Conventional Staging Research Articles

New insights and potential clinical implications of the odds ratio product.

The odds ratio product (ORP) is a continuous metric of sleep depth that ranges from 0 (very deep sleep) to 2. 5 (full wakefulness). Its advantage over the conventional method recommended by AASM is that it discloses different levels of stage wake (sleep propensity) and different sleep depths within the same sleep stage. As such, it can be used to identify differences in sleep depth between subjects, and in the same subjects under different circumstances, when differences are not discernible by conventional staging. It also identifies different sleep depths within stage rapid-eye-movement sleep, with possible implications to disorders during this stage. Epoch-by-epoch ORP can be displayed graphically across the night or as average values in conventional sleep stages. In addition, ORP can be reported as % of recording time in specific ORP ranges (e.g., deciles of the total ORP range) where it produces distinct distribution patterns (ORP-architecture) that have been associated with different clinical disorders and outcomes. These patterns offer unique research opportunities to identify different mechanisms and potential therapy for various sleep complaints and disorders. In this review I will discuss how ORP is measured, its validation, differences from delta power, and the various phenotypes, and their postulated mechanisms, identified by ORP architecture and the opportunities for research to advance management of sleep-disordered breathing, insomnia and idiopathic hypersomnia.

Development and External Validation of a Nomogram Including Body Composition Parameters for Predicting Early Recurrence of Hepatocellular Carcinoma After Hepatectomy

Body composition, including adipose and muscle tissues, evaluated by computer tomography is correlated with the prognosis of hepatocellular carcinoma (HCC). However, its relationship with early recurrence (ER) remains unclear. This study aimed at establishing and validating a nomogram based on body composition and clinicopathological indices to predict ER of HCC. One hundred ninety-five patients from institution A formed the training cohort and internal validation cohort, and 50 patients from institution B formed the external validation cohort. Independent predictors of ER were identified using LASSO and Cox regression analyses. The performance of nomogram was evaluated using the calibration curve, concordance index (C-index), area under the curve (AUC), and decision curve analysis (DCA). After data screening, the nomogram was constructed using eight independent predictors of ER, including the tumor size, alpha fetoprotein, body mass index, Edmondson Steiner grade, visceral adipose tissue radiodensity, intermuscular adipose tissue index, intramuscular adipose tissue content, and skeletal muscle area. The calibration curve exhibited excellent concordances, with C-indices of 0.808 (95%CI: 0.771-0.860), 0.802 (95%CI: 0.747-0.942), and 0.804 (95%CI: 0.701-0.861) in training, internal validation, and external validation cohorts, respectively. In addition, compared to conventional staging systems and pure clinical model, the nomogram exhibited a higher AUC and wider range of threshold probabilities in DCA, which indicated better discriminative ability and greater clinical benefit. Finally, patients with nomogram scores of <183.07, 183.07-243.09, and >243.09 were considered to have low, moderate, and high risks of ER, respectively. The nomogram exhibits excellent ER predictive ability for patients with HCC who underwent hepatectomy.

Prognostic Significance of the Novel Nutrition-Inflammation Marker of Lymphocyte-C-Reactive Protein Ratio in Patients with Nasopharyngeal Carcinoma Receiving Concurrent Chemoradiotherapy

Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between the LCR and overall survival (OS) in NPC and to develop a predictive model. A total of 841 NPC patients received concurrent chemoradiotherapy (CCRT) were retrospectively enrolled and randomly divided into training cohort (n = 589) and validation cohort (n = 252). Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)] and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally validated using an independent cohort. The novel nutrition-inflammation marker of LCR could serve as a simplified, affordable, easy-to-obtain, non-invasive, and readily promotive prognostic marker for NPC patients received CCRT, and the LCR-based prognostic nomogram outperformed the conventional staging system in terms of predictive power.

