Synergy of Radiotherapy and a Cancer Vaccine for the Treatment of HPV-Associated Head and Neck Cancer.

There is growing interest in the association of radiotherapy and immunotherapy for the treatment of solid tumors. Here, we report an extremely effective combination of local irradiation (IR) and Shiga Toxin B (STxB)-based human papillomavirus (HPV) vaccination for the treatment of HPV-associated head and neck squamous cell carcinoma (HNSCC). The efficacy of the irradiation and vaccine association was tested using a model of HNSCC obtained by grafting TC-1/luciferase cells at a submucosal site of the inner lip of immunocompetent mice. Irradiation and the STxB-E7 vaccine acted synergistically with both single and fractionated irradiation schemes, resulting in complete tumor clearance in the majority of the treated mice. A dose threshold of 7.5 Gy was required to elicit the dramatic antitumor response. The combined treatment induced high levels of tumor-infiltrating, antigen-specific CD8(+) T cells, which were required to trigger the antitumor activity. Treatment with STxB-E7 and irradiation induced CD8(+) T-cell memory, which was sufficient to exert complete antitumor responses in both local recurrences and distant metastases. We also report for the first time that a combination therapy based on local irradiation and vaccination induces an increased pericyte coverage (as shown by αSMA and NG2 staining) and ICAM-1 expression on vessels. This was associated with enhanced intratumor vascular permeability that correlated with the antitumor response, suggesting that the combination therapy could also act through an increased accessibility for immune cells. The combination strategy proposed here offers a promising approach that could potentially be transferred into early-phase clinical trials.

Available evidence on re-irradiation with stereotactic ablative radiotherapy following high-dose previous thoracic radiotherapy for lung malignancies.

Patients affected with intra-thoracic recurrences of primary or secondary lung malignancies after a first course of definitive radiotherapy have limited therapeutic options, and they are often treated with a palliative intent. Re-irradiation with stereotactic ablative radiotherapy (SABR) represents an appealing approach, due to the optimized dose distribution that allows for high-dose delivery with better sparing of organs at risk. This strategy has the goal of long-term control and even cure. Aim of this review is to report and discuss published data on re-irradiation with SABR in terms of efficacy and toxicity. Results indicate that thoracic re-irradiation may offer satisfactory disease control, however the data on outcome and toxicity are derived from low quality retrospective studies, and results should be cautiously interpreted. As SABR may be associated with serious toxicity, attention should be paid for an accurate patients' selection.

Complications of guided surgery and immediate loading in oral implantology: a report of 12 cases

Objectives: The growing interest in minimally invasive surgery, together with the possibility of fitting prostheses with immediate function, have led to the development of software capable of planning and manufacturing a surgical guide and prosthesis that can be placed upon conclusion of the implant surgery step. The present study evaluates the surgical and prosthetic complications of implant treatment with the guided surgery technique, together with patient comfort during and after treatment. Patients and methods: A retrospective observational study was made of 19 patients with partially or totally edentulous upper and/or lower maxillae, involving the placement of a total of 122 implants. All cases were planned and operated upon with the guided surgery technique. Results: A total of 122 implants were placed in 14 males and 5 females. The intraoperative surgical complications comprised a lack of primary stability, while the postoperative complications consisted of infections and a lack of implant osteointegration. Ten implants failed. The prosthetic complications in turn comprised loosening of the provisional prosthesis screws, prosthesis tooth fracture, and a lack of passive fit of the immediate prosthesis. The degree of patient satisfaction was evaluated using a verbal scale. Conclusions: Implant restoration with the guided surgery technique and immediate functional loading is a predictable procedure, provided patient selection and the surgical technique are adequate, affording lesser postoperative morbidity and increased patient satisfaction thanks to the immediate restoration of esthetics and function

Chest CT at a dose below 0.3 mSv : impact of iterative reconstruction on image quality and lung analysis

