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BACKGROUND An accurate staging system is crucial for cancer management. Evaluations for continual suitability and improvement are needed as staging and treatment methods evolve. METHODS This was a retrospective study of 1609 patients with nasopharyngeal carcinoma investigated by magnetic resonance imaging, staged with the 7th edition of the American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) staging system, and irradiated by intensity-modulated radiotherapy at 2 centers in Hong Kong and mainland China. RESULTS Among the patients without other T3/T4 involvement, there were no significant differences in overall survival (OS) between medial pterygoid muscle (MP)±lateral pterygoid muscle (LP), prevertebral muscle, and parapharyngeal space involvement. Patients with extensive soft tissue involvement beyond the aforementioned structures had poor OS similar to that of patients with intracranial extension and/or cranial nerve palsy. Only 2% of the patients had lymph nodes>6cm above the supraclavicular fossa (SCF), and their outcomes resembled the outcomes of those with low extension. Replacing SCF with the lower neck (extension below the caudal border of the cricoid cartilage) did not affect the hazard distinction between different N categories. With the proposed T and N categories, there were no significant differences in outcome between T4N0-2 and T1-4N3 disease. CONCLUSIONS After a review by AJCC/UICC preparatory committees, the changes recommended for the 8th edition include changing MP/LP involvement from T4 to T2, adding prevertebral muscle involvement as T2, replacing SCF with the lower neck and merging this with a maximum nodal diameter>6 cm as N3, and merging T4 and N3 as stage IVA criteria. These changes will lead not only to a better distinction of hazards between adjacent stages/categories but also to optimal balance in clinical practicability and global applicability.

PurposeTo ascertain the relationship among early (first 48 h) deep sedation, time to extubation, delirium and long-term mortality.MethodsWe conducted a multicentre prospective longitudinal cohort study in 11 Malaysian hospitals including medical/surgical patients (n = 259) who were sedated and ventilated ≥24 h. Patients were followed from ICU admission up to 28 days in ICU with 4-hourly sedation and daily delirium assessments and 180-day mortality. Deep sedation was defined as Richmond Agitation Sedation Score (RASS) ≤−3.ResultsThe cohort had a mean (SD) age of 53.1 (15.9) years and APACHE II score of 21.3 (8.2) with hospital and 180-day mortality of 82 (31.7 %) and 110/237 (46.4 %). Patients were followed for 2,657 ICU days and underwent 13,836 RASS assessments. Midazolam prescription was predominant compared to propofol, given to 241 (93 %) versus 72 (28 %) patients (P < 0.0001) for 966 (39.6 %) versus 183 (7.5 %) study days respectively. Deep sedation occurred in (182/257) 71 % patients at first assessment and in 159 (61 %) patients and 1,658 (59 %) of all RASS assessments at 48 h. Multivariable Cox proportional hazard regression analysis adjusting for a priori assigned covariates including sedative agents, diagnosis, age, APACHE II score, operative, elective, vasopressors and dialysis showed that early deep sedation was independently associated with longer time to extubation [hazard ratio (HR) 0.93, 95 % confidence interval (CI) 0.89–0.97, P = 0.003], hospital death (HR 1.11, 95 % CI 1.05–1.18, P < 0.001) and 180-day mortality (HR 1.09, 95 % CI 1.04–1.15, P = 0.002), but not time to delirium (HR 0.98, P = 0.23). Delirium occurred in 114 (44 %) of patients.ConclusionIrrespective of sedative choice, early deep sedation was independently associated with delayed extubation and higher mortality, and thus was a potentially modifiable risk in interventional trials.

BACKGROUND:A current recommendation for locoregionally advanced nasopharyngeal carcinoma (NPC) is conventional fractionated radiotherapy with concurrent cisplatin plus adjuvant cisplatin and fluorouracil (PF). In this randomized trial, the authors evaluated the potential therapeutic benefit from changing to an induction-concurrent chemotherapy sequence, replacing fluorouracil with oral capecitabine, and/or using accelerated rather than conventional radiotherapy fractionation. METHODS: Patients with stage III through IVB, nonkeratinizing NPC were randomly allocated to 1 of 6 treatment arms. The protocol was amended in 2009 to permit confining randomization to the conventional fractionation arms. The primary endpoint was progression-free survival. Secondary endpoints included overall survival and safety. RESULTS: In total, 803 patients were accrued, and 706 patients were randomly allocated to all 6 treatment arms. Comparisons of induction PF versus adjuvant PF did not indicate a significant improvement. Unadjusted comparisons of induction cisplatin and capecitabine (PX) versus adjuvant PF indicated a favorable trend in progression-free survival for the conventional fractionation arm (P 5.045); analyses that were adjusted for other significant factors and fractionation reflected a significant reduction in the hazards of disease progression (hazard ratio [HR], 0.54; 95% confidence interval [CI], 0.36-0.80) and death (HR, 0.42; 95% CI, 0.25-0.70). Unadjusted comparisons of induction sequences versus adjuvant sequences did not reach statistical significance, but adjusted comparisons indicated favorable improvements by induction sequence. Comparisons of induction PX versus induction PF revealed fewer toxicities (neutropenia and electrolyte disturbance), unadjusted comparisons of efficacy were statistically insignificant, but adjusted analyses indicated that induction PX had a lower hazard of death (HR, 0.57; 95% CI,. Changing the fractionation from conventional to accelerated did not achieve any benefit but incurred higher toxicities (acute mucositis and dehydration). CONCLUSIONS: Preliminary results indicate that the benefit of changing to an induction-concurrent sequence remains uncertain; replacing fluorouracil with oral capecitabine warrants further validation in view of its convenience, favorable toxicity profile, and favorable trends in efficacy; and accelerated fractionation is not recommended for patients with locoregionally advanced NPC who receive chemoradiotherapy. Cancer 2015;121:1328-38.

