End-to-end test for lung SBRT: An Italian multicentric pilot experience.

PURPOSE: Set up a lung SBRT end-to-end (e2e) test and perform a multicentre validation. MATERIAL AND METHODS: A group of medical physicists from four hospitals and the Italian Institute of Ionizing Radiation Metrology designed the present e2e test. One sub-group set up the test, while another tested its feasibility and ease of use. A satisfaction questionnaire was used to collect user feedback. Each participating centre (PC) received the ADAM breathing phantom, a microDiamond detector and radiochromic films. Following the e2e protocol, each PC performed its standard internal procedure for simulating, planning, and irradiating the phantom. Each PC uploaded its planning and treatment delivery data in a shared Google Drive. A single centre analyzed all the data. RESULTS: The e2e test was successfully performed by all PCs. Participants' comments indicated that ADAM was well suited to the purpose and the protocol well described. All PCs performed the test in static and dynamic modes. The ratio between measured and planned point dose obtained by PC1, PC2, PC3, PC4 was: 0.99, 0.96, 1.01 and 1.01 (static track) and 0.99, 1.02, 1.01 and 0.94 (dynamic track). The gamma passing rates (3 % global, 3 mm) between planned and measured dose maps were 98.5 %, 94.0 %, 99.1 % and 94.0 % (static track) and 99.5 %, 96.5 %, 86.0 % and 94.5 % (dynamic track) for PC1, PC2, PC3 and PC4, respectively. CONCLUSIONS: An e2e test for lung SBRT has been proposed and tested in a multicentre framework. The results and user feedback prove the validity of the proposed e2e test.

Improving dose delivery accuracy with EPID in vivo dosimetry: results from a multicenter study.

PURPOSE: To investigate critical aspects and effectiveness of in vivo dosimetry (IVD) tests obtained by an electronic portal imaging device (EPID) in a multicenter and multisystem context. MATERIALS AND METHODS: Eight centers with three commercial systems-SoftDiso (SD, Best Medical Italy, Chianciano, Italy), Dosimetry Check (DC, Math Resolution, LCC), and PerFRACTION (PF, Sun Nuclear Corporation, SNC, Melbourne, FL)-collected IVD results for a total of 2002 patients and 32,276 tests. Data are summarized for IVD software, radiotherapy technique, and anatomical site. Every center reported the number of patients and tests analyzed, and the percentage of tests outside of the tolerance level (OTL%). OTL% was categorized as being due to incorrect patient setup, incorrect use of immobilization devices, incorrect dose computation, anatomical variations, and unknown causes. RESULTS: The three systems use different approaches and customized alert indices, based on local protocols. For Volumetric Modulated Arc Therapy (VMAT) treatments OTL% mean values were up to 8.9% for SD, 18.0% for DC, and 16.0% for PF. Errors due to "anatomical variations" for head and neck were up to 9.0% for SD and DC and 8.0% for PF systems, while for abdomen and pelvis/prostate treatments were up to 9%, 17.0%, and 9.0% for SD, DC, and PF, respectively. The comparison among techniques gave 3% for Stereotactic Body Radiation Therapy, 7.0% (range 4.7-8.9%) for VMAT, 10.4% (range 7.0-12.2%) for Intensity Modulated Radiation Therapy, and 13.2% (range 8.8-21.0%) for 3D Conformal Radiation Therapy. CONCLUSION: The results obtained with different IVD software and among centers were consistent and showed an acceptable homogeneity. EPID IVD was effective in intercepting important errors.

Quality indicators for hyperthermia treatment: Italian survey analysis.