Le nombre d'examens tomodensitométriques (Computed Tomography, CT) effectués chaque année étant en constante augmentation, différentes techniques d'optimisation, dont les algorithmes de reconstruction itérative permettant de réduire le bruit tout en maintenant la résolution spatiale, ont étés développées afin de réduire les doses délivrées. Le but de cette étude était d'évaluer l'impact des algorithmes de reconstruction itérative sur la qualité image à des doses effectives inférieures à 0.3 mSv, comparables à celle d'une radiographie thoracique. Vingt CT thoraciques effectués à cette dose effective ont été reconstruits en variant trois paramètres: l'algorithme de reconstruction, rétroprojection filtrée versus reconstruction itérative iDose4; la matrice, 5122 versus 7682; et le filtre de résolution en densité (mou) versus spatiale (dur). Ainsi, 8 séries ont été reconstruites pour chacun des 20 CT thoraciques. La qualité d'image de ces 8 séries a d'abord été évaluée qualitativement par deux radiologues expérimentés en aveugle en se basant sur la netteté des parois bronchiques et de l'interface entre le parenchyme pulmonaire et les vaisseaux, puis quantitativement en utilisant une formule de merit, fréquemment utilisée dans le développement de nouveaux algorithmes et filtres de reconstruction. La performance diagnostique de la meilleure série acquise à une dose effective inférieure à 0.3 mSv a été comparée à celle d'un CT de référence effectué à doses standards en relevant les anomalies du parenchyme pulmonaire. Les résultats montrent que la meilleure qualité d'image, tant qualitativement que quantitativement a été obtenue en utilisant iDose4, la matrice 5122 et le filtre mou, avec une concordance parfaite entre les classements quantitatif et qualitatif des 8 séries. D'autre part, la détection des nodules pulmonaires de plus de 4mm étaient similaire sur la meilleure série acquise à une dose effective inférieure à 0.3 mSv et le CT de référence. En conclusion, les CT thoraciques effectués à une dose effective inférieure à 0.3 mSv reconstruits avec iDose4, la matrice 5122 et le filtre mou peuvent être utilisés avec confiance pour diagnostiquer les nodules pulmonaires de plus de 4mm.

Radiotherapy for GIST progressing during or after tyrosine kinase inhibitor therapy: A prospective study.

PURPOSE: Gastrointestinal stromal tumor (GIST) has been considered radiation-resistant, and radiotherapy is recommended only for palliation of bone metastases in current treatment guidelines. No registered prospective trial has evaluated GIST responsiveness to radiotherapy. PATIENTS AND METHODS: Patients with GIST progressing at intra-abdominal sites or the liver were entered to this prospective Phase II multicenter study (identifier NCT00515931). Metastases were treated with external beam radiotherapy using either conformal 3D planning or intensity modulated radiotherapy and conventional fractionation to a cumulative planning target volume dose of approximately 40Gy. Systemic therapy was maintained unaltered during the study. RESULTS: Of the 25 patients entered, 19 were on concomitant tyrosine kinase inhibitor therapy, most often imatinib. Two (8%) patients achieved partial remission, 20 (80%) had stable target lesion size for ⩾3months after radiotherapy with a median duration of stabilization of 16months, and 3 (12%) progressed. The median time to radiotherapy target lesion progression was 4-fold longer than the median time to GIST progression at any site (16 versus 4months). Radiotherapy was generally well tolerated. CONCLUSIONS: Responses to radiotherapy were infrequent, but most patients had durable stabilization of the target lesions. GIST patients with soft tissue metastases benefit frequently from radiotherapy.

Spatio-temporal image correlation (STIC): nova técnica para avaliação do coração fetal

As malformações cardíacas são as mais freqüentes anomalias congênitas ao nascimento, entretanto, a sua detecção pré-natal pela ultra-sonografia convencional permanece baixa. As ultra-sonografias de terceira e quarta dimensões surgiram no início da década de 90, apresentando grandes aplicações em obstetrícia, principalmente nos casos de diagnósticos duvidosos à ultra-sonografia bidimensional. O spatio-temporal image correlation (STIC) representa grande avanço na área de ultra-som de quarta dimensão; constitui-se em um software acoplado ao aparelho Voluson 730 Expert, que permite a aquisição volumétrica do coração fetal e suas conexões vasculares. As análises volumétricas são realizadas nos modos multiplanar e de renderização, podendo-se também utilizar o Doppler. Apresenta, como grandes vantagens, a aquisição rápida e a possibilidade de análise posterior por especialistas em ecocardiografia fetal. Pode ser aplicada para a pesquisa de quaisquer cardiopatias congênitas, pois permite a aquisição de qualquer plano, diferentemente do ultra-som bidimensional. Sua principal desvantagem está relacionada aos movimentos fetais. A maior difusão do método pode permitir um aumento na detecção de malformações cardíacas, pois possibilita ao ultra-sonografista geral encaminhar, via Internet, os volumes para a análise por especialistas em ecocardiografia fetal.

Body Image in Eating Disorders: The Influence of Exposure to Virtual-Reality Environments.