Diagnostic performance of additional imaging tests for staging purposes in a bicentric German series of low-risk early breast cancer patients

PurposeLow-risk early breast cancer rarely leads to the development of metastatic disease, and in these patients, additional imaging test is controversial. The aim of our study was to evaluate the conventional staging procedures in a bicentric German series of low-risk breast carcinoma patients.MethodsRetrospective evaluation of all patients diagnosed with early, low-risk breast cancer at Saarland University Hospital and Freiburg University Hospital in 2017 was performed. Clinical patient characteristics, the number and type of additional imaging examinations, follow-up examinations, and results were evaluated. The detection rate of metastases and the rate of false-positive findings were analyzed.ResultsA total of 203 patients were included, with all patients received at least one additional imaging test. Initially, a total of 562 additional imaging examinations were performed: 166 chest X-rays, 169 upper abdominal ultrasounds, 199 bone scans, 27 computer tomographies (CT) chest and abdomen, and 1 CT abdomen. 6.8% of patients had abnormal findings reported, requiring 38 additional imaging examinations. One patient (0.5%) was found to have bone metastases. The rate of false-positive findings in the performed additional imaging procedures was 6.6%.ConclusionMetastatic disease was detected in one of 203 patients with low-risk early breast cancer. A total of 562 examinations and additional 38 follow-up examinations were performed without detection of metastasis (this corresponds to approximately 3 examinations/patient). The rate of false-positive findings was 6.6%. The performance of additional imaging procedures for detection of distant metastases should be critically reconsidered in patients with low-risk early breast cancer.

Prognostic Significance of Volumetric Parameters Based on FDG PET/CT in Patients with Lung Adenocarcinoma Undergoing Curative Surgery.

FDG PET/CT is a robust imaging modality to diagnose and stratify prognoses for non-small cell lung carcinoma. However, the role of FDG PET/CT in operable lung adenocarcinoma patients has not been previously investigated in a large cohort with varying pathological stages. The prognostic value of volumetric parameters based on FDG PET/CT was investigated in patients with stage I-III lung adenocarcinoma receiving curative surgery. This retrospective study included 432 patients with lung adenocarcinoma undergoing preoperative FDG PET/CT between January 2016 and December 2017. Clinicopathologic variables, conventional image parameters, such as the maximum standardized uptake value (SUVmax) and mean SUV (SUVmean) of the primary tumor, and volumetric parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were included in Cox regression analysis. Subgroup analysis was conducted to compare hazard ratios (HRs) based on MTV in each pathological stage. A new staging system including volumetric parameters was suggested. A total of 432 patients (median age: 62 years; interquartile range: 56-70 years; 225 males) were evaluated. Sex, age, presence of EGFR mutation, pathological stage, MTV, and TLG of the primary tumor were selected as statistically significant prognostic factors for overall survival irrespective of other variables (OS; p < 0.05 for all). Pathological stage, MTV, and TLG of the primary tumor were selected as statistically significant prognostic factors for disease-free survival irrespective of other variables (p < 0.05 for all). The suggested new staging system including MTV as an additional criterion showed better discrimination and prediction for OS than the conventional pathological staging system despite statistical insignificance (concordance index: 0.698 vs. 0.673). The volumetric parameters of the primary tumor based on preoperative FDG PET/CT were independent prognostic factors in addition to pathological stage in patients with operable lung adenocarcinoma. The suggested new staging system considering MTV predicted the prognoses better than the conventional pathological staging system.

Construction of the survival nomograms for colon cancer patients of different ages based on the SEER database

IntroductionThree nomograms for predicting the outcomes of early- and late-onset colon cancer (COCA) among patients not stratified by age were constructed using data in the Epidemiology and End Results (SEER) database (1975–2019). The accuracy of the nomogram was then assessed.MethodClinical data of 6107 patients with COCA were obtained from the SEER database. The patients were randomly divided into training and validation cohorts in a ratio of 7:3. Univariate and multivariate COX analyses of factors that could independently impact the prognosis of COCA were performed, and the corresponding nomograms for early-onset and late-onset COCA were constructed. Calibration curves, ROC curves, and C-index were used to determine the predictive accuracy. The discriminatory ability of the nomograms to assess their clinical utility, which was compared with the TNM staging system of the 8th edition of AJCC, was verified using survival analysis.ResultTumor primary site, ethnicity, and serum carcinoembryonic antigen (CEA) level significantly impacted the prognosis of colon cancer. Race, brain metastasis, and CEA were independent factors for predicting COCA prognosis. C-index, ROC, and calibration curves demonstrated that the three nomograms were accurate and superior to the traditional TNM staging system. Among the three nomograms, the early-onset COCA nomogram had the highest predictive accuracy, followed by that of colon cancer not stratified by age.ConclusionThree nomograms for patients not stratified by age, early-onset colon cancer, and late-onset colon cancer were constructed. The accuracies of the nomograms were good and were all superior to the conventional TNM staging system. The early- and late-onset COCA nomograms are useful for clinical management and individualized treatment of COCA patients at different ages.

