| 1. |
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| 2. |
- Bousquet, J, et al.
(author)
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Nrf2-interacting nutrients and COVID-19: time for research to develop adaptation strategies
- 2020
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In: Clinical and translational allergy. - : Wiley. - 2045-7022. ; 10:1, s. 58-
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Journal article (peer-reviewed)abstract
- There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPARγ:Peroxisome proliferator-activated receptor, NFκB: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2α:Elongation initiation factor 2α). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT1R axis (AT1R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity.
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| 3. |
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| 4. |
- Bousquet, J., et al.
(author)
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Building Bridges for Innovation in Ageing : Synergies between Action Groups of the EIP on AHA
- 2017
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In: The Journal of Nutrition, Health & Aging. - : Springer Nature. - 1279-7707 .- 1760-4788. ; 21:1, s. 92-104
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Journal article (peer-reviewed)abstract
- The Strategic Implementation Plan of the European Innovation Partnership on Active and Healthy Ageing (EIP on AHA) proposed six Action Groups. After almost three years of activity, many achievements have been obtained through commitments or collaborative work of the Action Groups. However, they have often worked in silos and, consequently, synergies between Action Groups have been proposed to strengthen the triple win of the EIP on AHA. The paper presents the methodology and current status of the Task Force on EIP on AHA synergies. Synergies are in line with the Action Groups' new Renovated Action Plan (2016-2018) to ensure that their future objectives are coherent and fully connected. The outcomes and impact of synergies are using the Monitoring and Assessment Framework for the EIP on AHA (MAFEIP). Eight proposals for synergies have been approved by the Task Force: Five cross-cutting synergies which can be used for all current and future synergies as they consider overarching domains (appropriate polypharmacy, citizen empowerment, teaching and coaching on AHA, deployment of synergies to EU regions, Responsible Research and Innovation), and three cross-cutting synergies focussing on current Action Group activities (falls, frailty, integrated care and chronic respiratory diseases).
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| 5. |
- Anney, Richard, et al.
(author)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Journal article (peer-reviewed)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 7. |
- Papanikolaou, N, et al.
(author)
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Investigation of the Use of Transmission Type Detectors for Daily IMRT Patient Dose Reconstruction
- 2007
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In: Proceedings in 49th AAPM Annual Meeting, Minneapolis, Minnesota, USA, July 22-26, 2007. - : Wiley.
-
Conference paper (other academic/artistic)abstract
- Purpose: To study the feasibility of using transmission type detectors for daily IMRT patient dose reconstruction and verification. Methods and Materials: Because of the complexity of IMRT there is a need for quality assurance for every patient. However, the daily delivered intensities may vary slightly from the planned ones. In this work we investigated the use of transmission type detectors and films for the verification of daily dose delivered to the patient. Films were placed at various distances from the source in air to measure the beam intensity. The fluence maps were also reconstructed from calculations of the TPS at the same planes. Monte Carlo simulations of the same geometries were performed and the intensity maps were also extracted at the same planes. Intead of film, a tray mounted transmission detector can also be used. Results: The film measurements were compared to TPS predicted intensity maps. Corrections based on the Monte Carlo study were applied to remove the electron contamination from the measured intensity maps since it was not accounted by the TPS. MC results indicate that the corrections due to the contaminant electrons can be 15 to 20% for 6MV beams. The corrected measured intensity map was used to calculate and reconstruct the daily dose to the patient using Monte Carlo. The results show good agreement between measurements using films and Monte Carlo calculations. Conclusions: Transmission detectors such as films can be used in order to compare the delivered intensity maps against the TPS predicted ones. The dose to the patient can be reconstructed using Monte Carlo based on the delivered intensity map and the dose can be potentially verified for each fraction, especially if a cone beam CT is performed daily.
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| 8. |
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| 9. |
- Pinto, Dalila, et al.
(author)
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Functional impact of global rare copy number variation in autism spectrum disorders.
