Electronic nose, electronic tongue and computer vision systems, designed to artificially perceive flavour and appearance, have been increasingly used in the food industry as rapid and reliable tools ...for quality assessment. The use of multivariate analysis methods, together with electronic senses, has shown to be very powerful; however, due to the high complexity of food, the employment of just single sensor data is often insufficient. In recent years, much research has been performed to develop several data fusion strategies, combining the outputs of multiple instrumental sources, for improving the quality assessment and authentication of food. The aim of this work is to review the recent achievements in the field of artificial sensors’ application, in the evaluation of animal source food products.
•Electronic nose, electronic tongue and computer vision systems technologies are reviewed.•Last five year relevant contributions in animal source food authentication and assessment are considered.•Most used multivariate statistical analysis and pattern recognition techniques are briefly reviewed.•Multiple and complementary sensor data fusion strategies and its application have been reviewed.
Abstract
Objective
To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively.
Design
Multicentre ...cohort study.
Setting
36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre.
Participants
Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up.
Main outcome measures
Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain.
Results
The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125.
Conclusions
Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively.
Trial registration
ClinicalTrials.gov
NCT01698632
.
Background Accurate methods to preoperatively characterize adnexal tumors are pivotal for optimal patient management. A recent metaanalysis concluded that the International Ovarian Tumor Analysis ...algorithms such as the Simple Rules are the best approaches to preoperatively classify adnexal masses as benign or malignant. Objective We sought to develop and validate a model to predict the risk of malignancy in adnexal masses using the ultrasound features in the Simple Rules. Study Design This was an international cross-sectional cohort study involving 22 oncology centers, referral centers for ultrasonography, and general hospitals. We included consecutive patients with an adnexal tumor who underwent a standardized transvaginal ultrasound examination and were selected for surgery. Data on 5020 patients were recorded in 3 phases from 2002 through 2012. The 5 Simple Rules features indicative of a benign tumor (B-features) and the 5 features indicative of malignancy (M-features) are based on the presence of ascites, tumor morphology, and degree of vascularity at ultrasonography. Gold standard was the histopathologic diagnosis of the adnexal mass (pathologist blinded to ultrasound findings). Logistic regression analysis was used to estimate the risk of malignancy based on the 10 ultrasound features and type of center. The diagnostic performance was evaluated by area under the receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR–), positive predictive value (PPV), negative predictive value (NPV), and calibration curves. Results Data on 4848 patients were analyzed. The malignancy rate was 43% (1402/3263) in oncology centers and 17% (263/1585) in other centers. The area under the receiver operating characteristic curve on validation data was very similar in oncology centers (0.917; 95% confidence interval, 0.901–0.931) and other centers (0.916; 95% confidence interval, 0.873–0.945). Risk estimates showed good calibration. In all, 23% of patients in the validation data set had a very low estimated risk (<1%) and 48% had a high estimated risk (≥30%). For the 1% risk cutoff, sensitivity was 99.7%, specificity 33.7%, LR+ 1.5, LR– 0.010, PPV 44.8%, and NPV 98.9%. For the 30% risk cutoff, sensitivity was 89.0%, specificity 84.7%, LR+ 5.8, LR– 0.13, PPV 75.4%, and NPV 93.9%. Conclusion Quantification of the risk of malignancy based on the Simple Rules has good diagnostic performance both in oncology centers and other centers. A simple classification based on these risk estimates may form the basis of a clinical management system. Patients with a high risk may benefit from surgery by a gynecological oncologist, while patients with a lower risk may be managed locally.
Background
A study was made to evaluate peri‐implant conditions in compliers and erratic compliers with peri‐implant maintenance therapy (PIMT), and to assess the role of site‐specific confounders.
...Methods
Erratic PIMT compliers (EC) were defined as presenting attendance < 2×/year, while regular compliers (RC) attended ≥ 2×/year. Generalized estimating equations (GEE) were employed to perform a multivariable multilevel analysis in which the peri‐implant condition was established as dependent variable.