Construction of a Matrix Cancer-Associated Fibroblast Signature Gene-Based Risk Prognostic Signature for Directing Immunotherapy in Patients with Breast Cancer Using Single-Cell Analysis and Machine Learning.

Cancer-associated fibroblasts (CAFs) are heterogeneous constituents of the tumor microenvironment involved in the tumorigenesis, progression, and therapeutic responses of tumors. This study identified four distinct CAF subtypes of breast cancer (BRCA) using single-cell RNA sequencing (RNA-seq) data. Of these, matrix CAFs (mCAFs) were significantly associated with tumor matrix remodeling and strongly correlated with the transforming growth factor (TGF)-β signaling pathway. Consensus clustering of The Cancer Genome Atlas (TCGA) BRCA dataset using mCAF single-cell characteristic gene signatures segregated samples into high-fibrotic and low-fibrotic groups. Patients in the high-fibrotic group exhibited a significantly poor prognosis. A weighted gene co-expression network analysis and univariate Cox analysis of bulk RNA-seq data revealed 17 differential genes with prognostic values. The mCAF risk prognosis signature (mRPS) was developed using 10 machine learning algorithms. The clinical outcome predictive accuracy of the mRPS was higher than that of the conventional TNM staging system. mRPS was correlated with the infiltration level of anti-tumor effector immune cells. Based on consensus prognostic genes, BRCA samples were classified into the following two subtypes using six machine learning algorithms (accuracy > 90%): interferon (IFN)-γ-dominant (immune C2) and TGF-β-dominant (immune C6) subtypes. Patients with mRPS downregulation were associated with improved prognosis, suggesting that they can potentially benefit from immunotherapy. Thus, the mRPS model can stably predict BRCA prognosis, reflect the local immune status of the tumor, and aid clinical decisions on tumor immunotherapy.

Experimental study of gas-particle flow in the coal-fired industrial boiler applied radial air staging at variable over-fired air distributions

Radial air staging is an innovative method for reducing NOx emissions from coal-fired boilers compared to conventional axial air staging. However, an important issue in using this method is to set the over-fired air (OFA) distribution rationally to achieve good boiler performance. This paper aims to optimize the OFA distribution by evaluating important gas-particle (GP) parameters that influence the pulverized coal (PC) combustion performance. The GP flow experiment is conducted in a laboratory furnace model of a coal-fired boiler with different OFA distributions. The experimental results show that as RIO (Two-level OFA distribution ratio) changes from 0:1 to 1:0, the mixture of the OFA jet and airflow in the main combustion zone is advanced, which is conducive to PC burnout. Meanwhile, the size of the central recirculation zone decreases, resulting in poor PC ignition. It is worth noting that at RIO of 1:0, the central recirculation zone disappears at section y/d = 2.5, indicating that there is no high-temperature flue gas downstream to heat the fresh PC particles, which is extremely unfavorable for the stable combustion of the PC. In addition, at RIO of 0:1, compared to other cases, there are more particles in the central recirculation zone, which promotes the reduction reaction of N element released from PC particles, thus reducing NOx emission. According to the comprehensive evaluation, it is recommended that the RIO of the two-level OFA be set to 1:1 when using radial air staging in a coal-fired boiler. The results provide new insights into the application of the air staging method for efficient and clean PC utilization.

Novel online calculator to predict reduced risk of early recurrence from adjuvant transarterial chemoembolisation for patients with hepatocellular carcinoma

BackgroundThe role of adjuvant transarterial chemoembolisation (TACE) to reduce postoperative recurrence varies widely among patients undergoing hepatectomy with curative intent for hepatocellular carcinoma (HCC). Personalised predictive tool to select which...

Prognostic significance of the novel nutrition-inflammation marker of lymphocyte-C-reactive protein ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy.

Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. A total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. The pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

Conventional Imaging, MRI and 18F-FDG PET/MRI for N and M Staging in Patients with Newly Diagnosed Breast Cancer.

Background: This study compares the diagnostic potential of conventional staging (computed tomography (CT), axillary sonography and bone scintigraphy), whole-body magnetic resonance imaging (MRI) and whole-body 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET/)MRI for N and M staging in newly diagnosed breast cancer. Methods: A total of 208 patients with newly diagnosed breast cancer were prospectively included in this study and underwent contrast-enhanced thoracoabdominal CT, bone scintigraphy and axillary sonography as well as contrast-enhanced whole-body 18F-FDG PET/MRI. The datasets were analyzed with respect to lesion localization and characterization. Histopathology and follow-up imaging served as the reference standard. A McNemar test was used to compare the diagnostic performance of conventional staging, MRI and 18F-FDG PET/MRI and a Wilcoxon test was used to compare differences in true positive findings for nodal staging. Results: Conventional staging determined the N stage with a sensitivity of 80.9%, a specificity of 99.2%, a PPV (positive predictive value) of 98.6% and a NPV (negative predictive value) of 87.4%. The corresponding results for MRI were 79.6%, 100%, 100% and 87.0%, and were 86.5%, 94.1%, 91.7% and 90.3% for 18F-FDG PET/MRI. 18F-FDG PET/MRI was significantly more sensitive in determining malignant lymph nodes than conventional imaging and MRI (p < 0.0001 and p = 0.0005). Furthermore, 18F-FDG PET/MRI accurately estimated the clinical lymph node stage in significantly more cases than conventional imaging and MRI (each p < 0.05). Sensitivity, specificity, PPV and NPV for the M stage in conventional staging were 83.3%, 98.5%, 76.9% and 98.9%, respectively. The corresponding results for both MRI and 18F-FDG PET/MRI were 100.0%, 98.5%, 80.0% and 100.0%. No significant differences between the imaging modalities were seen for the staging of distant metastases. Conclusions:18F-FDG PET/MRI detects lymph node metastases in significantly more patients and estimates clinical lymph node stage more accurately than conventional imaging and MRI. No significant differences were found between imaging modalities with respect to the detection of distant metastases.

Development and Validation of Novel Models Including Tumor Micronecrosis for Predicting the Postoperative Survival of Patients with Hepatocellular Carcinoma.

The heterogeneity of hepatocellular carcinoma (HCC) leads to the unsatisfying predictive performance of current staging systems. HCC patients with pathological tumor micronecrosis have an immunosuppressive microenvironment. We aimed to develop novel prognostic models by integrating micronecrosis to predict the survival of HCC patients after hepatectomy more precisely. We enrolled 765 HCC patients receiving curative hepatic resection. They were randomly divided into a training cohort (n= 536) and a validation cohort (n = 229). We developed two prognostic models for postoperative recurrence-free survival (RFS) and overall survival (OS) based on independent factors identified through multivariate Cox regression analyses. The predictive performance was assessed using the Harrell concordance index (C-index) and the time-dependent area under the receiver operating characteristic curve, compared with six conventional staging systems. The RFS and OS nomograms were developed based on tumor micronecrosis, tumor size, albumin-bilirubin grade, tumor number and prothrombin time. The C-indexes for the RFS nomogram and OS nomogram were respectively 0.66 (95% CI, 0.62-0.69) and 0.74 (95% CI, 0.69-0.79) in the training cohort, which was significantly better than those of the six common staging systems (0.52-0.61 for RFS and 0.53-0.63 for OS). The results were further confirmed in the validation group, with the C-indexes being 0.66 and 0.77 for the RFS and OS nomograms, respectively. The two nomograms could more accurately predict RFS and OS in HCC patients receiving curative hepatic resection, thereby aiding in formulating personalized postoperative follow-up plans.

Deep Learning-Based Multiparametric MRI Model for Preoperative T-Stage in Rectal Cancer.