- 2010
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In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7304, s. 368-372
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Journal article (peer-reviewed)abstract
- The autism spectrum disorders (ASDs) are a group of conditions characterized by impairments in reciprocal social interaction and communication, and the presence of restricted and repetitive behaviours. Individuals with an ASD vary greatly in cognitive development, which can range from above average to intellectual disability. Although ASDs are known to be highly heritable ( approximately 90%), the underlying genetic determinants are still largely unknown. Here we analysed the genome-wide characteristics of rare (<1% frequency) copy number variation in ASD using dense genotyping arrays. When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for loci previously implicated in either ASD and/or intellectual disability (1.69 fold, P = 3.4 x 10(-4)). Among the CNVs there were numerous de novo and inherited events, sometimes in combination in a given family, implicating many novel ASD genes such as SHANK2, SYNGAP1, DLGAP2 and the X-linked DDX53-PTCHD1 locus. We also discovered an enrichment of CNVs disrupting functional gene sets involved in cellular proliferation, projection and motility, and GTPase/Ras signalling. Our results reveal many new genetic and functional targets in ASD that may lead to final connected pathways.
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| 10. |
- Anney, Richard, et al.
(author)
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Individual common variants exert weak effects on the risk for autism spectrum disorders.
- 2012
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:21, s. 4781-92
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Journal article (peer-reviewed)abstract
- While it is apparent that rare variation can play an important role in the genetic architecture of autism spectrum disorders (ASD), the contribution of common variation to ASD risk is less clear. To produce a more comprehensive picture, we report Stage 2 of the Autism Genome Project genome-wide association study, adding 1301 ASD families and bringing the total to 2705 families analysed (Stages 1 and 2). In addition to evaluating association of individual SNPs, we also sought evidence that common variants, en masse, might affect risk. Despite genotyping over a million SNPs covering the genome, no single SNP shows significant association with ASD or selected phenotypes at a genome-wide level. The SNP that achieves the smallest p-value from secondary analyses is rs1718101. It falls in CNTNAP2, a gene previously implicated in susceptibility for ASD. This SNP also shows modest association with age of word/phrase acquisition in ASD subjects, of interest because features of language development are also associated with other variation in CNTNAP2. By contrast, allele-scores derived from the transmission of common alleles to Stage 1 cases significantly predict case-status in the independent Stage 2 sample. Despite being significant, the variance explained by these allele scores was small (Vm< 1%). Based on results from individual SNPs and their en masse effect on risk, as inferred from the allele-score results, it is reasonable to conclude that common variants affect ASD risk but their individual effects are modest.
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| 11. |
- Casey, Jillian P, et al.
(author)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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In: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Journal article (peer-reviewed)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 12. |
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| 19. |
- Komisopoulos, Georgios, et al.
(author)
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Radiobiologic comparison of helical tomotherapy, intensity modulated radiotherapy, and conformal radiotherapy in treating lung cancer accounting for secondary malignancy risks
- 2014
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In: Medical Dosimetry. - : Elsevier BV. - 0958-3947 .- 1873-4022. ; 39:4, s. 337-347
-
Journal article (peer-reviewed)abstract
- The aim of the present study is to examine the importance of using measures to predict the risk of inducing secondary malignancies in association with the clinical effectiveness of treatment plans in terms of tumor control and normal tissue complication probabilities. This is achieved by using radiobiologic parameters and measures, which may provide a closer association between clinical outcome and treatment delivery. Overall, 4 patients having been treated for lung cancer were examined. For each of them, 3 treatment plans were developed based on the helical tomotherapy (HT), multileaf collimator-based intensity modulated radiation therapy (IMRT), and 3-dimensional conformal radiation therapy (CRT) modalities. The different plans were evaluated using the complication-free tumor control probability (p(t)), the overall probability of injury (p(1)), the overall probability of control/benefit (p(B)), and the biologically effective uniform dose (15). These radiobiologic measures were used to develop dose-response curves (p-D diagram), which can help to evaluate different treatment plans when used in conjunction with standard dosimetric criteria. The risks for secondary malignancies in the heart and the contralateral lung were calculated for the 3 radiation modalities based on the corresponding dose-volume histograms (DVHs) of each patient. Regarding the overall evaluation of the different radiation modalities based on the p(+) index, the average values of the HT, IMRT, and CRT are 67.3%, 61.2%, and 68.2%, respectively. The corresponding average values of p(B) are 75.6%, 70.5%, and 71.0%, respectively, whereas the average values of p(1) are 8.3%, 9.3%, and 2.8%, respectively. Among the organs at risk (OARS), lungs show the highest probabilities for complications, which are 7.1%, 8.0%, and 1.3% for the HT, IMRT, and CRT modalities, respectively. Similarly, the biologically effective prescription doses (D-B) for the HT, IMRT, and CRT modalities are 64.0, 60.9, and 60.8 Gy, respectively. Regarding the risk for secondary cancer, for the heart, the lowest average risk is produced by IMRT (0.10%) compared with the HT (0.17%) and CRT (0.12%) modalities, whereas the 3 radiation modalities show almost equivalent results regarding the contralateral lung (0.8% for HT, 0.9% for IMRT, and 0.9% for CRT). The use of radiobiologic parameters in the evaluation of different treatment plans and estimation of their expected clinical outcome is shown to provide very useful clinical information. The radiobiologic analysis of the response probabilities showed that different radiation modalities appear to be more effective in different patient geometries and target sizes and locations. Furthermore, there is not a clear pattern between the plans that appear to be more effective for the treatment and the risk of secondary malignancy. It seems that radiobiologically based treatment planning taking into account the risk of secondary cancer can be established as an effective clinical tool for a more clinically relevant treatment optimization.