AIM: Nowadays, no Quality Indicators (QI) have been proposed for Hyperthermia treatments. Starting from radiotherapy experience, the aim of this work is to adapt radiotherapy indicators to Hyperthermia and to propose a new specific set of QI in Hyperthermia field. MATERIAL AND METHODS: At first, radiotherapy quality indicators published in literature have been adapted to hyperthermia setting. Moreover, new specific indicators for the treatment of hyperthermia have been defined. To obtain the standard reference values of quality indicators, a questionnaire was sent to 7 Italian hyperthermia Institutes with a list of questions on physical and clinical hyperthermia treatment in order to highlight the different therapeutic approaches. RESULTS: Three structure, five process and two outcome QI were selected. It has been possible to adapt seven indicators from radiotherapy, while three indicators have been defined as new specific indicators for hyperthermia. Average values used as standard reference values have been obtained and proposed. CONCLUSION: The survey performed on 7 Italian centres allowed to derive the standard reference value for each indicator. The proposed indicators are available to be investigated and applied by a larger number of Institutes in which hyperthermia treatment is performed in order to monitor the operational procedures and to confirm or modify the reference standard value derived for each indicator.

Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18F-FDG PET and MRI radiomics features.

PURPOSE: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15-30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. METHODS: Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. RESULTS: In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). CONCLUSIONS: If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Determinants of Deep Gray Matter Atrophy in Multiple Sclerosis: A Multimodal MRI Study.

BACKGROUND AND PURPOSE: Deep gray matter involvement is a consistent feature in multiple sclerosis. The aim of this study was to evaluate the relationship between different deep gray matter alterations and the development of subcortical atrophy, as well as to investigate the possible different substrates of volume loss between phenotypes. MATERIALS AND METHODS: Seventy-seven patients with MS (52 with relapsing-remitting and 25 with progressive MS) and 41 healthy controls were enrolled in this cross-sectional study. MR imaging investigation included volumetric, DTI, PWI and Quantitative Susceptibility Mapping analyses. Deep gray matter structures were automatically segmented to obtain volumes and mean values for each MR imaging metric in the thalamus, caudate, putamen, and globus pallidus. Between-group differences were probed by ANCOVA analyses, while the contribution of different MR imaging metrics to deep gray matter atrophy was investigated via hierarchic multiple linear regression models. RESULTS: Patients with MS showed a multifaceted involvement of the thalamus and basal ganglia, with significant atrophy of all deep gray matter structures (P < .001). In the relapsing-remitting MS group, WM lesion burden proved to be the main contributor to volume loss for all deep gray matter structures (P ≤ .006), with a minor role of local microstructural damage, which, in turn, was the main determinant of deep gray matter atrophy in patients with progressive MS (P ≤ .01), coupled with thalamic susceptibility changes (P = .05). CONCLUSIONS: Our study confirms the diffuse involvement of deep gray matter in MS, demonstrating a different behavior between MS phenotypes, with subcortical GM atrophy mainly determined by global WM lesion burden in patients with relapsing-remitting MS, while local microstructural damage and susceptibility changes mainly accounted for the development of deep gray matter volume loss in patients with progressive MS.

Patient's Peak Skin Dose evaluation using Gafchromic films in interventional cardiology procedures and its correlation with other dose indicators.

OBJECTIVE: Number and complexity of interventional cardiology procedures have increased during last years and can result in patient skin dose high enough to cause deterministic skin effects. The aim of the work is to investigate the correlation between Peak Skin Dose (PSD) and the dosimetric indicators directly registered by the radiological equipment and provide the physicians a tool to identify patients at risk of deterministic effects and include them into a follow-up program. METHODS: PSD was measured in vivo using radiochromic Gafchromic XR-RV3 films, properly calibrated. DAP, Cumulative Dose at the interventional reference point (CD) and exposure time of each procedure were retrieved from the Radiation Dose Structured Reports created by an Allura Clarity Xper FD20 angiographic system. Linear correlation between PSD and both DAP and CD was investigated. RESULTS: 42 interventional cardiology procedures (16 CA and 26 PTCA) were involved in the study. The dosimetric indicators values for PTCA are generally higher than those for CA, due to the different levels of procedure complexity. Mean PSD values were (103 ±â€¯64) and (526 ±â€¯436) mGy for CA and PTCA procedures. For CA, we found strong correlation both between PSD and DAP (r = 0.753) and PSD and CD (r = 0.782). For PTCA, good correlation both for DAP (r = 0.648) and CD (r = 0.649) was found. CONCLUSIONS: DAP and CD show strong correlation with PSD measured with Gafchromic films during interventional procedures. The proposed method allows the physician to estimate patient's PSD from the dosimetric indicators that the radiological equipment display and record at the end of the procedure.