Objective To develop a nomogram for refining prognostication for patients with non-disseminated nasopharyngeal cancer (NPC) staged with the proposed AJCC/UICC 8th edition. Material and methods Consecutive patients investigated by magnetic resonance imaging, staged by the proposed AJCC/UICC 8th edition, and irradiated by intensity- modulated radiotherapy (IMRT) from June 2005 to December 2010 were analyzed. The cohort of 1197 patients treated at Fujian Provincial Cancer Hospital was used as the training set and the results were validated by 412 patients from Pamela Youde Nethersole Eastern Hospital. Cox regression analyses were performed to identify significant prognostic factors for developing a nomogram to predict overall survival (OS). The discriminative ability was assessed with concordance index (C-index). Patients were categorized into three risk groups by performing recursive partitioning algorithm (RPA) on the survival scores of the combined set. Results Multivariable analysis showed that age, gross primary tumor volume (GTV-P) and lactate dehydrogenase (LDH) were independent prognostic factors for OS in addition to stage-group. The OS nomogram based on all these factors had a statistically higher bias-corrected C-index than prognostication based on stage-group alone (0.712 vs 0.622, p<0.01). These results were consistent for both the training and the validation cohorts. Patients with <135 points were categorized as low-risk, ≥135–<160 points as intermediate-risk and ≥160 points as high-risk, respectively. Their 5-year OS rates were 92%, 84% and 58%, respectively. Conclusions The proposed nomogram could improve prognostication when compared with TNM stage-group. This could aid in risk stratification for individual NPC patients.

SummaryWe compared sedation levels in children following administration of intranasal dexmedetomidine. One hundred and sixteen children aged between 1 and 8 years were enrolled in this prospective, randomised trial. Children were assigned to receive either intranasal dexmedetomidine 1 lg.kg )1 (Group 1) or 2 lg.kg )1 (Group 2). Thirty-one (53%) patients from Group 1 and 38 (66%) patients from Group 2 were satisfactorily sedated at the time of anaesthetic induction. Logistic regression showed a significant interaction effect (p = 0.049), with the odds ratio between Group 2 over Group 1 estimated as 1.1 (95% CI 0.5-2.7) for the 1-4 year age group, and 10.5 (95% CI 1.4-80.2) for the 5-8 year age group. Both doses produced a similar level of satisfactory sedation in children aged 1-4 years, whereas 2 lg.kg )1 resulted in a higher proportion of satisfactory sedation in children aged 5-8 years. There were no adverse haemodynamic effects. We conclude that intranasal dexmedetomidine in a premedication dose of 2 lg.kg )1 resulted in excellent sedation in children. Dexmedetomidine is an a 2 -adrenergic receptor agonist that provides sedation without respiratory depression. Clinical trials have demonstrated that intranasal dexmedetomidine in a dose of 1 lg.kg )1 produces satisfactory sedation in between 53% and 57% of children at anaesthetic induction [1,2]. There are also reports using higher doses of intranasal dexmedetomidine [3]. We compared the sedative effect of 1 lg.kg )1 intranasal dexmedetomidine with those of 2 lg.kg )1 for premedication in children aged 1-8 years and hypothesised that the higher dose would produce satisfactory sedation in more children at the time of anaesthetic induction. MethodsThis study was approved by the local research ethics committee and written informed consent was obtained from the parents or legal guardians of all the patients. Children weighing between 7 and 17 kg, of ASA physical status 1 or 2, aged 1-8 years, who were scheduled for elective surgery at either Queen Mary Hospital, Hong Kong (QMH) or the University of Malaya, Kuala Lumpur Malaysia (UM) were enrolled in the study. If the child understood and discussed the need for premedication, then his ⁄ her assent was also obtained. Exclusion criteria included known allergy or

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Adequate tumor dose coverage was important for treating rT3 to rT4 NPC. Although late complications were common, treatment-related mortality was solely vascular in nature. Dose constraints of neurologic structures for reirradiation should be revised with the latest information on late toxicities. © 2016 Wiley Periodicals, Inc. Head Neck 39: 533-540, 2017.