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| 20. |
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| 21. |
- Mavroidis, Panayiotis, et al.
(author)
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Radiobiological and Dosimetric Analysis of Daily Megavoltage CT Registration on Adaptive Radiotherapy with Helical Tomotherapy
- 2011
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In: Technology in Cancer Research & Treatment. - 1533-0346 .- 1533-0338. ; 10:1, s. 1-13
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Journal article (peer-reviewed)abstract
- Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose (<(D)double over bar>) and the complication-free tumor control probability (P.). A new module of the Tomotherapy software (Tomo Therapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P, and <(D)double over bar> concepts and plotting the tissue response probabilities vs. <(D)double over bar> a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P. are 48.5% and 48.9% for a <(D)double over bar>(ITV) of 53.3 Gy. The respective total control probabilities, P(B) are 56.3% and 56.5%, whereas the corresponding total complication probabilities, P(I) are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 53.7% and 45.7% for a <(D)double over bar>(ITV) of 54.7 Gy and 53.8 Gy, respectively. The respective PB values are 53.7% and 45.8%, whereas the corresponding P, values are similar to 0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P. values are 10.9% for a <(D)double over bar>(ITV) of 75.2 Gy and 11.9% for a D(ITV) of 75.4 Gy, respectively. The respective PB values are 14.5% and 15.3%, whereas the corresponding P, values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within +/- 2% in terms of P(+). In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.
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| 22. |
- Poulios, A., et al.
(author)
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Post-Game High Protein Intake May Improve Recovery of Football-Specific Performance during a Congested Game Fixture: Results from the PRO-FOOTBALL Study
- 2018
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In: Nutrients. - : MDPI AG. - 2072-6643. ; 10:4
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Journal article (peer-reviewed)abstract
- The effects of protein supplementation on performance recovery and inflammatory responses during a simulated one-week in-season microcycle with two games (G1, G2) performed three days apart were examined. Twenty football players participated in two trials, receiving either milk protein concentrate (1.15 and 0.26 g/kg on game and training days, respectively) (PRO) or an energy-matched placebo (1.37 and 0.31 g/kg of carbohydrate on game and training days, respectively) (PLA) according to a randomized, repeated-measures, crossover, double-blind design. Each trial included two games and four daily practices. Speed, jump height, isokinetic peak torque, and muscle soreness of knee flexors (KF) and extensors (KE) were measured before G1 and daily thereafter for six days. Blood was drawn before G1 and daily thereafter. Football-specific locomotor activity and heart rate were monitored using GPS technology during games and practices. The two games resulted in reduced speed (by 3-17%), strength of knee flexors (by 12-23%), and jumping performance (by 3-10%) throughout recovery, in both trials. Average heart rate and total distance covered during games remained unchanged in PRO but not in PLA. Moreover, PRO resulted in a change of smaller magnitude in high-intensity running at the end of G2 (75-90 min vs. 0-15 min) compared to PLA (P = 0.012). KE concentric strength demonstrated a more prolonged decline in PLA (days 1 and 2 after G1, P = 0.014-0.018; days 1, 2 and 3 after G2, P = 0.016-0.037) compared to PRO (days 1 after G1, P = 0.013; days 1 and 2 after G2, P = 0.014-0.033) following both games. KF eccentric strength decreased throughout recovery after G1 (PLA: P=0.001-0.047-PRO: P =0.004-0.22) in both trials, whereas after G2 it declined throughout recovery in PLA (P = 0.000-0.013) but only during the first two days (P = 0.000-0.014) in PRO. No treatment effect was observed for delayed onset of muscle soreness, leukocyte counts, and creatine kinase activity. PRO resulted in a faster recovery of protein and lipid peroxidation markers after both games. Reduced glutathione demonstrated a more short-lived reduction after G2 in PRO compared to PLA. In summary, these results provide evidence that protein feeding may more efficiently restore football-specific performance and strength and provide antioxidant protection during a congested game fixture.
