To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC).
We conducted a systematic review and meta-analysis of the prevalence ...of HRD in PDAC from PubMed, Scopus, and Cochrane Library databases, and online cancer genomic data sets. The main outcome was pooled prevalence of somatic and germline mutations in the better characterized HRD genes (
,
,
,
,
,
,
, and the
genes). The secondary outcomes were prevalence of germline mutations overall, and in sporadic and familial cases; prevalence of germline
mutations in Ashkenazi Jewish (AJ); and prevalence of HRD based on other definitions (ie, alterations in other genes, genomic scars, and mutational signatures). Random-effects modeling with the Freeman-Tukey transformation was used for the analyses. PROSPERO registration number: (CRD42020190813).
Sixty studies with 21,842 participants were included in the systematic review and 57 in the meta-analysis. Prevalence of germline and somatic mutations was
: 0.9%,
: 3.5%,
: 0.2%,
: 2.2%,
: 0.3%,
: 0.5%,
: 0.0%, and
: 0.1%. Prevalence of germline mutations was
: 0.9% (2.4% in AJ),
: 3.8% (8.2% in AJ),
: 0.2%,
: 2%,
: 0.3%, and
: 0.4%. No significant differences between sporadic and familial cases were identified. HRD prevalence ranged between 14.5%-16.5% through targeted next-generation sequencing and 24%-44% through whole-genome or whole-exome sequencing allowing complementary genomic analysis, including genomic scars and other signatures (surrogate markers of HRD).
Surrogate readouts of HRD identify a greater proportion of patients with HRD than analyses limited to gene-level approaches. There is a clear need to harmonize HRD definitions and to validate the optimal biomarker for treatment selection. Universal HRD screening including integrated somatic and germline analysis should be offered to all patients with PDAC.
The present study aimed to provide a descriptive analysis of the nutrient profile of ultra-processed foods (UPFs) marketed in Italy according to three front-of-pack labeling (FOPL) schemes ...implemented by France, i.e., the Nutriscore; by the United Kingdom, i.e., Multiple Traffic Lights (MTL); and by Italy, i.e., the NutrInform battery. The analysis was made in fourteen food product categories, corresponding to 124 foods. The application of the Nutriscore scheme showed that a significant proportion of foods (23%) were awarded an A or B. Furthermore, the analysis according to the MTL showed that food products that were above the threshold (“red”) for fat, saturated fats, sugars, and salt ranged from 13% to 31%. Interestingly, even though all foods considered in the analysis were UPF, they were heterogeneous in nutritional composition, as demonstrated by the FOPL schemes applied, showing that UPF represent a heterogeneous group of foods with different characteristics. Such a finding may have relevant implications for epidemiological studies that analyze the association between UPF consumption and health outcomes, suggesting the need for better characterization of the effects of UPF intake on human health.
Radioembolization is a valuable therapeutic option in patients with unresectable intrahepatic cholangiocarcinoma. The essential implementation of the absorbed dose calculation methods should take ...into account also the specific tumor radiosensitivity, expressed by the α parameter. Purpose of this study was to retrospectively calculate it in a series of patients with unresectable intrahepatic cholangiocarcinoma submitted to radioembolization. Twenty-one therapeutic procedures in 15 patients were analysed. Tumor absorbed doses were calculated processing the post-therapeutic
Y-PET/CT images and the pre-treatment contrast-enhanced CT scans. Tumor absorbed dose and pre- and post-treatment tumor volumes were used to calculate α and α
parameters (dividing targeted liver in n voxels of the same volume with specific voxel absorbed dose). A tumor volume reduction was observed after treatment. The median of tumor average absorbed dose was 93 Gy (95% CI 81-119) and its correlation with the residual tumor mass was statistically significant. The median of α and α
parameters was 0.005 Gy
(95% CI 0.004-0.008) and 0.007 Gy
(95% CI 0.005-0.015), respectively. Multivariate analysis showed tumor volume and tumor absorbed dose as significant predictors of the time to tumor progression. The knowledge of radiobiological parameters gives the possibility to decide the administered activity in order to improve the outcome of the treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Objectives
To retrospectively compare long-term outcomes of first-line drug-eluting particle (DEB)- transarterial chemoembolization (TACE) and lipiodol-TACE, in patients with unresectable ...hepatocellular (HCC).
Methods
We retrospectively reviewed our database to identify adult patients with treatment-naïve unresectable HCC, who underwent TACE from 2006 to 2013. Patients were excluded in the absence of complete medical records relative to first TACE, 1-month follow-up, and/or sufficient follow-up data. Periprocedural complications, duration of hospitalization, 1-month tumor response by mRECIST, time to tumor progression (TTP) and target tumor progression (TTTP), and overall survival (OS) were evaluated.