Impact of a rectal and bladder preparation protocol on prostate cancer outcome in patients treated with external beam radiotherapy.

PURPOSE AND OBJECTIVE: To test the hypothesis that a rectal and bladder preparation protocol is associated with an increase in prostate cancer specific survival (PCSS), clinical disease free survival (CDFS) and biochemical disease free survival (BDFS). PATIENTS AND METHODS: From 1999 to 2012, 1080 prostate cancer (PCa) patients were treated with three-dimensional conformal radiotherapy (3DCRT). Of these patients, 761 were treated with an empty rectum and comfortably full bladder (RBP) preparation protocol, while for 319 patients no rectal/bladder preparation (NRBP) protocol was adopted. RESULTS: Compared with NRBP patients, patients with RBP had significantly higher BDFS (64% vs 48% at 10 years, respectively), CDFS (81% vs 70.5% at 10 years, respectively) and PCSS (95% vs 88% at 10 years, respectively) (log-rank test p < 0.001). Multivariate analysis (MVA) indicated for all treated patients and intermediate high-risk patients that the Gleason score (GS) and the rectal and bladder preparation were the most important prognostic factors for PCSS, CDFS and BDFS. With regard to high- and very high-risk patients, GS, RBP, prostate cancer staging and RT dose were predictors of PCSS, CDFS and BDFS in univariate analysis (UVA). CONCLUSION: We found strong evidence that rectal and bladder preparation significantly decreases biochemical and clinical failures and the probability of death from PCa in patients treated without daily image-guided prostate localization, presumably since patients with RBP are able to maintain a reproducibly empty rectum and comfortably full bladder across the whole treatment compared with NRPB patients.

Multiple gut-liver axis abnormalities in children with obesity with and without hepatic involvement.

BACKGROUND: Gut-liver axis (GLA) dysfunction appears to play a role in obesity and obesity-related hepatic complications. OBJECTIVES: This study sought to concurrently explore several GLA components in a paediatric obese population with/without liver disease. METHODS: Thirty-two children (mean age 11.2 years) were enrolled: nine controls with normal weight and 23 patients with obesity (OB+). Of the 23 patients OB(+), 12 had not steatosis (ST-), and 11 had steatosis (ST+) (associated [n = 8] or not [n = 3] with hypertransaminasaemia [ALT +/-]). Subjects were characterized by using auxologic, ultrasonographic and laboratory parameters. A glucose hydrogen breath test was performed to test for small intestinal bacterial overgrowth, a urinary lactulose/mannitol ratio (LMR) was obtained to assess intestinal permeability, and tests for transaminases, blood endogenous ethanol, endotoxin and faecal calprotectin were also conducted. RESULTS: Eleven out of 23 patients OB(+) (p < 0.05) exhibited pathological (>90th percentile of the control group values) LMR, with values paralleling the grade of liver involvement (normal weight < OB[+] < OB[+]ST[+]ALT[-] < OB[+)]ST[+]ALT[+] [p < 0.05]). LMR significantly correlated with ethanolaemia (r = 0.38, p = 0.05) and endotoxaemia (r = 0.48, p = 0.015) concentrations. Increased permeability was a risk factor for the development of steatosis (p < 0.002). SIBO was present only in patients with obesity. Faecal calprotectin concentrations were within normal limits in all subjects. CONCLUSIONS: Increased permeability, endogenous ethanol and systemic endotoxin concentrations reflect some GLA dysfunction in obesity and its hepatic complications. Pending further results to establish their potential causative roles, the modulation of the GLA appears to represent a possible target for the prevention and treatment of these conditions.

Quality indicators in the intensity modulated/image-guided radiotherapy era.

