What is an acceptably smoothed fluence? Dosimetric and delivery considerations for dynamic sliding window IMRT

<p>Abstract</p> <p>Background</p> <p>The study summarised in this report aimed to investigate the interplay between fluence complexity, dose calculation algorithms, dose calculation spatial resolution and delivery characteristics (monitor units, effective field width and dose delivery against dose prediction agreement) was investigated. A sample set of complex planning cases was selected and tested using a commercial treatment planning system capable of inverse optimisation and equipped with tools to tune fluence smoothness.</p> <p>Methods</p> <p>A set of increasingly smoothed fluence patterns was correlated to a generalised expression of the Modulation Index (MI) concept, in nature independent from the specific planning system used that could therefore be recommended as a predictor to score fluence "quality" at a very early stage of the IMRT QA process. Fluence complexity was also correlated to delivery accuracy and characteristics in terms of number of MU, dynamic window width and agreement between calculation and measurement (expressed as percentage of field area with a <it>γ </it>> 1 (%FA)) when comparing calculated vs. delivered modulated dose maps. Different resolutions of the calculation grid and different photon dose algorithms (pencil beam and anisotropic analytical algorithm) were used for the investigations.</p> <p>Results and Conclusion</p> <p>i) MI can be used as a reliable parameter to test different approaches/algorithms to smooth fluences implemented in a TPS, and to identify the preferable default values for the smoothing parameters if appropriate tools are implemented; ii) a MI threshold set at MI < 19 could ensure that the planned beams are safely and accurately delivered within stringent quality criteria; iii) a reduction in fluence complexity is strictly correlated to a corresponding reduction in MUs, as well as to a decrease of the average sliding window width (for dynamic IMRT delivery); iv) a smoother fluence results in a reduction of dose in the healthy tissue with a potentially relevant clinical benefit; v) increasing the smoothing parameter s, MI decreases with %FA: fluence complexity has a significant impact on the accuracy of delivery and the agreement between calculation and measurements improves with the advanced algorithms.</p

Neo-adjuvant chemo-radiation of rectal cancer with Volumetric Modulated Arc Therapy: summary of technical and dosimetric features and early clinical experience

<p>Abstract</p> <p>Background</p> <p>To report about initial technical and clinical experience in preoperative radiation treatment of rectal cancer with volumetric modulated arcs with the RapidArc^®(RA) technology.</p> <p>Methods</p> <p>Twenty-five consecutive patients (pts) were treated with RA. All showed locally advanced rectal adenocarcinoma with stage T2-T4, N0-1. Dose prescription was 44 Gy in 22 fractions (or 45 Gy in 25 fractions). Delivery was performed with single arc with a 6 MV photon beam. Twenty patients were treated preoperatively, five did not receive surgery. Twenty-three patients received concomitant chemotherapy with oral capecitabine. A comparison with a cohort of twenty patients with similar characteristics treated with conformal therapy (3DC) is presented as well.</p> <p>Results</p> <p>From a dosimetric point of view, RA improved conformality of doses (CI_95%= 1.1 vs. 1.4 for RA and 3DC), presented similar target coverage with lower maximum doses, significant sparing of femurs and significant reduction of integral and mean dose to healthy tissue. From the clinical point of view, surgical reports resulted in a down-staging in 41% of cases. Acute toxicity was limited to Grade 1-2 diarrhoea in 40% and Grade 3 in 8% of RA pts, 45% and 5% of 3DC pts, compatible with known effects of concomitant chemotherapy. RA treatments were performed with an average of 2.0 vs. 3.4 min of 3DC.</p> <p>Conclusion</p> <p>RA proved to be a safe, qualitatively advantageous treatment modality for rectal cancer, showing some improved results in dosimetric aspects.</p

Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy

<p>Abstract</p> <p>Background</p> <p>To report about initial clinical experience in radiation treatment of carcinoma of prostate with volumetric modulated arcs with the RapidArc (RA) technology.</p> <p>Methods</p> <p>Forty-five patients with a median age of 72 ± 3, affected by prostate carcinoma (T1c: 22 patients, T2a-b: 17 patients, T3a-b: 6 patients. N0: 43 patients, N1-Nx: 2 patients, all M0), with initial PSA of 10.0 ± 3.0 ng/mL, were treated with RapidArc in a feasibility study. All patients were treated with single arc using 6MV photons. Dose prescription ranged between 76 (7 patients) and 78 Gy (38 patients) in 2Gy/fraction. Plan quality was assessed by means of Dose Volume Histogram (DVH) analysis. Technical parameters of arcs and pre-treatment quality assurance results (Gamma Agreement Index, GAI) are reported to describe delivery features. Early toxicity was scored (according to the Common Terminology Criteria of Adverse Effects scale, CTCAE, scale) at the end of treatment together with biochemical outcome (PSA).</p> <p>Results</p> <p>From DVH data, target coverage was fulfilling planning objectives: V_95%was in average higher than 98% and V_107%~0.0% (D_2%~104.0% in average). Homogeneity D_5%-D_95%ranged between 6.2 ± 1.0% to 6.7 ± 1.3%. For rectum, all planning objectives were largely met (e.g. V_70Gy= 10.7 ± 5.5% against an objective of < 25%) similarly for bladder (e.g. D_2%= 79.4 ± 1.2Gy against an objective of 80.0Gy). Maximum dose to femurs was D_2%= 36.7 ± 5.4Gy against an objective of 47Gy. Monitor Units resulted: MU/Gy = 239 ± 37. Average beam on time was 1.24 ± 0.0 minutes. Pre-treatment GAI resulted in 98.1 ± 1.1%. Clinical data were recorded as PSA at 6 weeks after RT, with median values of 0.4 ± 0.4 ng/mL. Concerning acute toxicity, no patient showed grade 2-3 rectal toxicity; 5/42 (12%) patients experienced grade 2 dysuria; 18/41 (44%) patients preserved complete or partial erectile function.</p> <p>Conclusion</p> <p>RapidArc proved to be a safe, qualitative and advantageous treatment modality for prostate cancer.</p

Hippocampus avoidance with fan beam and volumetric arc radiotherapy for base of skull tumours

Radiosensitive neurogenic stem cells reside in the hippocampi, suggesting that avoidance of the hippocampi may be an important strategy to reduce potential radiation-related cognitive effects. Six patients treated for base of skull tumours were re-planned using co-planar helical fan beam arc therapy (tomotherapy) and co-planar and non-coplanar volumetric arc techniques (RapidArc). The hippocampi were contoured as avoidance structures with the specific goal of minimising the dose. Two gross target volume (GTV) to planning target volume (PTV) expansions (10 and 2 mm) were considered to evaluate the impact of margin selection on organ at risk (OAR) sparing. The dose prescription was 50 Gy to >95% of the PTV. Comparison of the hippocampus avoidance plans demonstrated the importance of non-coplanar delivery when the 10 mm margin was used. With the 2 mm margin, both co-planar and non-coplanar delivery provided similar degrees of sparing. A mean dose of 3-4 Gy and a V6Gy <5% to the hippocampi was realised with the hippocampus sparing techniques. Our comparisons suggest interventions to minimise GTV to PTV margins will have a more profound influence on multiple OAR sparing than the choice of intensity modulated arc delivery techniqu

The Mucosae-Associated Epithelial Chemokine (MEC/CCL28) Modulates Immunity in HIV Infection

BACKGROUND. CCL28 (MEC) binds to CCR3 and CCR10 and recruits IgA-secreting plasma cells (IgA-ASC) in the mucosal lamina propria (MLP). Mucosal HIV-specific IgA are detected in HIV-infection and exposure. The CCL28 circuit was analyzed in HIV-infected and-exposed individuals and in HIV-unexposed controls; the effect of CCL28 administration on gastrointestinal MLP IgA-ASC was verified in a mouse model. METHODOLOGY/FINDINGS. CCL28 was augmented in breast milk (BM) plasma and saliva of HIV-infected and –exposed individuals; CCR3+ and CCR10+ B lymphocytes were increased in these same individuals. Additionally: 1) CCL28 concentration in BM was associated with longer survival in HIV vertically-infected children; and 2) gastro-intestinal mucosal IgA-ASC were significantly increased in VSV-immunized mice receiving CCL28. CONCLUSIONS. CCL28 mediates mucosal immunity in HIV exposure and infection. CCL28-including constructs should be considered in mucosal vaccines to prevent HIV infection of the gastro-intestinal MLP via modulation of IgA-ASC.Istituto Superiore di Sanita' "Programma Nazionale di Ricerca sull' AIDS"; DG Right to Health and Solidarity Policy; EMPRO and AVIP EC WP6 Projects; Japan Health Science Foundation; National Institutes of Child Health and Human Development (HD 39611, HD 40777

