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Kiljunen T.,Docrates Cancer Center | Kaasalainen T.,University of Helsinki | Suomalainen A.,University of Helsinki | Kortesniemi M.,University of Helsinki
Physica Medica | Year: 2015

For the maxillofacial region, there are various indications that cannot be interpreted from 2D images and will benefit from multiplanar viewing. Dental cone beam CT (CBCT) utilises a cone- or pyramid-shaped X-ray beam using mostly flat-panel detectors for 3D image reconstruction with high spatial resolution. The vast increase in availability and amount of these CBCT devices offers many clinical benefits, and their ongoing development has potential to bring various new clinical applications for medical imaging. Additionally, there is also a need for high quality research and education. European guidelines promote the use of a medical physics expert for advice on radiation protection, patient dose optimisation, and equipment testing. In this review article, we perform a comparison of technical equipment based on manufacturer data, including scanner specific X-ray spectra, and describe issues concerning CBCT image reconstruction and image quality, and also address radiation dose issues, dosimetry, and optimisation. We also discuss clinical needs and what type of education users should have in order to operate CBCT systems safely. We will also take a look into the future and discuss the issues that still need to be solved. © 2015 Associazione Italiana di Fisica Medica. Source

Hodolic M.,IASON GmbH | Fettich J.,Bled Diagnostic Center | Kairemo K.,Docrates Cancer Center
Current Radiopharmaceuticals | Year: 2015

Over the years, external beam radiotherapy (EBRT) has been used in the treatment management of many malignancies, including head and neck squamous cell carcinomas (HNSCC). Hypoxia is a common feature in HNSCC. Hypoxic segments in HNSCC have proven to be more resistant to radiotherapy. The ability to identify hypoxia using SPECT and PET tracers has been investigated since the late 1970s. Nitroimidazole-based compounds labelled with positron emitters have been developed to more specifically image hypoxia. This article reviews the current data from research publications on18F–FMISO, 18F-FAZA, 18F-EF5 and 64Cu-ATSM. © 2015 Bentham Science Publishers. Source

Koivisto J.,University of Helsinki | Kiljunen T.,Docrates Cancer Center | Kadesjo N.,Karolinska Institutet | Shi X.-Q.,Karolinska Institutet | Wolff J.,VU University Amsterdam
Journal of Foot and Ankle Research | Year: 2015

Background: The aim of this study was to assess and compare the effective doses (ICRP 103) in the ankle region of X-ray imaging resulting from a multi slice computed tomography (MSCT) device, two cone beam CT (CBCT) devices and one conventional x-ray device. Methods: Organ dose measurements were performed using 20 metal oxide field effect transistor (MOSFET) dosimeters that were placed in a custom made anthropomorphic RANDO ankle phantom. The following scanners were assessed in this study: Siemens Sensation Open 24-slice MSCT-scanner (120 kVp, 54 mAs), NewTom 5G CBCT scanner (110 kVp, 2.3 - 59 mAs), Planmed Verity CBCT-scanner (90 kVp, 48 mAs), Shimadzu FH-21 HR direct radiography equipment (AP + LAT), (57 kVp, 16 mAs). Results: Measurements of the MSCT device resulted in 21.4 μSv effective dose. The effective doses of CBCTs were between 1.9 μSv and 14.3 μSv for NewTom 5G and 6.0 μSv for Planmed Verity. Effective doses for the Shimadzu FH-21 HR conventional radiography were 1.0 μSv (LAT) and 0.5 μSv (AP), respectively. Conclusions: Compared with a conventional 2D radiographic device, this study showed a 14-fold effective dose for standard MSCT and 1.3 -10 fold effective dose for standard CBCT protocols. CBCT devices offers a 3D view of ankle imaging and exhibited lower effective doses compared with MSCT. © 2015 Koivisto et al.; licensee BioMed Central. Source

Liikanen I.,University of Helsinki | Koski A.,University of Helsinki | Merisalo-Soikkeli M.,University of Helsinki | Hemminki O.,University of Helsinki | And 6 more authors.
OncoImmunology | Year: 2015

With the emergence of effective immunotherapeutics, which nevertheless harbor the potential for toxicity and are expensive to use, biomarkers are urgently needed for identification of cancer patients who respond to treatment. In this clinical-epidemiological study of 202 cancer patients treated with oncolytic adenoviruses, we address the biomarker value of serum high-mobility group box 1 (HMGB1) protein. Overall survival and imaging responses were studied as primary endpoints and adjusted for confounding factors in two multivariate analyses (Cox and logistic regression). Mechanistic studies included assessment of circulating tumor-specific T-cells by ELISPOT, virus replication by quantitative PCR, and inflammatory cytokines by cytometric bead array. Patients with low HMGB1 baseline levels (below median concentration) showed significantly improved survival (p D 0.008, Log-Rank test) and radiological disease control rate (49.2% vs. 30.0%, p D 0.038, x2 test) as compared to high-baseline patients. In multivariate analyses, the low HMGB1 baseline status was a strong prognostic (HR 0.638, 95% CI 0.462–0.881) and the best predictive factor for disease control (OR 2.618, 95% CI 1.004–6.827). Indicative of an immune-mediated mechanism, antitumor T-cell activity in blood and response to immunogenic-transgene coding viruses associated with improved outcome only in HMGB1-low patients. Our results suggest that serum HMGB1 baseline is a useful prognostic and predictive biomarker for oncolytic immunotherapy with adenoviruses, setting the stage for prospective clinical studies. © Ilkka Liikanen, Anniina Koski, Maiju Merisalo-Soikkeli, Otto Hemminki, Minna Oksanen, Kalevi Kairemo, Timo Joensuu, Anna Kanerva, and Akseli Hemminki. Source

Hemminki O.,University of Helsinki | Parviainen S.,University of Helsinki | Juhila J.,University of Helsinki | Turkki R.,Institute for Molecular Medicine Finland FIMM | And 16 more authors.
Oncotarget | Year: 2015

Oncolytic viruses that selectively replicate in tumor cells can be used for treatment of cancer. Accumulating data suggests that virus induced oncolysis can enhance anti-tumor immunity and break immune tolerance. To capitalize on the immunogenic nature of oncolysis, we generated a quadruple modified oncolytic adenovirus expressing granulocyte-macrophage colony-stimulating factor (GMCSF). Ad5/3-E2F-Δ24-GMCSF (CGTG-602) was engineered to contain a tumor specific E2F1 promoter driving an E1 gene deleted at the retinoblastoma protein binding site ("Δ24"). The fiber features a knob from serotype 3 for enhanced gene delivery to tumor cells. The virus was tested preclinically in vitro and in vivo and then 13 patients with solid tumors refractory to standard therapies were treated. Treatments were well tolerated and frequent tumor- and adenovirus-specific T-cell immune responses were seen. Overall, with regard to tumor marker or radiological responses, signs of antitumor efficacy were seen in 9/12 evaluable patients (75%). The radiological disease control rate with positron emission tomography was 83% while the response rate (including minor responses) was 50%. Tumor biopsies indicated accumulation of immunological cells, especially T-cells, to tumors after treatment. RNA expression analyses of tumors indicated immunological activation and metabolic changes secondary to virus replication. Source

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