Conventional MRI staging can be challenging in the preoperative assessment of rectal cancer. Deep learning methods based on MRI have shown promise in cancer diagnosis and prognostication. However, the value of deep learning in rectal cancer T-staging is unclear. To develop a deep learning model based on preoperative multiparametric MRI for evaluation of rectal cancer and to investigate its potential to improve T-staging accuracy. Retrospective. After cross-validation, 260 patients (123 with T-stage T1-2 and 134 with T-stage T3-4) with histopathologically confirmed rectal cancer were randomly divided to the training (N = 208) and test sets (N = 52). 3.0 T/Dynamic contrast enhanced (DCE), T2-weighted imaging (T2W), and diffusion-weighted imaging (DWI). The deep learning (DL) model of multiparametric (DCE, T2W, and DWI) convolutional neural network were constructed for evaluating preoperative diagnosis. The pathological findings served as the reference standard for T-stage. For comparison, the single parameter DL-model, a logistic regression model composed of clinical features and subjective assessment of radiologists were used. The receiver operating characteristic curve (ROC) was used to evaluate the models, the Fleiss' kappa for the intercorrelation coefficients, and DeLong test for compare the diagnostic performance of ROCs. P-values less than 0.05 were considered statistically significant. The Area Under Curve (AUC) of the multiparametric DL-model was 0.854, which was significantly higher than the radiologist's assessment (AUC = 0.678), clinical model (AUC = 0.747), and the single parameter DL-models including T2W-model (AUC = 0.735), DWI-model (AUC = 0.759), and DCE-model (AUC = 0.789). In the evaluation of rectal cancer patients, the proposed multiparametric DL-model outperformed the radiologist's assessment, the clinical model as well as the single parameter models. The multiparametric DL-model has the potential to assist clinicians by providing more reliable and precise preoperative T staging diagnosis. 3 TECHNICAL EFFICACY: Stage 2.

Node-negative colon cancer: histological, molecular, and stromal features predicting disease recurrence

BackgroundWithin the group of node-negative colon cancer patients, presumed to have a good prognosis, a significant percentage of patients develops cancer-recurrence. Current high-risk features prove inadequate to select these particular high-risk patients. In the process of tailor-made care and shared decision-making the need to identify these patients grows. In this study we investigate the value of adding molecular markers and the tumour-stroma ratio (TSR) to conventional histological tumour staging methods to improve the selection of high risk patients.MethodsWe retrospectively analysed 201 patients diagnosed with TNM-stage I-II colon cancer and treated by complete oncological resection between November 1st 2002 and December 31st 2012 at the Jeroen Bosch Hospital. Conventional histological tumour staging, BRAF mutations, KRAS mutations, MSI status and TSR were determined. Differences between groups based on TSR and mutation status, in disease free survival were analysed using Cox-Regression analyses.ResultsPoorly differentiated histology (p = 0.002), high-TSR (p = 0.033), BRAF-mutation (p = 0.008) and MSI (p = 0.011) were identified as significant risk factors for cancer recurrence. The risk of recurrence increased in the presence of both a BRAF-mutation and high-TSR compared to the absence of both factors or presence of only one factor (HR = 3.66 BRAF-mt/TSR-low (p = 0.006), HR 2.82 BRAF-wt/TSR-high (p = 0.015), HR = 4.39 BRAF-mt/TSR-high (p = 0.023)). This was also seen in tumours with MSI and high-TSR (HR = 2.46 MSS/TSR-high (p = 0.041), HR = 3.31 MSI/TSR-high (p = 0.045).ConclusionJudging by the higher HR for the combination of the prognostic factors TSR and BRAF compared to the HRs of these prognostic factors individually, the prognostication for disease free survival can be improved by determining both TSR and BRAF instead of BRAF alone, as is done in current daily practise. In this study MSI also shows additional value to TSR in the prognostication of disease free survival. Adopting TSR into daily diagnostics will be of additional value next to currently used molecular markers in risk stratification of patients with node negative colon cancer and is therefore advised.

E-Cadherin Expression Varies Depending on the Location within the Primary Tumor and Is Higher in Colorectal Cancer with Lymphoid Follicles.

