PD-1/PD-L1 inhibitor activity in patients with gene-rearrangement positive non-small cell lung cancer-an IMMUNOTARGET case series.

BACKGROUND Prior IMMUNOTARGET registry data had suggested that responses to immune [anti PD(L)1] monotherapy in gene-arranged non-small cell lung cancer (NSCLC) were rare or absent, depending on the specific oncogene. METHODS IMMUNOTARGET sites reporting prior registry data or new individual cases of gene rearranged NSCLC seeming to benefit from immune monotherapy were explored in detail looking to both validate their diagnosis of a functional gene rearrangement and to look for features potentially differentiating them from other such cases associated with low response rates. RESULTS Five cases of NSCLC with a gene rearrangement with reported responses or prolonged stabilization from immune monotherapy were identified in total. All had little or no prior smoking history and had programmed death-ligand 1 (PD-L1) values ranging from zero to 100%. A confirmed rearrangement partner was reported in only 2 of the cases (CD74-ROS1 and KIF5B-RET), however in one of the other three cases [analplastic lymophoma kinase (ALK)], significant benefit from a relevant prior targeted therapy was noted, also consistent with the rearrangement status being correctly assigned. CONCLUSIONS Not all driver oncogene subtypes of NSCLC are equally responsive to immune monotherapy, however even among patients with well-validated gene rearranged NSCLC which has traditionally been considered immune hyporesponsive, objective responses can occur. Additional explorations of the features associated with and underlying the immune hypo-responsiveness of most, but not all, cases of gene-rearranged NSCLC are required

Service Platform for Converged Interactive Broadband Broadcast and Cellular Wireless

A converged broadcast and telecommunication service platform is presented that is able to create, deliver, and manage interactive, multimedia content and services for consumption on three different terminal types. The motivations of service providers for designing converged interactive multimedia services, which are crafted for their individual requirements, are investigated. The overall design of the system is presented with particular emphasis placed on the operational features of each of the sub-systems, the flows of media and metadata through the sub-systems and the formats and protocols required for inter-communication between them. The key features of tools required for creating converged interactive multimedia content for a range of different end-user terminal types are examined. Finally possible enhancements to this system are discussed. This study is of particular interest to those organizations currently conducting trials and commercial launches of DVB-H services because it provides them with an insight of the various additional functions required in the service provisioning platforms to provide fully interactive services to a range of different mobile terminal types

Analyse des délais de prise en charge des cancers thoraciques : étude prospective

RésuméIntroductionLe cancer broncho-pulmonaire est la première cause de décès par cancer en France. Son diagnostic est le plus souvent tardif, alors que le délai entre le début des symptômes et la prise en charge est considéré comme un facteur aggravant.Matériel et méthodesNotre étude prospective a recueilli les différentes dates de prise en charge de 139 patients consécutifs bénéficiant d’un traitement primaire pour un cancer thoracique dans notre hôpital entre novembre 2008 et mai 2009. L’objectif de cette étude était d’évaluer différents délais de prise en charge des patients porteurs d’un cancer thoracique quelle que soit sa prise en charge thérapeutique (médicale ou chirurgicale) et de déterminer la cause de ces délais.RésultatsLe délai médian entre la première imagerie pathologique et le traitement est de 9,6 semaines. Les délais étaient significativement plus courts dans les stades tardifs et les carcinomes à petites cellules (p=0,001). Il existait une tendance à des délais plus courts pour les femmes et des délais plus longs pour les classes d’âge les plus élevées.ConclusionL’évaluation des délais de prise en charge, en particulier pour les stades précoces, s’intègre dans le contrôle de la qualité de prise en charge de ces pathologies.SummaryIntroductionLung cancer is the main cause of cancer death in France. The diagnosis is often late and the delay between the onset of symptoms and management is considered an aggravating factor.Material and methodsOur prospective study collected the dates of the start of management of 139 consecutive patients receiving first line treatment for thoracic cancer in our hospital between November 2008 and May 2009. The aim of this study was to evaluate the delays in medical or surgical treatments in patients with thoracic cancer and to determine the cause of these delays.ResultsThe median delay between the first abnormal chest X-ray and treatment was 9.6 weeks. The delays were significantly shorter in the late stages and in small cell cancer (P=0.001). There was a tendency for shorter delays in women and for longer delays in older patients.ConclusionEvaluation of the delays in treatment, particularly in the early stages, is part of the quality control of management of these diseases

