to preserve the enormous resource that each patient represents.