Results
Overall, 86 non‐smoker patients (42 RC and 44 EC) attending the Department of Periodontology of the Universitat Internacional de Catalunya were recruited consecutively on a cross‐sectional basis. The mean period of loading was 9.5 year. An implant placed in an erratic patient has 88% higher probability of presenting peri‐implant diseases versus RC. Furthermore, the probability of diagnosis of peri‐implantitis was significantly higher in EC versus RC (odds ratio OR 5.26; p = 0.009). Among other factors, history of periodontitis, non‐hygienic prosthesis, period of implant loading, and modified plaque index (mPI) at implant level were shown to significantly increase the risk of peri‐implantitis diagnosis. Although not associated with peri‐implantitis diagnosis risk, keratinized mucosa (KM) width, and vestibular depth (VD) were significantly associated to plaque accumulation (mPI).
Conclusions
Compliance with PIMT was found to be significantly associated with peri‐implant condition. In this sense, attending PIMT < 2×/year may be ineffective to prevent peri‐implantitis.
Summary Background We previously found that dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumour growth in patient-derived xenografts of HER2 -amplified metastatic colorectal ...cancer. In this study, we aimed to assess the antitumour activity of trastuzumab and lapatinib in patients with HER2-positive colorectal cancer. Methods HERACLES was a proof-of-concept, multicentre, open-label, phase 2 trial done at four Italian academic cancer centres. We enrolled adult patients with KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer refractory to standard of care (including cetuximab or panitumumab), an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion. We defined HER2 positivity in tumour samples by use of immunohistochemistry and fluorescence in-situ hybridisation in accordance with our previously validated colorectal cancer-specific diagnostic criteria. Eligible patients received intravenous trastuzumab at 4 mg/kg loading dose followed by 2 mg/kg once per week, and oral lapatinib at 1000 mg per day until evidence of disease progression. The primary endpoint was the proportion of patients achieving an objective response (defined as complete response or partial response), which was assessed by independent central review in the intention-to-treat population. This trial is registered with EudraCT, number 2012-002128-33. Findings Between Aug 27, 2012, and May 15, 2015, we screened 914 patients with KRAS exon 2 (codons 12 and 13) wild-type metastatic colorectal cancer and identified 48 (5%) patients with HER2-positive tumours, although two died before enrolment. Of these patients, 27 were eligible for the trial. All were evaluable for response. At the time of data cutoff on Oct 15, 2015, with a median follow-up of 94 weeks (IQR 51–127), eight (30%, 95% CI 14–50) of 27 patients had achieved an objective response, with one patient (4%, 95% CI −3 to 11) achieving a complete response, and seven (26%, 95% CI 9–43) achieving partial responses; 12 (44%, 95% CI 25–63) patients had stable disease. Six (22%) of 27 patients had grade 3 adverse events, which consisted of fatigue in four patients, skin rash in one patient, and increased bilirubin concentration in one patient. No grade 4 or 5 adverse events were reported. We detected no drug-related serious adverse events. Interpretation The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer. Funding Associazione Italiana Ricerca Cancro (AIRC), Fondazione Oncologia Niguarda Onlus, and Roche.
Objective To compare the efficiency of hysterosalpingo-contrast-sonography performed with air and saline (Hydro-HyCoSy) with HyCoSy performed with contrast media (SonoVue) and contrast-tuned imaging ...technology (CnTI-SonoVue-HyCoSy) considering hysterosalpingography (HSG) and laparoscopy (LPS) as reference tests and to evaluate the learning curve of this procedure. Design Retrospective study. Setting Reproductive unit of a university hospital. Patient(s) Forty-two infertile female patients. Intervention(s) HyCoSy were performed with a 2.4-mm intrauterine catheter. Patients underwent HSG or LPS as controls. Main Outcome Measure(s) Mean age, sensitivity, specificity, positive and negative predictive value, kappa value, and diagnostic accuracy were evaluated for statistical analysis. Result(s) Sensitivity, specificity, and positive and negative predictive values of Hydro-HyCoSy were 91%, 71%, 55%, and 95%, respectively, while for CnTI-SonoVue-HyCoSy they were 87%, 84%, 69%, and 94%. The diagnostic accuracy of Hydro-HyCoSy and of CnTI-SonoVue-HyCoSy were 77% and 85%, with a Cohen's kappa of 0.52 and 0.66, respectively. CnTI-SonoVue-HyCoSy does not require a learning curve period. Conclusion(s) CnTI-SonoVue-HyCoSy is more accurate than Hydro-HyCoSy for the assessment of fallopian tubes. The very high normal predictive value of Hydro-HyCoSy suggests that this procedure could be performed as a screening examination, whereas CnTI-SonoVue-HyCoSy could be used as a second-step technique.
