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The primary goal of precision medicine is to minimize side effects and optimize efficacy of treatments. Recent advances in medical imaging technology allow the use of more advanced image analysis methods beyond simple measurements of tumor size or radiotracer uptake metrics. The extraction of quantitative features from medical images to characterize tumor pathology or heterogeneity is an interesting process to investigate, in order to provide information that may be useful to guide the therapies and predict survival. This paper discusses the rationale supporting the concept of radiomics and the feasibility of its application to Non-Small Cell Lung Cancer in the field of radiation oncology research. We studied 91 stage III patients treated with concurrent chemoradiation and adaptive approach in case of tumor reduction during treatment. We considered 12 statistics features and 230 textural features extracted from the CT images. In our study, we used an ensemble learning method to classify patients’ data into either the adaptive or non-adaptive group during chemoradiation on the basis of the starting CT simulation. Our data supports the hypothesis that a specific signature can be identified (AUC 0.82). In our experience, a radiomic signature mixing semantic and image-based features has shown promising results for personalized adaptive radiotherapy in non-small cell lung cancer. [ABSTRACT FROM AUTHOR]

Lung 4D computed tomography (4D-CT) plays an important role in high-precision radiotherapy because it characterizes respiratory motion, which is crucial for accurate target definition. However, the manual segmentation of a lung tumor is a heavy workload for doctors because of the large number of lung 4D-CT data slices. Meanwhile, tumor segmentation is still a notoriously challenging problem in computer-aided diagnosis. In this paper, we propose a new method based on an improved graph cut algorithm with context information constraint to find a convenient and robust approach of lung 4D-CT tumor segmentation. We combine all phases of the lung 4D-CT into a global graph, and construct a global energy function accordingly. The sub-graph is first constructed for each phase. A context cost term is enforced to achieve segmentation results in every phase by adding a context constraint between neighboring phases. A global energy function is finally constructed by combining all cost terms. The optimization is achieved by solving a max-flow/min-cut problem, which leads to simultaneous and robust segmentation of the tumor in all the lung 4D-CT phases. The effectiveness of our approach is validated through experiments on 10 different lung 4D-CT cases. The comparison with the graph cut without context constraint, the level set method and the graph cut with star shape prior demonstrates that the proposed method obtains more accurate and robust segmentation results. [ABSTRACT FROM AUTHOR]

Radiomics studies require many patients in order to power them, thus patients are often combined from different institutions and using different imaging protocols. Various studies have shown that imaging protocols affect radiomics feature values. We examined whether using data from cohorts with controlled imaging protocols improved patient outcome models. We retrospectively reviewed 726 CT and 686 PET images from head and neck cancer patients, who were divided into training or independent testing cohorts. For each patient, radiomics features with different preprocessing were calculated and two clinical variables—HPV status and tumor volume—were also included. A Cox proportional hazards model was built on the training data by using bootstrapped Lasso regression to predict overall survival. The effect of controlled imaging protocols on model performance was evaluated by subsetting the original training and independent testing cohorts to include only patients whose images were obtained using the same imaging protocol and vendor. Tumor volume, HPV status, and two radiomics covariates were selected for the CT model, resulting in an AUC of 0.72. However, volume alone produced a higher AUC, whereas adding radiomics features reduced the AUC. HPV status and one radiomics feature were selected as covariates for the PET model, resulting in an AUC of 0.59, but neither covariate was significantly associated with survival. Limiting the training and independent testing to patients with the same imaging protocol reduced the AUC for CT patients to 0.55, and no covariates were selected for PET patients. Radiomics features were not consistently associated with survival in CT or PET images of head and neck patients, even within patients with the same imaging protocol. [ABSTRACT FROM AUTHOR]