PURPOSE: To propose new Quality Indicators (QIs) for the Intensity Modulated(IMRT)/Image-Guided(IGRT) Radiotherapy techniques. MATERIALS AND METHODS: Two structure, 10 process and 2 outcome QIs were elaborated. A working group including Radiation Oncologist, Medical Physicist and Radiation Technologists was made up. A preliminary set of indicators was selected on the basis of evidenced critical issues; the criteria to identify more relevant and specific QIs for IMRT/IGRT were defined; structure, process and outcome QIs were defined. The elaborated indicators were tested in four Italian Radiotherapy Centers. RESULTS: Fourteen indicators were proposed. Seven indicators were completely new while a new standard is proposed for four indicators based on Validation Centers (VC) data. No change was reported for 3 indicators. The indicators were applied in the four VC. The VC considered were able to respect all indicators except indicator 2 for one Center. DISCUSSION AND CONCLUSION: QIs may provide useful measures of workload and service performances.

NOD-SCID mice irradiation with medical accelerators: Dosimetric and radiobiological results.

PURPOSE: Preclinical studies normally requires dedicated instruments due to the small anatomical scales involved, but the possibility of using clinical devices for this purpose may be of economical, scientific and translational interest. In the present work the accurate description of treatment planning, dosimetric results, radiotoxicity and tumor response of the irradiation of NOD-SCID mice were presented. Two medical linear accelerators, TrueBeam STx and Tomotherapy Hi-ART, were compared. NOD-SCID mice irradiation with Tomotherapy is a novelty, as well as the comparison of different irradiation techniques, devices and dose fractionations. METHODS: Human derived glioblastoma multiforme neurospheres were injected in immunocompromised NOD-SCID mice to establish xenograft models. Mice were anaesthetized and placed in a plexiglas cage pieboth to perform CT scan for treatment planning purposes and for the irradiation. Three fractionation schedules were evaluated: 4Gy/1 fraction, 4Gy/2 fractions and 6Gy/3 fractions. Tomotherapy planning parameters, the presence of a bolus layer and the irradiation time were reported. After irradiation, mice were examined daily and sacrificed when they showed signs of suffering or when tumor volume reached the established endpoint. Outcomes regarding both radiotoxicity and tumor response were evaluated comparing irradiated mice as respect to their controls. RESULTS: Survival analysis showed that Tomotherapy irradiation with 6Gy/3 fractions with a bolus layer prolong mice survival (log-rank test, p<0.02). Tumor volume and mice survival were significantly different in irradiated xenografts as compared to their controls (t-test, p<0.03; log-rank, p<0.05). CONCLUSION: The radiobiological potential of Tomotherapy in inducing tumor growth stabilization is demonstrated.

Red marrow and blood dosimetry in (131)I treatment of metastatic thyroid carcinoma: pre-treatment versus in-therapy results.

Treatment with radioiodine is a standard procedure for patients with well-differentiated thyroid cancer, but the main approach to the therapy is still empiric, consisting of the administration of fixed activities. A predictive individualized dosimetric study may represent an important tool for physicians to determine the best activity to prescribe. The aim of this work is to compare red marrow and blood absorbed dose values obtained in the pre-treatment (PT) dosimetry phase with those obtained in the in-treatment (IT) dosimetry phase in order to estimate the predictive power of PT trial doses and to determine if they can be used as a decision-making tool to safely administer higher (131)I activity to potentially increase the efficacy of treatment. The PT and IT dosimetry for 50 patients has been evaluated using three different dosimetric approaches. In all three approaches blood and red marrow doses, are calculated as the sum of two components, the dose from (131)I activity in the blood and the dose from (131)I activity located in the remainder of the body (i.e. the blood and whole-body contributions to the total dose). PT and IT dose values to blood and red marrow appear to be well correlated irrespective of the dosimetric approach used. Linear regression analyses of PT and IT total doses, for blood and red marrow, and the whole-body contribution to these doses, showed consistent best fit slope and correlation coefficient values of approximately 0.9 and 0.6, respectively: analyses of the blood dose contribution to the total doses also yielded similar values for the best fit slope but with correlation coefficient values of approximately 0.4 reflecting the greater variance in these dose estimates. These findings suggest that pre-treatment red marrow dose assessments may represent an important tool to personalize metastatic thyroid cancer treatment, removing the constraints of a fixed activity approach and permitting potentially more effective higher (131)I activities to be safely used in-treatment.

