Testing the portal imager GLAaS algorithm for machine quality assurance

<p>Abstract</p> <p>Background</p> <p>To report about enhancements introduced in the GLAaS calibration method to convert raw portal imaging images into absolute dose matrices and to report about application of GLAaS to routine radiation tests for linac quality assurance procedures programmes.</p> <p>Methods</p> <p>Two characteristic effects limiting the general applicability of portal imaging based dosimetry are the over-flattening of images (eliminating the "horns" and "holes" in the beam profiles induced by the presence of flattening filters) and the excess of backscattered radiation originated by the detector robotic arm supports. These two effects were corrected for in the new version of GLAaS formalism and results are presented to prove the improvements for different beams, detectors and support arms. GLAaS was also tested for independence from dose rate (fundamental to measure dynamic wedges).</p> <p>With the new corrections, it is possible to use GLAaS to perform standard tasks of linac quality assurance. Data were acquired to analyse open and wedged fields (mechanical and dynamic) in terms of output factors, MU/Gy, wedge factors, profile penumbrae, symmetry and homogeneity. In addition also 2D Gamma Evaluation was applied to measurement to expand the standard QA methods. GLAaS based data were compared against calculations on the treatment planning system (the Varian Eclipse) and against ion chamber measurements as consolidated benchmark. Measurements were performed mostly on 6 MV beams from Varian linacs. Detectors were the PV-as500/IAS2 and the PV-as1000/IAS3 equipped with either the robotic R- or Exact- arms.</p> <p>Results</p> <p>Corrections for flattening filter and arm backscattering were successfully tested. Percentage difference between PV-GLAaS measurements and Eclipse calculations relative doses at the 80% of the field size, for square and rectangular fields larger than 5 × 5 cm²showed a maximum range variation of -1.4%, + 1.7% with a mean variation of <0.5%. For output factors, average percentage difference between GLAaS and Eclipse (or ion chamber) data was -0.4 ± 0.7 (-0.2 ± 0.4) respectively on square fields. Minimum, maximum and average percentage difference between GLAaS and Eclipse (or ion chamber) data in the flattened field region were: 0.1 ± 1.0, 0.7 ± 0.8, 0.1 ± 0.4 (1.0 ± 1.4, -0.3 ± 0.2, -0.1 ± 0.2) respectively. Similar minimal deviations were observed for flatness and symmetry.</p> <p>For Dynamic wedges, percentage difference of MU/Gy between GLAaS and Eclipse (or ion chamber) was: -1.1 ± 1.6 (0.4 ± 0.7). Minimum, maximum and average percentage difference between GLAaS and Eclipse (or ion chamber) data in the flattened field region were: 0.4 ± 1.6, -1.5 ± 1.8, -0.1 ± 0.3 (-2.2 ± 2.3, 2.3 ± 1.2, 0.8 ± 0.3) respectively.</p> <p>For mechanical wedges differences of transmission factors were <1.6% (Eclipse) and <1.1% (ion chamber) for all wedges. Minimum, maximum and average percentage difference between GLAaS and Eclipse (or ion chamber) data in the flattened field region were: -1.3 ± 0.7, -0.7 ± 0.7, -0.2 ± 0.2 (-0.8 ± 0.8, 0.7 ± 1.1, 0.2 ± 0.3) respectively.</p> <p>Conclusion</p> <p>GLAaS includes now efficient methods to correct for missing "horns" and "holes" induced by flattening filter in the beam and to compensate for excessive backscattering from the support arm. These enhancements allowed to use GLAaS based dosimetric measurement to perform standard tasks of Linac quality assurance with reliable and consistent results. This fast method could be applied to routine practice being also fast in usage and because it allows the introduction of new analysis tools in routine QA by means, e.g., of the Gamma Index analysis.</p

A systems biology approach to investigate the mechanism of action of trabectedin in a model of myelomonocytic leukemia