To evaluate the utility of preoperative diagnostic models for ovarian cancer based on ultrasound and/or biomarkers for referring patients to specialized oncology care. The investigated models were ...RMI, ROMA, and 3 models from the International Ovarian Tumor Analysis (IOTA) group LR2, ADNEX, and the Simple Rules risk score (SRRisk).
A secondary analysis of prospectively collected data from 2 cross-sectional cohort studies was performed to externally validate diagnostic models. A total of 2,763 patients (2,403 in dataset 1 and 360 in dataset 2) from 18 centers (11 oncology centers and 7 nononcology hospitals) in 6 countries participated. Excised tissue was histologically classified as benign or malignant. The clinical utility of the preoperative diagnostic models was assessed with net benefit (NB) at a range of risk thresholds (5%-50% risk of malignancy) to refer patients to specialized oncology care. We visualized results with decision curves and generated bootstrap confidence intervals.
The prevalence of malignancy was 41% in dataset 1 and 40% in dataset 2. For thresholds up to 10% to 15%, RMI and ROMA had a lower NB than referring all patients. SRRisks and ADNEX demonstrated the highest NB. At a threshold of 20%, the NBs of ADNEX, SRrisks, and RMI were 0.348, 0.350, and 0.270, respectively. Results by menopausal status and type of center (oncology vs. nononcology) were similar.
All tested IOTA methods, especially ADNEX and SRRisks, are clinically more useful than RMI and ROMA to select patients with adnexal masses for specialized oncology care.
.
Correct diagnosis of ovarian cancer results in better prognosis. Adnexal lesions can be stratified into the Ovarian-Adnexal Reporting and Data System (O-RADS) risk of malignancy categories with ...either the O-RADS lexicon, proposed by the American College of Radiology, or the International Ovarian Tumor Analysis (IOTA) 2-step strategy.
To investigate the diagnostic performance of the O-RADS lexicon and the IOTA 2-step strategy.
Retrospective external diagnostic validation study based on interim data of IOTA5, a prospective international multicenter cohort study, in 36 oncology referral centers or other types of centers. A total of 8519 consecutive adult patients presenting with an adnexal mass between January 1, 2012, and March 1, 2015, and treated either with surgery or conservatively were included in this diagnostic study. Twenty-five patients were excluded for withdrawal of consent, 2777 were excluded from 19 centers that did not meet predefined data quality criteria, and 812 were excluded because they were already in follow-up at recruitment. The analysis included 4905 patients with a newly detected adnexal mass in 17 centers that met predefined data quality criteria. Data were analyzed from January 31 to March 1, 2022.
Stratification into O-RADS categories (malignancy risk <1%, 1% to <10%, 10% to <50%, and ≥50%). For the IOTA 2-step strategy, the stratification is based on the individual risk of malignancy calculated with the IOTA 2-step strategy.
Observed prevalence of malignancy in each O-RADS risk category, as well as sensitivity and specificity. The reference standard was the status of the tumor at inclusion, determined by histology or clinical and ultrasonographic follow-up for 1 year. Multiple imputation was used for uncertain outcomes owing to inconclusive follow-up information.
Median age of the 4905 patients was 48 years (IQR, 36-62 years). Data on race and ethnicity were not collected. A total of 3441 tumors (70%) were benign, 978 (20%) were malignant, and 486 (10%) had uncertain classification. Using the O-RADS lexicon resulted in 1.1% (24 of 2196) observed prevalence of malignancy in O-RADS 2, 4% (34 of 857) in O-RADS 3, 27% (246 of 904) in O-RADS 4, and 78% (732 of 939) in O-RADS 5; the corresponding results for the IOTA 2-step strategy were 0.9% (18 of 1984), 4% (58 of 1304), 30% (206 of 690), and 82% (756 of 927). At the 10% risk threshold (O-RADS 4-5), the O-RADS lexicon had 92% sensitivity (95% CI, 87%-96%) and 80% specificity (95% CI, 74%-85%), and the IOTA 2-step strategy had 91% sensitivity (95% CI, 84%-95%) and 85% specificity (95% CI, 80%-88%).
The findings of this external diagnostic validation study suggest that both the O-RADS lexicon and the IOTA 2-step strategy can be used to stratify patients into risk groups. However, the observed malignancy rate in O-RADS 2 was not clearly below 1%.
