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Anthracycline–taxane chemotherapy for early-stage breast cancer substantially improves survival compared with no chemotherapy. However, concerns about short-term and long-term side-effects of anthracyclines have led to increased use of taxane chemotherapy without anthracycline, which could compromise efficacy. We aimed to better characterise the benefits and risks of including anthracycline, and the comparative benefits of different anthracycline–taxane regimens.

Background: A 70-gene signature was previously shown to have prognostic value in patients with node-negative breast cancer. Our goal was to validate the signature in an independent group of patients. Methods: Patients (n = 307, with 137 events after a median follow-up of 13.6 years) from five European centers were divided into high- and low-risk groups based on the gene signature classification and on clinical risk classifications. Patients were assigned to the gene signature low-risk group if their 5-year distant metastasis-free survival probability as estimated by the gene signature was greater than 90%. Patients were assigned to the clinicopathologic low-risk group if their 10-year survival probability, as estimated by Adjuvant! software, was greater than 88% (for estrogen receptor [ER]-positive patients) or 92% (for ER-negative patients). Hazard ratios (HRs) were estimated to compare time to distant metastases, disease-free survival, and overall survival in high- versus low-risk groups. Results: The 70-gene signature outperformed the clinicopathologic risk assessment in predicting all endpoints. For time to distant metastases, the gene signature yielded HR = 2.32 (95% confidence interval [CI] = 1.35 to 4.00) without adjustment for clinical risk and hazard ratios ranging from 2.13 to 2.15 after adjustment for various estimates of clinical risk; clinicopathologic risk using Adjuvant! software yielded an unadjusted HR = 1.68 (95% CI = 0.92 to 3.07). For overall survival, the gene signature yielded an unadjusted HR = 2.79 (95% CI = 1.60 to 4.87) and adjusted hazard ratios ranging from 2.63 to 2.89; clinicopathologic risk yielded an unadjusted HR = 1.67 (95% CI = 0.93 to 2.98). For patients in the gene signature high-risk group, 10-year overall survival was 0.69 for patients in both the low- and high-clinical risk groups; for patients in the gene signature low-risk group, the 10-year survival rates were 0.88 and 0.89, respectively. Conclusions: The 70-gene signature adds independent prognostic information to clinicopathologic risk assessment for patients with early breast cancer.

Increasing the dose intensity of cytotoxic therapy by shortening the intervals between cycles, or by giving individual drugs sequentially at full dose rather than in lower-dose concurrent treatment schedules, might enhance efficacy.

Assessment of tumour burden has become an integral part of most oncology clinical trials, and enables the evaluation of the activity and efficacy of new cancer therapeutics in solid tumours. Although RECIST was developed to assess treatment activity in early phase II trials with tumour response as the primary end point, it is now applied across the spectrum from early phase I trials through to confirmatory phase III trials. Several questions regarding the role of RECIST in the rapidly changing landscape of oncology therapeutics, and the challenges faced in its evaluation, are highlighted.

Pathological complete response has been proposed as a surrogate endpoint for prediction of long-term clinical benefit, such as disease-free survival, event-free survival (EFS), and overall survival (OS). We had four key objectives: to establish the association between pathological complete response and EFS and OS, to establish the definition of pathological complete response that correlates best with long-term outcome, to identify the breast cancer subtypes in which pathological complete response is best correlated with long-term outcome, and to assess whether an increase in frequency of pathological complete response between treatment groups predicts improved EFS and OS.

This paper describes a back-side illuminated 1 Megapixel CMOS image sensor made in 0.18um CMOS process for EUV detection. The sensor applied a so-call "dual-transfer" scheme to achieve low noise, high dynamic range. The EUV sensitivity is achieved with backside illumination use SOI-based solution. The epitaxial silicon layer is thinned down to less than 3um. The sensor is tested and characterized at 5nm to 30nm illumination. At 17.4nm targeted wavelength, the detector external QE (exclude quantum yield factor) reaches almost 60%. The detector reaches read noise of 1.2 ph- (@17.4nm), i.e. close to performance of EUV photon counting.

In this paper, we address the issues of designing a CMOS image sensor for space applications. The performance of a 4T pinned photodiode pixel under irradiation is shown and an example of a CMOS image sensor designed for sun tracking is given. It has been shown that the radiation tolerance level of the pixel is improved by using more advanced pixel architecture and more advanced fabrication process. Special measures are required in the sensor design to increases the sensor immunity on single event upset and latch-up.

The present article reviews the randomized trials contributing to the establishment of current standards for the treatment of head and neck cancer. It provides critical analysis of their methodology in order to facilitate future trial design.

The development of the 70-gene prognosis signature for breast cancer was evaluated in the MINDACT (Microarray In Node negative Disease may Avoid ChemoTherapy) trial to assess the clinical relevance of the 70-gene prognosis signature, and how this compares with traditional prognostic factors for assigning adjuvant chemotherapy for patients with node-negative breast cancer. This review outlines the background work and rationale behind the final design of the MINDACT trial and how these considerations can help to optimize future trials and aim to improve individualization of cancer therapy.

We develop a high-quantum-efficiency, high-exposure-durability backside-illuminated CMOS image sensor for soft-X-ray detection. The backside fabrication process is optimized to reduce the dead-layer thickness, and the Si-layer thickness is increased to 9.5 ?m to reduce radiation damage. Our sensor demonstrates a high quantum efficiency of >90% in the photon-energy range of 80-1000 eV. Further, its EUV-regime efficiency is ?100% because the dead-layer thickness is only 5 nm. The readout noise is as low as 2.5 e?rms and the frame rate as high as 48 fps, which makes the device practical for general soft X-ray experiments.

We recently developed a backside-illuminated CMOS image sensor for soft X-ray detection based on a commercial CMOS sensor. This sensor demonstrated a high quantum efficiency, low readout noise of 2.6 e?rms, and high frame rate of 48 fps. This sensor also showed an energy resolution of 80 eV to 1,000 eV photon. We demonstrated fluorescence detection from highly-oriented graphite and a polymethyl methacrylate film using a simple setup, where the samples faced a CMOS sensor without a monochromator. This energy-resolving performance and high frame rate will facilitate new applications for soft X-ray and EUV experiments.

Emerging technologies and progress in data processing allowed for new insights on gene expression, genomics and epigenomics, and mechanisms of cancer genesis and progression. The development of new therapeutic strategies should therefore be triggered by the understanding of the underlying biology through sophisticated clinical trials. Therefore, the methodology and the design of cancer clinical trials as well as the methods of their implementation are under profound changes. Targeting specific pathways has open the hope of a more focused and personalized medicine which has the potential to bring more efficient and tailored treatments to patients. It has been questioned therefore whether clinical trials traditionally designed for specific tumor types could not re-visited towards trials gathering patients based on molecular features rather than pure pathology criteria. The complexity of the cancer biology being the result of so many different interactive mechanisms whether driving or not the process of cancer cells is an additional level of complexity to approach more inclusive clinical trial access. Nevertheless, a number of innovative solutions to address biological challenges across histologies have been initiated and the question of whether histology agnostic trials could be conceived is a logical next question. This paper questions the advantages and the limits of clinical trials performed across tumor types bearing similar selected molecular features and looks further into the feasibility of such histology agnostic trials.