An Adaptive Thresholding Method for BTV Estimation Incorporating PET Reconstruction Parameters: A Multicenter Study of the Robustness and the Reliability.

OBJECTIVE: The aim of this work was to assess robustness and reliability of an adaptive thresholding algorithm for the biological target volume estimation incorporating reconstruction parameters. METHOD: In a multicenter study, a phantom with spheres of different diameters (6.5-57.4 mm) was filled with (18)F-FDG at different target-to-background ratios (TBR: 2.5-70) and scanned for different acquisition periods (2-5 min). Image reconstruction algorithms were used varying number of iterations and postreconstruction transaxial smoothing. Optimal thresholds (TS) for volume estimation were determined as percentage of the maximum intensity in the cross section area of the spheres. Multiple regression techniques were used to identify relevant predictors of TS. RESULTS: The goodness of the model fit was high (R(2): 0.74-0.92). TBR was the most significant predictor of TS. For all scanners, except the Gemini scanners, FWHM was an independent predictor of TS. Significant differences were observed between scanners of different models, but not between different scanners of the same model. The shrinkage on cross validation was small and indicative of excellent reliability of model estimation. CONCLUSIONS: Incorporation of postreconstruction filtering FWHM in an adaptive thresholding algorithm for the BTV estimation allows obtaining a robust and reliable method to be applied to a variety of different scanners, without scanner-specific individual calibration.

Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness.

To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean); -0.522, 0.821 (median); -0.569, 0.854 (10th percentile); -0.556, 0.854 (25th percentile); -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

Comparison of mathematical models for red marrow and blood absorbed dose estimation in the radioiodine treatment of advanced differentiated thyroid carcinoma.

Metastatic and recurrent differentiated thyroid carcinoma is preferably treated with (131)I, whose administered activity is limited by red marrow (RM) toxicity, originally correlated by Benua to a blood absorbed dose higher than 2 Gy. Afterward a variety of dosimetric approaches has been proposed. The aim of this work is to compare the results of the Benua formula with the ones of other three blood and RM absorbed dose formulae. Materials and methods have been borrowed by the dosimetric protocol of the Italian Internal Dosimetry group and adapted to the routine of our centre. Wilcoxon t-tests and percentage differences have been applied for comparison purposes. Results are significantly different (p < 0.05) from each other, with an average percentage difference between Benua versus other results of -22%. The dosimetric formula applied to determine blood or RM absorbed dose may contribute significantly to increase heterogeneity in absorbed dose and dose-response results. Standardization should be a major objective.

Accelerated partial breast irradiation using 3D conformal radiotherapy: toxicity and cosmetic outcome.

PURPOSE: The aim of this paper is to analyze the incidence of acute and late toxicity and cosmetic outcome in breast cancer patients submitted to breast conserving surgery and three-dimensional conformal radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI). METHODS AND MATERIALS: 84 patients were treated with 3D-CRT for APBI. This technique was assessed in patients with low risk stage I breast cancer enrolled from September 2005 to July 2011. The prescribed dose was 34/38.5 Gy delivered in 10 fractions twice daily over 5 consecutive days. Four to five no-coplanar 6 MV beams were used. In all CT scans Gross Tumor Volume (GTV) was defined around the surgical clips. A 1.5 cm margin was added by defining a Clinical Target Volume (CTV). A margin of 1 cm was added to CTV to define the planning target volume (PTV). The dose-volume constraints were followed in accordance with the NSABP/RTOG protocol. Late toxicity was evaluated according to the RTOG grading schema. The cosmetic assessment was performed using the Harvard scale. RESULTS: Median patient age was 66 years (range 51-87). Median follow-up was 36.5 months (range 13-83). The overall incidence of acute skin toxicities was 46.4% for grade 1 and 1% for grade 2. The incidence of late toxicity was 16.7% for grade 1, 2.4% for grade 2 and 3.6% for grade 3. No grade 4 toxicity was observed. The most pronounced grade 2 late toxicity was telangiectasia, developed in three patients. Cosmetics results were excellent for 52%, good for 42%, fair for 5% and poor for 1% of the patients. There was no statistical correlation between toxicity rates and prescribed doses (p = 0.33) or irradiated volume (p = 0.45). CONCLUSIONS: APBI using 3D-CRT is technically feasible with very low acute and late toxicity. Long-term results are needed to assess its efficacy in reducing the incidence of breast relapse.