Advanced algorithms for information science

This is the final report of a one-year, Laboratory Directed Research and Development (LDRD) project at Los Alamos National Laboratory (LANL). In a modern information-controlled society the importance of fast computational algorithms facilitating data compression and image analysis cannot be overemphasized. Feature extraction and pattern recognition are key to many LANL projects and the same types of dimensionality reduction and compression used in source coding are also applicable to image understanding. The authors have begun developing wavelet coding which decomposes data into different length-scale and frequency bands. New transform-based source-coding techniques offer potential for achieving better, combined source-channel coding performance by using joint-optimization techniques. They initiated work on a system that compresses the video stream in real time, and which also takes the additional step of analyzing the video stream concurrently. By using object-based compression schemes (where an object is an identifiable feature of the video signal, repeatable in time or space), they believe that the analysis is directly related to the efficiency of the compression

Epigenetic regulation of RhoB loss of expression in lung cancer

<p>Abstract</p> <p>Background</p> <p>RhoB is down-regulated in most lung cancer cell lines and tumor tissues when compared with their normal counterparts. The mechanism of this loss of expression is not yet deciphered.</p> <p>Methods</p> <p>Since no mutation has been reported in the RhoB sequence, we investigated the epigenetic regulation of RhoB expression by analyzing the effect of HDAC inhibitors and methyltransferase inhibitors, by direct sequencing after bisulfite treatment and by methylation specific PCR.</p> <p>Results</p> <p>We first showed that histone deacetylase (HDAC) inhibitors induce a significant RhoB re-expression in lung cancer cell lines whereas only a slight effect was observed with methyl transferase inhibitors. As promoter methylation is the most common epigenetic process in lung cancer, we performed methylation specific PCR and sequence analysis after bisulfite treatment and demonstrated that RhoB was methylated neither in lung cancer cell lines nor in tumor tissues. We also showed that a variable number of tandem repeats sequences in the 5' region of the RhoB gene was involved in HDAC response.</p> <p>Conclusion</p> <p>We thus propose that RhoB regulation of expression occurs mainly by histone deacetylation rather than by promoter hypermethylation and that this process can be modulated by specific 5' sequences within the promoter.</p

Results of screening in early and advanced thoracic malignancies in the EORTC pan-European SPECTAlung platform.

Access to a comprehensive molecular alteration screening is patchy in Europe and quality of the molecular analysis varies. SPECTAlung was created in 2015 as a pan-European screening platform for patients with thoracic malignancies. Here we report the results of almost 4 years of prospective molecular screening of patients with thoracic malignancies, in terms of quality of the program and molecular alterations identified. Patients with thoracic malignancies at any stage of disease were recruited in SPECTAlung, from June 2015 to May 2019, in 7 different countries. Molecular tumour boards were organised monthly to discuss patients' molecular and clinical profile and possible biomarker-driven treatments, including clinical trial options. FFPE material was collected and analysed for 576 patients with diagnosis of pleural, lung, or thymic malignancies. Ultimately, 539 patients were eligible (93.6%) and 528 patients were assessable (91.7%). The turn-around time for report generation and molecular tumour board was 214 days (median). Targetable molecular alterations were observed in almost 20% of cases, but treatment adaptation was low (3% of patients). SPECTAlung showed the feasibility of a pan-European screening platform. One fifth of the patients had a targetable molecular alteration. Some operational issues were discovered and adapted to improve efficiency