Circulating tumor DNA as a marker of treatment response in BRAF V600E mutated non-melanoma solid tumors

Purpose: We evaluated longitudinal tracking of BRAF V600E in circulating cellfree DNA (cfDNA) as a marker of treatment response to BRAF inhibitor (BRAFi) combination therapies in non-melanoma solid tumors included in the Copenhagen Prospective Personalized Oncology (CoPPO) program. Experimental design: Patients with BRAF V600E-mutated tumors were treated with combination therapies including BRAFi. Quantification of mutant cfDNA from plasma was determined and correlated to clinical outcomes. Exome sequencing was performed to identify possible resistance mutations. Results: Twenty-three patients had BRAF-mutated tumors out of 455 patients included in CoPPO and 17 started BRAFi combination (EGFRi/MEKi) therapy. Tumor responses were achieved in 8 out of 16 evaluable patients and the median overalland progression-free survival (OS and PFS) was 15 and 4.8 months, respectively. Longitudinal measurements of BRAF V600E-mutant cfDNA indicated disease progression prior to radiological evaluation and a reduction in the mutant fraction of more than 50% after 4 and 12 weeks of therapy was associated with a significantly longer PFS (p=0.003 and p=0.029) and OS (p=0.029 and p=0.017). Furthermore, the baseline mutant fraction and total level of cfDNA positively correlated with tumor burden (p=0.026 and p=0.024). Finally, analysis of cfDNA at progression revealed novel mutations potentially affecting the MAPK pathway. Conclusion: BRAFi combination therapies showed a response rate of 50% in BRAF V600E-mutated non-melanoma tumors. The fraction of BRAF-mutant cfDNA represent a sensitive indicator for clinical outcomes with plasma collected at week 4 and 12 as crucial time points for monitoring response and disease progression.This study was supported by the Danish Cancer Society, The Harboe Foundation, and the Oncological Research Fund, Department of Oncology, Copenhagen University Hospital, Denmark

Power conservation schemes for energy efficient data propagation in heterogeneous wireless sensor networks

We propose, implement and evaluate new energy conservation schemes for efficient data propagation in wireless sensor networks. Our protocols are adaptive, i.e. locally monitor the network conditions and accordingly adjust towards optimal operation choices. This dynamic feature is particularly beneficial in heterogeneous settings and in cases of re-deployment of sensor devices in the network area. We implement our protocols and evaluate their performance through a detailed simulation study using our extended version of ns-2. In particular we combine our schemes with known communication paradigms. The simulation findings demonstrate significant gains and good trade-offs in terms of delivery success, delay and energy dissipation. © 2005 IEEE

Sink mobility protocols for data collection in wireless sensor networks

In wireless sensor networks data propagation is usually performed by sensors transmitting data towards a static control center (sink). Inspired by important applications (mostly related to ambient intelligence) and as a first step towards introducing mobility, we propose the idea of having a sink moving in the network area and collecting data from sensors. We propose four characteristic mobility patterns for the sink along with different data collection strategies. Through a detailed simulation study, we evaluate several important performance properties of each protocol. Our findings demonstrate that by taking advantage of the sink's mobility, we can significantly reduce the energy spent in relaying traffic and thus greatly extend the lifetime of the network. Copyright 2006 ACM

An adaptive power conservation scheme for heterogeneous wireless sensor networks with node redeployment

We introduce a new modelling assumption in wireless sensor networks, that of node redeployment (addition of sensor devices during the protocol evolution) and we extend the modelling assumption of heterogeneity (having sensor devices of various types). These two features further increase the highly dynamic nature of such networks and adaptation becomes a powerful technique for protocol design. Under this model, we design, implement and evaluate a power conservation scheme for efficient data propagation. Our protocol is adaptive: it locally monitors the network conditions (density, energy) and accordingly adjusts the sleep-awake schedules of the nodes towards best operation choices. Our protocol operates does not require exchange of control messages between nodes to coordinate. Implementing our protocol we combine it with two well-known data propagation protocols and evaluate the achieved performance through a detailed simulation study using our extended version of ns-2. We focus in highly dynamic scenarios with respect to network density, traffic conditions and sensor node resources. We propose a new general and parameterized metric capturing the trade-off between delivery rate, energy efficiency and latency. The simulation findings demonstrate significant gains (such as more than doubling the success rate of the well-known Directed Diffusion propagation paradigm) and good trade-offs. Furthermore, redeployment of sensors during network evolution and/or heterogeneous deployment of sensors drastically improve (when compared to equal total "power" simultaneous deployment of identical sensors at the start) the protocol performance (the success rate increases up to four times while reducing energy dissipation and, interestingly, keeping latency low). Copyright 2005 ACM

Adaptive energy management for incremental deployment of heterogeneous wireless sensors