Background: Prognostic models based on individual patient characteristics can improve treatment decisions and outcome in the future. In many (radiomic) studies, small size and heterogeneity of datasets is a challenge that often limits performance and potential clinical applicability of these models. The current study is example of a retrospective multi-centric study with challenges and caveats. To highlight common issues and emphasize potential pitfalls, we aimed for an extensive analysis of these multi-center pre-treatment datasets, with an additional 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) scan acquired during treatment. Methods: The dataset consisted of 138 stage II-IV non-small cell lung cancer (NSCLC) patients from four different cohorts acquired from three different institutes. The differences between the cohorts were compared in terms of clinical characteristics and using the so-called ‘cohort differences model’ approach. Moreover, the potential prognostic performances for overall survival of radiomic features extracted from CT or FDG-PET, or relative or absolute differences between the scans at the two time points, were assessed using the LASSO regression method. Furthermore, the performances of five different classifiers were evaluated for all image sets. Results: The individual cohorts substantially differed in terms of patient characteristics. Moreover, the cohort differences model indicated statistically significant differences between the cohorts. Neither LASSO nor any of the tested classifiers resulted in a clinical relevant prognostic model that could be validated on the available datasets. Conclusion: The results imply that the study might have been influenced by a limited sample size, heterogeneous patient characteristics, and inconsistent imaging parameters. No prognostic performance of FDG-PET or CT based radiomics models can be reported. This study highlights the necessity of extensive evaluations of cohorts and of validation datasets, especially in retrospective multi-centric datasets. [ABSTRACT FROM AUTHOR]

Purpose: Portal vein thrombosis (PVT) is generally recognized as a prognostic factor in HCC. Our purpose is to assess and compare the survival of patients with PVT and without PVT, after Y-90 Trans-Arterial Radio-Embolization (TARE) of unresectable HCC, unresponsive to other loco-regional treatments. Materials and methods: Between November 2005 and November 2012, Y-90 resin-based TARE was performed in an IRB-approved prospective protocol, on 89 patients with unresectable HCC. 33/89 patients had PVT, the remaining 56 were resistant-to-cTACE or underwent TARE as a downstaging therapy. All patients were studied with Multi-Detector Computed Tomography (MDCT), angiography, 99mTc-MAA-scintigraphy and liver biopsy. Gastro-duodenal artery was embolized in most cases. Proton-Pump Inhibitors were administered to prevent gastritis and ulcers. χ2 test with Yates correction and log rank test were used to compare the two proportions and Kaplan-Meier survival curves, respectively. Results: The average activity administered was 1.7 ± 0.4 GBq. After the treatment, CTCAE grade 2 adverse events occurred in 46% (41/89) patients: in particular, fever and abdominal pain were found in 25 and 16 patients, respectively. No major side-effect was observed. According to mRECIST criteria, partial response or complete response was found in 70% of patient three months after the treatment, and in 90.5% nine months after the treatment. No significant difference was found in survival of patients with PVT compared to those without PVT (p-value = 0.672). A complete regression of PVT was observed in almost half patients (13/27, 48.1%). Conclusions: Portal vein invasion does not affect survival in advanced stage HCC-patients undergoing TARE using Y-90 resin-based microspheres. Y90 procedure is associated with regression of portal vein tumor thrombus. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to evaluate the dosimetric accuracy of respiratory gated volumetric modulated arc therapy (VMAT) for lung stereotactic body radiation therapy (SBRT) under simulation conditions similar to the actual clinical situation using patient-specific lung phantoms and realistic target movements. Methods: Six heterogeneous lung phantoms were fabricated using a 3D-printer (3DISON, ROKIT, Seoul, Korea) to be dosimetrically equivalent to actual target regions of lung SBRT cases treated via gated VMAT. They were designed to move realistically via a motion device (QUASAR, Modus Medical Devices, Canada). Using the lung phantoms and a homogeneous phantom (model 500–3315, Modus Medical Devices), film dosimetry was performed with and without respiratory gating for VMAT delivery (TrueBeam STx; Varian Medical Systems, Palo Alto, CA, USA). The measured results were analyzed with the gamma passing rates (GPRs) of 2%/1 mm criteria, by comparing with the calculated dose via the AXB and AAA algorithms of the Eclipse Treatment Planning System (version 10.0.28; Varian Medical Systems). Results: GPRs were greater than the acceptance criteria 80% for all film measurements with the stationary and homogeneous phantoms in conventional QAs. Regardless of the heterogeneity of phantoms, there were no significant differences (p > 0.05) in GPRs obtained with and without target motions; the statistical significance (p = 0.031) was presented between both algorithms under the utilization of heterogeneous phantoms. Conclusions: Dosimetric verification with heterogeneous patient-specific lung phantoms could be successfully implemented as the evaluation method for gated VMAT delivery. In addition, it could be dosimetrically confirmed that the AXB algorithm improved the dose calculation accuracy under patient-specific simulations using 3D printed lung phantoms. [ABSTRACT FROM AUTHOR]

