Quantitative assessment of inter-observer variability in target volume delineation on stereotactic radiotherapy treatment for pituitary adenoma and meningioma near optic tract

<p>Abstract</p> <p>Background</p> <p>To assess inter-observer variability in delineating target volume and organs at risk in benign tumor adjacent to optic tract as a quality assurance exercise.</p> <p>Methods</p> <p>We quantitatively analyzed 21 plans made by 11 clinicians in seven CyberKnife centers. The clinicians were provided with a raw data set (pituitary adenoma and meningioma) including clinical information, and were asked to delineate the lesions and create a treatment plan. Their contouring and plans (10 adenoma and 11 meningioma plans), were then compared. In addition, we estimated the influence of differences in contouring by superimposing the respective contours onto a default plan.</p> <p>Results</p> <p>The median planning target volume (PTV) and the ratio of the largest to the smallest contoured volume were 9.22 cm³(range, 7.17 - 14.3 cm³) and 1.99 for pituitary adenoma, and 6.86 cm³(range 6.05 - 14.6 cm³) and 2.41 for meningioma. PTV volume was 10.1 ± 1.74 cm³for group 1 with a margin of 1 -2 mm around the CTV (n = 3) and 9.28 ± 1.8 cm³(p = 0.51) for group 2 with no margin (n = 7) in pituitary adenoma. In meningioma, group 1 showed larger PTV volume (10.1 ± 3.26 cm³) than group 2 (6.91 ± 0.7 cm³, p = 0.03). All submitted plan keep the irradiated dose to optic tract within the range of 50 Gy (equivalent total doses in 2 Gy fractionation). However, contours superimposed onto the dose distribution of the default plan indicated that an excessive dose 23.64 Gy (up to 268% of the default plan) in pituitary adenoma and 24.84 Gy (131% of the default plan) in meningioma to the optic nerve in the contours from different contouring.</p> <p>Conclusion</p> <p>Quality assurance revealed inter-observer variability in contour delineation and their influences on planning for pituitary adenoma and meningioma near optic tract.</p

Geographical inequalities in lung cancer management and survival in South East England: evidence of variation in access to oncology services?

This study aimed to determine whether the management and survival of patients with lung cancer varied among 26 health authorities in South East England. The Thames Cancer Registry identified patients diagnosed with lung cancer (ICD-10 codes C33-C34) between 1995 and 1999. After excluding death certificate only patients, 32,818 (81%) patients were analysed. The proportions of patients receiving active treatment varied among health authorities between 5 and 17% for non-investigative surgery, 4 and 17% for any chemotherapy, 8 and 30% for any radiotherapy and 15 and 42% for any active treatment. One-year patient survival ranged from 11 to 34%. There was evidence of health authority level variation even after adjusting for case mix. Patients whose first hospital attendance was at a radiotherapy centre were more likely to receive active treatment (OR 1.72, 95% CI 1.21-2.46), chemotherapy (1.38, 1.06-1.79) or radiotherapy (1.86, 1.28-2.71). There was some evidence that patients whose first hospital attendance was at a radiotherapy centre survived longer. This study shows there is geographical inequality in the treatment given to lung cancer patients and patient survival in South East England. There was some evidence to suggest that these inequalities might be explained by variations in access to oncology services. Future studies should investigate the pathways and barriers to specialist care in this condition

Stereotactic body radiotherapy for stage I lung cancer and small lung metastasis: evaluation of an immobilization system for suppression of respiratory tumor movement and preliminary results

<p>Abstract</p> <p>Background</p> <p>In stereotactic body radiotherapy (SBRT) for lung tumors, reducing tumor movement is necessary. In this study, we evaluated changes in tumor movement and percutaneous oxygen saturation (SpO₂) levels, and preliminary clinical results of SBRT using the BodyFIX immobilization system.</p> <p>Methods</p> <p>Between 2004 and 2006, 53 consecutive patients were treated for 55 lesions; 42 were stage I non-small cell lung cancer (NSCLC), 10 were metastatic lung cancers, and 3 were local recurrences of NSCLC. Tumor movement was measured with fluoroscopy under breath holding, free breathing on a couch, and free breathing in the BodyFIX system. SpO₂levels were measured with a finger pulseoximeter under each condition. The delivered dose was 44, 48 or 52 Gy, depending on tumor diameter, in 4 fractions over 10 or 11 days.</p> <p>Results</p> <p>By using the BodyFIX system, respiratory tumor movements were significantly reduced compared with the free-breathing condition in both craniocaudal and lateral directions, although the amplitude of reduction in the craniocaudal direction was 3 mm or more in only 27% of the patients. The average SpO₂did not decrease by using the system. At 3 years, the local control rate was 80% for all lesions. Overall survival was 76%, cause-specific survival was 92%, and local progression-free survival was 76% at 3 years in primary NSCLC patients. Grade 2 radiation pneumonitis developed in 7 patients.</p> <p>Conclusion</p> <p>Respiratory tumor movement was modestly suppressed by the BodyFIX system, while the SpO₂level did not decrease. It was considered a simple and effective method for SBRT of lung tumors. Preliminary results were encouraging.</p

