Radio(chemo)therapy in Elderly Patients with Esophageal Cancer: A Feasible Treatment with an Outcome Consistent with Younger Patients

BACKGROUND: Although the prevalence of esophageal cancer increases in elderly patients, its clinical history and outcome after treatment remain poorly described. METHODS: Between January 2001 and December 2011, 58 patients (pts) older than 75 years received 3D-conformal radiotherapy (mean dose 51 Gy) in two French cancer centers. 47/58 (82%) patients received concomitant chemotherapy (with CDDP and/or FU regimens) and 8 patients underwent surgery after primary radiochemotherapy (RCT). RESULTS: Median age was 77.9 years and the performance status (PS) was 0 or 1 in 89%. Tumors were mainly adenocarcinoma of lower esophagus or gastroesophageal junction (n = 51, 89%), T3T4 (n = 54, 95%), and N1 (n = 44, 77%). The mean follow-up was 21.9 months. In the overall population, the median progression-free survival was 9.6 months and median overall survival (OS) was 14.5 months. Using univariate analysis, OS was significantly associated with age (p = 0.048), PS (p < 0.001), and surgery (p = 0.035). 35 (60.3%) and 18 patients (31%) experienced grade 1-2 or 3-4 toxicity, respectively (CTCAE v4.0). CONCLUSION: Radiochemotherapy in elderly patients is a feasible treatment and its outcome is close to younger patient's outcome published in the literature. Surgical resection, after comprehensive geriatric assessment, should be recommended as the standard treatment for adenocarcinoma of lower esophagus or gastroesophageal junction in elderly patients with good PS and low co-morbidity profile, as it is in younger patients

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

The European Virus Archive goes global: A growing resource for research

The European Virus Archive (EVA) was created in 2008 with funding from the FP7-EU Infrastructure Programme, in response to the need for a coordinated and readily accessible collection of viruses that could be made available to academia, public health organisations and industry. Within three years, it developed from a consortium of nine European laboratories to encompass associated partners in Africa, Russia, China, Turkey, Germany and Italy. In 2014, the H2020 Research and Innovation Framework Programme (INFRAS projects) provided support for the transformation of the EVA from a European to a global organization (EVAg). The EVAg now operates as a non-profit consortium, with 26 partners and 20 associated partners from 21 EU and non-EU countries. In this paper, we outline the structure, management and goals of the EVAg, to bring to the attention of researchers the wealth of products it can provide and to illustrate how end-users can gain access to these resources. Organisations or individuals who would like to be considered as contributors are invited to contact the EVAg coordinator, Jean-Louis Romette, at [email protected]

Drug-drug interactions with proton pump inhibitors in cancer patients: an underrecognized cause of treatment failure.

New concepts and drugs have revolutionized medical treatment for cancers. These drugs, which are very expensive and usually well tolerated, have dramatically improved cancer prognosis. We must use them wisely for patients to fully benefit. Gastric acid antisecretory drugs and particularly proton pump inhibitors (PPIs) revolutionized the treatment of gastroduodenal ulcers and severe gastroesophageal reflux, but are frequently overused for symptomatic treatment of epigastric pain or heartburn. Long-term acid suppression may alter the efficacy of many anticancer drugs, such as tyrosine kinase inhibitors (TKIs), cyclin-dependent kinase (CDK) 4/6 inhibitors and immune checkpoint inhibitors (ICIs), by either decreasing gastric acid secretion and thus drug absorption, or by modifying the gut microbiome that modulates the response to ICIs. Oncologists thus need to pay particular attention to the concomitant use of PPIs and anticancer drugs. These interactions translate into major clinical impacts, with demonstrated loss of efficacy for some TKIs (erlotinib, gefitinib, pazopanib), and conflicting results with many other oral drugs, including capecitabine and CDK 4/6 inhibitors. Furthermore, the profound changes in the gut microbiome due to using PPIs have shown that the benefit of using ICIs may be suppressed in patients treated with PPIs. As the use of PPIs is not essential, we must apply the precautionary principle. The first sentence of a recent Comment in Nature was "Every day, millions of people are taking medications that will not help them". We fear that every day millions of cancer patients are taking medications that harm them. While this may well be only association and not causation, there is enough to make us pause until we reach a clear answer. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician

Role of the multidisciplinary team in the diagnosis and treatment of hepatocellular carcinoma

It has long been appreciated that hepatocellular carcinoma (HCC) is a complex disease. HCC is typically preceded by liver cirrhosis, which is itself caused by various types of hepatitis of both viral and nonviral etiologies. Thus, the treatment of patients with HCC requires multiple healthcare professionals, including hepatologists, medical oncologists, surgical oncologists, transplantation surgeons, diagnostic radiologists, pathologists, nurses, nurse practitioners and interventional radiologists. These specialists should meet regularly to review patients' progress, ensure that treatments are individualized for each patient and agree on next steps. We review case presentations provided by the authors to illustrate the benefits and advantages of the multidisciplinary team matrix in the management of patients with HCC, including the effects of this treatment technique on patient outcome, survival and quality of life

Photon acceleration by laser produced wakefields on Astra

This chapter looks at photon acceleration by laser produced wakefields on Astr

Single event transient injection on an operational amplifier: a case study

International audienceThis paper reports a case study about effects produced by the radiation Single Event Transient (SET) injection on a custom operational amplifier. SETs were injected in the operational amplifier transistors in order to evaluate their sensitivity to the radiation transient faults. The circuit was designed using a non-rad-hard AMS-CMOS 0.8μm process. In this case, simulation results allow us to identify the operational amplifier most sensitive transistors. This work will form the basis to further development of design techniques for radiation hard analog circuits

Single event transient injection on an operational amplifier: a case study

International audienceThis paper reports a case study about effects produced by the radiation Single Event Transient (SET) injection on a custom operational amplifier. SETs were injected in the operational amplifier transistors in order to evaluate their sensitivity to the radiation transient faults. The circuit was designed using a non-rad-hard AMS-CMOS 0.8μm process. In this case, simulation results allow us to identify the operational amplifier most sensitive transistors. This work will form the basis to further development of design techniques for radiation hard analog circuits