Interventions for the treatment of oral cavity and oropharyngeal cancer:chemotherapy

<b>Background:</b> Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.<p></p> <b>Objectives:</b> To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes.<p></p> <b>Search strategy:</b> Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th July 2010. Reference lists of recent reviews and included studies were also searched to identify further trials.<p></p> <b>Selection criteria:</b> Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included.<p></p> <b>Data collection and analysis:</b> Trials which met the inclusion criteria were assessed for risk of bias using six domains: sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting and other possible sources of bias. Data were extracted using a specially designed form and entered into the characteristics of included studies table and the analysis sections of the review. The proportion of participants in each trial with oral cavity and oropharyngeal cancers are recorded in Additional Table 1.<p></p> <b>Main results:</b> There was no statistically significant improvement in overall survival associated with induction chemotherapy compared to locoregional treatment alone in 25 trials (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00). Post-surgery adjuvant chemotherapy was associated with improved overall survival compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88, 95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality 0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved survival compared to radiotherapy alone in patients whose tumours were considered unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However, the additional toxicity attributable to chemotherapy in the combined regimens remains unquantified.<p></p> <b>Authors' conclusions:</b> Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is associated with a 9% increase in survival and adjuvant concomitant chemoradiotherapy is associated with a 16% increase in overall survival following surgery. In patients with unresectable tumours, concomitant chemoradiotherapy showed a 22% benefit in overall survival compared with radiotherapy alone.<p></p&gt

Evolution of BCL-2/IgH hybrid gene RNA expression during treatment of T(14;18)-bearing follicular lymphomas

Bcl-2, the gene over-expressed in follicular lymphomas (FL), is able to block chemotherapy-induced apoptosis. Consequently, we wondered whether bcl-2/IgH expression variations during treatment of FL could predict the outcome of patients with t(14;18)-bearing FL. For this purpose, we used a reverse transcription polymerase chain reaction (RT-PCR) assay to analyse 180 serial peripheral blood samples (PBS) during 34 treatment phases in 25 patients with t(14;18)-bearing FL. In all patients but two, bcl-2/IgH gene expression was demonstrated in pre-treatment samples. During 16 out of the 34 treatment phases (47%), bcl-2/IgH expression became negative: all but one were responders to chemotherapy. This conversion was transient in six cases. In 18 treatment phases, bcl2/IgH expression remained detectable: eight were clinically considered as treatment failures, while eight others achieved PR and two achieved CR. We observed a significant correlation between treatment response and RNA PCR results (P = 0.002). Three-year overall survival of patients with stable bcl2/IgH-negative conversion was 100% compared to 54% for the remaining patients (P = 0.069); 3-year freedom from progression was respectively 87.5% and 13% (P = 0.005). These results indicate a correlation between bcl-2/IgH expression variations and both clinical response and outcome. Whether this might predict disease outcome early remains to be confirmed. © 1999 Cancer Research Campaig

Neoadjuvant chemotherapy prior to preoperative chemoradiation or radiation in rectal cancer: should we be more cautious?

Neoadjuvant chemotherapy (NACT) is a term originally used to describe the administration of chemotherapy preoperatively before surgery. The original rationale for administering NACT or so-called induction chemotherapy to shrink or downstage a locally advanced tumour, and thereby facilitate more effective local treatment with surgery or radiotherapy, has been extended with the introduction of more effective combinations of chemotherapy to include reducing the risks of metastatic disease. It seems logical that survival could be lengthened, or organ preservation rates increased in resectable tumours by NACT. In rectal cancer NACT is being increasingly used in locally advanced and nonmetastatic unresectable tumours. Randomised studies in advanced colorectal cancer show high response rates to combination cytotoxic therapy. This evidence of efficacy coupled with the introduction of novel molecular targeted therapies (such as Bevacizumab and Cetuximab), and long waiting times for radiotherapy have rekindled an interest in delivering NACT in locally advanced rectal cancer. In contrast, this enthusiasm is currently waning in other sites such as head and neck and nasopharynx cancer where traditionally NACT has been used. So, is NACT in rectal cancer a real advance or just history repeating itself? In this review, we aimed to explore the advantages and disadvantages of the separate approaches of neoadjuvant, concurrent and consolidation chemotherapy in locally advanced rectal cancer, drawing on theoretical principles, preclinical studies and clinical experience both in rectal cancer and other disease sites. Neoadjuvant chemotherapy may improve outcome in terms of disease-free or overall survival in selected groups in some disease sites, but this strategy has not been shown to be associated with better outcomes than postoperative adjuvant chemotherapy. In particular, there is insufficient data in rectal cancer. The evidence for benefit is strongest when NACT is administered before surgical resection. In contrast, the data in favour of NACT before radiation or chemoradiation (CRT) is inconclusive, despite the suggestion that response to induction chemotherapy can predict response to subsequent radiotherapy. The observation that spectacular responses to chemotherapy before radical radiotherapy did not result in improved survival, was noted 25 years ago. However, multiple trials in head and neck cancer, nasopharyngeal cancer, non-small-cell lung cancer, small-cell lung cancer and cervical cancer do not support the routine use of NACT either as an alternative, or as additional benefit to CRT. The addition of NACT does not appear to enhance local control over concurrent CRT or radiotherapy alone. Neoadjuvant chemotherapy before CRT or radiation should be used with caution, and only in the context of clinical trials. The evidence base suggests that concurrent CRT with early positioning of radiotherapy appears the best option for patients with locally advanced rectal cancer and in all disease sites where radiation is the primary local therapy