We introduce a new modelling assumption for wireless sensor networks, that of node redeployment (addition of sensor devices during protocol evolution) and we extend the modelling assumption of heterogeneity (having sensor devices of various types). These two features further increase the highly dynamic nature of such networks and adaptation becomes a powerful technique for protocol design. Under these modelling assumptions, we design, implement and evaluate a new power conservation scheme for efficient data propagation. Our scheme is adaptive: it locally monitors the network conditions (density, energy) and accordingly adjusts the sleep-awake schedules of the nodes towards improved operation choices. The scheme is simple, distributed and does not require exchange of control messages between nodes. Implementing our protocol in software we combine it with two well-known data propagation protocols and evaluate the achieved performance through a detailed simulation study using our extended version of the network simulator ns-2. We focus on highly dynamic scenarios with respect to network density, traffic conditions and sensor node resources. We propose a new general and parameterized metric capturing the trade-offs between delivery rate, energy efficiency and latency. The simulation findings demonstrate significant gains (such as more than doubling the success rate of the well-known Directed Diffusion propagation protocol) and good trade-offs achieved. Furthermore, the redeployment of additional sensors during network evolution and/or the heterogeneous deployment of sensors, drastically improve (when compared to "equal total power" simultaneous deployment of identical sensors at the start) the protocol performance (i.e. the success rate increases up to four times while reducing energy dissipation and, interestingly, keeping latency low). © 2007 Springer Science+Business Media, LLC

Efficient data propagation strategies in wireless sensor networks using a single mobile sink

Data collection is usually performed in wireless sensor networks by the sensors relaying data towards a static control center (sink). Motivated by important applications (mostly related to ambient intelligence and remote monitoring) and as a first step towards introducing mobility, we propose the basic idea of having a sink moving in the network area and collecting data from sensors. We propose four characteristic mobility patterns for the sink that we combine with different data collection strategies. Through a detailed simulation study, we evaluate several important performance properties of each approach. Our findings demonstrate that by taking advantage of the sinks mobility and shifting work from sensors to the powerful sink, we can significantly reduce the energy spent in relaying traffic and thus greatly extend the lifetime of the network. © 2007 Elsevier B.V. All rights reserved

Fault-tolerant and efficient data propagation in wireless sensor networks using local, additional network information

We propose a new data dissemination protocol for wireless sensor networks, that basically pulls some additional knowledge about the network in order to subsequently improve data forwarding towards the sink. This extra information is still local, limited and obtained in a distributed manner. This extra knowledge is acquired by only a small fraction of sensors thus the extra energy cost only marginally affects the overall protocol efficiency. The new protocol has low latency and manages to propagate data successfully even in the case of low densities. Furthermore, we study in detail the effect of failures and show that our protocol is very robust. In particular, we implement and evaluate the protocol using large scale simulation, showing that it significantly outperforms well known relevant solutions in the state of the art. © 2007

Adaptive techniques for proactive collision avoidance for multi-path data propagation in wireless sensor networks

Data propagation in wireless sensor networks can be performed either by hop-by-hop single transmissions or by multi-path broadcast of data. Although several energy-aware MAC layer protocols exist that operate very well in the case of single point-to-point transmissions, none is especially designed and suitable for multiple broadcast transmissions. The key idea of our protocols is the passive monitoring of local network conditions and the adaptation of the protocol operation accordingly. The main contribution of our adaptive method is to proactively avoid collisions by implicitly and early enough sensing the need for collision avoidance. Using the above ideas, we design, implement and evaluate three different, new strategies for proactive adaptation. We show, through a detailed and extended simulation evaluation, that our parameter-based family of protocols for multi-path data propagation significantly reduce the number of collisions and thus increase the rate of successful message delivery (to above 90%) by achieving satisfactory trade-offs with the average propagation delay. At the same time, our protocols are shown to be very energy efficient, in terms of the average energy dissipation per delivered message. © 2006

Priority based adaptive coordination of wireless sensors and actors

Wireless sensor and actor networks are comprised of a large number of small, fully autonomous computing, communication, sensing and actuation devices, with very restricted energy and computing capabilities. Such devices co-operate to accomplish a large sensing and acting task. Sensors gather information for an event in the physical world and notify the actors that perform appropriate actions by making a decision on receipt of the sensed information. Such networks can be very useful in practice i.e. in the local detection of remote crucial events and the propagation of relevant data to decision centers that perform appropriate actions upon the environment, thus realizing sensing and acting from a distance. In this work we present a communication protocol that enables scalable, energy efficient and fault tolerant coordination while allowing to prioritize sensing tasks in situated wireless sensor and actor networks. The sensors react locally on environment and context changes and interact with each other in order to adjust the performance of the network in terms of energy, latency and success rate on a per-task basis. To deal with the increased complexity of such large-scale systems, our protocol pulls some additional knowledge about the network in order to subsequently improve data forwarding towards the actors. We implement and evaluate the protocol using large scale simulation, showing its suitability in networks where sensor to actor and actor to actor coordination are important for accomplishing tasks of different priorities. Copyright 2006 ACM

Wireless sensor networks protocols for efficient collision avoidance in multi-path data propagation

Data propagation in wireless sensor networks can be performed either by hop-by-hop single transmissions or by multi-path broadcast of data. Although several energy-aware MAC layer protocols exist that operate very well in the case of single point-to-point transmissions, none is especially designed and suitable for multiple broadcast transmissions. In this paper we propose a family of new protocols suitable of multi-path broadcast of data, and show, through a detailed and extended simulation evaluation, that our parameter-based protocols significantly reduce the number of collisions and thus increase the rate of successful message delivery (to above 90%) by trading off the average propagation delay. At the same time, our protocols are shown to be very energy efficient, in terms of the average energy dissipation per delivered message. Copyright 2004 ACM