Background: Non-small-cell lung cancer (NSCLC) patients often demonstrate varying clinical courses and outcomes, even within the same tumor stage. This study explores deep learning applications in medical imaging allowing for the automated quantification of radiographic characteristics and potentially improving patient stratification.Methods and Findings: We performed an integrative analysis on 7 independent datasets across 5 institutions totaling 1,194 NSCLC patients (age median = 68.3 years [range 32.5-93.3], survival median = 1.7 years [range 0.0-11.7]). Using external validation in computed tomography (CT) data, we identified prognostic signatures using a 3D convolutional neural network (CNN) for patients treated with radiotherapy (n = 771, age median = 68.0 years [range 32.5-93.3], survival median = 1.3 years [range 0.0-11.7]). We then employed a transfer learning approach to achieve the same for surgery patients (n = 391, age median = 69.1 years [range 37.2-88.0], survival median = 3.1 years [range 0.0-8.8]). We found that the CNN predictions were significantly associated with 2-year overall survival from the start of respective treatment for radiotherapy (area under the receiver operating characteristic curve [AUC] = 0.70 [95% CI 0.63-0.78], p < 0.001) and surgery (AUC = 0.71 [95% CI 0.60-0.82], p < 0.001) patients. The CNN was also able to significantly stratify patients into low and high mortality risk groups in both the radiotherapy (p < 0.001) and surgery (p = 0.03) datasets. Additionally, the CNN was found to significantly outperform random forest models built on clinical parameters-including age, sex, and tumor node metastasis stage-as well as demonstrate high robustness against test-retest (intraclass correlation coefficient = 0.91) and inter-reader (Spearman's rank-order correlation = 0.88) variations. To gain a better understanding of the characteristics captured by the CNN, we identified regions with the most contribution towards predictions and highlighted the importance of tumor-surrounding tissue in patient stratification. We also present preliminary findings on the biological basis of the captured phenotypes as being linked to cell cycle and transcriptional processes. Limitations include the retrospective nature of this study as well as the opaque black box nature of deep learning networks.Conclusions: Our results provide evidence that deep learning networks may be used for mortality risk stratification based on standard-of-care CT images from NSCLC patients. This evidence motivates future research into better deciphering the clinical and biological basis of deep learning networks as well as validation in prospective data. [ABSTRACT FROM AUTHOR]

This study investigates the impact of whole-body MRI (WB-MRI) in addition to CT of chest-abdomen-pelvis (CT-CAP) and 18F-FDG PET/CT (PET/CT) on systemic treatment decisions in standard clinical practice for patients with advanced breast cancer (ABC). WB-MRI examinations in ABC patients were extracted from our WB-MRI registry (2009–2017). Patients under systemic treatment who underwent WB-MRI and a control examination (CT-CAP or PET/CT) were included. Data regarding progressive disease (PD) reported either on WB-MRI or on the control examinations were collected. Data regarding eventual change in treatment after the imaging evaluation were collected. It was finally evaluated whether the detection of PD by any of the two modalities had induced a change in treatment. Among 910 WB-MRI examinations in ABC patients, 58 had a paired control examination (16 CT-CAP and 42 PET/CT) and were analysed. In 23/58 paired examinations, additional sites of disease were reported only on WB-MRI and not on the control examination. In 17/28 paired examinations, PD was reported only on WB-MRI and not on the control examination. In 14 out of the 28 pairs of examinations that were followed by a change in treatment, PD had been reported only on WBMRI (14/28; 50%), while stable disease had been reported on the control examination. In conclusion, WB-MRI disclosed PD earlier than the control examination (CT-CAP or PET/CT), and it was responsible alone for 50% of all changes in treatment. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers in the United States with a five-year survival rate of 7.2% for all stages. Although surgical resection is the only curative treatment, currently we are unable to differentiate between resectable patients with occult metastatic disease from those with potentially curable disease. Identification of patients with poor prognosis via early classification would help in initial management including the use of neoadjuvant chemotherapy or radiation, or in the choice of postoperative adjuvant therapy. PDAC ranges in appearance from homogeneously isoattenuating masses to heterogeneously hypovascular tumors on CT images; hence, we hypothesize that heterogeneity reflects underlying differences at the histologic or genetic level and will therefore correlate with patient outcome. We quantify heterogeneity of PDAC with texture analysis to predict 2-year survival. Using fuzzy minimum-redundancy maximum-relevance feature selection and a naive Bayes classifier, the proposed features achieve an area under receiver operating characteristic curve (AUC) of 0.90 and accuracy (Ac) of 82.86% with the leave-one-image-out technique and an AUC of 0.80 and Ac of 75.0% with three-fold cross-validation. We conclude that texture analysis can be used to quantify heterogeneity in CT images to accurately predict 2-year survival in patients with pancreatic cancer. From these data, we infer differences in the biological evolution of pancreatic cancer subtypes measurable in imaging and identify opportunities for optimized patient selection for therapy. [ABSTRACT FROM AUTHOR]