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| 28. |
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| 29. |
- Su, F-C, et al.
(author)
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Assessing four-dimensional radiotherapy planning and respiratory motion-induced dose difference based on biologically effective uniform dose.
- 2009
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In: Technology in Cancer Research & Treatment. - : SAGE Publications. - 1533-0346 .- 1533-0338. ; 8:3, s. 187-200
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Journal article (peer-reviewed)abstract
- Four-dimensional (4D) radiotherapy is considered as a feasible and ideal solution to accommodate intra-fractional respiratory motion during conformal radiation therapy. With explicit inclusion of the temporal changes in anatomy during the imaging, planning, and delivery of radiotherapy, 4D treatment planning in principle provides better dose conformity. However, the clinical benefits of developing 4D treatment plans in terms of tumor control rate and normal tissue complication probability as compared to other treatment plans based on CT images of a fixed respiratory phase remains mostly unproven. The aim of our study is to comprehensively evaluate 4D treatment planning for nine lung tumor cases with both physical and biological measures using biologically effective uniform dose (D =) together with complication-free tumor control probability, P+. Based on the examined lung cancer patients and PTV margin applied, we found similar but not identical curves of DVH, and slightly different mean doses in tumor (up to 1.5%) and normal tissue in all cases when comparing 4D, P0%, and P50% plans. When it comes to biological evaluations, we did not observe definitively PTV size dependence in P+ among these nine lung cancer patients with various sizes of PTV. Moreover, it is not necessary that 4D plans would have better target coverage or higher P+ as compared to a fixed phase IMRT plan. However, on the contrary to significant deviations in P+ (up to 14.7%) observed if delivering the IMRT plan made at end-inhalation incorrectly at end-exhalation phase, we estimated the overall P+, PB, and PI for 4D composite plans that have accounted for intra-fractional respiratory motion.
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| 30. |
- Giantsoudi, D., et al.
(author)
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A gEUD-based inverse planning technique for HDR prostate brachytherapy : Feasibility study
- 2013
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In: Medical physics (Lancaster). - : Wiley. - 0094-2405 .- 2473-4209. ; 40:4, s. 041704-
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Journal article (peer-reviewed)abstract
- Purpose: The purpose of this work was to study the feasibility of a new inverse planning technique based on the generalized equivalent uniform dose for image-guided high dose rate (HDR) prostate cancer brachytherapy in comparison to conventional dose-volume based optimization. Methods: The quality of 12 clinical HDR brachytherapy implants for prostate utilizing HIPO (Hybrid Inverse Planning Optimization) is compared with alternative plans, which were produced through inverse planning using the generalized equivalent uniform dose (gEUD). All the common dose-volume indices for the prostate and the organs at risk were considered together with radiobiological measures. The clinical effectiveness of the different dose distributions was investigated by comparing dose volume histogram and gEUD evaluators. Results: Our results demonstrate the feasibility of gEUD-based inverse planning in HDR brachytherapy implants for prostate. A statistically significant decrease in D-10 or/and final gEUD values for the organs at risk (urethra, bladder, and rectum) was found while improving dose homogeneity or dose conformity of the target volume. Conclusions: Following the promising results of gEUD-based optimization in intensity modulated radiation therapy treatment optimization, as reported in the literature, the implementation of a similar model in HDR brachytherapy treatment plan optimization is suggested by this study. The potential of improved sparing of organs at risk was shown for various gEUD-based optimization parameter protocols, which indicates the ability of this method to adapt to the user's preferences.
