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  • 1
    Keywords: radiation ; POSITRON-EMISSION-TOMOGRAPHY ; COMPUTED-TOMOGRAPHY ; PET ; MOTION ; CANCER NSCLC ; CT SCANS ; phantom ; EARLY-STAGE ; STEREOTACTIC ABLATIVE RADIOTHERAPY
    Abstract: PURPOSE: Evaluation of the effect of co-registered 4D-(18)FDG-PET/CT for SBRT target delineation in patients with central versus peripheral lung tumors. METHODS: Analysis of internal target volume (ITV) delineation of central and peripheral lung lesions in 21 SBRT-patients. Manual delineation was performed by 4 observers in 2 contouring phases: on respiratory gated 4DCT with diagnostic 3DPET available aside (CT-ITV) and on co-registered 4DPET/CT (PET/CT-ITV). Comparative analysis of volumes and inter-reader agreement. RESULTS: 11 cases of peripheral and 10 central lesions were evaluated. In peripheral lesions, average CT-ITV was 6.2cm(3) and PET/CT-ITV 8.6cm(3), resembling a mean change in hypothetical radius of 2mm. For both CT-ITVs and PET/CT-ITVs inter reader agreement was good and unchanged (0.733 and 0.716; p=0.58). All PET/CT-ITVs stayed within the PTVs derived from CT-ITVs. In central lesions, average CT-ITVs were 42.1cm(3), PET/CT-ITVs 44.2cm(3), without significant overall volume changes. Inter-reader agreement improved significantly (0.665 and 0.750; p〈0.05). 2/10 PET/CT-ITVs exceeded the PTVs derived from CT-ITVs by 〉1ml in average for all observers. CONCLUSION: The addition of co-registered 4DPET data to 4DCT based target volume delineation for SBRT of centrally located lung tumors increases the inter-observer agreement and may help to avoid geographic misses.
    Type of Publication: Journal article published
    PubMed ID: 26116339
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  • 2
    Abstract: PURPOSE: Oncologic imaging is a key for successful cancer treatment. While the quality assurance (QA) of image acquisition protocols has already been focussed, QA of reading and reporting offers still room for improvement. The latter was addressed in the context of a prospective multicentre trial on fluoro-deoxyglucose (FDG)-positron-emission tomography (PET)/CT-based chemoradiotherapy for locally advanced non-small cell lung cancer (NSCLC). MATERIAL AND METHODS: An expert panel was prospectively installed performing blinded reviews of mediastinal NSCLC involvement in FDG-PET/CT. Due to a high initial reporting inter-observer disagreement, the independent data monitoring committee (IDMC) triggered an interventional harmonisation process, which overall involved 11 experts uttering 6855 blinded diagnostic statements. After assessing the baseline inter-observer agreement (IOA) of a blinded re-review (phase 1), a discussion process led to improved reading criteria (phase 2). Those underwent a validation study (phase 3) and were then implemented into the study routine. After 2months (phase 4) and 1year (phase 5), the IOA was reassessed. RESULTS: The initial overall IOA was moderate (kappa 0.52 CT; 0.53 PET). After improvement of reading criteria, the kappa values improved substantially (kappa 0.61 CT; 0.66 PET), which was retained until the late reassessment (kappa 0.71 CT; 0.67 PET). Subjective uncertainty was highly predictive for low IOA. CONCLUSION: The IOA of an expert panel was significantly improved by a structured interventional harmonisation process which could be a model for future clinical trials. Furthermore, the low IOA in reporting nodal involvement in NSCLC may bear consequences for individual patient care.
    Type of Publication: Journal article published
    PubMed ID: 26277100
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  • 3
    Abstract: PURPOSE: The aim was to assess changes of tumour hypoxia during primary radiochemotherapy (RCT) for head and neck cancer (HNC) and to evaluate their relationship with treatment outcome. MATERIAL AND METHODS: Hypoxia was assessed by FMISO-PET in weeks 0, 2 and 5 of RCT. The tumour volume (TV) was determined using FDG-PET/MRI/CT co-registered images. The level of hypoxia was quantified on FMISO-PET as TBRmax (SUVmaxTV/SUVmean background). The hypoxic subvolume (HSV) was defined as TV that showed FMISO uptake 1.4 times blood pool activity. RESULTS: Sixteen consecutive patients (T3-4, N+, M0) were included (mean follow-up 31, median 44months). Mean TBRmax decreased significantly (p〈0.05) from 1.94 to 1.57 (week 2) and 1.27 (week 5). Mean HSV in week 2 and week 5 (HSV2=5.8ml, HSV3=0.3ml) were significantly (p〈0.05) smaller than at baseline (HSV1=15.8ml). Kaplan-Meier plots of local recurrence free survival stratified at the median TBRmax showed superior local control for less hypoxic tumours, the difference being significant at baseline and after 2weeks (p=0.031, p=0.016). CONCLUSIONS: FMISO-PET documented that in most HNC reoxygenation starts early during RCT and is correlated with better outcome.