Background
Immunotherapy with immune checkpoint inhibitors (ICIs) is highly effective in microsatellite instability–high (MSI‐H) metastatic colorectal cancer (mCRC); however, specific predictive ...biomarkers are lacking.
Patients and Methods
Data and samples from 85 patients with MSI‐H mCRC treated with ICIs were gathered. Tumor infiltrating lymphocytes (TILs) and tumor mutational burden (TMB) were analyzed in an exploratory cohort of “super” responders and “clearly” refractory patients; TILs were then evaluated in the whole cohort of patients. Primary objectives were the correlation between the number of TILs and TMB and their role as biomarkers of ICI efficacy. Main endpoints included response rate (RR), progression‐free survival (PFS), and overall survival (OS).
Results
In the exploratory cohort, an increasing number of TILs correlated to higher TMB (Pearson's test, p = .0429). In the whole cohort, median number of TILs was 3.6 in responders compared with 1.8 in nonresponders (Mann‐Whitney test, p = .0448). RR was 70.6% in patients with high number of TILs (TILs‐H) compared with 42.9% in patients with low number of TILs (odds ratio = 3.20, p = .0291). Survival outcomes differed significantly in favor of TILs‐H (PFS: hazard ratio HR = 0.42, p = .0278; OS: HR = 0.41, p = .0463).
Conclusion
A significant correlation between higher TMB and increased number of TILs was shown. A significantly higher activity and better PFS and OS with ICI in MSI‐H mCRC were reported in cases with high number of TILs, thus supporting further studies of TIL count as predictive biomarker of ICI efficacy.
Implications for Practice
Microsatellite instability is the result of mismatch repair protein deficiency, caused by germline mutations or somatic modifications in mismatch repair genes. In metastatic colorectal cancer (mCRC), immunotherapy (with immune checkpoint inhibitors ICIs) demonstrated remarkable clinical benefit in microsatellite instability–high (MSI‐H) patients. ICI primary resistance has been observed in approximately 25% of patients with MSI‐H mCRC, underlining the need for predictive biomarkers. In this study, tumor mutational burden (TMB) and tumor infiltrating lymphocyte (TIL) analyses were performed in an exploratory cohort of patients with MSI‐H mCRC treated with ICIs, demonstrating a significant correlation between higher TMB and increased number of TILs. Results also demonstrated a significant correlation between high number of TILs and clinical responses and survival benefit in a large data set of patients with MSI‐H mCRC treated with ICI. TMB and TILs could represent predictive biomarkers of ICI efficacy in MSI‐H mCRC and should be incorporated in future trials testing checkpoint inhibitors in colorectal cancer.
This article explores the role of tumor mutational burden and number of tumor infiltrating lymphocytes in determining response and outcome of patients with microsatellite high metastatic colorectal cancer treated with immune checkpoint inhibitors.
Targeting HER2 is effective in 24% of ERBB2 amplified metastatic colorectal cancer; however, secondary resistance occurs in most of the cases. We studied the evolution of individual metastases during ...treatment to discover spatially resolved determinants of resistance. Circulating tumor DNA (ctDNA) analysis identified alterations associated with resistance in the majority of refractory patients. ctDNA profiles and lesion-specific radiographic reports revealed organ- or metastasis-private evolutionary patterns. When radiologic assessments documented progressive disease in target lesions, response to HER2 blockade was retained in other metastases. Genomic and functional analyses on samples and cell models from eight metastases of a patient co-recruited to a postmortem study unveiled lesion-specific evolutionary trees and pharmacologic vulnerabilities. Lesion size and contribution of distinct metastases to plasma ctDNA were correlated.
Display omitted
•ERBB2, RAS, PIK3CA mutations are associated with resistance to HER2 blockade in mCRC•A liquid biopsy test would have identified >85% primary resistance cases•Lesion size and contribution to plasma ctDNA were correlated•Patterns of lesion-specific mutations and TCR were longitudinally compared in blood
Siravegna et al. identify genetic events associated with ERBB2 amplified metastatic colorectal cancers resistant to trastuzumab plus lapatinib treatment and reveal lesion-private evolutionary patterns. Analyses of metastases from a patient unveil metastasis-specific evolution and pharmacologic vulnerabilities.
PDF