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| 43. |
- Mavroidis, Panayiotis, et al.
(author)
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Comparing the Expected Effectiveness of Helical Tomotherapy and MLC-Based IMRT Using Biological Measures
- 2007
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In: Proceedings in 49th AAPM Annual Meeting, Minneapolis, Minnesota, USA, July 22-26, 2007.
-
Conference paper (other academic/artistic)abstract
- Purpose: Presently, the radiobiological parameters of the different tumours and normal tissues are typically not taken into account during dose prescription and optimization of a treatment plan. In this study, to investigate a more comprehensive treatment plan evaluation, the biologically effective uniform dose () is applied together with the complication-free tumour control probability (P+).Material and Methods: Three different cancer types at different anatomical sites were investigated: head & neck, lung and prostate cancers. For each cancer type, a linac MLC-based step-and-shoot IMRT plan and a Helical Tomotherapy plan were developed. By using as the common prescription point of the treatment plans and plotting the tissue response probabilities vs. for a range of prescription doses, a number of plan trials can be compared based on radiobiological measures.Results: The applied plan evaluation method shows that in the head & neck cancer case the HT treatment gives better results than the MLC-based IMRT (P+ of 62.2% and 46.0%, to the internal target volume (ITV) of 72.3Gy and 70.7Gy, respectively). In the lung cancer and prostate cancer cases, the MLC-based IMRT plans are better. For the lung cancer case, the HT and MLC-based IMRT plans give a P+ of 66.9% and 72.9%, to the ITV of 64.0Gy and 66.9Gy, respectively. Similarly, for the prostate cancer case, the two radiation modalities give a P+ of 68.7% and 72.2%, to the ITV of 86.0Gy and 85.9Gy, respectively.Discussion and Conclusions: Both MLC based-IMRT and HT can encompass the often large ITV required while they minimize the volume of the organs at risk receiving high dose. There may exist clinical cases, which may look dosimetrically similar but in radiobiological terms may be quite different. In such situations, traditional dose based evaluation tools can be complemented by the use of P+ − diagrams to compare treatment plans.
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| 44. |
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| 45. |
- Mavroidis, P., et al.
(author)
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Comparison of the 3D-conformal, helical tomotherapy and multileaf collimators-based intensity modulated radiotherapy modalities using radiobiological measures
- 2008
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In: JOURNAL OF BUON. - 1107-0625. ; 13:1, s. 75-86
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Journal article (peer-reviewed)abstract
- Purpose: Intensity modulated radiotherapy (IMRT) using multileaf collimators (MLC) and helical tomotherapy (HT) have become increasingly popular over the past few years. However their clinical efficacy and effectiveness continue to be investigated. In order to provide a more thorough evaluation and comparison of treatment plans, the utilization of the biologically effective uniform dose (D) together with the complication-free tumor control probability (P+) are examined. Materials and methods:In this study, a typical case of lung cancer was investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and a HT plan. The 3 different treatment plans were compared based on radiobiological measures by using the P+ index and the D concept as the common prescription point of the plans and plotting the tissue response probabilities vs. D for a range of prescription doses. Results: The applied plan evaluation method showed that in this lung cancer case the MLC-based IMRT plan was best over the clinically useful dose prescription range. The 3D-conformal, MLC-based IMRT and HT treatment plans gave a P+ of 55.4%, 72.9% and 66.9%, for a D to the internal target volume (ITV) of 57.0 Gy, 66.9 Gy and 64.0 Gy, respectively. Conclusion: In comparison to 3D conformal radiotherapy, both Affi based-IMRT and HT can better encompass the often large ITV required while minimizing the volume of the organs at risk receiving high dose. Taking into account the dose-response relations of the irradiated tumors and normal tissues, a radiobiological treatment plan evaluation can be performed, which may provide a closer association of the delivered treatment with the clinical outcome.
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| 46. |
- Mavroidis, Panayiotis, et al.