Clinical evidence continuous medical education: a randomised educational trial of an open access e-learning program for transferring evidence-based information – ICEKUBE (Italian Clinical Evidence Knowledge Utilization Behaviour Evaluation) – study protocol

<p>Abstract</p> <p>Background</p> <p>In an effort to ensure that all physicians have access to valid and reliable evidence on drug effectiveness, the Italian Drug Agency sponsored a free-access e-learning system, based on <it>Clinical Evidence</it>, called ECCE. Doctors have access to an electronic version and related clinical vignettes. Correct answers to the interactive vignettes provide Continuing Medical Education credits. The aims of this trial are to establish whether the e-learning program (ECCE) increases physicians' basic knowledge about common clinical scenarios, and whether ECCE is superior to the passive diffusion of information through the printed version of <it>Clinical Evidence</it>.</p> <p>Design</p> <p>All Italian doctors naïve to ECCE will be randomised to three groups. Group one will have access to ECCE for <it>Clinical Evidence </it>chapters and vignettes lot A and will provide control data for <it>Clinical Evidence </it>chapters and vignettes lot B; group two vice versa; group three will receive the concise printed version of <it>Clinical Evidence</it>. There are in fact two designs: a before and after pragmatic trial utilising a two by two incomplete block design (group one versus group two) and a classical design (group one and two versus group three). The primary outcome will be the retention of <it>Clinical Evidence </it>contents assessed from the scores for clinical vignettes selected from ECCE at least six months after the intervention. To avoid test-retest effects, we will randomly select vignettes out of lot A and lot B, avoiding repetitions. In order to preserve the comparability of lots, we will select vignettes with similar, optimal psychometric characteristics.</p> <p>Trial registration</p> <p>ISRCTN27453314</p

On the performances of different IMRT treatment planning systems for selected paediatric cases

BACKGROUND: To evaluate the performance of seven different TPS (Treatment Planning Systems: Corvus, Eclipse, Hyperion, KonRad, Oncentra Masterplan, Pinnacle and PrecisePLAN) when intensity modulated (IMRT) plans are designed for paediatric tumours. METHODS: Datasets (CT images and volumes of interest) of four patients were used to design IMRT plans. The tumour types were: one extraosseous, intrathoracic Ewing Sarcoma; one mediastinal Rhabdomyosarcoma; one metastatic Rhabdomyosarcoma of the anus; one Wilm's tumour of the left kidney with multiple liver metastases. Prescribed doses ranged from 18 to 54.4 Gy. To minimise variability, the same beam geometry and clinical goals were imposed on all systems for every patient. Results were analysed in terms of dose distributions and dose volume histograms. RESULTS: For all patients, IMRT plans lead to acceptable treatments in terms of conformal avoidance since most of the dose objectives for Organs At Risk (OARs) were met, and the Conformity Index (averaged over all TPS and patients) ranged from 1.14 to 1.58 on primary target volumes and from 1.07 to 1.37 on boost volumes. The healthy tissue involvement was measured in terms of several parameters, and the average mean dose ranged from 4.6 to 13.7 Gy. A global scoring method was developed to evaluate plans according to their degree of success in meeting dose objectives (lower scores are better than higher ones). For OARs the range of scores was between 0.75 ± 0.15 (Eclipse) to 0.92 ± 0.18 (Pinnacle(3 )with physical optimisation). For target volumes, the score ranged from 0.05 ± 0.05 (Pinnacle(3 )with physical optimisation) to 0.16 ± 0.07 (Corvus). CONCLUSION: A set of complex paediatric cases presented a variety of individual treatment planning challenges. Despite the large spread of results, inverse planning systems offer promising results for IMRT delivery, hence widening the treatment strategies for this very sensitive class of patients