The purpose of this study is to investigate the optimal reference geometry for gamma camera calibration. Yet another question of interest was to assess the influence of the number of 3D Ordered Subsets Expectation Maximization (3D-OSEM) updates on activity quantification for SPECT imaging with 177Lu. The accuracy of 177Lu activity quantification was assessed both in small and in large objects. Two different reference geometries, namely a cylindrical homogeneous phantom and a Jaszczak 16 ml sphere surrounded by cold water, were used to determine the gamma camera calibration factor of a commercial SPECT/CT system. Moreover, the noise level and the concentration recovery coefficient were evaluated as a function of the number of 3D-OSEM updates by using the SPECT/CT images of the reference geometry phantoms and those of a cold Jaszczak phantom with three hot spheres (16ml, 8ml and 4ml), respectively. The optimal choice of the number of 3D-OSEM updates was based on a compromise between the noise level achievable in the reconstructed SPECT images and the concentration recovery coefficients. The quantitative accuracy achievable was finally validated on a test phantom, where a spherical insert composed of two concentric spheres was used to simulate a lesion in a warm background. Our data confirm and extend previous observations. Using the calibration factor obtained with the cylindrical homogeneous phantom and the Jaszczak 16 ml sphere, the recovered activity in the test phantom was underestimated by -16.4% and -24.8%, respectively. Our work has led us to conclude that gamma camera calibration performed with large homogeneous phantom outperforms calibration executed with the Jaszczak 16ml sphere. Furthermore, the results obtained support the assumption that approximately 50 OSEM updates represent a good trade-off to reach convergence in small volumes, meanwhile minimizing the noise level. [ABSTRACT FROM AUTHOR]

Background: As Medicare expands the use of computed tomography (CT) for diagnosing lung cancer, there is increased opportunity to diagnose lung cancer in asymptomatic patients. This descriptive study characterizes the disease-specific diagnostic and treatment services that patients with a positive diagnosis following CT received, stratified by presentation at CT. Methods: Patients who were diagnosed with lung cancer following CT in 2013, had no history of lung cancer, survived at least 1 year, were aged 55–80 years, and had Medicare Advantage insurance were included. Patients were grouped based upon presentation at CT: morbidities unrelated to lung cancer, classic lung cancer symptoms, and cancer syndromes. Patients with none of these factors were categorized into a no diagnoses/symptoms group. The type and intensity of services used in the year following the CT was reported for each group. Results: 1,261 patients were included. Early treatment services were most common in the group with morbidities unrelated to lung cancer (13.7%) and least common in the cancer syndromes group (6.6%). Advanced treatment services were used by 47.3% of the cancer syndromes group versus 23.5% of the no diagnoses/symptoms group. Conclusions: The intensity of disease-specific diagnostic and treatment services varied by presentation at CT. Patients with no symptoms or morbidities at the time of CT less frequently received advanced interventions. Learning about the utilization patterns of others with a similar presentation at CT may help patients with positive lung cancer diagnoses engage in shared decision making and in norming their experiences against those of other similarly-situated patients. [ABSTRACT FROM AUTHOR]

The combination external-beam radiotherapy and high-dose-rate brachytherapy is a standard form of treatment for patients with locally advanced uterine cervical cancer. Personalized radiotherapy in cervical cancer requires efficient and accurate dose planning and assessment across these types of treatment. To achieve radiation dose assessment, accurate mapping of the dose distribution from HDR-BT onto EBRT is extremely important. However, few systems can achieve robust dose fusion and determine the accumulated dose distribution during the entire course of treatment. We have therefore developed a toolbox (FZUImageReg), which is a user-friendly dose fusion system based on hybrid image registration for radiation dose assessment in cervical cancer radiotherapy. The main part of the software consists of a collection of medical image registration algorithms and a modular design with a user-friendly interface, which allows users to quickly configure, test, monitor, and compare different registration methods for a specific application. Owing to the large deformation, the direct application of conventional state-of-the-art image registration methods is not sufficient for the accurate alignment of EBRT and HDR-BT images. To solve this problem, a multi-phase non-rigid registration method using local landmark-based free-form deformation is proposed for locally large deformation between EBRT and HDR-BT images, followed by intensity-based free-form deformation. With the transformation, the software also provides a dose mapping function according to the deformation field. The total dose distribution during the entire course of treatment can then be presented. Experimental results clearly show that the proposed system can achieve accurate registration between EBRT and HDR-BT images and provide radiation dose warping and fusion results for dose assessment in cervical cancer radiotherapy in terms of high accuracy and efficiency. [ABSTRACT FROM AUTHOR]

