Establishment and Validation of Prognostic Nomograms for Patients With Parotid Gland Adenocarcinoma Not Otherwise Specified: A SEER Analysis From 2004 to 2016

Background: Parotid gland adenocarcinoma not otherwise specified (PANOS) is a rare malignant tumor with limited data on its characteristics and prognosis. This research is aimed at characterizing PANOS and developing prognostic prediction models for patients with PANOS.Methods: Cases from 2004–2016 were selected from the Surveillance, Epidemiology, and End Results (SEER) Program database. Univariate and multivariate Cox regression were applied to ascertain the factors associated with survival. Competing risk analysis and Gray's tests were employed to analyze cancer-specific death. Propensity score matching (1:1) was conducted to reduce the influence of confounding variables.Results: A total of 446 patients with a median age of 66 years were selected, of which 307 were diagnosed with stage III/IV PANOS. The 5-year overall survival (OS) rate of all patients was 51.8%, and the median survival time was 66 months. Surgical treatment clearly improved survival time (p < 0.001). In the subgroup analysis, radiotherapy showed survival benefits in patients with stage III/IV disease (p < 0.001). Multivariate Cox regression analyses showed that age, T classification, N classification, M classification and surgery were independent prognostic indicators for OS; T classification, N classification, M classification and surgery were independent risk factors for cancer-specific survival (CSS). In addition, age was independently associated with other cause-specific death. Based on the results of multivariate analysis, two nomograms were developed and verified by the concordance index (C-index) (0.747 and 0.780 for OS and CSS) and the area under the time-dependent receiver operating characteristic (ROC) curve (0.756, 0.764, and 0.819 regarding for nomograms predicting 3-, 5-, and 10- year OS, respectively and 0.794, 0.789, and 0.806 for CSS, respectively).Conclusions: Our study clearly presents the clinicopathological features and survival analysis of patients with PANOS. In addition, our constructed nomogram prediction models may assist physicians in evaluating the individualized prognosis and deciding on treatment for patients.

Accuracy of the Brief Cognitive Screening Battery for diagnosing Alzheimer's disease defined by cerebrospinal fluid biomarkers and AT(N) classification: a case-control study

ABSTRACT Background: Validation of cognitive instruments for detection of Alzheimer's disease (AD) based on correlation with diagnostic biomarkers allows more reliable identification of the disease. Objectives: To investigate the accuracy of the Brief Cognitive Screening Battery (BCSB) in the differential diagnosis between AD, non-AD cognitive impairment (both defined by cerebrospinal fluid [CSF] biomarkers) and healthy cognition, and to correlate CSF biomarker results with cognitive performance. Methods: Overall, 117 individuals were evaluated: 45 patients with mild cognitive impairment (MCI) or mild dementia within the AD continuum defined by the AT(N) classification [A+T+/-(N)+/]; 27 non-AD patients with MCI or mild dementia [A-T+/-(N)+/-]; and 45 cognitively healthy individuals without CSF biomarker results. All participants underwent evaluation using the BCSB. Results: The total BCSB and delayed recall (DR) scores of the BCSB memory test showed high diagnostic accuracy, as indicated by areas under the ROC curve (AUC): 0.89 and 0.87, respectively, for discrimination between AD and non-AD versus cognitively healthy controls. Similarly, total BCSB and DR displayed high accuracy (AUC-ROC curves of 0.89 and 0.91, respectively) for differentiation between AD and controls. BCSB tests displayed low accuracy for differentiation between AD and non-AD. The CSF levels of biomarkers correlated significantly, though weakly, with DR. Conclusions: Total BCSB and DR scores presented good accuracy for differentiation between patients with a biological AD diagnosis and cognitively healthy individuals, but low accuracy for differentiating AD from non-AD patients.

Comparison of Different Staging Systems Applied to a Cohort of Patients With Oral Tongue and Floor of the Mouth Cancer

Purpose: The present work compares the effects produced by the application of the 7th edition of the tumor node metastasis (TNM) staging system (TNM7), 8th Edition (TNM8) with its two subsequent revisions, and pN-N+ classification on a cohort of patients with oral tongue and floor of the mouth cancer.Methods: A monocentric cohort of 148 patients was retrospectively analyzed. Patients were staged according to the TNM7, TNM8 and revisions, and pN-N+ classification. Stage migration was assessed and overall survival (OS) analyzed with the Kaplan–Meier method. The pT, pN, and stage stratification was evaluated with univariate and multivariate Cox regression and comparing adjacent categories with the log-rank method.Results: pT3-T4a categories showed significant differences in comparison to pT1-T2 for each staging metric employed in both uni- and multivariate analysis. When comparing adjacent pT categories, OS was significantly different only between pT2 and pT3 categories of the TNM8. Disproportionate patient distribution among pN categories was observed in the TNM8, and stratification was scarce. Conversely, in the pN-N+ classification the difference between pN2 and pN3a categories was significant. Only stage IVa reached statistical significance in TNM7, whereas stage III and above were significant in TNM8 and revisions in both uni- and multivariate analysis. However, no significant difference was noted comparing adjacent stages.Conclusion: The TNM8 pT classification differentiated low- from high-risk diseases. Nonetheless, it failed to separate pT1 from pT2 and pT3 from pT4a categories. Conversely, although TNM8 nodal staging was inaccurate, the number of metastatic lymph nodes was more valuable.