Understanding the Challenges of Immersive Authoring for End-Users

International audienceOver the years, virtual reality (VR) gains in popularity. Although VR becomes more affordable, VR content creation is restricted to expert developers which limits both its expansion and adoption. Enabling the authoring of VR experiences to non-developers would empower end-users and allow them to design their own VR applications. To do so, it is however necessary to support the onboarding process in VR. In this paper, we present our work and research direction planned for this PhD. We implemented a prototype for immersive authoring of interactive experiences, investigated VR onboarding, and provided a framework. Finally, we plan on exploring the authoring of data-driven storytelling

Editer des expériences interactives et immersives en utilisant la programmation par démonstration

International audienceImmersive technologies, like virtual and augmented reality, allow engaging the general public in interactive experiences, which are particularly promising in educational and cultural activities (e.g. museums, exhibits). For now, the design of such interactive experiences requires extensive knowledge of expert programming tools, and thus they are not accessible to non-developers. A promising method to ease the prototyping of interactive scenes for non-expert users stands on the concept of programming-by-demonstration. With such an approach, novice users can simply demonstrate an interaction or the expected behavior of a virtual object to build their prototype, without knowing the underlying coding mechanisms. In this paper, we propose an immersive authoring system that bases on that approach. We prototyped two use cases based on this system, as well as a user study. Using our observations and the results of the study, we discuss challenges associated with the design of such systems and provide guidelines for the development of future immersive programming-by-demonstration tools.Les technologies immersives, comme la réalité virtuelle et augmentée, permettent de proposer au grand public des expériences interactives, particulièrement dans les activités éducatives et culturelles. Pour l’instant, la conception de telles expériences nécessite une connaissance approfondie de langages de programmation, difficilement accessibles aux non-développeurs. La programmation par démonstration est une approche qui permet de faciliter le prototypage de scènes interactives pour les utilisateurs non experts. Avec cette approche, les utilisateurs peuvent construire un prototype sans connaître les mécanismes de codages sous-jacents, simplement en effectuant l’interaction ou le comportement attendu d’un objet virtuel. Dans cet article, nous proposons un système de création immersif basé sur cette approche. Nous avons prototypé deux cas d’utilisations, ainsi que réalisé une étude utilisateur. En s’appuyant sur nos observations et les résultats de l’étude, nous discutons des défis et des lignes directrices pour le développement de futurs outils de programmation immersive par démonstration

User Onboarding in Virtual Reality: An Investigation of Current Practices

International audienceExplaining to novice users how to interact in immersive VR applications may be challenging. This is in particular due to the fact that the learners are isolated from the real world, and they are asked to manipulate hardware and software objects they are not used to. Consequently, the onboarding phase, which consists in teaching the user how to interact with the application is particularly crucial. In this paper, we aim at giving a better understanding of current VR onboarding methods, their benefits and challenges. We performed 21 VR tutorial ergonomic reviews and 15 interviews with VR experts with experience in VR onboarding. Building on the results, we propose a conceptual framework for VR onboarding and discuss important research directions to explore the design of future efficient onboarding solutions adapted to VR