The aim of this article was to study the effect of virtual-reality exposure to situations that are emotionally significant for patients with eating disorders (ED) on the stability of body-image distortion and body-image dissatisfaction. A total of 85 ED patients and 108 non-ED students were randomly exposed to four experimental virtual environments: a kitchen with low-calorie food, a kitchen with high-calorie food, a restaurant with low-calorie food, and a restaurant with high-calorie food. In the interval between the presentation of each situation, body-image distortion and body-image dissatisfaction were assessed. Several 2 x 2 x 2 repeated measures analyses of variance (high-calorie vs. low-calorie food x presence vs. absence of people x ED group vs. control group) showed that ED participants had significantly higher levels of body-image distortion and body dissatisfaction after eating high-calorie food than after eating low-calorie food, while control participants reported a similar body image in all situations. The results suggest that body-image distortion and body-image dissatisfaction show both trait and state features. On the one hand, ED patients show a general predisposition to overestimate their body size and to feel more dissatisfied with their body image than controls. On the other hand, these body-image disturbances fluctuate when participants are exposed to virtual situations that are emotionally relevant for them.

Spleen Volume Variation in Patients with Locally Advanced Non-Small Cell Lung Cancer Receiving Platinum-Based Chemo-Radiotherapy.

There is renewed interest in the immune regulatory role of the spleen in oncology. To date, very few studies have examined macroscopic variations of splenic volume in the setting of cancer, prior to or during therapy, especially in humans. Changes in splenic volume may be associated with changes in splenic function. The purpose of this study was to investigate variations in spleen volume in NSCLC patients during chemo-radiotherapy. Sixty patients with stage I-IIIB NSCLC underwent radiotherapy (60Gy/30 fractions) for six weeks with concomitant carboplatin/paclitaxel (Ca/P; n = 32) or cisplatin/etoposide (Ci/E; n = 28). A baseline PET/CT scan was performed within 2 weeks prior to treatment and during Weeks 2 and 4 of chemo-radiotherapy. Spleen volume was measured by contouring all CT slices. Significant macroscopic changes in splenic volume occurred early after the commencement of treatment. A significant decrease in spleen volume was observed for 66% of Ca/P and 79% of Ci/E patients between baseline and Week 2. Spleen volume was decreased by 14.2% for Ca/P (p<0.001) and 19.3% for Ci/E (p<0.001) patients. By Week 4, spleen volume was still significantly decreased for Ca/P patients compared to baseline, while for Ci/E patients, spleen volume returned to above baseline levels. This is the first report demonstrating macroscopic changes in the spleen in NSCLC patients undergoing radical chemo-radiotherapy that can be visualized by non-invasive imaging.

Image quality in CT: From physical measurements to model observers.

Evaluation of image quality (IQ) in Computed Tomography (CT) is important to ensure that diagnostic questions are correctly answered, whilst keeping radiation dose to the patient as low as is reasonably possible. The assessment of individual aspects of IQ is already a key component of routine quality control of medical x-ray devices. These values together with standard dose indicators can be used to give rise to 'figures of merit' (FOM) to characterise the dose efficiency of the CT scanners operating in certain modes. The demand for clinically relevant IQ characterisation has naturally increased with the development of CT technology (detectors efficiency, image reconstruction and processing), resulting in the adaptation and evolution of assessment methods. The purpose of this review is to present the spectrum of various methods that have been used to characterise image quality in CT: from objective measurements of physical parameters to clinically task-based approaches (i.e. model observer (MO) approach) including pure human observer approach. When combined together with a dose indicator, a generalised dose efficiency index can be explored in a framework of system and patient dose optimisation. We will focus on the IQ methodologies that are required for dealing with standard reconstruction, but also for iterative reconstruction algorithms. With this concept the previously used FOM will be presented with a proposal to update them in order to make them relevant and up to date with technological progress. The MO that objectively assesses IQ for clinically relevant tasks represents the most promising method in terms of radiologist sensitivity performance and therefore of most relevance in the clinical environment.

Optimization of Radiation Dose and Image Quality in Musculoskeletal CT: Emphasis on Iterative Reconstruction Techniques (Part 1).

Computed tomography (CT) is a modality of choice for the study of the musculoskeletal system for various indications including the study of bone, calcifications, internal derangements of joints (with CT arthrography), as well as periprosthetic complications. However, CT remains intrinsically limited by the fact that it exposes patients to ionizing radiation. Scanning protocols need to be optimized to achieve diagnostic image quality at the lowest radiation dose possible. In this optimization process, the radiologist needs to be familiar with the parameters used to quantify radiation dose and image quality. CT imaging of the musculoskeletal system has certain specificities including the focus on high-contrast objects (i.e., in CT of bone or CT arthrography). These characteristics need to be taken into account when defining a strategy to optimize dose and when choosing the best combination of scanning parameters. In the first part of this review, we present the parameters used for the evaluation and quantification of radiation dose and image quality. In the second part, we discuss different strategies to optimize radiation dose and image quality at CT, with a focus on the musculoskeletal system and the use of novel iterative reconstruction techniques.