Choline-containing compounds quantification by 1H NMR spectroscopy using external reference and noise measurements.

Proton magnetic resonance spectroscopy ((1)H-MRS) is largely exploited in clinical settings to non-invasively investigate chemical compounds in human tissues. Applications of (1)H-MRS in oncology field are connected to the detection of abnormal levels of choline compounds in more active tumours, providing useful information for cancer diagnosis and treatment monitoring. Since benign lesions may also show presence of a choline peak, implementing absolute evaluation will help differentiating benign from malignant tumours. An external reference procedure was described to provide choline quantification in standard unit of measurements. Spectra were acquired on a 1.5 T scanner using both phantoms and healthy volunteers with a PRESS sequence. The implemented quantification procedure used metabolite and noise measurements on the spectrum to remove large part of scanner settings contributing to metabolites of interest. A standard quantification was also used to compare performances of the noise-based method. In vitro quantification had accuracy and precision in the range (95-99)% and (5-13)%, respectively. When applied to in vivo studies on healthy volunteers, the method provided very close values of choline concentration, more exactly (1.73 ± 0.24) mmol/l. The method proposed can quantify the proper choline content in phantoms as well as in human structures, as brain. The method is ease of use, computational costless and it can be rapidly calibrated and implemented in any centre.

Pretreatment patient-specific IMRT quality assurance: a correlation study between gamma index and patient clinical dose volume histogram.

PURPOSE: The aim of this work is to investigate the predictive power of a common conventional intensity modulated radiation therapy (IMRT) quality assurance (QA) performance metric, the gamma passing rate (%GP), through the analysis of the sensitivity and of the correlation between %GP and different dose discrepancies between planned dose-volume histogram (DVH) and perturbed DVH. The perturbed DVH is calculated by using a dedicated software, 3DVH (Sun Nuclear Corporation, Melbourne, FL), which is able to modify the dose distribution calculated by the treatment planning system (TPS) according to the dose discrepancies detected with planar measurements in order to predict the delivered 3D dose distribution in the patient. METHODS: Twenty-seven high-risk prostate cancer (PP) patients and 15 head and neck (HN) cancer patients, treated with IMRT technique, were analyzed. Pretreatment verifications were performed for all patients' plans by acquiring planar dose distributions of each treatment field with 2D-diode array. Measured dose distributions were compared to the calculated ones using the gamma index (GI) method applying both global (Van Dyk) and local normalization, and %GP were generated for each pair of planar doses using the following acceptance criteria: 1%∕1, 2%∕2, and 3%∕3 mm. Planar dose distributions acquired during pretreatment verifications, together with patient's DICOM RT plan, RT structure set, and RT dose files from TPS were loaded into the 3DVH software. Percentage dose differences (%DE) between DVHs, obtained by TPS and by 3DVH, were calculated; statistical correlation between %DE and %GP was studied by using Pearson's correlation coefficient (r). This analysis was performed, for each patient, on planning target volumes and on some typical organs at risk of the prostatic and head and neck anatomical district. The sensitivity was calculated to correctly identify the pretreatment plans with high dose errors and to quantify the incidence of false negatives, on varying the gamma index method. RESULTS: Analysis of %DE vs %GP showed that there were only weak correlations (Pearson's r-values < 0.8). The results also showed numerous instances of false negatives (cases where high IMRT QA passing rates did not imply good agreement in anatomy dose metrics) and the reverse, mainly for the 3%∕3 mm global gamma passing rate. CONCLUSIONS: The lack of correlation between conventional IMRT QA performance metrics gamma passing rates and dose errors in DVHs values and the low sensitivity of 3%∕3 mm global gamma method show that the most common published acceptance criteria have disputable predictive power for per-patient IMRT QA.