Objective: To prospectively evaluate the ability of CT urography with a low-dose multi-phasic excretory phase for opacification of the urinary system. Materials and methods: Thirty-two patients underwent CT urography with low-dose multi-phasic s using adaptive iterative dose reduction 3D acquired at 5-, 10-, and 15-minute delays. Opacification scores of the upper urinary tracts and the urinary bladder were assigned for each excretory phase by two radiologists, who recorded whether adequate (>75%) or complete (100%) opacification of the upper urinary tract and urinary bladder was achieved in each patient. Adequate and complete opacification rates of the upper urinary tracts and the urinary bladder were compared among three excretory phases and among combined multi-phasic excretory phases using Cochran's Q test. Results: There was no significant difference among three excretory phases with 5-, 10-, and 15-minute delays in adequate (56.3, 43.8, and 63.5%, respectively; P = 0.174) and complete opacification rates (9.3, 15.6, and 18.7%, respectively; P = 0.417) of the upper urinary tracts. Combined tri-phasic excretory phases significantly improved adequate and complete opacification rates to 84.4% and 43.8%, respectively (P = 0.002). In contrast, there were significant differences among three excretory phases for the rate of adequate (31.3, 84.4, and 93.8%, respectively; P<0.001) and complete opacification (21.9, 53.1, and 81.3%, respectively; P<0.001) of the urinary bladder. Multi-phasic excretory phases did not improve these rates because opacification was always better with a longer delay. Conclusion: Although multi-phasic acquisition of excretory phases is effective at improving opacification of the upper urinary tracts, complete opacification is difficult even with tri-phasic acquisition. [ABSTRACT FROM AUTHOR]

Radiotherapy of lung and liver lesions has changed from normofractioned 3D-CRT to stereotactic treatment in a single or few fractions, often employing volumetric arc therapy (VMAT)-based techniques. Potential unintended interference of respiratory target motion and dynamically changing beam parameters during VMAT dose delivery motivates establishing 4D quality assurance (4D QA) procedures to assess appropriateness of generated VMAT treatment plans when taking into account patient-specific motion characteristics. Current approaches are motion phantom-based 4D QA and image-based 4D VMAT dose simulation. Whereas phantom-based 4D QA is usually restricted to a small number of measurements, the computational approaches allow simulating many motion scenarios. However, 4D VMAT dose simulation depends on various input parameters, influencing estimated doses along with mitigating simulation reliability. Thus, aiming at routine use of simulation-based 4D VMAT QA, the impact of such parameters as well as the overall accuracy of the 4D VMAT dose simulation has to be studied in detail–which is the topic of the present work. In detail, we introduce the principles of 4D VMAT dose simulation, identify influencing parameters and assess their impact on 4D dose simulation accuracy by comparison of simulated motion-affected dose distributions to corresponding dosimetric motion phantom measurements. Exploiting an ITV-based treatment planning approach, VMAT treatment plans were generated for a motion phantom and different motion scenarios (sinusoidal motion of different period/direction; regular/irregular motion). 4D VMAT dose simulation results and dose measurements were compared by local 3% / 3 mm γ-evaluation, with the measured dose distributions serving as ground truth. Overall γ-passing rates of simulations and dynamic measurements ranged from 97% to 100% (mean across all motion scenarios: 98% ± 1%); corresponding values for comparison of different day repeat measurements were between 98% and 100%. Parameters of major influence on 4D VMAT dose simulation accuracy were the degree of temporal discretization of the dose delivery process (the higher, the better) and correct alignment of the assumed breathing phases at the beginning of the dose measurements and simulations. Given the high γ-passing rates between simulated motion-affected doses and dynamic measurements, we consider the simulations to provide a reliable basis for assessment of VMAT motion effects that–in the sense of 4D QA of VMAT treatment plans–allows to verify target coverage in hypofractioned VMAT-based radiotherapy of moving targets. Remaining differences between measurements and simulations motivate, however, further detailed studies. [ABSTRACT FROM AUTHOR]