Results
Out of an initial series of 656 patients, 329 patients were excluded for unavailability of sufficient baseline and/or follow-up data. The remaining 327 patients underwent either lipiodol-TACE (
n
= 160) or DEB-TACE (
n
= 167). Patients treated with lipiodol-TACE had a significantly higher tumor burden. By propensity score, patients were matched according to baseline differences (BCLC stage, uninodular or multinodular HCC, and unilobar or bilobar HCC), resulting in 101 patients in each treatment group. Lipiodol-TACE was associated with a significantly higher incidence of adverse events (
p
= 0.03), and longer hospitalization (mean, 2.5 days vs 1.9 days;
p
= 0.03), while tumor response, TTP, and OS were comparable. In patients achieving 1-month complete response (CR) of target tumor, TTTP was significantly (
p
= 0.009) longer after DEB-TACE compared to lipiodol-TACE (median, 835 vs 353 days), resulting in a lower number of re-treatments during the entire follow-up (0.75 vs 1.6,
p
= 0.01).
Conclusion
Compared to lipiodol-TACE, DEB-TACE offers higher tolerability, reduced hospitalization, and more durable target tumor response after CR.
Key Points
• Compared to lipiodol-TACE, DEB-TACE is better tolerated and has reduced side effects, which translates into shorter hospitalization.
• When complete radiological response according to the mRECIST is obtained 1 month after the procedure, DEB-TACE offers a more durable local tumor control compared to lipiodol-TACE.
• In these patients, the longer duration of response after DEB-TACE translates into a lower number of re-interventions.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ
Atrial functional mitral regurgitation (aFMR) has a peculiar pathophysiology that may have distinctive outcomes. We investigated the impact of transcatheter edge-to-edge repair in aFMR compared with ...other FMR etiologies. The GIOTTO (GIse registry Of Transcatheter treatment of MR) is a multicenter, prospective study enrolling patients with symptomatic MR treated with MitraClip up to 2020. We categorized patients with FMR as aFMR, ischemic FMR (iFMR), and nonischemic ventricular FMR (niFMR). The clinical end points were defined according to the Mitral Valve Academic Research Consortium. Of 1,153 patients, 6% had aFMR, 47% iFMR, and 47% niFMR. Patients with aFMR were older, mostly women, and had a higher atrial fibrillation rate. They had better left ventricular ejection fraction and smaller left ventricular volumes, with no difference in mitral effective regurgitant orifice area. The acute device and procedural success rates were similar among the groups. At the longest available follow-up (median 478 days, interquartile range 91 to 741 days), the rate of MR ≥2+ was similar among the groups. Patients with aFMR had a lower rate of cardiovascular death and heart failure than patients with iFMR (hazard ratio HR 0.43, p = 0.02) and niFMR (HR 0.45, p = 0.03). The aFMR etiology remained independently associated with the composite outcome, together with postprocedural MR ≤1+ (HR 0.63, p <0.01) and peripheral arteriopathy (HR 1.82, p = 0.003). The results of this GIOTTO subanalysis suggested that aFMR is less prevalent and associated with better outcomes compared with other causes of FMR treated by transcatheter edge-to-edge repair. Postprocedural MR >1+, peripheral vasculopathy, non-aFMR were independent predictors of worse outcomes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objectives
Results after trans-arterial radioembolisation (TARE) for intrahepatic cholangiocarcinoma (iCC) depend on the architecture of the tumour. This latter can be quantified through computed ...tomography (CT) texture analysis. The aims of the present study were to analyse relationships between CT textural features prior to TARE and objective response (OR), progression-free survival (PFS), and overall survival (OS).
Methods
Texture analysis was retrospectively applied to 55 pre-TARE CT scans of iCCs, focusing attention on the histogram-based features and the grey-level co-occurrence matrix (GLCM). Texture features were harmonised using the ComBat procedure. Objective response was assessed using the Response Evaluation Criteria In Solid Tumours 1.1. The least absolute shrinkage and selection operator (LASSO) method was applied to select the most useful textural features related to OR.
Results
Of the 55 patients, 53 had post-TARE imaging available, showing OR in 56.6% of cases. Texture analysis showed that iCCs showing OR after TARE had a higher uptake of iodine contrast in the arterial phase (higher
mean
histogram values,
p
< 0.001) and more homogeneous distribution (lower
kurtosis
,
p
= 0.043;
GLCM contrast
,
p
= 0.004;
GLCM dissimilarity
,
p
= 0.005, and higher
GLCM homogeneity
,
p
= 0.005; and
GLCM correlation p
= 0.030) at the pre-TARE CT scan. A favourable radiomic signature was calculated and observed in 15 of the 55 patients. The median PFS of these 15 patients was 12.1 months and that of the remaining 40 patients was 5.1 months (
p
= 0.008).
