Strategies to promote translational research within the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Group: a report from the Translational Research Subcommittee.

Head and neck squamous cell cancer (HNSCC) is the sixth leading cause of cancer-related deaths worldwide. These tumors are commonly diagnosed at advanced stages and mortality rates remain high. Even cured patients suffer the consequences of aggressive treatment that includes surgery, chemotherapy, and radiotherapy. In the past, in clinical trials, HNSCC was considered as a single disease entity. Advances in molecular biology with the development of genomic and proteomic approaches have demonstrated distinct prognostic HNSCC patient subsets beyond those defined by traditional clinical-pathological factors such as tumor subsite and stage [Cho W (ed). An Omics Perspective on Cancer Research. New York/Berlin: Springer 2010]. Validation of these biomarkers in large prospective clinical trials is required before their clinical implementation. To promote this research, the European Organisation for Research and Treatment of Cancer (EORTC) Head and Neck Cancer Program will develop the following strategies-(i) biobanking: prospective tissue collection from uniformly treated patients in the setting of clinical trials; (ii) a group of physicians, physician-scientists, and EORTC Headquarters staff devoted to patient-oriented head and neck cancer research; (iii) a collaboration between the basic scientists of the Translational Research Division interested in head and neck cancer research and the physicians of the Head and Neck Cancer Group; and (iv) funding through the EORTC Grant Program and the Network Core Institutions Consortium. In the present report, we summarize our strategic plans to promote head and neck cancer research within the EORTC framework.

Assessment and analysis of mechanical allodynia-like behavior induced by spared nerve injury (SNI) in the mouse

Rrésumé: La première description dans une publication médicale des douleurs neuropathiques remonte à 1872, le Dr S.W. Mitchell les résumant ainsi [...]" la causalgie est la plus terrible des tortures qu'une lésion nerveuse puisse entraîner "[...]. Par définition, la douleur neuropathique est une douleur chronique faisant suite à une lésion ou dysfonction du système nerveux. Malgré les progrès faits dans la compréhension de ce syndrome, le détail des mécanismes impliqués nous échappe encore et son traitement reste insuffisant car moins de 50% des patients sont soulagés par les thérapies actuelles. Différents modèles expérimentaux ont été élaborés chez l'animal de laboratoire, en particulier des modèles de lésion de nerfs périphériques chez le rat, permettant des investigations tant moléculaires que fonctionnelles des mécanismes impliqués dans le développement de ces douleurs. En revanche, peu de modèles existent chez la souris, alors que cet animal, grâce à la transgénèse, est très fréquemment utilisé pour l'approche fonctionnelle ciblée sur un gène. Dans l'étude présentée ici, nous avons évalué chez la souris C57BL/6 l'adaptation d'un modèle neuropathique, proposé une nouvelle modalité de mesure de la sensibilité douloureuse adaptée à la souris et défini une méthode d'analyse performante des résultats. Ce modèle, dit de lésion avec épargne nerveuse (spared Werve injury, SNI), consiste en la lésion de deux des trois branches du nerf sciatique, soit les nerfs peronier commun et tibial. La troisième branche, le nerf sural est laissé intact et c'est dans le territoire cutané de ce dernier que la sensibilité douloureuse à des stimulations mécaniques est enregistrée. Des filaments calibrés de force croissante sont appliqués sur la surface de la patte impliquée et la fréquence relative de retrait de la patte a été modélisée mathématiquement et analysée par un modèle statistique intégrant tous les paramètres de l'expérience (mixed-effects model). Des variantes chirurgicales lésant séquentiellement les trois branches du nerf sciatique ainsi que la réponse en fonction du sexe de l'animal ont également été évaluées. La lésion SNI entraîne une hypersensibilité mécanique marquée comparativement aux souris avec chirurgie contrôle; cet effet est constant entre les animaux et persiste durant les quatre semaines de l'étude. De subtiles différences entre les variables, y compris une divergence de sensibilité mécanique entre les sexes, ont été démontrées. La nécessité de léser le nerf tibial pour le développement des symptômes a également été documentée par notre méthode d'évaluation et d'analyse. En conclusion, nous avons validé le modèle SNI chez la souris par l'apparition d'un symptôme reproductible et apparenté à l'allodynie mécanique décrite par les patients souffrant de douleurs neuropathiques. Nous avons développé des méthodes d'enregistrement et d'analyse de la sensibilité douloureuse sensibles qui permettent la mise en évidence de facteurs intrinsèques et extrinsèques de variation de la réponse. Le modèle SNI utilisé chez des souris génétiquement modifiées, de par sa précision et reproductibilité, pourra permettre la discrimination de facteurs génétiques et épigénétiques contribuant au développement et à la persistance de douleurs neuropathiques.

Acute and usual drinking among emergency trauma patients: a study on alcohol consumption and injury patterns.

