Design Guidelines for Database-Driven Internet of Things-Enabled Dynamic Spectrum Access.

The radio-frequency spectrum shortage, which is primarily caused by the fixed allocation policy, is one of the main bottlenecks to the deployment of existing wireless communication networks, and to the development of new ones. The dynamic spectrum access policy is foreseen as the solution to this problem, since it allows shared spectrum usage by primary licensed and secondary unlicensed networks. In order to turn this policy into reality, the secondary network must be capable of acquiring reliable, real-time information on available bands within the service area, which can be achieved by means of spectrum sensing, spectrum occupancy databases, or a combination of them. This Review presents guidelines related to the design of a framework that can be adopted to foster dynamic spectrum access policies. The framework applies special-purpose Internet of Things (IoT) devices that perform spectrum sensing, subsequently feeding a spectrum occupancy database, which in turn will be used by the secondary network to gather information on location-dependent spectrum availability. The guidelines address technological enablers capable of making the framework feasible, reliable and secure.

NovaGenesis Applied to Information-Centric, Service-Defined, Trustable IoT/WSAN Control Plane and Spectrum Management.

We integrate, for the first time in the literature, the following ingredients to deal with emerging dynamic spectrum management (DSM) problem in heterogeneous wireless sensors and actuators networks (WSANs), Internet of things (IoT) and Wi-Fi: (i) named-based routing to provide provenance and location-independent access to control plane; (ii) temporary storage of control data for efficient and cohesive control dissemination, as well as asynchronous communication between software-controllers and devices; (iii) contract-based control to improve trust-ability of actions; (iv) service-defined configuration of wireless devices, approximating their configurations to real services needs. The work is implemented using NovaGenesis architecture and a proof-of-concept is evaluated in a real scenario, demonstrating our approach to automate radio frequency channel optimization in Wi-Fi and IEEE 802.15.4 networks in the 2.4 GHz bands. An integrated cognitive radio system provides the dual-mode best channel indications for novel DSM services in NovaGenesis. By reconfiguring Wi-Fi/IoT devices to best channels, the proposed solution more than doubles the network throughput, when compared to the case of mutual interference. Therefore, environments equipped with the proposal provide enhanced performance to their users.

Increasing the Lifetime of Mobile WSNs via Dynamic Optimization of Sensor Node Communication Activity.

In this paper, a simple and flexible method for increasing the lifetime of fixed or mobile wireless sensor networks is proposed. Based on past residual energy information reported by the sensor nodes, the sink node or another central node dynamically optimizes the communication activity levels of the sensor nodes to save energy without sacrificing the data throughput. The activity levels are defined to represent portions of time or time-frequency slots in a frame, during which the sensor nodes are scheduled to communicate with the sink node to report sensory measurements. Besides node mobility, it is considered that sensors' batteries may be recharged via a wireless power transmission or equivalent energy harvesting scheme, bringing to the optimization problem an even more dynamic character. We report large increased lifetimes over the non-optimized network and comparable or even larger lifetime improvements with respect to an idealized greedy algorithm that uses both the real-time channel state and the residual energy information.

Frequency and Genomic Aspects of Intrinsic Resistance to Vismodegib in Locally Advanced Basal Cell Carcinoma.

PURPOSE: Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms. EXPERIMENTAL DESIGN: Response to vismodegib was evaluated in a cohort of 148 laBCC patients. Comprehensive genomic and transcriptomic profiling was performed in a subset of five intrinsically resistant BCC (IR-BCC). RESULTS: We identified that IR-BCC represents 6.1% of laBCC in the studied cohort. Prior treatment with chemotherapy was associated with IR. Genetic events that were previously associated with acquired resistance (AR) in BCC or medulloblastoma were observed in three out of five IR-BCC. However, IR-BCCs were distinct by highly rearranged polyploid genomes. Functional analyses identified hyperactivation of the HIPPO-YAP and WNT pathways at RNA and protein levels in IR-BCC. In vitro assay on the BCC cell line further confirmed that YAP1 overexpression increases the cell proliferation rate. CONCLUSIONS: IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.

Massive perineal defect after radio-chemotherapy.

Herein, we present a rare complication of radio-chemotherapy. A young man presented with loss of urine from the posterior perineum that showed a massive disappearance. He underwent Hartmann procedure for rectal neoplasia, afterwards treated with intensity-modulated radiotherapy (IMRT) (until 67 Gy) and chemotherapy with FOLFOX protocol (Leucoverin calcium, Fluorouracil, Oxaliplatin).

Local Control and Toxicity of Adaptive Radiotherapy Using Weekly CT Imaging: Results from the LARTIA Trial in Stage III NSCLC.