Conclusions
Texture analysis of pre-TARE CT scans can quantify vascularisation and homogeneity of iCC architecture, providing clinical information useful in identifying ideal TARE candidates.
Key Points
• Hypervascular tumours with a more homogeneous uptake of iodine contrast in the arterial phase were those most likely to be effectively treated by TARE.
• The arterial phase was observed to be the best acquisition phase for providing information regarding the “sensitivity” of the tumour to TARE.
• Patients with favourable radiomic signature showed a median progression-free survival of 12.1 months versus 5.1 months of patients with an unfavourable signature (p = 0.008).
Background
Y90 transarterial radioembolization (Y90-RE) may improve clinical outcomes of unresectable intrahepatic cholangiocarcinoma (ICC); however, the optimal timing for Y90-RE is still debated. ...The purpose of this multicenter study was to retrospectively evaluate clinical outcomes of RE in patients with unresectable ICC, comparing three different settings: chemotherapy naïve patients (group A), patients with disease control after first-line chemotherapy (group B) and patients with progression after first-line chemotherapy (group C).
Materials and Methods
The study included 81 consecutive patients (49 male, mean age 62.4 ± 11.8 years): 35 (43.2%) patients were in group A, 19 (23.5%) in group B, and 27 (33.3%) in group C. Preprocedural clinical variables, tumour response according to RECIST 1.1 and overall survival (OS) were analysed and compared.
Results
Baseline demographic and clinical features did not differ significantly among groups, with the exception of prior surgical procedures that were significantly higher in group C patients, and macrovascular invasion that was more frequent in group B. Radiological response was available in 79 patients; objective response and disease control rates were 41.8% and 83.6%, respectively, without significant differences among groups. Median OS was 14.5 months (95% CI: 11.1–16.9) and was not significantly different among treatment groups. At multivariate analysis, tumour burden > 50%, neutrophil-to-lymphocyte (N/L) ratio ≥ 3 and radiological progression as best response resulted to be significant (
P
< 0.05) independent factors, negatively associated with OS.
Conclusion
Y90-RE is a valuable treatment option in unresectable ICC, irrespectively from the timing of treatment. Tumour extension, N/L ratio and radiological response affect post-treatment survival.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The outbreak poses a relevant burden on hospital resources, with a marked increase in the intensive care unit (ICU) occupancy rates 1. SEE PDF These findings suggest that testing also ...asymptomatic/mild symptomatic patients would help reduce the proportion of most severe cases eventually requiring ICU and thus limiting the risk of saturation of ICU units. Regression modeling strategies with applications to linear models, logistic and ordinal regression and survival analysis (2nd Edition).
Cardiac complications are a leading cause of mortality after orthotopic liver transplantation (LT) and pre-operative risk stratification is challenging. We evaluated whether coronary artery calcium ...(CAC) score calculated on a standard (non-thin layer, non-ECG gated) chest computed tomography (CT) predicted cardiac outcome after LT.
We included a consecutive series of LT recipients who underwent pre-operative cardiac evaluation including stress-testing or cardiac catheterization in high-risk patients. Patients with a history of coronary artery disease or coronary revascularization were excluded. The CAC score was calculated from the chest CT routinely performed before LT. CAC values were not available at the time of pre-transplant cardiac evaluation and did not affect LT eligibility. The primary end-point included peri-operative arrhythmic cardiac arrest and sustained ventricular arrhythmias; heart failure, myocardial infarction and cardiac death within 1-year after LT.
The study population consisted of 301 patients (median age 56 years, 76% males). At chest CT, 49% had CAC = 0; 27% had CAC = 1–99, 15% had CAC = 100–399 and 9% CAC > 400. The primary end-point incidence increased from 7% in patients with CAC = 0 to 27% in patients with CAC > 400 (p = 0.007). At multivariable analysis including traditional risk factors, CAC remained an independent predictor of cardiac events (p = 0.01).
CAC score calculated on a standard chest CT stratified the risk of cardiac events in patients who underwent LT after negative pre-transplant cardiac evaluation. These findings suggest that evaluation of CAC from a standard chest CT performed for other reasons can be used as an early cardiac risk stratification tool before LT.
•Cardiac complications are a leading cause of mortality after OLT•Pre-operative cardiological risk stratification is challenging and not standardized•Standard chest CT is routinely performed before OLT to exclude contraindications•CAC score on standard chest CT may be used as an early cardiac risk stratification tool
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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