MRI-Based Metastatic Nodal Number and Associated Nomogram Improve Stratification of Nasopharyngeal Carcinoma Patients: Potential Indications for Individual Induction Chemotherapy.

BACKGROUND: Metastatic lymph nodal number (LNN) is associated with the survival of nasopharyngeal carcinoma (NPC); however, counting multiple nodes is cumbersome. PURPOSE: To explore LNN threshold and evaluate its use in risk stratification and induction chemotherapy (IC) indication. STUDY TYPE: Retrospective. POPULATION: A total of 792 radiotherapy-treated NPC patients (N classification: N0 182, N1 438, N2 113, N3 59; training group: 396, validation group: 396; receiving IC: 390). FIELD STRENGTH/SEQUENCE: T1-, T2- and postcontrast T1-weighted fast spin echo MRI at 1.5 or 3.0 T. ASSESSMENT: Nomogram with (model B) or without (model A) LNN was constructed to evaluate the 5-year overall (OS), distant metastasis-free (DMFS), and progression-free survival (PFS) for the group as a whole and N1 stage subgroup. High- and low-risk groups were divided (above vs below LNN- or model B-threshold); their response to IC was evaluated among advanced patients in stage III/IV. STATISTICAL TESTS: Maximally selected rank, univariate and multivariable Cox analysis identified the optimal LNN threshold and other variables. Harrell's concordance index (C-index) and 2-fold cross-validation evaluated discriminative ability of models. Matched-pair analysis compared survival outcomes of adding IC or not. A P value < 0.05 was considered statistically significant. RESULTS: Median follow-up duration was 62.1 months. LNN ≥ 4 was independently associated with decreased 5-year DMFS, OS, and PFS in entire patients or N1 subgroup. Compared to model A, model B (adding LNN, LNN ≥ 4 vs <4) presented superior C-indexes in the training (0.755 vs 0.727) and validation groups (0.676 vs 0.642) for discriminating DMFS. High-risk patients benefited from IC with improved post-IC response and OS, but low-risk patients did not (P = 0.785 and 0.690, respectively). CONCLUSIONS: LNN ≥ 4 is an independent risk stratification factor of worse survival in entire or N1 staging NPC patients. LNN ≥ 4 or the associated nomogram has potential to identify high-risk patients requiring IC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: 4.

RuleFit-Based Nomogram Using Inflammatory Indicators for Predicting Survival in Nasopharyngeal Carcinoma, a Bi-Center Study.

Purpose: Traditional prognostic studies utilized different cut-off values, without evaluating potential information contained in inflammation-related hematological indicators. Using the interpretable machine-learning algorithm RuleFit, this study aimed to explore valuable inflammatory rules reflecting prognosis in nasopharyngeal carcinoma (NPC) patients. Patients and Methods: In total, 1706 biopsy-proven NPC patients treated in two independent hospitals (1320 and 386) between January 2010 and March 2014 were included. RuleFit was used to develop risk-predictive rules using hematological indicators with no distributive difference between the two centers. Time-event-dependent hematological rules were further selected by stepwise multivariate Cox analysis. Combining high-efficiency hematological rules and clinical predictors, a final model was established. Models based on other algorithms (AutoML, Lasso) and clinical predictors were built for comparison, as well as a reported nomogram. Area under the receiver operating characteristic curve (AUROC) and concordance index (C-index) were used to verify the predictive precision of different models. A site-based app was established for convenience. Results: RuleFit identified 22 combined baseline hematological rules, achieving AUROCs of 0.69 and 0.64 in the training and validation cohorts, respectively. By contrast, the AUROCs of the optimal contrast model based on AutoML were 1.00 and 0.58. For overall survival, the final model had a much higher C-index than the base model using TN staging in two cohorts (0.769 vs 0.717, P<0.001; 0.752 vs 0.688, P<0.001), and showing great generalizability in training and validation cohorts. The two models based on RuleFit rules performed best, compared with other models. As for other endpoints, the final model showed a similar trend. Kaplan-Meier curve exhibited 22.9% (390/1706) patients were "misclassified" by AJCC staging, but the final model could assess risk classification accurately. Conclusion: The proposed final models based on inflammation-related rules based on RuleFit showed significantly elevated predictive performance.

Systematic construction and external validation of an immune-related prognostic model for nasopharyngeal carcinoma.

BACKGROUND: We attempted to identify the most reliable immune-related index for predicting nasopharyngeal carcinoma (NPC) prognosis and to reveal its precise and integrated relationship with NPC progression. METHOD: One thousand seven hundred and six patients with newly diagnosed NPC (1320 from the primary cohort and 386 from the validated cohort) from January 2010 to March 2014 were enrolled. Clinical features and 12 immune-related variables were analyzed. RESULTS: A high absolute lymphocyte count (ALC; >3.2 × 109 /L) correlated with a poor prognosis of patients with NPC. Significant OS differences were discovered between patients with high ALC and no ALC elevation (p < 0.05, in primary cohort), showing similar prognostic risk to patients with advanced NPC (p > 0.05, in validated cohort). ALC improved the predictive performance of the basic tumor-node-metastasis prognostic model (p = 0.025), which was reliably validated in the external independent cohort. CONCLUSION: High ALC is a surrogate marker for improved prognostic risk stratification in NPC.

Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement.

BACKGROUND & AIM: Several studies explored the association of vitamin B6 intake with the risk of cancers. However, it is unclear whether different doses of vitamin B6 have distinct effects on the prognosis of nasopharyngeal carcinoma (NPC) patients. This study investigated the relationship between different doses of B6 intake and the prognosis of NPC patients. METHODS: This retrospective cohort analysis included 792 newly diagnosed NPC patients with a median follow-up of 62.05 months. Restricted cubic spline and maximally selected rank statistics were performed to determine the cut-off value of vitamin B6 during treatment (VB6DT). Kaplan-Meier method and log-rank tests were performed to analyze survival outcomes. A multivariable Cox proportional hazard model was performed to determine the independent prognostic factors. RESULTS: NPC patients were divided into three groups according to the cut-off value of VB6DT: non-users (0 mg/d), VB6DT > 8.6 mg/d, and VB6DT ≤ 8.6 mg/d. Patients with VB6DT > 8.6 mg/d had significantly lower 5-year overall survival (OS) (83.5% vs. 90.8%, p = 0.006), distant metastasis-free survival (DMFS) (83.5% vs. 91.0%, p = 0.004), and progression-free survival (PFS) (73.7% vs. 81.7%, p = 0.011) and slightly but not significantly lower 5-year local recurrence-free survival (LRFS) (87.7% vs. 90.7%, p = 0.214) than the non-users. Patients with VB6DT ≤ 8.6 mg/d had slightly but not significantly better 5-year OS (93.3% vs. 90.8%, p = 0.283) than the non-users, while all other primary endpoints were similar (p > 0.50). Multivariable analyses confirmed that VB6DT > 8.6 mg/d was an independent negative prognostic factor of OS (p = 0.010), DMFS (p = 0.017), and PFS (p = 0.030) but not of LRFS (p = 0.428). CONCLUSIONS: Excessive VB6DT higher than the cut-off value is an independent negative prognostic factor for NPC patients. Additionally, low dose intake improved OS only slightly but not significantly.

Grading and prognosis of weight loss before and after treatment with optimal cutoff values in nasopharyngeal carcinoma.

OBJECTIVES: Weight loss has been validated as a prognostic predictor of nasopharyngeal carcinoma (NPC); however, no global unitary indicator and criteria exist for the definition of weight loss as a prognostic factor. The aim of this study was to determine the most effective indicator for weight loss, evaluate its effect on the prognosis of NPC, and further propose a cutoff value to identify patients in need of nutritional care. METHODS: This retrospective cohort analysis with a median follow-up of 62.3 mo included 681 newly diagnosed patients with NPC. Principal component analysis was performed to select the best continuous variable including weight loss (kg; value of weight loss [VWL]), percent weight loss (PWL), and body mass index loss (BMIL). Multivariable Cox regression analysis and multiple correspondence analysis were performed to select the best cutoff values by different cutoff methods including the median, receiver operating characteristic curve, and threshold searching. RESULTS: PWL was the highest contributor to the prognosis of NPC compared with VWL and BMIL. Cutoff values of PWL (6.3 and 12.3%) were confirmed to be more important and were proposed to differentiate patients into low-, medium-, and high-risk NPC groups, with their 5-y progression-free survival (84.5 versus 77.9%, P = 0.046; 77.9 versus 67.3%, P = 0.046). PWL was an independent adverse prognostic factor (P = 0.002) for NPC. CONCLUSIONS: PWL is a promising predictor for NPC, and cutoff values could be validated for nutritional risk grading in patients with NPC. These stratified criteria may help accelerate the extensive application of grading nutritional management in NPC therapy.

Impact of quercetin on systemic levels of inflammation: a meta-analysis of randomised controlled human trials.

Knowledge regarding the anti-inflammatory capability of quercetin remains inconclusive and controversial due to the heterogeneous methods and inconsistent results of RCTs. We performed a series of meta-analyses of RCTs to evaluate the impact of quercetin supplementation on inflammatory biomarkers. Three cytokines (CRP, IL-6, TNF-α) with enough eligible studies (n = 6, 5 and 4, respectively) were selected for further meta-analyses. Data from these RCTs were pooled, and both overall effect and stratified subgroup analyses were performed. No relevant overall effects on peripheral CRP, IL-6 and TNF-α were observed. Subgroup analyses revealed a significant reduction in circulating CRP in participants with diagnosed diseases (SMD: -0.24, 95% CI: -0.49, 0.00) and IL-6 in females (SMD: -1.37, 95% CI: -1.93, -0.81), subjects with diagnosed diseases (SMD: -1.37, 95% CI: -1.93, -0.81) and with high-dose interventions (SMD: -0.69, 95% CI: -1.10, -0.38). In conclusion, consumption of quercetin is a promising therapeutic strategy for chronic disease management.