Background: The National Lung Screening Trial (NLST) results indicate that computed tomography (CT) lung cancer screening for current and former smokers with three annual screens can be cost-effective in a trial setting. However, the cost-effectiveness in a population-based setting with >3 screening rounds is uncertain. Therefore, the objective of this study was to estimate the cost-effectiveness of lung cancer screening in a population-based setting in Ontario, Canada, and evaluate the effects of screening eligibility criteria.Methods and Findings: This study used microsimulation modeling informed by various data sources, including the Ontario Health Insurance Plan (OHIP), Ontario Cancer Registry, smoking behavior surveys, and the NLST. Persons, born between 1940 and 1969, were examined from a third-party health care payer perspective across a lifetime horizon. Starting in 2015, 576 CT screening scenarios were examined, varying by age to start and end screening, smoking eligibility criteria, and screening interval. Among the examined outcome measures were lung cancer deaths averted, life-years gained, percentage ever screened, costs (in 2015 Canadian dollars), and overdiagnosis. The results of the base-case analysis indicated that annual screening was more cost-effective than biennial screening. Scenarios with eligibility criteria that required as few as 20 pack-years were dominated by scenarios that required higher numbers of accumulated pack-years. In general, scenarios that applied stringent smoking eligibility criteria (i.e., requiring higher levels of accumulated smoking exposure) were more cost-effective than scenarios with less stringent smoking eligibility criteria, with modest differences in life-years gained. Annual screening between ages 55-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago yielded an incremental cost-effectiveness ratio of $41,136 Canadian dollars ($33,825 in May 1, 2015, United States dollars) per life-year gained (compared to annual screening between ages 60-75 for persons who smoked ≥40 pack-years and who currently smoke or quit ≤10 y ago), which was considered optimal at a cost-effectiveness threshold of $50,000 Canadian dollars ($41,114 May 1, 2015, US dollars). If 50% lower or higher attributable costs were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $38,240 ($31,444 May 1, 2015, US dollars) or $48,525 ($39,901 May 1, 2015, US dollars), respectively. If 50% lower or higher costs for CT examinations were assumed, the incremental cost-effectiveness ratio of this scenario was estimated to be $28,630 ($23,542 May 1, 2015, US dollars) or $73,507 ($60,443 May 1, 2015, US dollars), respectively. This scenario would screen 9.56% (499,261 individuals) of the total population (ever- and never-smokers) at least once, which would require 4,788,523 CT examinations, and reduce lung cancer mortality in the total population by 9.05% (preventing 13,108 lung cancer deaths), while 12.53% of screen-detected cancers would be overdiagnosed (4,282 overdiagnosed cases). Sensitivity analyses indicated that the overall results were most sensitive to variations in CT examination costs. Quality of life was not incorporated in the analyses, and assumptions for follow-up procedures were based on data from the NLST, which may not be generalizable to a population-based setting.Conclusions: Lung cancer screening with stringent smoking eligibility criteria can be cost-effective in a population-based setting. [ABSTRACT FROM AUTHOR]

Purpose: To develop and validate fully automated generation of VMAT plan-libraries for plan-of-the-day adaptive radiotherapy in locally-advanced cervical cancer. Material and Methods: Our framework for fully automated treatment plan generation (Erasmus-iCycle) was adapted to create dual-arc VMAT treatment plan libraries for cervical cancer patients. For each of 34 patients, automatically generated VMAT plans (autoVMAT) were compared to manually generated, clinically delivered 9-beam IMRT plans (CLINICAL), and to dual-arc VMAT plans generated manually by an expert planner (manVMAT). Furthermore, all plans were benchmarked against 20-beam equi-angular IMRT plans (autoIMRT). For all plans, a PTV coverage of 99.5% by at least 95% of the prescribed dose (46 Gy) had the highest planning priority, followed by minimization of V45Gy for small bowel (SB). Other OARs considered were bladder, rectum, and sigmoid. Results: All plans had a highly similar PTV coverage, within the clinical constraints (above). After plan normalizations for exactly equal median PTV doses in corresponding plans, all evaluated OAR parameters in autoVMAT plans were on average lower than in the CLINICAL plans with an average reduction in SB V45Gy of 34.6% (p<0.001). For 41/44 autoVMAT plans, SB V45Gy was lower than for manVMAT (p<0.001, average reduction 30.3%), while SB V15Gy increased by 2.3% (p = 0.011). AutoIMRT reduced SB V45Gy by another 2.7% compared to autoVMAT, while also resulting in a 9.0% reduction in SB V15Gy (p<0.001), but with a prolonged delivery time. Differences between manVMAT and autoVMAT in bladder, rectal and sigmoid doses were ≤ 1%. Improvements in SB dose delivery with autoVMAT instead of manVMAT were higher for empty bladder PTVs compared to full bladder PTVs, due to differences in concavity of the PTVs. Conclusions: Quality of automatically generated VMAT plans was superior to manually generated plans. Automatic VMAT plan generation for cervical cancer has been implemented in our clinical routine. Due to the achieved workload reduction, extension of plan libraries has become feasible. [ABSTRACT FROM AUTHOR]