OBJECTIVE: To investigate the relationship between usual and acute alcohol consumption among injured patients and, when combined, how they covary with other injury attributes. METHODS: Data from a randomised sample of 486 injured patients interviewed in an emergency department (Lausanne University Hospital, Switzerland) were analysed using the chi(2) test for independence and cluster analysis. RESULTS: Acute alcohol consumption (24.7%) was associated with usual drinking and particularly with high volumes of consumption. Six injury clusters were identified. Over-representations of acute consumption were found in a cluster typical of injuries sustained through interpersonal violence and in another formed by miscellaneous circumstances. A third cluster, typical of sports injuries, was linked to a group of frequent heavy episodic drinkers (without acute consumption). CONCLUSIONS: Among injured patients, acute alcohol consumption is common and associated with usual drinking. Acute and/or usual consumption form part of some, but not all, injury clusters.

Energy balance in elderly patients after surgery for a femoral neck fracture.

To study energy and protein balances in elderly patients after surgery, spontaneous energy and protein intake and resting energy expenditure (REE) were measured in 20 elderly female patients with a femoral neck fracture (mean age 81 +/- 4, SD, range 74-87 years; weight 53 +/- 8, range 42-68 kg) during a 5-6 day period following surgery. REE, measured over 20-40 min by indirect calorimetry using a ventilated canopy, averaged 0.98 +/- 0.15 kcal/min on day 3 and decreased to 0.93 +/- 0.15 kcal/min on day 8-9 postsurgery (p less than 0.02). REE was positively correlated with body weight (r = 0.69, p less than 0.005). Mean REE extrapolated to 24 hr (24-REE) was 1283 +/- 194 kcal/day. Mean daily food energy intake measured over the 5-day follow-up period was 1097 +/- 333 kcal/day and was positively correlated with 24-REE (r = 0.50, p less than 0.05). Daily energy balance was -235 +/- 351 kcal/day on day 3 (p less than 0.01 vs zero) and -13 +/- 392 kcal/day on day 8-9 postsurgery (NS vs zero) with a mean over the study period of -185 +/- 289 kcal/day (p less than 0.01 vs zero). When an extra 100 kcal/day was allowed for the energy cost of physical activity, mean daily energy balance over the 5-day study period was calculated to be -285 +/- 289 kcal/day (p less than 0.01 vs zero). Measurements of total 24-hr urinary nitrogen (N) excretion were obtained in a subgroup of 14 patients.(ABSTRACT TRUNCATED AT 250 WORDS)

L'immunothérapie des carcinomes epidermoïdes de la sphère ORL [Immunotherapy for head and neck squamous cell carcinoma]

In the past decades, prognosis of head and neck squamous cell carcinoma (HNSCC) has not improved despite substantial progress in treatment options. Since antitumoral immunity was described, immunotherapy has shown promising results as an adjunctive treatment in various cancer types. Tumor-associated antigens (TAAs) have been identified and shown to stimulate selective T-cell-mediated antitumoral immune response. This article briefly reviews the work done in the field of immunotherapy of HNSCC in the past few years. It gives confidence that immunotherapy may play an important role in the treatment of head and neck squamous cell carcinoma. Among various TAAs, the family of cancer testis antigens (CTAs) may be promising candidates for specific immune therapy in HNSCC. Ongoing studies will confirm whether CTAs may generate an immune response in clinical vaccine trials.

The Recovery of Health Service Costs in Cases Involving Personal Injury Compensation (205KB)

A Consultation Document

Concomitant cisplatin and hyperfractionated radiotherapy in locally advanced head and neck cancer: 10-year follow-up of a randomized phase III trial (SAKK 10/94).

Purpose: To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer.Methods and Materials: From July 1994 to July 2000, a total of 224 patients with squamous cell carcinoma of the head and neck were randomized to receive either hyperfractionated radiotherapy alone (median total dose, 74.4 Gy; 1.2 Gy twice daily; 5 days per week) or the same radiotherapy combined with two cycles of cisplatin (20 mg/m(2) for 5 consecutive days during weeks 1 and 5). The primary endpoint was the time to any treatment failure; secondary endpoints were locoregional failure, metastatic failure, overall survival, and late toxicity assessed according to Radiation Therapy Oncology Group criteria.Results: Median follow-up was 9.5 years (range, 0.1-15.4 years). Median time to any treatment failure was not significantly different between treatment arms (hazard ratio [HR], 1.2 [95% confidence interval [CM 0.9-1.7; p = 0.17]). Rates of locoregional failure-free survival (HR, 1.5 [95% CI, 1.1-2.1;p = 0.021), distant metastasis-free survival (HR, 1.6 [95% CI, 1.1-2.5; p = 0.021), and cancer-specific survival (HR, 1.6 [95% CI, 1.0-2.5;p = 0.03]) were significantly improved in the combined-treatment arm, with no difference in major late toxicity between treatment arms. However, overall survival was not significantly different (HR, 1.3 [95% CI, 0.9-1.8; p = 0.11]).Conclusions: After long-term follow-up, combined-treatment with cisplatin and hyperfractionated radiotherapy maintained improved rates of locoregional control, distant metastasis-free survival, and cancer-specific survival compared to that of hyperfractionated radiotherapy alone, with no difference in major late toxicity. (C) 2012 Elsevier Inc.