    Type of Publication: Journal article published
    PubMed ID: 26432067
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  • 4
    Abstract: PURPOSE: We performed a voxel-wise comparison of (68)Ga-HBED-CC-PSMA PET/CT with prostate histopathology to evaluate the performance of (68)Ga-HBED-CC-PSMA for the detection and delineation of primary prostate cancer (PCa). METHODOLOGY: Nine patients with histopathological proven primary PCa underwent (68)Ga-HBED-CC-PSMA PET/CT followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and histopathologically prepared. Histopathological information was matched to ex-vivo CT. PCa volume (PCa-histo) and non-PCa tissue in the prostate (NPCa-histo) were processed to obtain a PCa-model, which was adjusted to PET-resolution (histo-PET). Each histo-PET was coregistered to in-vivo PSMA-PET/CT data. RESULTS: Analysis of spatial overlap between histo-PET and PSMA PET revealed highly significant correlations (p 〈 10(-5)) in nine patients and moderate to high coefficients of determination (R(2)) from 42 to 82 % with an average of 60 +/- 14 % in eight patients (in one patient R(2) = 7 %). Mean SUVmean in PCa-histo and NPCa-histo was 5.6 +/- 6.1 and 3.3 +/- 2.5 (p = 0.012). Voxel-wise receiver-operating characteristic (ROC) analyses comparing the prediction by PSMA-PET with the non-smoothed tumor distribution from histopathology yielded an average area under the curve of 0.83 +/- 0.12. Absolute and relative SUV (normalized to SUVmax) thresholds for achieving at least 90 % sensitivity were 3.19 +/- 3.35 and 0.28 +/- 0.09, respectively. CONCLUSIONS: Voxel-wise analyses revealed good correlations of (68)Ga-HBED-CC-PSMA PET/CT and histopathology in eight out of nine patients. Thus, PSMA-PET allows a reliable detection and delineation of PCa as basis for PET-guided focal therapies.
    Type of Publication: Journal article published
    PubMed ID: 27446496
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  • 5
    Abstract: BACKGROUND: Tumor hypoxia is associated with poor prognosis and outcome and can be visualized using 18F-MISO-positron emission tomography (PET) imaging. The goal of this study was to evaluate the correlation between biological markers and biological imaging in a group of patients in whom a correlation between biological imaging and outcome has previously been demonstrated. MATERIAL AND METHODS: In a prospective pilot project, 16 patients with locally advanced cancer of the head and neck underwent 18F-MISO-PET scans before and during primary radiochemotherapy in addition to 18F-FDG-PET and computed tomography (CT). Tumor biopsies were stained for three tissue-based markers (Ku80, CAIX, CD44); in addition, human papillomavirus (HPV) status was assessed. H-scores of marker expression were generated and the results were correlated with the biological imaging and clinical outcome. RESULTS: No statistically significant correlation was established between the H-scores for Ku80, CD44 and CAIX or between any of the H-scores and the imaging variables (tumor volume on 18F-FDG-PET in ml, hypoxic subvolume as assessed by 18F-MISO-PET in ml, and SUVmax tumor/SUVmean muscle during the 18F-MISO-PET). A statistically significant negative correlation was found between CD44 H-score and HPV status (p = .004). Cox regression analysis for overall survival and recurrence-free survival showed one significant result for CAIX being associated with improved overall survival [hazard ratio 0.96 (0.93-1.00), p = .047]. CONCLUSION: Expression of Ku80, CAIX and CD44 as assessed by immunohistochemistry of tumor biopsies were not correlated to one another or the biological imaging data. However, there was a significant influence of CAIX on overall survival and between CD44 and HPV.