Background: Proton beam therapy (PBT) achieves good local control for hepatocellular carcinoma (HCC), and toxicity tends to be lower than for photon radiotherapy. Focal liver parenchymal damage in radiotherapy is described as the focal liver reaction (FLR); the threshold doses (TDs) for FLR in the background liver have been analyzed in stereotactic ablative body radiotherapy and brachytherapy. To develop a safer approach for PBT, both TD and liver volume changes are considered clinically important in predicting the extent of damage before treatment, and subsequently in reducing background liver damage. We investigated appearance time, TDs and volume changes regarding FLR after PBT for HCC. Material and Methods: Patients who were treated using PBT and were followed up using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging (Gd-EOB-DTPA MRI) after PBT were enrolled. Sixty-eight lesions in 58 patients were eligible for analysis. MRI was acquired at the end of treatment, and at 1, 2, 3 and 6 months after PBT. We defined the FLR as a clearly depicted hypointense area on the hepatobiliary phase of Gd-EOB-DTPA MRI, and we monitored TDs and volume changes in the FLR area and the residual liver outside of the FLR area. Results: FLR was depicted in all lesions at 3 months after PBT. In FLR expressed as the 2-Gy equivalent dose (α/β = 3 Gy), TDs did not differ significantly (27.0±6.4 CGE [10 fractions [Fr] vs. 30.5±7.3 CGE [20 Fr]). There were also no correlations between the TDs and clinical factors, and no significant differences between Child-Pugh A and B scores. The volume of the FLR area decreased and the residual liver volume increased, particularly during the initial 3 months. Conclusion: This study established the FLR dose for liver with HCC, which might be useful in the prediction of remnant liver volume for PBT. [ABSTRACT FROM AUTHOR]

Purpose: There is an increasing need for small animal in vivo imaging in murine orthotopic glioma models. Because dedicated small animal scanners are not available ubiquitously, the applicability of a clinical CT scanner for visualization and measurement of intracerebrally growing glioma xenografts in living mice was validated. Materials and Methods: 2.5x106 U87MG cells were orthotopically implanted in NOD/SCID/ᵞc-/- mice (n = 9). Mice underwent contrast-enhanced (300 μl Iomeprol i.v.) imaging using a micro-CT (80 kV, 75 μAs, 360° rotation, 1,000 projections, scan time 33 s, resolution 40 x 40 x 53 μm) and a clinical CT scanner (4-row multislice detector; 120 kV, 150 mAs, slice thickness 0.5 mm, feed rotation 0.5 mm, resolution 98 x 98 x 500 μm). Mice were sacrificed and the brain was worked up histologically. In all modalities tumor volume was measured by two independent readers. Contrast-to-noise ratio (CNR) and Signal-to-noise ratio (SNR) were measured from reconstructed CT-scans (0.5 mm slice thickness; n = 18). Results: Tumor volumes (mean±SD mm3) were similar between both CT-modalities (micro-CT: 19.8±19.0, clinical CT: 19.8±18.8; Wilcoxon signed-rank test p = 0.813). Moreover, between reader analyses for each modality showed excellent agreement as demonstrated by correlation analysis (Spearman-Rho >0.9; p<0.01 for all correlations). Histologically measured tumor volumes (11.0±11.2) were significantly smaller due to shrinkage artifacts (p<0.05). CNR and SNR were 2.1±1.0 and 1.1±0.04 for micro-CT and 23.1±24.0 and 1.9±0.7 for the clinical CTscanner, respectively. Conclusion: Clinical CT scanners may reliably be used for in vivo imaging and volumetric analysis of brain tumor growth in mice. [ABSTRACT FROM AUTHOR]

