Phase I/II trial evaluating carbon ion radiotherapy for the treatment of recurrent rectal cancer: the PANDORA-01 trial

<p>Abstract</p> <p>Background</p> <p>Treatment standard for patients with rectal cancer depends on the initial staging and includes surgical resection, radiotherapy as well as chemotherapy. For stage II and III tumors, radiochemotherapy should be performed in addition to surgery, preferentially as preoperative radiochemotherapy or as short-course hypofractionated radiation. Advances in surgical approaches, especially the establishment of the total mesorectal excision (TME) in combination with sophisticated radiation and chemotherapy have reduced local recurrence rates to only few percent. However, due to the high incidence of rectal cancer, still a high absolute number of patients present with recurrent rectal carcinomas, and effective treatment is therefore needed.</p> <p>Carbon ions offer physical and biological advantages. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increase relative biological effectiveness (RBE), which can be calculated between 2 and 5 depending on the cell line as well as the endpoint analyzed.</p> <p>Japanese data on the treatment of patients with recurrent rectal cancer previously not treated with radiation therapy have shown local control rates of carbon ion treatment superior to those of surgery. Therefore, this treatment concept should also be evaluated for recurrences after radiotherapy, when dose application using conventional photons is limited. Moreover, these patients are likely to benefit from the enhanced biological efficacy of carbon ions.</p> <p>Methods and design</p> <p>In the current Phase I/II-PANDORA-01-Study the recommended dose of carbon ion radiotherapy for recurrent rectal cancer will be determined in the Phase I part, and feasibilty and progression-free survival will be assessed in the Phase II part of the study.</p> <p>Within the Phase I part, increasing doses from 12 × 3 Gy E to 18 × 3 Gy E will be applied.</p> <p>The primary endpoint in the Phase I part is toxicity, the primary endpoint in the Phase II part is progression-free survival.</p> <p>Discussion</p> <p>With conventional photon irradiation treatment of recurrent rectal cancer is limited, and the clinical effect is only moderate. With carbon ions, an improved outcome can be expected due to the physical and biological characteristics of the carbon ion beam. However, the optimal dose applicable in this clincial situation as re-irradiation still has to be determined. This, as well as efficacy, is to be evaluated in the present Phase I/II trial.</p> <p>Trial registration</p> <p><a href="http://www.clinicaltrials.gov/ct2/show/NCT01528683">NCT01528683</a></p

ABSTRACT Reflections on Money and Lean Construction REFLECTIONS ON MONEY

Money is a particularly tricky resource to manage because it comes with its own set of rules. Value is created by the application of cost concerns to choices in design. Likewise cash flow considerations during construction may lead to adjusting design to minimize risk of schedule overrun. Here again the role of money is to help clarify value for the client. In some cases the speed of the project may be limited by the rate of cash flow and while managing to assure no overrun how ever small is simplified by reliable work flow, some additional time should be added to the schedule to account for variations in cash flow. By contrast, if a precise and rapid completion date established early in the project is important to an owner, steps must be taken to insure the project is not sensitive to disruptions which might cause the project to be late. In this case, a buffer of additional money is prudent. In either case, the problem of matching cash flow to construction demands is eased by reliable workflow

Localized techniques for broadcasting in wireless sensor networks.

In this paper we tackle the problem of designing simple, localized, low energy consuming, reliable protocols for one-to-all communication in large scale wireless sensor networks. Our first proposed technique, called the Irrigator protocol, relies on the idea to first build a sparse overlay network, and then flood over it. The overlay network is set up by means of a simple, distributed, localized probabilistic protocol and spans all the sensor nodes with high probability. Based on the algorithmic ideas of the Irrigator protocol we then develop a second protocol, dubbed Fireworks, with similar performance that does not require any overlay network to be set up in advance. Asymptotic analytical results are provided which assess the reliability of the Irrigator and Fireworks techniques. The theoretical analysis of the proposed protocols is complemented and validated by a (simulation based) comparative performance evaluation that assesses several advantages of our new protocols with respect to gossiping and simple flooding. Differently from previous studies, we analyze and demonstrate the performance of our protocols for two different node distributions: The typical uniform distribution and a newly defined “hill” distribution, here introduced to capture some of the important and more realistic aspects of node deployment in heterogeneous terrain. Simulation results show that the proposed schemes achieve very good trade-offs between low overhead, low energy consumption and high reliability. In particular, the Irrigator and Fireworks protocols are more reliable than gossiping, and significantly reduce the number of links along which a message is sent over both flooding and gossiping

ENLIGHT

n/

Towards clinical evidence in particle therapy: ENLIGHT, PARTNER, ULICE and beyond

Since the middle of the 20th century, particle therapy has been in focus for patient treatments. In 1946, Robert Wilson proposed the use of charged particles for tumor therapy, and since then, the clinical use of protons and heavier ions, mainly carbon ions, has become more widespread. The first clinical evidence was obtained in Berkeley, treating radiation-resistant targets with various ion species. The main advantage of particle beams derive from their physical properties: through an inverted dose profile, regions within the entry channel of the beam can be spared of dose, while a steep dose deposition can be directed in an energydependent manner into the defined treatment volume (Bragg Peak). The following dose fall-off spares tissue behind the target volume, thus reducing integral dose significantly compared to when using photons. Heavier charged particles, such as carbon ions or oxygen, are additionally associated with an increased relative biological effectiveness (RBE), while the RBE of protons is commonly accepted to be about 1.1. Recent observation, however, suggests that this may be an oversimplification