Ultraviolet singularities in classical brane theory

We construct for the first time an energy-momentum tensor for the electromagnetic field of a p-brane in arbitrary dimensions, entailing finite energy-momentum integrals. The construction relies on distribution theory and is based on a Lorentz-invariant regularization, followed by the subtraction of divergent and finite counterterms supported on the brane. The resulting energy-momentum tensor turns out to be uniquely determined. We perform the construction explicitly for a generic flat brane. For a brane in arbitrary motion our approach provides a new paradigm for the derivation of the, otherwise divergent, self-force of the brane. The so derived self-force is automatically finite and guarantees, by construction, energy-momentum conservation.Comment: 41 pages, no figures, minor change

Respiratory-gated (4D) contrast-enhanced FDG PET-CT for radiotherapy planning of lower oesophageal carcinoma: Feasibility and impact on planning target volume

Background: To assess the feasibility and potential impact on target delineation of respiratory-gated (4D) contrast-enhanced 18 Fluorine fluorodeoxyglucose (FDG) positron emission tomography - computed tomography (PET-CT), in the treatment planning position, for a prospective cohort of patients with lower third oesophageal cancer. Methods: Fifteen patients were recruited into the study. Imaging included 4D PET-CT, 3D PET-CT, endoscopic ultrasound and planning 4D CT. Target volume delineation was performed on 4D CT, 4D CT with co-registered 3D PET and 4D PET-CT. Planning target volumes (PTV) generated with 4D CT (PTV 4DCT), 4D CT co-registered with 3D PET-CT (PTV 3DPET4DCT) and 4D PET-CT (PTV 4DPETCT ) were compared with multiple positional metrics. Results: Mean PTV 4DCT , PTV 3DPET4DCT and PTV 4DPETCT were 582.4 ± 275.1 cm 3 , 472.5 ± 193.1 cm 3 and 480.6 ± 236.9 cm 3 respectively (no significant difference). Median DICE similarity coefficients comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.85 (range 0.65-0.9), 0.85 (range 0.69-0.9) and 0.88 (range 0.79-0.9) respectively. The median sensitivity index for overlap comparing PTV 4DCT with PTV 3DPET4DCT, PTV 4DCT with PTV 4DPETCT and PTV 3DPET4DCT with PTV 4DPETCT were 0.78 (range 0.65-0.9), 0.79 (range 0.65-0.9) and 0.89 (range 0.68-0.94) respectively. Conclusions: Planning 4D PET-CT is feasible with careful patient selection. PTV generated using 4D CT, 3D PET-CT and 4D PET-CT were of similar volume, however, overlap analysis demonstrated that approximately 20% of PTV 3DPETCT and PTV 4DPETCT are not included in PTV 4DCT , leading to under-coverage of target volume and a potential geometric miss. Additionally, differences between PTV 3DPET4DCT and PTV 4DPETCT suggest a potential benefit for 4D PET-CT. Trial registration: ClinicalTrials.gov Identifier - NCT02285660(Registered 21/10/2014)

An integrative multi-dimensional genetic and epigenetic strategy to identify aberrant genes and pathways in cancer

<p>Abstract</p> <p>Background</p> <p>Genomics has substantially changed our approach to cancer research. Gene expression profiling, for example, has been utilized to delineate subtypes of cancer, and facilitated derivation of predictive and prognostic signatures. The emergence of technologies for the high resolution and genome-wide description of genetic and epigenetic features has enabled the identification of a multitude of causal DNA events in tumors. This has afforded the potential for large scale integration of genome and transcriptome data generated from a variety of technology platforms to acquire a better understanding of cancer.</p> <p>Results</p> <p>Here we show how multi-dimensional genomics data analysis would enable the deciphering of mechanisms that disrupt regulatory/signaling cascades and downstream effects. Since not all gene expression changes observed in a tumor are causal to cancer development, we demonstrate an approach based on multiple concerted disruption (MCD) analysis of genes that facilitates the rational deduction of aberrant genes and pathways, which otherwise would be overlooked in single genomic dimension investigations.</p> <p>Conclusions</p> <p>Notably, this is the first comprehensive study of breast cancer cells by parallel integrative genome wide analyses of DNA copy number, LOH, and DNA methylation status to interpret changes in gene expression pattern. Our findings demonstrate the power of a multi-dimensional approach to elucidate events which would escape conventional single dimensional analysis and as such, reduce the cohort sample size for cancer gene discovery.</p

IMRT treatment plans and functional planning with functional lung imaging from 4D-CT for thoracic cancer patients