    Type of Publication: Journal article published
    PubMed ID: 27593107
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  • 6
    Keywords: CT ; QUALITY-ASSURANCE ; POSTOPERATIVE RADIOTHERAPY ; PHASE-II ; 3-DIMENSIONAL CONFORMAL RADIOTHERAPY ; DEFINITION ; OBSERVER VARIATION ; GROSS TUMOR VOLUME ; DOSE-ESCALATION TRIAL ; PET-BASED DELINEATION
    Abstract: INTRODUCTION: Interobserver variability in the definition of target volumes (TVs) is a well-known confounding factor in (multicentre) clinical studies employing radiotherapy. Therefore, detailed contouring guidelines are provided in the prospective randomised multicentre PET-Plan (NCT00697333) clinical trial protocol. This trial compares strictly FDG-PET-based TV delineation with conventional TV delineation in patients with locally advanced non-small cell lung cancer (NSCLC). Despite detailed contouring guidelines, their interpretation by different radiation oncologists can vary considerably, leading to undesirable discrepancies in TV delineation. Considering this, as part of the PET-Plan study quality assurance (QA), a contouring dummy run (DR) consisting of two phases was performed to analyse the interobserver variability before and after teaching. MATERIALS AND METHODS: In the first phase of the DR (DR1), radiation oncologists from 14 study centres were asked to delineate TVs as defined by the study protocol (gross TV, GTV; and two clinical TVs, CTV-A and CTV-B) in a test patient. A teaching session was held at a study group meeting, including a discussion of the results focussing on discordances in comparison to the per-protocol solution. Subsequently, the second phase of the DR (DR2) was performed in order to evaluate the impact of teaching. RESULTS: Teaching after DR1 resulted in a reduction of absolute TVs in DR2, as well as in better concordance of TVs. The Overall Kappa(kappa) indices increased from 0.63 to 0.71 (GTV), 0.60 to 0.65 (CTV-A) and from 0.59 to 0.63 (CTV-B), demonstrating improvements in overall interobserver agreement. CONCLUSION: Contouring DRs and study group meetings as part of QA in multicentre clinical trials help to identify misinterpretations of per-protocol TV delineation. Teaching the correct interpretation of protocol contouring guidelines leads to a reduction in interobserver variability and to more consistent contouring, which should consequently improve the validity of the overall study results.
    Type of Publication: Journal article published
    PubMed ID: 25665799
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  • 7
    Abstract: PURPOSE: To demonstrate the feasibility and to evaluate the tumour control probability (TCP) and normal tissue complication probability (NTCP) of IMRT dose painting using (68)Ga-HBED-CC PSMA PET/CT for target delineation in prostate cancer (PCa). METHODS AND MATERIALS: 10 patients had PSMA PET/CT scans prior to prostatectomy. GTV-PET was generated on the basis of an intraprostatic SUVmax of 30%. Two IMRT plans were generated for each patient: Plan(77) which consisted of whole-prostate IMRT to 77Gy, and Plan(95) which consisted of whole-prostate IMRT to 77Gy and a simultaneous integrated boost to the GTV-PET up to 95Gy (35 fractions). The feasibility of these plans was judged by their ability to adhere to the FLAME trial protocol. TCP-histo/-PET were calculated on co-registered histology (GTV-histo) and GTV-PET, respectively. NTCPs for rectum and bladder were calculated. RESULTS: All plans reached prescription doses whilst adhering to dose constraints. In Plan(77) and Plan(95) mean doses in GTV-histo were 75.8+/-0.3Gy and 96.9+/-1Gy, respectively. Average TCP-histo values for Plan(77) and Plan(95) were 70% (range: 15-97%), and 96% (range: 78-100%, p〈0.0001). Average TCP-PET values for Plan(77) and Plan(95) were 55% (range: 27-82%), and 100% (range: 99-100%, p〈0.0001). There was no significant difference between TCP-PET and TCP-histo in Plan(95) (p=0.25). There were no significant differences in rectal (p=0.563) and bladder (p=0.3) NTCPs. CONCLUSIONS: IMRT dose painting using PSMA PET/CT was technically feasible and resulted in significantly higher TCPs without higher NTCPs.