Reliable indicators of cancer advancement have actively been sought recently. The detection of colorectal cancer progression markers is essential in improving diagnostic and therapeutic protocols. The aim of the study was to investigate the profile of E-cadherin expression in colorectal cancer tissue depending on the TNM staging and its correlation with several clinical and histopathological features. The study included 55 colorectal cancer patients admitted to the surgical ward for elective surgery. Tissue samples were obtained from resected specimens. Different distributions of E-cadherin expression within tumors were observed; the highest percentage of positive E-cadherin expression was found in the invasive front and in the tumor center. Additionally, the different cellular distribution of E-cadherin expression was noticed; weak membranous E-cadherin expression was the highest in the invasive front and in the budding sites, but a strong membranous pattern was most frequent in the tumor center. Various distributions of E-cadherin expression depending on cancer progression were also found; E-cadherin expression in node-positive patients was lower in the tumor center and in the tumor invasive front, whereas, in patients with distant metastases, the expression of E-Cadherin was lower in the budding sites. In patients with higher TNM stages, E-cadherin expression was lower within the tumor (in the budding sites, tumor center, and invasive front). In tumors with lymphoid follicles, E-cadherin expression was higher in all localizations within the primary tumor. E-cadherin expression in the tumor center was also lower in tumors with some higher tumor budding parameters (areas of poorly differentiated components and poorly differentiated clusters). E-cadherin expression was found to be lower at the tumor center in younger individuals, at the budding sites in men, and at the surrounding lymph nodes in rectal tumors. Low E-cadherin expression appears to be a reliable indicator of higher cancer staging and progression. When assessing the advancement of cancer, apart from the TNM classification, it is beneficial to also consider the expression of E-cadherin. High tumor budding, the poverty of lymphoid follicles, and low E-cadherin expression analyzed simultaneously may contribute to a reliable assessment of colorectal cancer staging. These three histopathological features complement each other, and their investigation, together with conventional tumor staging and grading, may be very helpful in predicting the prognosis of colorectal cancer patients and qualifying them for the best treatment. The role of E-cadherin in the diagnosis and treatment of colorectal cancer, as a part of a personalized medicine strategy, still requires comprehensive, prospective clinical evaluations to precisely target the optimal therapies for the right patients at the right time.

Relationship between circulating tumour DNA and skeletal muscle stores at diagnosis of pancreatic ductal adenocarcinoma: a cross-sectional study

Low skeletal muscle index (SMI) and low skeletal muscle radiodensity (SMD) are associated with reduced survival time in pancreatic ductal adenocarcinoma (PDAC). The negative prognostic impact of low SMI and low SMD is often reported as independent of cancer stage when using traditional clinical staging tools. Therefore, this study sought to explore the relationship between a novel marker of tumour burden (circulating tumour DNA) and skeletal muscle abnormalities at diagnosis of PDAC. A retrospective cross-sectional study was conducted in patients who had plasma and tumour tissue samples stored in the Victorian Pancreatic Cancer Biobank (VPCB) at diagnosis of PDAC, between 2015 and 2020. Circulating tumour DNA (ctDNA) of patients with G12 and G13 KRAS mutations was detected and quantified. Pre-treatment SMI and SMD derived from analysis of diagnostic computed tomography imaging was tested for its association to presence and concentration of ctDNA, as well as conventional staging, and demographic variables. The study included 66 patients at PDAC diagnosis; 53% female, mean age 68.7 years (SD ± 10.9). Low SMI and low SMD were present in 69.7% and 62.1% of patients, respectively. Female gender was an independent risk factor for low SMI (OR 4.38, 95% CI 1.23–15.55, p = 0.022), and older age an independent risk factor for low SMD (OR 1.066, 95% CI 1.002–1.135, p = 0.044). No association between skeletal muscle stores and concentration of ctDNA (SMI r = − 0.163, p = 0.192; SMD r = 0.097, p = 0.438) or stage of disease according to conventional clinical staging [SMI F(3, 62) = 0.886, p = 0.453; SMD F(3, 62) = 0.717, p = 0.545] was observed. These results demonstrate that low SMI and low SMD are highly prevalent at diagnosis of PDAC, and suggest they are comorbidities of cancer rather than related to the clinical stage of disease. Future studies are needed to identify the mechanisms and risk factors for low SMI and low SMD at diagnosis of PDAC to aid screening and intervention development.

