Computed tomographic atlas for the new international lymph node map for lung cancer: A radiation oncologist perspective

International audiencePurpose : To develop a reproducible definition for each mediastinal lymph node station based on the new TNM classification for lung cancer. Methods and Materials : This paper proposes an atlas using the new international lymph node map used in the seventh edition of the TNM classification for lung cancer. Four radiation oncologists and 1 diagnostic radiologist were involved in the project to put forward a reproducible radiologic description for the lung lymph node stations.Results : The International Association for the Study of Lung Cancer lymph node definitions for stations 1 to 11 have been described and illustrated on axial computed tomographic scan images using a certified radiotherapy planning system. Conclusions : This atlas will assist both diagnostic radiologists and radiation oncologists in accurately defining the lymph node stations on computed tomographic scan in patients diagnosed with lung cancer

OC-0549: Improving the clinical applicability of markerless lung tumour tracking with contrast-enhanced kV imaging

In-room kV imaging is widely applied for intrafraction motion compensation in image-guided radiation therapy (IGRT). The low contrast of lung tumours in kV images and the overlap of high-intensity surrounding structures, such as the mediastinum, may limit the applicability of IGRT techniques in lung cancer treatments. The aim of this study is to apply a CT-based contrast enhancement method to improve markerless lung tumour tracking in kV images, thus enhancing the potential of X-raybased image guidance in lung cancer patients

Extraction of the respiratory signal from cone-beam projections for 4D CT imaging

To be efficient, the treatement of the lung cancers with radiation therapy must take into account the respiratory motion. The knowledge of this motion requires the acquisition of 4D computed tomography (CT) images. The free-breathing thorax 4D CT images currently acquired use gated or respiratory-correlated methods. These methods involve the collection of a respiratory signal during the acquisition of data in order to sort them into different groups. The quality of the 4D CT image thus depends on an accurate description by the signal of the position of the thorax in the respiratory cycle. The signal is generally acquired by independent measurements of densitometric data (spirometer, thermometer, ...). We propose to extract it directly from the sequence of 2D cone-beam (CB) projections acquired around the free-breathing thorax. Our method derives the motion between two consecutive 2D CB projections using a block matching algorithm. Blocks are positioned around points of interest constituting a regular sampling of the 2D CB projections. A unidimensional signal is derived from the trajectory of each block in the sequence after projection. Aggregation of a subset of selected makes it possible to derive the respiratory signal during the acquisition time. Our method is validated quantitatively on simulated data and qualitatively on real data. On simulated data, we obtain a respiratory signal with 97.5 % linear correlation with the reference. On real data, the extracted signal allow to reconstruct 4D CT images for comparison with the blurred 3D CT image obtained without taking into account the respiratory motion.Le traitement des cancers des poumons par radiothérapie doit prendre en compte les mouvements respiratoires pour être efficace. La connaissance de ce mouvement passe par l'obtention d'images tomodensitométriques (TDM) 4D. Les images TDM 4D du thorax en respiration libre acquises actuellement utilisent les méthodes de type gated ou respiration-correlated. Ces méthodes nécessitent un signal respiratoire, recueilli pendant l'acquisition des données, pour trier celles-ci en différents groupes. La qualité de l'image TDM 4D dépend alors d'une description correcte, par le signal respiratoire, de la position du thorax dans le cycle respiratoire au cours de l'acquisition. Ce signal est généralement acquis par une mesure indépendante des données densitométriques (spiromètre, thermomètre,...). Nous proposons de l'extraire directement de la séquence de projections cone-beam (CB) 2D acquises autour du thorax en respiration libre. Notre méthode extrait le mouvement entre deux projections CB 2D consécutives par un algorithme de mise en correspondance de blocs. Ces blocs sont positionnés autour de points d'intérêt constituant un sous-échantillonnage régulier des projections CB 2D. Nous déduisons de la trajectoire de chaque bloc dans la séquence un signal unidimensionnel après projection. Une sélection d'un sous-ensemble de ces signaux nous permet d'obtenir, après agrégation, le signal respiratoire pendant le temps de l'acquisition. Notre méthode est validée quantitativement sur données simulées et qualitativement sur données réelles. Sur données simulées, nous obtenons un signal respiratoire corrélé linéairement à 97,5 % avec la référence. Sur données réelles, le signal extrait nous permet de reconstruire l'image TDM 4D d'un patient que l'on compare à l'image TDM 3D floue, obtenue sans prise en compte du mouvement respiratoire

A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients

Background: Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. Methods: Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo biodistribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. Results: From January 2012 to June 2015, 20 pts. (median age 43 years [21–67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. Conclusions: Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. Trial registration: The study was registered on the NCT01469975 ( https://clinicaltrials.gov/ct2/show/NCT01469975 ) website with a registration code NCT01469975 on November the third, 2011