    Type of Publication: Journal article published
    PubMed ID: 28499607
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  • 8
    Abstract: PURPOSE: The exact detection and delineation of the intraprostatic tumour burden is crucial for treatment planning in primary prostate cancer (PCa). We compared (68)Ga-HBED-CC-PSMA PET/CT with multiparametric MRI (mpMRI) for diagnosis and tumour delineation in patients with primary PCa based on slice by slice correlation with histopathological reference material. METHODOLOGY: Seven patients with histopathologically proven primary PCa underwent (68)Ga-HBED-CC-PSMA PET/CT and MRI followed by radical prostatectomy. Resected prostates were scanned by ex-vivo CT in a special localizer and prepared for histopathology. Invasive PCa was delineated on a HE stained histologic tissue slide and matched to ex-vivo CT to obtain gross tumor volume (GTV-)histo. Ex-vivo CT including GTV-histo and MRI data were matched to in-vivo CT(PET). Consensus contours based on MRI (GTV-MRI), PSMA PET (GTV-PET) or the combination of both (GTV-union/-intersection) were created. In each in-vivo CT slice the prostate was separated into 4 equal segments and sensitivity and specificity for PSMA PET and mpMRI were assessed by comparison with histological reference material. Furthermore, the spatial overlap between GTV-histo and GTV-PET/-MRI and the Sorensen-Dice coefficient (DSC) were calculated. In the case of multifocal PCa (4/7 patients), SUV values (PSMA PET) and ADC-values (diffusion weighted MRI) were obtained for each lesion. RESULTS: PSMA PET and mpMRI detected PCa in all patients. GTV-histo was detected in 225 of 340 segments (66.2%). Sensitivity and specificity for GTV-PET, GTV-MRI, GTV-union and GTV-intersection were 75% and 87%, 70% and 82%, 82% and 67%, 55% and 99%, respectively. GTV-histo had on average the highest overlap with GTV-union (57+/-22%), which was significantly higher than overlap with GTV-MRI (p=0.016) and GTV-PET (p=0.016), respectively. The mean DSC for GTV-union, GTV-PET and GTV-MRI was 0.51 (+/-0.18), 0.45 (+/-0.17) and 0.48 (+/-0.19), respectively. In every patient with multifocal PCa there was one lesion which had both the highest SUV and the lowest ADC-value (mean and max). CONCLUSION: In a slice by slice analysis with histopathology, (68)Ga-HBED-CC-PSMA PET/CT and mpMRI showed high sensitivity and specificity in detection of primary PCa. A combination of both methods performed even better in terms of sensitivity (GTV-union) and specificity (GTV-intersection). A moderate to good spatial overlap with GTV-histo was observed for PSMA PET/CT and mpMRI alone which was significantly improved by GTV-union. Further studies are warranted to analyse the impact of these preliminary findings for diagnostic (multimodal guided TRUS biopsy) and therapeutic (focal therapy) strategies in primary PCa.
    Type of Publication: Journal article published
    PubMed ID: 28042330
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  • 9
    ISSN: 1365-2761
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Abstract. The circulating haemocytes of the tanner crab, Chionocetes bairdi, were studied and classified as hyalinocytes, intermediate granulocytes and eosinophilic granulocytes. Differential haemocyte counts of normal crabs and crabs infected with an apparently pathogenic unnamed ascomycete fungus revealed a shift in the hyalinocyte-granulocyte ratio in infected crabs. There was a highly significant increase in the percentage of granulocytes and a corresponding decrease in hyalinocytes in infected crabs. This shift was thought to be caused by a marked increase in the relative number of eosinophilic gianulocytes. There was also a highly significant statistical relationship between the severity of the internal fungus infection, established by histopathological analysis of the major organ systems, and the increased number of circulating eosinophilic granulocytes. The results of the study indicate that differential haemocyte counts may be a valuable tool in monitoring the health of C. bairdi populations.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1365-2761
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Abstract. The occurrence, prevalence, seasonality and histopathological progression of a cellular disorder, thought to be a haemic neoplasm, were studied in subpopulations of Mytilus edulis inhabiting different sites in Yaquina Bay, Oregon, from 1976–1981. There were significant differences in the occurrence of the disorder that were related to geographical location. In the subpopulation with the highest levels of the disease, the prevalence rates ranged from 0 to 20% with a 5-year mean of 9.8 %. There was a statistically significant relationship between prevalence and season. During the 5-year study period, there was a consistent pattern characterized by highest prevalences during January to March followed by a period of decline to lower levels during the summer and early autumn, after which there was an increase. Data analyses revealed that there was no seasonal histopathological progression of the disorder. Numbers of stage 1 (early), 2, 3 and 4 (advanced) cases were not related to season but occurred in a random manner throughout the entire year.
    Type of Medium: Electronic Resource
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