THE ROLE OF DENTISTRY IN THE EARLY DIAGNOSIS AND FOLLOW-UP OF POTENTIALLY MALIGNANT DISORDERS: A CASE REPORT

In 2017, a 66-year-old male patient, smoker and alcohol-addicted for the last 52 years, presented a white plaque with a diagnosis of epithelial hyperplasia with papillomatosis and mild epithelial dysplasia. The patient did not continue with follow-up care. Later, in May 2021, he returned for further exams, presenting an extensive, hard, ulcerated exophytic erythroleukoplakia, with undefined limits on the edge of the tongue. New biopsies were performed, and the anatomopathological examination showed moderately epithelial dysplasia in the soft palate region. The left tongue was diagnosed with moderately differentiated conventional squamous cell carcinoma staging cT3acN1cM0 tongue squamous cell carcinoma. Treatment consisted of left partial glossectomy, together with radiotherapy (20 fractions x 250cGy/field). These findings are important because they imply that many patients with oral premalignant lesions are not diagnosed in a timely manner. thereby failing to receive the benefits of early detection. In 2017, a 66-year-old male patient, smoker and alcohol-addicted for the last 52 years, presented a white plaque with a diagnosis of epithelial hyperplasia with papillomatosis and mild epithelial dysplasia. The patient did not continue with follow-up care. Later, in May 2021, he returned for further exams, presenting an extensive, hard, ulcerated exophytic erythroleukoplakia, with undefined limits on the edge of the tongue. New biopsies were performed, and the anatomopathological examination showed moderately epithelial dysplasia in the soft palate region. The left tongue was diagnosed with moderately differentiated conventional squamous cell carcinoma staging cT3acN1cM0 tongue squamous cell carcinoma. Treatment consisted of left partial glossectomy, together with radiotherapy (20 fractions x 250cGy/field). These findings are important because they imply that many patients with oral premalignant lesions are not diagnosed in a timely manner. thereby failing to receive the benefits of early detection.

Log Odds of Positive Lymph Nodes (LODDS) as an Independent Predictor of Overall Survival Following Radical Cystectomy in Urothelial Bladder Cancer: Time to Rethink Conventional Node Staging.

Radical cystectomy (RC) with lymph node dissection is the mainstay of treatment for patients with muscle-invasive bladder cancer (MIBC) and high risk non-MIBC. The American Joint Committee on Cancer's (AJCC) node staging and lymph node ratio (LNR) systems are used in estimating prognosis; however, they do not directly factor in negative dissected nodes. In this study, we evaluated the log odds of positive lymph nodes (LODDS), a novel measure of nodal involvement, as a predictor of survival. Eighty-three patients who underwent RC were retrospectively included and their demographic and clinical data were collected. Kaplan-Meier curve and Cox regression were used for survival analyses. Median number of dissected lymph nodes was 13 (range 3-45). ROC curve analysis indicated -0.92 as the optimal LODDS cutoff. LODDS > -0.92 was associated with higher T stage, lymphovascular invasion, and significantly worse overall survival (OS) (mean OS 18.6 vs. 45.1 months, P-value < .001). Furthermore, we evaluated AJCC node staging, LNR, and LODDS in three separate multivariable Cox regression models. Among 3 different measures of nodal disease burden, only LODDS was an independent predictor of OS (HR 2.71, 95% CI 1.28-5.73, P=.009). Our results show that LODDS is an independent predictor of OS and outperforms AJCC node staging and LNR in forecasting prognosis among patients with urothelial bladder cancer who undergo RC.

Early prediction of endocrine responsiveness in ER+/HER2 negative MBC: Pilot study with 18F-fluoroestradiol (18F-FES) CT/PET.