(author)
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Comparison of the helical tomotherapy against the multileaf collimator-based intensity-modulated radiotherapy and 3D conformal radiation modalities in lung cancer radiotherapy
- 2011
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In: British Journal of Radiology. - : British Institute of Radiology. - 0007-1285 .- 1748-880X. ; 84:998, s. 161-172
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Journal article (peer-reviewed)abstract
- Objectives: The aim of this study was to compare three-dimensional (3D) conformal radiotherapy and the two different forms of IMRT in lung cancer radiotherapy. Methods: Cases of four lung cancer patients were investigated by developing a 3D conformal treatment plan, a linac MLC-based step-and-shoot IMRT plan and an HT plan for each case. With the use of the complication-free tumour control probability (P(+)) index and the uniform dose concept as the common prescription point of the plans, the different treatment plans were compared based on radiobiological measures. Results: The applied plan evaluation method shows the MLC-based IMRT and the HT treatment plans are almost equivalent over the clinically useful dose prescription range; however, the 3D conformal plan inferior. At the optimal dose levels, the 3D conformal treatment plans give an average P(+) of 48.1% for a effective uniform dose to the internal target volume (ITV) of 62.4 Gy, whereas the corresponding MLC-based IMRT treatment plans are more effective by an average Delta P(+) of 27.0% for a D effective uniform dose of 16.3 Gy. Similarly, the HT treatment plans are more effective than the 3D-conformal plans by an average Delta P(+) of 23.8% for a Delta effective uniform dose of 11.6 Gy. Conclusion: A radiobiological treatment plan evaluation can provide a closer association of the delivered treatment with the clinical outcome by taking into account the dose-response relations of the irradiated tumours and normal tissues. The use of P - effective uniform dose diagrams can complement the traditional tools of evaluation to compare and effectively evaluate different treatment plans.
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| 47. |
- Mavroidis, Panayiotis, et al.
(author)
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Consequences of anorectal cancer atlas implementation in the cooperative group setting : Radiobiologic analysis of a prospective randomized in silico target delineation study
- 2014
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 112:3, s. 418-424
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Journal article (peer-reviewed)abstract
- Purpose: The aim of this study is to ascertain the subsequent radiobiological impact of using a consensus guideline target volume delineation atlas.Materials and methods: Using a representative case and target volume delineation instructions derived from a proposed IMRT rectal cancer clinical trial, gross tumor volume (GTV) and clinical/planning target volumes (CTV/PTV) were contoured by 13 physician observers (Phase 1). The observers were then randomly assigned to follow (atlas) or not-follow (control) a consensus guideline/atlas for anorectal cancers, and instructed to re-contour the same case (Phase 2).Results: The atlas group was found to have increased tumor control probability (TCP) after the atlas intervention for both the CTV (p < 0.0001) and PTV1 (p = 0.0011) with decreasing normal tissue complication probability (NTCP) for small intestine, while the control group did not. Additionally, the atlas group had reduced variance in TCP for all target volumes and reduced variance in NTCP for the bowel. In Phase 2, the atlas group had increased TCP relative to the control for CTV (p = 0.03).Conclusions: Visual atlas and consensus treatment guideline usage in the development of rectal cancer IMRT treatment plans reduced the inter-observer radiobiological variation, with clinically relevant TCP alteration for CTV and PTV volumes.
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| 48. |
- Mavroidis, Panayiotis, et al.
(author)
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Expected Clinical Impact of the Differences Between Planned and Delivered IMRT Dose Distributions
- 2007
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In: Proceedings in 49th AAPM Annual Meeting, Minneapolis, Minnesota, USA, July 22-26, 2007. - : Wiley.
