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    Arts Undergraduate Handbook 2009

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    PURPOSE: Anemia is associated with poor tumor control. It was previously observed that accelerated radiotherapy combined with carbogen breathing and nicotinamide (ARCON) can correct this adverse outcome in patients with head and neck cancer. The purpose of this study was to validate this observation based on data from a randomized trial. EXPERIMENTAL DESIGN: Of 345 patients with cT2-4 laryngeal cancer, 174 were randomly assigned to accelerated radiotherapy and 171 to ARCON. Hemoglobin levels, measured before treatment, were defined as low when <7.5 mmol/L for women and <8.5 mmol/L for men. The hypoxia marker pimonidazole was used to assess the oxygenation status in tumor biopsies. Data were analyzed 2 years after inclusion of the last patient. RESULTS: Pretreatment hemoglobin levels were available and below normal in 27 of 173 (16%) accelerated radiotherapy and 27 of 167 (16%) ARCON patients. In patients with normal pretreatment, hemoglobin levels treatment with ARCON had no significant effect on 5-year loco-regional control (LRC, 79% versus 75%; P = 0.44) and disease-free survival (DFS, 75% vs. 70%; P = 0.46) compared with accelerated radiotherapy. However, in patients with low pretreatment, hemoglobin levels ARCON significantly improved 5-year LRC (79% vs. 53%; P = 0.03) and DFS (68% vs. 45%; P = 0.04). In multivariate analysis including other prognostic factors, pretreatment hemoglobin remained prognostic for LRC and DFS in the accelerated radiotherapy treatment arm. No correlation between pretreatment hemoglobin levels and pimonidazole uptake was observed. CONCLUSION: Results from the randomized phase III trial support previous observations that ARCON has the potential to correct the poor outcome of cancer patients with anemia (ClinicalTrials.gov number, NCT00147732). Clin Cancer Res; 20(5); 1345-54. (c)2014 AACR

    Effect of high-intensity submaximal work, with or without rest, on subsequent VO2max

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    BACKGROUND: The prognostic and predictive value of the proliferation marker Ki-67 was investigated in a randomized trial comparing accelerated radiotherapy with carbogen breathing and nicotinamide (ARCON) to accelerated radiotherapy in laryngeal carcinoma. METHODS: Labeling index of Ki-67 (Li Ki-67) in immunohistochemically stained biopsies and the colocalization with carbonic anhydrase IX (CAIX) were related to tumor control and patient survival. RESULTS: On average, node-positive patients had a higher Li Ki-67 (median 14% vs 8%; p < .01). In patients with a high Li Ki-67, the 5-year regional control and metastases-free survival were 79% versus 96% (p < .01) and 71% versus 88% (p = .05) for accelerated radiotherapy and ARCON, respectively. The 5-year local control and disease-specific survival were not significantly different. Patients with low Ki-67 expression had an excellent outcome with accelerated radiotherapy alone. CONCLUSION: Patients with laryngeal carcinomas with high proliferative activity are at increased risk of regional and distant metastases formation. This risk can be reduced by treatment with ARCON

    Computed tomography-based tumour volume as a predictor of outcome in laryngeal cancer: Results of the phase 3 ARCON trial.

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    Item does not contain fulltextPURPOSE: Retrospective studies indicate that larger tumour volume is a strong prognostic indicator for poor tumour control after (chemo)radiotherapy for laryngeal cancer. The impact of tumour volume on the outcome of patients treated within a prospective study comparing accelerated radiotherapy (AR)+/-carbogen breathing and nicotinamide (ARCON) was investigated. METHODS AND MATERIALS: Of 345 patients with cT2-4 laryngeal cancer, pre-treatment computed tomography (CT) scans of 270 patients were available for tumour volume calculation. Contouring of the primary tumour and involved lymph nodes was reviewed by one experienced head and neck radiation oncologist. Kaplan-Meier plots were used for analysis of outcome. RESULTS: Of 137 AR and 133 ARCON patients, 57 and 80 versus 56 and 77 patients had glottic and supraglottic tumours, respectively. A correlation between primary tumour volume and T-stage was observed (Rs=.51, P<.01). In both treatment arms no correlation was detected between the primary tumour volume and local control (LC), regional control (RC) and metastasis-free survival (MFS). A strong correlation between total nodal volume and N-stage was found (Rs=.93, P<.01). Both in the AR and ARCON groups total nodal volume was not associated with poorer RC rate. However, based on individual lymph node analyses, nodal control was in favour of ARCON, irrespective of volume (P<.01). CONCLUSION: Neither primary tumour volume, nor total nodal volume is a prognostic factor for patients with cT2-4 laryngeal cancer treated with accelerated radiotherapy+/-carbogen breathing and nicotinamide. Additional analyses based on individual nodal volumes demonstrate an excellent regional control rate and a significant benefit of ARCON.1 april 201
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