Serum and CSF levels of neuron-specific enolase (NSE) in cardiac surgery with cardiopulmonary bypass: a marker of brain injury?

We investigated whether neuron-specific enolase (NSE) in serum or cerebrospinal fluid (CSF) reflects subtle or manifest brain injury in children undergoing cardiac surgery using cardiopulmonary bypass (CPB). NSE was measured in serum (s-NSE) before, and up to, 102 h after surgery in 27 children undergoing cardiac surgery with CPB. In 11 children, CSF-NSE was also measured 48 or 66 h post-surgery. As erythrocytes contain NSE, hemoglobin concentration in the samples was determined spectrophotometrically at 550 nm (cut-off limit: absorbance 0.4 = 560 mg/l) in 14 children and in a further 13 children by spectroscopic multicomponent analysis (cut-off limit 5 micromol/l = 80 mg/l). One hundred and one of 214 post-operative serum samples (47%) had to be discarded because of hemolysis (18% spectrophotometrically at 550 nm and 88% with spectroscopic multicomponent analysis). On the first and second post-operative day, the median s-NSE values were significantly higher when compared with samples taken after 54 h or longer (P = 0.008 and P = 0.002). All CSF-NSE levels were within the normal range and below the s-NSE measured in the same patient. Although in our study elevated s-NSE seems to indicate brain injury in CPB-surgery, the low concentration of NSE in the post-operative CSF of 11 children puts the neuronal origin of s-NSE in question. NSE from other non-neuronal tissues probably contributes to the elevated s-NSE. Additionally, normal post-operative CSF-NSE values in two children with post-operative neurological sequelae might question the predictive value of CSF-NSE with regard to brain injury.

A new automated method versus continuous positive airway pressure method for measuring pressure-volume curves in patients with acute lung injury

Objective: To compare pressure–volume (P–V) curves obtained with the Galileo ventilator with those obtained with the CPAP method in patients with ALI or ARDS receiving mechanical ventilation. P–V curves were fitted to a sigmoidal equation with a mean R2 of 0.994 ± 0.003. Lower (LIP) and upper inflection (UIP), and deflation maximum curvature (PMC) points calculated from the fitted variables showed a good correlation between methods with high intraclass correlation coefficients. Bias and limits of agreement for LIP, UIP and PMC obtained with the two methods in the same patient were clinically acceptable.

Effect of mannitol and hypertonic saline on cerebral oxygenation in patients with severe traumatic brain injury and refractory intracranial hypertension.

BACKGROUND: The impact of osmotic therapies on brain oxygen has not been extensively studied in humans. We examined the effects on brain tissue oxygen tension (PbtO(2)) of mannitol and hypertonic saline (HTS) in patients with severe traumatic brain injury (TBI) and refractory intracranial hypertension. METHODS: 12 consecutive patients with severe TBI who underwent intracranial pressure (ICP) and PbtO(2) monitoring were studied. Patients were treated with mannitol (25%, 0.75 g/kg) for episodes of elevated ICP (>20 mm Hg) or HTS (7.5%, 250 ml) if ICP was not controlled with mannitol. PbtO(2), ICP, mean arterial pressure, cerebral perfusion pressure (CPP), central venous pressure and cardiac output were monitored continuously. RESULTS: 42 episodes of intracranial hypertension, treated with mannitol (n = 28 boluses) or HTS (n = 14 boluses), were analysed. HTS treatment was associated with an increase in PbtO(2) (from baseline 28.3 (13.8) mm Hg to 34.9 (18.2) mm Hg at 30 min, 37.0 (17.6) mm Hg at 60 min and 41.4 (17.7) mm Hg at 120 min; all p<0.01) while mannitol did not affect PbtO(2) (baseline 30.4 (11.4) vs 28.7 (13.5) vs 28.4 (10.6) vs 27.5 (9.9) mm Hg; all p>0.1). Compared with mannitol, HTS was associated with lower ICP and higher CPP and cardiac output. CONCLUSIONS: In patients with severe TBI and elevated ICP refractory to previous mannitol treatment, 7.5% hypertonic saline administered as second tier therapy is associated with a significant increase in brain oxygenation, and improved cerebral and systemic haemodynamics.

Cetuximab for the treatment of metastatic and/or recurrent squamous cell carcinoma of the head and neck: appraisal consultation

Appraisal consultation document - Cetuximab for the treatment of recurrent and/or metastatic squamous cell cancer of the head and neck.To take part in the 'Cetuximab for the treatment of metastatic and/or recurrent squamous cell carcinoma of the head and neck: appraisal consultation'