Comparison between PUN and Tofts models in the quantification of dynamic contrast-enhanced MR imaging.

Dynamic contrast-enhanced study in magnetic resonance imaging (DCE-MRI) is an important tool in oncology to visualize tissues vascularization and to define tumour aggressiveness on the basis of an altered perfusion and permeability. Pharmacokinetic models are generally used to extract hemodynamic parameters, providing a quantitative description of the contrast uptake and wash-out. Empirical functions can also be used to fit experimental data without the need of any assumption about tumour physiology, as in pharmacokinetic models, increasing their diagnostic utility, in particular when automatic diagnosis systems are implemented on the basis of an MRI multi-parametric approach. Phenomenological universalities (PUN) represent a novel tool for experimental research and offer a simple and systematic method to represent a set of data independent of the application field. DCE-MRI acquisitions can thus be advantageously evaluated by the extended PUN class, providing a convenient diagnostic tool to analyse functional studies, adding a new set of features for the classification of malignant and benign lesions in computer aided detection systems. In this work the Tofts pharmacokinetic model and the class EU1 generated by the PUN description were compared in the study of DCE-MRI of the prostate, evaluating complexity of model implementation, goodness of fitting results, classification performances and computational cost. The mean R² obtained with the EU1 and Tofts model were equal to 0.96 and 0.90, respectively, and the classification performances achieved by the EU1 model and the Tofts implementation discriminated malignant from benign tissues with an area under the receiver operating characteristic curve equal to 0.92 and 0.91, respectively. Furthermore, the EU1 model has a simpler functional form which reduces implementation complexity and computational time, requiring 6 min to complete a patient elaboration process, instead of 8 min needed for the Tofts model analysis.

Late rectal bleeding after 3D-CRT for prostate cancer: development of a neural-network-based predictive model.

The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.

In vivo characterisation of soft tissue tumours by 1.5-T proton MR spectroscopy.

OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (1H-MRS) can help differentiate between benign and malignant soft tissue lesions, and to assess if there is a correlation between 1H-MRS data and the mitotic index. METHODS: MR measurements were performed in 43 patients with soft tissue tumours >15 mm in diameter. Six cases were excluded for technical failure. Examinations were performed at 1.5 T using a single-voxel point resolved spectroscopy sequence (PRESS) with TR/TE = 2000/150 ms. The volume of interest was positioned within the lesion avoiding inclusion of necrotic regions. In all patients, a histological diagnosis was obtained and the corresponding mitotic index was also computed. 1H-MRS results and histopathological findings were compared using the chi-squared test and correlation coefficient. RESULTS: Choline was detected in 18/19 patients with malignant tumours and in 3/18 patients with benign lesions. The three benign lesions included one desmoid tumour, one ossificans myositis and one eccrine spiradenoma. Choline was not detected in 15 patients with benign lesions or in one patient with dermatofibrosarcoma protuberans. Resulting 1H-MRS sensitivity and specificity were 95% and 83% respectively. CONCLUSIONS: Absence of choline peak is highly predictive of benign tumours suggesting that 1H-MRS can help to differentiate malignant from benign tumours. KEY POINTS: • 1H-MRS may allow differentiation between benign and malignant soft tissue lesions • Absence of choline peak is highly predictive of benign soft tissue lesions • Malignant tumours with a mitotic index >2/10 HPF had a positive choline peak • A choline peak may still be identified in some benign tumours.