<p>Abstract</p> <p>Background and purpose</p> <p>Currently, the inhomogeneity of the pulmonary function is not considered when treatment plans are generated in thoracic cancer radiotherapy. This study evaluates the dose of treatment plans on highly-functional volumes and performs functional treatment planning by incorporation of ventilation data from 4D-CT.</p> <p>Materials and methods</p> <p>Eleven patients were included in this retrospective study. Ventilation was calculated using 4D-CT. Two treatment plans were generated for each case, the first one without the incorporation of the ventilation and the second with it. The dose of the first plans was overlapped with the ventilation and analyzed. Highly-functional regions were avoided in the second treatment plans.</p> <p>Results</p> <p>For small targets in the first plans (PTV < 400 cc, 6 cases), all V5, V20 and the mean lung dose values for the highly-functional regions were lower than that of the total lung. For large targets, two out of five cases had higher V5 and V20 values for the highly-functional regions. All the second plans were within constraints.</p> <p>Conclusion</p> <p>Radiation treatments affect functional lung more seriously in large tumor cases. With compromise of dose to other critical organs, functional treatment planning to reduce dose in highly-functional lung volumes can be achieved</p

Designed-seamless irradiation technique for extended whole mediastinal proton-beam irradiation for esophageal cancer

<p>Abstract</p> <p>Background</p> <p>Proton-beam therapy (PBT) provides therapeutic advantages over conformal x-ray therapy in sparing organs at risk when treating esophageal cancer because of the fundamental physical dose distribution of the proton-beam. However, cases with extended esophageal lesions are difficult to treat with conventional PBT with a single isocentric field, as the length of the planning target volume (PTV) is longer than the available PBT field size in many facilities. In this study, the feasibility of a practical technique to effectively match PBT fields for esophageal cancer with a larger regional field beyond the available PBT field size was investigated.</p> <p>Methods</p> <p>Twenty esophageal cancer patients with a larger regional field than the available PBT single-field size (15 cm in our facility) were analyzed. The PTV was divided into two sections to be covered by a single PBT field. Subsequently, each PTV isocenter was aligned in a cranial-caudal (CC) axis to rule out any influence by the movement of the treatment couch in anterior-posterior and left-right directions. To obtain the appropriate dose distributions, a designed-seamless irradiation technique (D-SLIT) was proposed. This technique requires the following two adjustments: (A) blocking a part of the PTV by multi-leaf collimator(s) (MLCs); and (B) fine-tuning the isocenter distance by the half-width of the MLC leaf (2.5 mm in our facility). After these steps, the inferior border of the cranial field was designed to match the superior border of the caudal field. Dose distributions along the CC axis around the field junction were evaluated by the treatment-planning system. Dose profiles were validated with imaging plates in all cases.</p> <p>Results</p> <p>The average and standard deviation of minimum dose, maximum dose, and dose range between maximum and minimum doses around the field junction by the treatment-planning system were 95.9 ± 3.2%, 105.3 ± 4.1%, and 9.4 ± 5.2%. The dose profile validated by the imaging plate correlated with the results of the treatment-planning system in each case, with an error range within 4.3%.</p> <p>Conclusions</p> <p>Dose distributions around the field junction were applied using D-SLIT. D-SLIT can be a useful treatment strategy for PBT of extended esophageal cancer.</p

Multimodal hypoxia imaging and intensity modulated radiation therapy for unresectable non-small-cell lung cancer: the HIL trial

<p>Abstract</p> <p>Background</p> <p>Radiotherapy, preferably combined with chemotherapy, is the treatment standard for locally advanced, unresectable non-small cell lung cancer (NSCLC). The tumor response to different therapy protocols is variable, with hypoxia known to be a major factor that negatively influences treatment effectiveness. Visualisation of tumor hypoxia prior to the use of modern radiation therapy strategies, such as intensity modulated radiation therapy (IMRT), might allow optimized dose applications to the target volume, leading to improvement of therapy outcome. ¹⁸ F-fluoromisonidazole dynamic positron emission tomography and computed tomography (¹⁸ F-FMISO dPET-CT) and functional magnetic resonance imaging (functional MRI) are attractive options for imaging tumor hypoxia.</p> <p>Methods/design</p> <p>The HIL trial is a single centre study combining multimodal hypoxia imaging with ¹⁸ F-FMISO dPET-CT and functional MRI, with intensity modulated radiation therapy (IMRT) in patients with inoperable stage III NSCLC. 15 patients will be recruited in the study. All patients undergo initial FDG PET-CT and serial ¹⁸ F-FMISO dPET-CT and functional MRI before treatment, at week 5 of radiotherapy and 6 weeks post treatment. Radiation therapy is performed as inversely planned IMRT based on 4D-CT.</p> <p>Discussion</p> <p>Primary objectives of the trial are to characterize the correlation of ¹⁸ F-FMISO dPET-CT and functional MRI for tumor hypoxia imaging in NSCLC and evaluate possible effects of radiation therapy on tumor re-oxygenation. Further objectives include the generation of data regarding the prognostic value of ¹⁸ F-FMISO dPET-CT and functional MRI for locoregional control, progression free survival and overall survival of NSCLC treated with IMRT, which will form the basis for larger clinical trials focusing on possible interactions between tumor oxygenation and radiotherapy outcome.</p> <p>Trial registration</p> <p>The ClinicalTrials.gov protocol ID is NCT01617980</p