INTRODUCTION: Anatomical change of tumor during radiotherapy contributes to target missing. However, in the case of tumor shrinkage, adaptation of volume could result in an increased incidence of recurrence in the area of target reduction. This study aims to investigate the incidence of failure of the adaptive approach and, in particular, the risk for local recurrence in the area excluded after replanning. METHODS: In this prospective study, patients with locally advanced NSCLC treated with concomitant chemoradiation underwent weekly chest computed tomography simulation during treatment. In the case of tumor shrinkage, a new tumor volume was delineated and a new treatment plan outlined (replanning). Toxicity was evaluated with the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer scale. Patterns of failures were classified as in field (dimensional and/or metabolic progression within the replanning planning target volume [PTV]), marginal (recurrence in initial the PTV excluded from the replanning PTV), and out of field (recurrence outside the initial PTV). RESULTS: Replanning was outlined in 50 patients selected from a total of 217 patients subjected to weekly simulation computed tomography in our center from 2012 to 2014. With a median follow-up of 20.5 months, acute grade 3 or higher pulmonary and esophageal toxicity were reported in 2% and 4% of cases and late toxicity in 4% and 2%, respectively. Marginal relapse was recorded in 6% of patients, and 20% and 4% of patients experienced in-field and out-of-field local failure, respectively. CONCLUSIONS: The reduced toxicity and the documented low rate of marginal failures make the adaptive approach a modern option for future randomized studies. The best scenario to confirm its application is probably in neoadjuvant chemoradiation trials.

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: a real-world experience.

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-naïve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-naïve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-naïve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p<0.0001), while overall survival was positively affected by lower ECOG PS (p<0.0001), absence of brain metastases (p 0.05), and clinical benefit (p<0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order.

Incidence, clinical features and possible etiology of early onset (≤40 years) colorectal neoplasms.

The aim of the study was to investigate the clinical features, including survival, of patients with colorectal malignancies developed at a very early age (≤40 years), together with possible factors involved in the pathogenesis of these rare neoplasms. The study took advantage of the existence of a specialized colorectal cancer Registry active from 1984. 57 patients met the criteria of early onset cancer; main epidemiological data, morphology, stage, familial aggregation, possible role of inheritance and survival were analyzed. Despite the relevant increase over time of all registered patients, joiningpoint analysis of crude incidence rate of early onset colorectal neoplasms revealed a certain stability of these tumors (EAPC: 2.4, CI 14-22) with a constant prevalence of the male sex. Stage at diagnosis did not show significant variations between early onset and maturity onset colorectal neoplasms. Hereditary as well as familial cases were significantly (P < 0.005 and 0.03) more frequent among patients with early onset tumors, although in the majority of them no specific etiological factor could be identified. Survival was more favorable in patients with early onset tumors, though this had to be attributed to the higher presence of some histological types in early onset cases. Survival was significantly more favorable for patients of all ages registered in the last decade. Incidence of early onset colorectal cancer was relatively stable between 1984 and 2008. A male preponderance was evident through the registration period. Hereditary and familial cases were significantly more frequent among early onset case. A well defined etiology could be observed in 16% of the cases (versus 2-3% in older individuals). Five-year survival showed a significant improvement over time.

Erlotinib and concurrent chemoradiation in pretreated NSCLC patients: radiobiological basis and clinical results.

AIMS: To establish feasibility of the combination of Erlotinib and concurrent chemoradiation in pre-treated patients with locally advanced or metastatic NSCLC. MATERIALS AND METHODS: Data regarding 60 consecutive patients with NSCLC previously treated with chemotherapy alone were prospectically collected. All patients started Erlotinib concurrently with chemotherapy and radiation delivered to primary tumor. These data were retrospectively analyzed (observational study). Feasibility and toxicity were the primary endpoints, with response rate and progression being the secondary ones, while survival data are reported just as exploratory analysis. The EGFR mutational status was recorded in 32% of cases and it was always wild type. RESULTS: Compliance to the combination protocol was good. Grade 3-4 esophagitis and acute lung toxicity occurred in 2% and 8% of patients, respectively. No progressive disease was recorded in the majority of cases (65%). Median OS and PFS were 23.3 and 4.7 months, respectively. Patients not responding to chemotherapy administered prior to chemoradiation achieved an objective response rate of 53.3% and complete response in 13.3% of cases. CONCLUSIONS: The addition of Erlotinib to chemoradiation in inoperable NSCLCs is feasible with interesting efficacy profile. These preliminary results warrant further investigation in patients with locally advanced nonmetastatic NSCLC with EGFR mutations.