Development and Validation of Prognostic Nomograms Based on Gross Tumor Volume and Cervical Nodal Volume for Nasopharyngeal Carcinoma Patients With Concurrent Chemoradiotherapy.

PURPOSE: Our study aimed to establish and validate prognostic nomograms based on gross tumor volume (GTV) and cervical nodal volume (CNV) for nasopharyngeal carcinoma (NPC) patients treated with two cycles of concurrent chemoradiotherapy (CCRT). METHODS: From 2012 to 2015, 620 eligible patients who received radical treatment at the Cancer Hospital of Shantou University Medical College were recruited for a nomogram study. Variables were determined in a training set of 463 patients from 2012 to 2014 by X-tile analysis, univariate and multivariate Cox proportional hazard analyses, and the least absolute shrinkage and selection operator (LASSO). Another cohort of 157 patients in 2015 was validated with bootstrap resampling. The concordance index (C-index) and calibration curves were applied to assess its predictive discriminative and accuracy ability, while decision curve analysis (DCA), X-tile analysis and Kaplan-Meier curve for clinical application. RESULTS: Independent prognostic variables for overall survival (OS) were age, GTV, CNV, cranial nerve, positive cervical lymph node laterality below the caudal border of cricoid cartilage (LNBC), and were selected for the nomogram. Optimal prognostic factors including Karnofsky performance status (KPS), age, GTV, CNV, LNBC were incorporated in the nomogram for progression-free survival (PFS). In the training set, the C-index of our nomograms for OS and PFS were 0.755 (95% CI, 0.704 to 0.807) and 0.698 (95% CI, 0.652 to 0.744). The calibration curve showed good agreement between nomogram-predicted and actual survival. DCA indicated that our nomograms were of clinical benefit. CONCLUSION: Our nomograms are capable of effective prognostic prediction for patients with NPC.

Noradrenaline depresses spontaneous complex spikes activity of cerebellar Purkinje cells via α2-adrenergic receptor in vivo in mice.

Locus coeruleus (LC) noradrenergic neurons afferents release noradrenaline (NA) in the cerebellar cortex for modulating cerebellar neuronal circuitry function. Our previous study found that NA inhibited the spontaneous simple spikes activity of cerebellar Purkinje cells (PC) through activation of molecular layer interneurons (MLIs) in vivo in mice. We here examined the effects of NA on spontaneous complex spikes (CSs) activity of cerebellar PC in urethane-anesthetized mice by electrophysiology recording technique and pharmacological methods. Our results showed that cerebellar surface perfusion of NA significantly reduced the number of spikelets and the area under curve (AUC) of the spontaneous CSs. Application of nonselective adrenergic receptor (AR) antagonist, phentolamine, abolished the NA-induced inhibition of CSs. However applying a nonselective ß-AR blocker, propranolol, failed to prevent the NA-induced inhibition of CSs activity. The NA-induced inhibition of CSs activity was not blocked by α1-AR antagonist, prazosin, but it was abolished by α2-AR antagonist, yohimibine. Moreover, application of α2-AR agonist, UK14304 induced a depression of CSs activity and mimicked the NA-induced inhibition of CS activity. These results indicate that NA regulates spontaneous CSs activity of cerebellar PCs via activation of α2-AR in vivo in mice. Our present results suggest that noradrenergic neurons of LC may modulate the outputs of cerebellar PCs via inhibition of CSs activity.