This study was designed to investigate the mode of action of trabectedin in myelomonocytic leukemia cells by applying systems biology approaches to mine gene expression profiling data and pharmacological assessment of the cellular effects. Significant enrichment was found in regulons of target genes inferred for specific transcription factors, among which MAFB was the most upregulated after treatment and was central in the transcriptional network likely to be relevant for the specific therapeutic effects of trabectedin against myelomonocytic cells. Using the Connectivity Map, similarity among transcriptional signatures elicited by treatment with different compounds was investigated, showing a high degree of similarity between transcriptional signatures of trabectedin and those of the topoisomerase I inhibitor, irinotecan, and an anti-dopaminergic antagonist, thioridazine. The study highlights the potential importance of systems biology approaches to generate new hypotheses that are experimentally testable to define the specificity of the mechanism of action of drugs.The Pharmacogenomics Journal advance online publication, 13 December 2016; doi:10.1038/tpj.2016.76

FusionArc optimization: A hybrid volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT) planning strategy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134837/1/mp8153.pd

Characterization of a new trabectedin-resistant myxoid liposarcoma cell line that shows collateral sensitivity to methylating agents

Myxoid Liposarcomas (MLS), characterized by the expression of FUS-CHOP fusion gene are clinically very sensitive to the DNA binding antitumor agent, trabectedin. However, resistance eventually occurs, preventing disease eradication. To investigate the mechanisms of resistance, a trabectedin resistant cell line, 402-91/ET, was developed. The resistance to trabectedin was not related to the expression of MDR related proteins, uptake/efflux of trabectedin or GSH levels that were similar in parental and resistant cells. The 402-91/ET cells were hypersensitive to UV light because of a nucleotide excision repair defect: XPG complementation decreased sensitivity to UV rays, but only partially to trabectedin. 402-91/ET cells showed collateral sensitivity to temozolomide due to the lack of O(6) -methylguanine-DNA-methyltransferase (MGMT) activity, related to the hypermethylation of MGMT promoter. In 402-91 cells chromatin immunoprecipitation (ChIP) assays showed that FUS-CHOP was bound to the PTX3 and FN1 gene promoters, as previously described, and trabectedin caused FUS-CHOP detachment from DNA. Here we report that, in contrast, in 402-91/ET cells, FUS-CHOP was not bound to these promoters. Differences in the modulation of transcription of genes involved in different pathways including signal transduction, apoptosis and stress response between the two cell lines were found. Trabectedin activates the transcription of genes involved in the adipogenic-program such as c/EBPα and β, in 402-91 but not in 402-91/ET cell lines. The collateral sensitivity of 402-91/ET to temozolomide provides the rationale to investigate the potential use of methylating agents in MLS patients resistant to trabectedin

Health-related quality of life in patients with primary open-angle glaucoma. An italian multicentre observational study

PurposeAs a progressive condition, glaucoma may impair health-related quality of life (HRQoL), due to vision loss and other factors. This study evaluated HRQoL in a cohort of patients treated for primary open-angle glaucoma (POAG) and assessed its association with clinical features. MethodsThis was an Italian, multicentre, cross-sectional, observational study with the subgroup of newly diagnosed patients with POAG prospectively followed up for one year. Patients with previous or new diagnosis (or strong clinical suspicion) of POAG aged >18years were considered eligible. Information was collected on demographic characteristics, medical history, clinical presentation and POAG treatments. HRQoL was measured using the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and Glaucoma Symptom Scale (GSS). Subscale and total scores were obtained and a Pearson correlation coefficient between instruments' scores calculated. ResultsA total of 3227 patients were enrolled from 2012 to 2013 and 3169 were analysed. Mean age was 66.9years. A total of 93.8% had a previous diagnosis (median duration: 8.0years). Median values for mean deviation and pattern standard deviation were 3.9 and 3.6 dB, respectively. Mean scores on most subscales of the NEI-VFQ-25 exceeded 75.0 and mean GSS subscale scores ranged between 70.8 and 79.7 (with a total mean score of 74.8). HRQoL scores on both scales were significantly inversely associated with POAG severity. ConclusionIn this large sample of Italians treated for POAG, disease severity was limited and HRQoL scores were high. QoL decreased with advancing disease severity. These findings confirm the role of vision loss in impairing QoL in POAG, underlying the importance of timely detection and appropriate treatment