1024 Background: Estrogen receptors (ER) are considered predictive biomarkers to identify ER+ MBC patients who would likely benefit from endocrine therapies (ET). However, 30 to 40% of ER+ MBC patients fail to achieve a durable response. 18F-FES PET/CT has been shown to represent a valuable and accurate diagnostic tool to determine ER status at the level of metastatic sites and can be proposed as a valid alternative to biopsy of metastatic lesions. In this trial, we evaluated 18F-FES PET/CT as a predictive tool for endocrine responsiveness in ER+ MBC. Methods: ET-FES is an international, multicenter, academic clinical trial, conducted within the JTC-2011 ERA-NET TRANSCAN programme. Patients with ER+/HER2- MBC and first evidence of relapse were eligible for the study. All patients underwent a baseline 18F-FES PET/CT in addition to conventional staging procedures. Tumors were classified as endocrine sensitive if overall Standardized Uptake Value (SUV) ≥ 2; SUVmax was measured in the 3 largest lesions to quantify ER expression and a cutoff value of 2 was used to dichotomize results (endocrine sensitive vs resistant). In the ET-FES trial, patients with SUV ≥ 2 received single agent ET until PD; patients with SUV &lt; 2 were randomized to receive single agent ET or chemotherapy (CT). The predictive role of 18F-FES PET/CT results was assessed for PFS and OS by univariate and multivariate analyses. Results: Overall, 147 patients (142 for ITT analysis) were enrolled from 04/2015 to 12/2020; 113 presented with 18F-FES SUV ≥ 2 and received ET; 29 pts, with SUV &lt; 2 were randomly assigned to ET or first line chemotherapy (CT), following local clinical practice. After a median follow up of 4.6 years, 51 deaths had occurred (54.2%). Median PFS was 18,0 months (95%CI 11,2- 22,9) in the overall population and in 18F-FES SUV ≥ 2 versus 12,4 months (95%CI 3,1 – NR) in patients with SUV &lt;2 treated with ET and 23.0 months (95%CI 7,7 – 30,0) if treated with CT. Median OS was not reached in the overall patient population and in patients with SUV ≥2, treated with single agent ET. Median OS was 28.1 months (95%CI 14,2 – NR) in patients with SUV &lt;2 treated with ET versus 52,8 months (95%CI 16,1 – NR) if treated with CT. The Kaplan–Meier estimate of OS at 48 months was 64.4% (SE +/-5%) in all patients and 66% in 18F-FES SUV ≥ 2; at 60 months was 54.4% (SE +/-6%) and 57% (SE +/-5%), respectively. Among the 113 pts with SUV ≥ 2 treated with ET, the Kaplan–Meier estimate of OS at 60 months was 73.0% if treated with aromatase inhibitors versus 35% in case of fulvestrant or tamoxifen (p&lt; 0.0005). Conclusions: ET-FES is the first prospective trial to assess the efficacy of ET alone in patients selected for endocrine responsiveness on the basis of whole body molecular ER imaging by 18F-FES PET/CT. These results suggest that the efficacy of ET may be maximized by using the appropriate assessment of endocrine responsiveness at the different metastatic sites. Clinical trial information: EUDRACT 2013-000-287-29 .

The Changing Face of cN0M0 Prostate Cancer Being Found With pN+ After Surgery in the Contemporary Era: Results of an International European Survey on Disease Management.

The urological community's opinion over the management of men being found with pathologically positive nodes (pN+) following radical prostatectomy (RP) performed with curative intent after preoperative negative conventional staging (cN0M0) has never been assessed. This remains crucial, especially considering the advent of novel imaging modalities. Our aim was to investigate the current opinion on management of pN+ cN0M0 prostate cancer (PCa) in the European urological community. Following validation, a 31-item survey, complying with the Cherries checklist, was distributed using a web link from December 2021 to April 2022 to 10 urological societies mailing list. Social media (Twitter, Facebook) were also used. We received 253 replies. The majority were Urologists (96.8%), younger than 60 (90.5%); 5.2% did not have access to PET-scans; 78.9% believed pN+ is a multifaceted category; 10-years CSS was marked as 71 to 95% by 17.5%. Gold standard management was stated not being ADT by 80.8% and being RT±ADT by 52.3%. Early sRT±ADT was considered an option vs. aRT±ADT by 72.4%. In case of BCR 71% would perform and decide management based on PSMA-PET whilst 3.7% would not perform PSMA-PET. pN+ management is still unclear for 77.1%. On multivariate analysis PSMA-PET availability related to a lower and higher likelihood of considering aRT±ADT as standard and of considering early salvage versus aRT respectively (P < .05). The Urological community has an acceptable awareness of pN+ disease and management, although it may overestimate disease aggressiveness. The majority consider pN+ PCa as a multifaceted category and rely on a risk-adapted approach. Expectant compared to immediate upfront management and new imaging modalities are increasingly considered.