Quality of life after curative gastrectomy for gastric cancer in a randomised controlled trial

Quality of life (QOL) was studied in gastric cancer patients treated on a randomised, controlled trial comparing D1 (level 1) with D3 (levels 1, 2 and 3) lymphadenectomy. A total of 221 patients were randomly assigned to D1 (n=110) and D3 (n=111) surgery. Quality-of-life assessments included functional outcomes (a 14-item survey about treatment-specific symptoms) and health perception (Spitzer QOL Index) was performed before and after surgery at disease-free status. Patients suffered from irrelative events such as loss of partners was excluded thereafter. Main analyses were done by intention-to-treat. Thus, 214 D1 (106/110=96.4%) and D3 (108/111=97.3%) R0 patients were assessed. Longitudinal analysis showed that functional outcomes decreased at 6 months after surgery and increased over time thereafter, while health perceptions increased over time in general. On the basis of linear mixed model analyses, patients having total gastrectomy, advanced cancer and hemipancreaticosplenectomy, but not complications had poorer QOL than those without. D1 and D3 patients showed no significant difference in QOL. The results suggest that changes of QOL were largely due to scope of gastric resection, disease status and distal pancreaticosplenectomy, rather than the extent of lymph node dissection. This indicates that nodal dissection can be performed for a potentially curable gastric cancer

Genomic Characterization of Haemophilus parasuis SH0165, a Highly Virulent Strain of Serovar 5 Prevalent in China

Haemophilus parasuis can be either a commensal bacterium of the porcine respiratory tract or an opportunistic pathogen causing Glässer's disease, a severe systemic disease that has led to significant economical losses in the pig industry worldwide. We determined the complete genomic sequence of H. parasuis SH0165, a highly virulent strain of serovar 5, which was isolated from a hog pen in North China. The single circular chromosome was 2,269,156 base pairs in length and contained 2,031 protein-coding genes. Together with the full spectrum of genes detected by the analysis of metabolic pathways, we confirmed that H. parasuis generates ATP via both fermentation and respiration, and possesses an intact TCA cycle for anabolism. In addition to possessing the complete pathway essential for the biosynthesis of heme, this pathogen was also found to be well-equipped with different iron acquisition systems, such as the TonB system and ABC-type transport complexes, to overcome iron limitation during infection and persistence. We identified a number of genes encoding potential virulence factors, such as type IV fimbriae and surface polysaccharides. Analysis of the genome confirmed that H. parasuis is naturally competent, as genes related to DNA uptake are present. A nine-mer DNA uptake signal sequence (ACAAGCGGT), identical to that found in Actinobacillus pleuropneumoniae and Mannheimia haemolytica, followed by similar downstream motifs, was identified in the SH0165 genome. Genomic and phylogenetic comparisons with other Pasteurellaceae species further indicated that H. parasuis was closely related to another swine pathogenic bacteria A. pleuropneumoniae. The comprehensive genetic analysis presented here provides a foundation for future research on the metabolism, natural competence and virulence of H. parasuis

Gut microbiota and sirtuins in obesity-related inflammation and bowel dysfunction

Obesity is a chronic disease characterized by persistent low-grade inflammation with alterations in gut motility. Motor abnormalities suggest that obesity has effects on the enteric nervous system (ENS), which controls virtually all gut functions. Recent studies have revealed that the gut microbiota can affect obesity and increase inflammatory tone by modulating mucosal barrier function. Furthermore, the observation that inflammatory conditions influence the excitability of enteric neurons may add to the gut dysfunction in obesity. In this article, we discuss recent advances in understanding the role of gut microbiota and inflammation in the pathogenesis of obesity and obesity-related gastrointestinal dysfunction. The potential contribution of sirtuins in protecting or regulating the circuitry of the ENS under inflamed states is also considered

Pubertal high fat diet: effects on mammary cancer development

INTRODUCTION: Epidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD. METHODS: Pubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis. RESULTS: HFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-κB activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages. CONCLUSIONS: Taken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD

Myxopapillary ependymoma with intracranial metastases.

We report spontaneous seeding within the subarachnoid space from a myxopapillary ependymoma that progressed despite surgery and radiotherapy treatment

Non-small-cell lung cancer dimensions: CT-pathological correlation and interobserver variation.

The aim of the study was to identify the most accurate CT window level setting for the measurement of non-small-cell lung cancer to optimise CT planning for radiotherapy treatment. 27 patients who underwent resection for non-small-cell lung cancer in a single institution were studied. The maximal superior-inferior, anteroposterior and mediolateral dimensions of the resected tumours were measured by a consultant pathologist. Two radiologists made corresponding measurements using pre-operative CT scans independently of each other and of the pathologist's findings. The measurements were obtained using four different CT window settings. The mean pathological size of the superior-inferior tumours, the anteroposterior tumours and the mediolateral tumours was 32 mm, 28 mm and 25 mm, respectively. A total of 648 CT measurements were taken, of which 321 were within +/-5 mm of the pathological size (49.5%). There was significant interobserver variability between the two radiologists. There was poor correlation between the pathological and radiological measurements of tumour size. Significant interobserver variability was noted between the two radiologists and no window setting could be identified as being superior in accurately assessing the tumour size