Everolimus (EVE) and exemestane (EXE) in patients with advanced breast cancer aged 65 65 years: New lessons for clinical practice from the EVA study

BACKGROUND: The present analysis focuses on real-world data of Everolimus-Exemestane in advanced HR+ve, HER2-ve elderly breast cancer patients (aged 65 years) included in the EVA study, with unique findings in those aged 70 years. METHODS: Data are collected from clinical records and analysed according to age cut-off (< 65 years; 65 - 69 years and {greater than or equal to} 70 years). Relationship of analyzed variables with response were tested by mean of a Mantel-Haenszel chi square test. Time to event analysis was described by Kaplan Meier approach and association with baseline characteristics was analysed by stratified log-rank test and proportional hazard model. RESULTS: From July 2013 to December 2015, the EVA study enrolled overall 404 pts. 154 patients out of 404 (38,1%) were aged {greater than or equal to} 65 years, of whom 87 were {greater than or equal to} 70 years. Median duration of EVE treatment was 28.5 weeks (95% CI 19.0 - 33.8) in patients aged 65-69 years and 24,4 weeks (95% CI 19,2 - 33,2) in those aged {greater than or equal to} 70 years. Fewer patients aged 65 years received the highest EVE Dose-Intensity (>7.5 mg/day) in comparison to younger patients (49,6% vs. 66,8%). Grade 3-4 toxicities occurred to 55 patients (35,7%), mainly stomatitis (10,9%), rash (5,8%) and non-infectious pneumonitis (NIP) (3,6%). Some toxicities, such as weight loss and anaemia were peculiarly observed in patients aged {greater than or equal to} 70 years. Five treatment-related deaths were collected (3,2%). CONCLUSIONS: EVE-EXE combination remains one of the potential treatments in HR+ patients also for elderly ones

Dosimetric evaluation of Acuros XB Advanced Dose Calculation algorithm in heterogeneous media

<p>Abstract</p> <p>Background</p> <p>A study was realised to evaluate and determine relative figures of merit of a new algorithm for photon dose calculation when applied to inhomogeneous media.</p> <p>Methods</p> <p>The new Acuros XB algorithm implemented in the Varian Eclipse treatment planning system was compared against a Monte Carlo method (VMC++), and the Analytical Anisotropic Algorithm (AAA). The study was carried out in virtual phantoms characterized by simple geometrical structures. An insert of different material and density was included in a phantom built of skeletal-muscle and HU = 0 (setting "A"): Normal Lung (lung, 0.198 g/cm³); Light Lung (lung, 0.035 g/cm³); Bone (bone, 1.798 g/cm³); another phantom (setting "B") was built of adipose material and including thin layers of bone (1.85 g/cm³), adipose (0.92 g/cm³), cartilage (1.4745 g/cm³), air (0.0012 g/cm³). Investigations were performed for 6 and 15 MV photon beams, and for a large (13 × 13 cm²) and a small (2.8 × 13 cm²) field.</p> <p>Results</p> <p>Results are provided in terms of depth dose curves, transverse profiles and Gamma analysis (3 mm/3% and 2 mm/2% distance to agreement/dose difference criteria) in planes parallel to the beam central axis; Monte Carlo simulations were assumed as reference. Acuros XB gave an average gamma agreement, with a 3 mm/3% criteria, of 100%, 86% and 100% for Normal Lung, Light Lung and Bone settings, respectively, and dose to medium calculations. The same figures were 86%, 11% and 100% for AAA, where only dose rescaled to water calculations are possible.</p> <p>Conclusions</p> <p>In conclusion, Acuros XB algorithm provides a valid and accurate alternative to Monte Carlo calculations for heterogeneity management.</p