Taking the A Train? Limited Consistency of Aβ42 and the Aβ42/40 Ratio in the AT(N) Classification

The consistency of cerebrospinal fluid amyloid-β (Aβ)42/40 ratio and Aβ 42 has not been assessed in the AT(N) classification system. We analyzed the classification changes of the dichotomized amyloid status (A+/A–) in 363 patients tested for Alzheimer’s disease biomarkers after Aβ 42 was superseded by the Aβ 42/40 ratio. The consistency of Aβ 42 and the Aβ 42/40 ratio was very low. Notably, the proportions of “false” A+T–patients were considerable (74–91%) and corresponded mostly to patients not clinically diagnosed with Alzheimer’s disease. Our results suggest that the interchangeability of Aβ 42/40 ratio and Aβ 42 is limited for classifying patients in clinical setting using the AT(N) scheme.

The Lymph Node Ratio Optimizes Staging System while Adjuvant Chemotherapy Plays an Invalid Role for Patients with Nonmetastatic Colorectal Neuroendocrine Carcinomas: A Propensity Score Matching Analysis of Patients from the Surveillance, Epidemiology, and End-Results Database

Objective: Colorectal neuroendocrine carcinoma (CRNEC) is rare and little is known about survival benefit between lymph node ratio (LNR) and improved overall survival (OS), and so is the adjuvant chemotherapy (AC). We aim to evaluate the survival benefit of LNR and AC in patients with nonmetastatic CRNEC following resection. Methods: Patients with resected nonmetastatic CRNECs were identified in Surveillance, Epidemiology, and End Results (SEER) during year 1992 to 2016. A Log-rank test was conducted to determine the survival difference. The survival benefit was evaluated using a competing-risks regression model and propensity score-matched (PSM) techniques were used to reduce the selection bias.Results: A total of 251 patients met the inclusion criteria, of which, 152 patients (60.56%) received AC. The age of 60 (P=0.848) and number of 12 of resected regional lymph nodes (P=0.082) acted as an optimal cutoff value in terms of survival, failing to reach a significance. Chemotherapy failed to bring survival benefit (hazard ratio [HR], 0.959; 95% confidence interval [CI], 0.649-1.416; P=0.832). Current N classification was not a significant predictor of patient survival (N1: P = 0.174; N2: P=0.028, compared to N0, respectively). Multivariate analyses explored the revised Nr classification, based on LNR of 0.30 and 0.75 as cutoff value (Nr0: LNR£0.30; Nr1: 0.3<LNR£0.75; Nr2: LNR >0.75), as an independent prognostic factor (Nr1: P = 0. 003; Nr2: P<0.001, compared to Nr0, respectively). With the foundation of revised Nr classification, a revised TNrM was proposed for nonmetastatic CRNEC: stage I (T1–2Nr0), stage II (T1-2Nr1 or T3Nr0–1 or T4Nr0), and stage III (TxNr2 or T4Nr1). TNrM stage had better stratification according to Kaplan-Meier survival curves (P <0.001). Conclusions: AC seems invalid for improving the survival of patients with nonmetastatic CRNECs following resection. The LNR more accurately predict survival of CRNEC patients than current N classification.

Liver Metastases Pattern in Rectal Cancer: A Real-World Analysis in the SEER Database

Background: The liver is a common metastatic site of colorectal cancer. Rectal cancer patients with organ metastases are more liable to show poor prognosis. The hazard and forecast elements of liver metastases are need to be estimated in rectal cancer patients. Methods: The data of newly diagnosed patients of rectal cancer with liver metastases are evaluated according to Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2016. The Overall Survival (OS) for dierent subgroups are appraised by Kaplan-Meier analysis and log-rank tests. Univariate and multivariable logistic analysis and Cox regression are performed to evaluate predictors and elements of the presence of liver metastases in new diagnosis, respectively. Results: There are a total of 6,662 (11.1%) rectal cancer patients paired with liver metastases. Factors including age (below), gender (female), marital status (unmarried), race (black), advanced T or N classification, presence of bone or lung metastases, and the absence of surgical treatments are importantly related to the occurrence of liver metastases. The median survival for liver metastases rectal cancer patients was 16.0 months. Indicators referring to elder age, black race, unmarried status, presence of bone, brain or lung metastases, and the absence of surgical treatments all predicted worse survival. Conclusion: The data of our research provide corresponding risks and prognostic elements for liver metastases rectal cancer patients, which offer a way to predict the occurrence of rectal cancer and guide prophylactic treatment in clinical settings.

Use of plasma biomarkers for AT(N) classification of neurodegenerative dementias

ObjectivesAll categories included in the AT(N) classification can now be measured in plasma. However, their agreement with cerebrospinal fluid (CSF) markers is not fully established. A blood signature to generate the AT(N) classification would facilitate early diagnosis of patients with Alzheimer’s disease (AD) through an easy and minimally invasive approach.MethodsWe measured Aβ, pTau181 and neurofilament light (NfL) in 150 plasma samples of the Sant Pau Initiative on Neurodegeneration cohort including patients with mild cognitive impairment, AD dementia, frontotemporal dementia, dementia with Lewy bodies and cognitively normal participants. We classified participants in the AT(N) categories according to CSF biomarkers and studied the diagnostic value of plasma biomarkers within each category individually and in combination.ResultsThe plasma Aβ composite, pTau181 and NfL yielded areas under the curve (AUC) of 0.75, 0.78 and 0.88 to discriminate positive and negative participants in their respective A, T and N categories. The combination of all three markers did not outperform pTau181 alone (AUC=0.81) to discriminate A+T+ from A–T– participants. There was a moderate correlation between plasma Aβ composite and CSF Aβ1–42/Aβ1–40 (Rho=−0.5, p<0.001) and between plasma pTau181 and CSF pTau181 in the entire cohort (Rho=0.51, p<0.001). NfL levels in plasma showed high correlation with those in CSF (Rho=0.78, p<0.001).ConclusionsPlasma biomarkers are useful to detect the AT(N) categories, and their use can differentiate patients with pathophysiological evidence of AD. A blood AT(N) signature may facilitate early diagnosis and follow-up of patients with AD through an easy and minimally invasive approach.