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Conference paper (other academic/artistic)abstract
- Purpose: Due to the highly conformal distributions that can be obtained with intensity modulated radiation therapy (IMRT), any discrepancy between the intended and delivered distributions would likely affect the clinical outcome. Consequently, there is a need for a measure that would quantify those differences in terms of a change in the expected clinical outcome.Material and Methods: To evaluate such a measure, the case of a cervix cancer was used where the bladder and rectum, are proximal and partially overlapping with the internal target volume. A solid phantom simulating the pelvic anatomy was fabricated and a treatment plan was developed to deliver the prescribed dose to the phantom. The phantom was then irradiated with films positioned in several transverse planes. The racetrack microtron at 50MV was used in the treatment planning and delivery processes. The dose distribution delivered was analyzed based on the film measurements and compared against the treatment plan. The differences in the measurements were evaluated using both physical and biological criteria.Results: For the computerized treatment plan, the maximum value of P+ was 84.1%, for a mean dose to the ITV of = 93.3Gy, associated relative standard deviation D/ = 16.8% and biologically effective uniform dose, ITV of 89.2 Gy. The delivered dose distribution from all the beams produced a P+ value of 77.0% for ITV = 93.2Gy, D/ = 19.0% and ITV of 83.5 Gy.Discussion and Conclusions: Whereas the physical comparison of dose distributions can assess the geometric accuracy of delivery, it does not reflect the clinical impact of any measured dose discrepancies. With highly conformal IMRT, the accuracy of the patient setup and treatment delivery, are critical for the success of the treatment. A method is proposed to evaluate the precision of the delivered plan based on changes in complication and control rates as they relate to uncertainties in dose delivery.
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| 49. |
- Mavroidis, P, et al.
(author)
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Radiobiological and dosimetric analysis of daily megavoltage CT registration on adaptive radiotherapy with Helical Tomotherapy
- 2011
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In: Technology in cancer research & treatment. - : SAGE Publications. - 1533-0338 .- 1533-0346. ; 10:1, s. 1-13
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Journal article (peer-reviewed)abstract
- Pre-treatment patient repositioning in highly conformal image-guided radiation therapy modalities is a prerequisite for reducing setup uncertainties. In Helical Tomotherapy (HT) treatment, a megavoltage CT (MVCT) image is usually acquired to evaluate daily changes in the patient's internal anatomy and setup position. This MVCT image is subsequently compared to the kilovoltage CT (kVCT) study that was used for dosimetric planning, by applying a registration process. This study aims at investigating the expected effect of patient setup correction using the Hi-Art tomotherapy system by employing radiobiological measures such as the biologically effective uniform dose ([Formula: see text]) and the complication-free tumor control probability ( P+). A new module of the Tomotherapy software (TomoTherapy, Inc, Madison, WI) called Planned Adaptive is employed in this study. In this process the delivered dose can be calculated by using the sinogram for each delivered fraction and the registered MVCT image set that corresponds to the patient's position and anatomical distribution for that fraction. In this study, patients treated for lung, pancreas and prostate carcinomas are evaluated by this method. For each cancer type, a Helical Tomotherapy plan was developed. In each cancer case, two dose distributions were calculated using the MVCT image sets before and after the patient setup correction. The fractional dose distributions were added and renormalized to the total number of fractions planned. The dosimetric and radiobiological differences of the dose distributions with and without patient setup correction were calculated. By using common statistical measures of the dose distributions and the P+ and [Formula: see text] concepts and plotting the tissue response probabilities vs. [Formula: see text] a more comprehensive comparison was performed based on radiobiological measures. For the lung cancer case, at the clinically prescribed dose levels of the dose distributions, with and without patient setup correction, the complication-free tumor control probabilities, P+ are 48.5% and 48.9% for a [Formula: see text] of 53.3 Gy. The respective total control probabilities, PB are 56.3% and 56.5%, whereas the corresponding total complication probabilities, PI are 7.9% and 7.5%. For the pancreas cancer case, at the prescribed dose levels of the two dose distributions, the P+ values are 53.7% and 45.7% for a [Formula: see text] of 54.7 Gy and 53.8 Gy, respectively. The respective PB values are 53.7% and 45.8%, whereas the corresponding PI values are ~0.0% and 0.1%. For the prostate cancer case, at the prescribed dose levels of the two dose distributions, the P+ values are 10.9% for a [Formula: see text] of 75.2 Gy and 11.9% for a [Formula: see text] of 75.4 Gy, respectively. The respective PB values are 14.5% and 15.3%, whereas the corresponding PI values are 3.6% and 3.4%. Our analysis showed that the very good daily patient setup and dose delivery were very close to the intended ones. With the exception of the pancreas cancer case, the deviations observed between the dose distributions with and without patient setup correction were within ±2% in terms of P+. In the radiobiologically optimized dose distributions, the role of patient setup correction using MVCT images could appear to be more important than in the cases of dosimetrically optimized treatment plans were the individual tissue radiosensitivities are not precisely considered.
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| 50. |
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