An image-based method to synchronize cone-beam CT and optical surface tracking

open5siThe integration of in-room X-ray imaging and optical surface tracking has gained increasing importance in the field of image guided radiotherapy (IGRT). An essential step for this integration consists of temporally synchronizing the acquisition of X-ray projections and surface data. We present an image-based method for the synchronization of cone-beam computed tomography (CBCT) and optical surface systems, which does not require the use of additional hardware. The method is based on optically tracking the motion of a component of the CBCT/gantry unit, which rotates during the acquisition of the CBCT scan. A calibration procedure was implemented to relate the position of the rotating component identified by the optical system with the time elapsed since the beginning of the CBCT scan, thus obtaining the temporal correspondence between the acquisition of X-ray projections and surface data. The accuracy of the proposed synchronization method was evaluated on a motorized moving phantom, performing eight simultaneous acquisitions with an Elekta Synergy CBCT machine and the AlignRT optical device. The median time difference between the sinusoidal peaks of phantom motion signals extracted from the synchronized CBCT and AlignRT systems ranged between -3.1 and 12.9 msec, with a maximum interquartile range of 14.4 msec. The method was also applied to clinical data acquired from seven lung cancer patients, demonstrating the potential of the proposed approach in estimating the individual and daily variations in respiratory parameters and motion correlation of internal and external structures. The presented synchronization method can be particularly useful for tumor tracking applications in extracranial radiation treatments, especially in the field of patient-specific breathing models, based on the correlation between internal tumor motion and external surface surrogates.Fassi, Aurora; Schaerer, Joël; Riboldi, Marco; Sarrut, David; Baroni, GuidoFassi, Aurora; Schaerer, Joël; Riboldi, Marco; Sarrut, David; Baroni, Guid

Distributions of secondary particles in proton and carbon-ion therapy: a comparison between GATE/Geant4 and FLUKA Monte Carlo codes.

Monte Carlo simulations play a crucial role for in-vivo treatment monitoring based on PET and prompt gamma imaging in proton and carbon-ion therapies. The accuracy of the nuclear fragmentation models implemented in these codes might affect the quality of the treatment verification. In this paper, we investigate the nuclear models implemented in GATE/Geant4 and FLUKA by comparing the angular and energy distributions of secondary particles exiting a homogeneous target of PMMA. Comparison results were restricted to fragmentation of (16)O and (12)C. Despite the very simple target and set-up, substantial discrepancies were observed between the two codes. For instance, the number of high energy (>1 MeV) prompt gammas exiting the target was about twice as large with GATE/Geant4 than with FLUKA both for proton and carbon ion beams. Such differences were not observed for the predicted annihilation photon production yields, for which ratios of 1.09 and 1.20 were obtained between GATE and FLUKA for the proton beam and the carbon ion beam, respectively. For neutrons and protons, discrepancies from 14% (exiting protons-carbon ion beam) to 57% (exiting neutrons-proton beam) have been identified in production yields as well as in the energy spectra for neutrons

Listeria pathogenesis and molecular virulence determinants

The gram-positive bacterium Listeria monocytogenes is the causative agent of listeriosis, a highly fatal opportunistic foodborne infection. Pregnant women, neonates, the elderly, and debilitated or immunocompromised patients in general are predominantly affected, although the disease can also develop in normal individuals. Clinical manifestations of invasive listeriosis are usually severe and include abortion, sepsis, and meningoencephalitis. Listeriosis can also manifest as a febrile gastroenteritis syndrome. In addition to humans, L. monocytogenes affects many vertebrate species, including birds. Listeria ivanovii, a second pathogenic species of the genus, is specific for ruminants. Our current view of the pathophysiology of listeriosis derives largely from studies with the mouse infection model. Pathogenic listeriae enter the host primarily through the intestine. The liver is thought to be their first target organ after intestinal translocation. In the liver, listeriae actively multiply until the infection is controlled by a cell-mediated immune response. This initial, subclinical step of listeriosis is thought to be common due to the frequent presence of pathogenic L. monocytogenes in food. In normal indivuals, the continual exposure to listerial antigens probably contributes to the maintenance of anti-Listeria memory T cells. However, in debilitated and immunocompromised patients, the unrestricted proliferation of listeriae in the liver may result in prolonged low-level bacteremia, leading to invasion of the preferred secondary target organs (the brain and the gravid uterus) and to overt clinical disease. L. monocytogenes and L. ivanovii are facultative intracellular parasites able to survive in macrophages and to invade a variety of normally nonphagocytic cells, such as epithelial cells, hepatocytes, and endothelial cells. In all these cell types, pathogenic listeriae go through an intracellular life cycle involving early escape from the phagocytic vacuole, rapid intracytoplasmic multiplication, bacterially induced actin-based motility, and direct spread to neighboring cells, in which they reinitiate the cycle. In this way, listeriae disseminate in host tissues sheltered from the humoral arm of the immune system. Over the last 15 years, a number of virulence factors involved in key steps of this intracellular life cycle have been identified. This review describes in detail the molecular determinants of Listeria virulence and their mechanism of action and summarizes the current knowledge on the pathophysiology of listeriosis and the cell biology and host cell responses to Listeria infection. This article provides an updated perspective of the development of our understanding of Listeria pathogenesis from the first molecular genetic analyses of virulence mechanisms reported in 1985 until the start of the genomic era of Listeria research

Recalage déformable en radiothérapie guidée par l'image

National audienceLa radiothérapie guidée par l’image (IGRT) a pour but d’adapter la dosimétrie du patient pour prendre en compte les variations anatomiques survenues en cours de traitement