Objective: The study was designed to evaluate diffusion-weighted magnetic resonance imaging (DWI) vs. PET-CT of the thorax in the determination of gross tumor volume (GTV) in radiotherapy planning of non-small-cell lung cancer (NSCLC). Materials and Methods: Eligible patients with NSCLC who were supposed to receive definitive radio(chemo)therapy were prospectively recruited. For MRI, a respiratory gated T2-weighted sequence in axial orientation and non-gated DWI (b = 0, 800, 1,400 and apparent diffusion coefficient map [ADC]) were acquired on a 1.5 Tesla scanner. Primary tumors were delineated on FDG-PET/CT (stGTV) and DWI images (dwGTV). The definition of stGTV was based on the CT and visually adapted to the FDG-PET component if indicated (e.g., in atelectasis). For DWI, dwGTV was visually determined and adjusted for anatomical plausibility on T2w sequences. Beside a statistical comparison of stGTV and dwGTB, spatial agreement was determined with the “Hausdorff-Distance” (HD) and the “Dice Similarity Coefficient” (DSC). Results: Fifteen patients (one patient with two synchronous NSCLC) were evaluated. For 16 primary tumors with UICC stages I (n = 4), II (n = 3), IIIA (n = 2) and IIIB (n = 7) mean values for dwGTV were significantly larger than those of stGTV (76.6 ± 84.5 ml vs. 66.6 ± 75.2 ml, p<0.01). The correlation of stGTV and dwGTV was highly significant (r = 0.995, p<0.001). Yet, some considerable volume deviations between these two methods were observed (median 27.5%, range 0.4–52.1%). An acceptable agreement between dwGTV and stGTV regarding the spatial extent of primary tumors was found (average HD: 2.25 ± 0.7 mm; DC 0.68 ± 0.09). Conclusion: The overall level of agreement between PET-CT and MRI based GTV definition is acceptable. Tumor volumes may differ considerably in single cases. DWI-derived GTVs are significantly, yet modestly, larger than their PET-CT based counterparts. Prospective studies to assess the safety and efficacy of DWI-based radiotherapy planning in NSCLC are warranted. [ABSTRACT FROM AUTHOR]

Objectives: 18F-FDG-PET/CT is a useful tool used to evidence persistent/recurrent disease (PRD) in patients with differentiated thyroid cancer and iodine-refractory lesions. The aim of this study was to compare the diagnostic value at the cervical level of the routine whole-body (WB) acquisition and that of a complementary head and neck (HN) acquisition, performed successively during the same PET/CT study. Methods: PET/CT studies combining WB and HN acquisitions performed in 85 consecutive patients were retrospectively reviewed by two nuclear medicine physicians. 18F-FDG uptake in cervical lymph nodes (LN) or in the thyroid bed was assessed. Among the 85 patients, the PET/CT results of the 26 who subsequently underwent neck surgery were compared with surgical and pathological reports. The size of each largest nodal metastasis was assessed by a pathologist. Results: In the 85 patients, inter-observer agreement was excellent for both WB and HN PET/CT interpretation. Of the 26 patients who underwent surgery, 25 had pathology proven PRD in the neck. Of these 25 patients, 15 displayed FDG uptake on either WB or HN PET. In these 15 patients, HN PET detected more malignant lesions than WB PET did (21/27 = 78% vs. 12/27 = 44%, P = 0.006). Node/background ratios were significantly higher on HN than on WB PET (P<0.0001). Three false-negative studies (20%) on WB PET were upstaged as true-positive on HN PET. The mean size of the largest LN metastasis was 3 mm for the LN detected neither on WB nor on HN PET, 7 mm for the metastasis detected on HN but not on WB PET, and 13 mm for those detected on both acquisitions (P = 0.0004). Receiver-Operating Characteristic analysis showed that area under the curve was higher for HN PET than for WB PET (0.97 [95%CI, 0.90–0.99] vs 0.88 [95%CI, 0.78–0.95], P = 0.009). Conclusions: HN acquisition improves the ability to detect PRD in the neck compared with WB acquisition alone. We recommend systematically adding an HN acquisition when PET/CT is performed to detect PRD in the neck. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to assess the utility of [Lys40(Ahx-HYNIC-99mTc/EDDA)NH2]-exendin-4 scintigraphy in the management of patients with hypoglycemia, particularly in the detection of occult insulinoma. Materials and Methods: Forty patients with hypoglycemia and increased/confusing results of serum insulin and C-peptide concentration and negative/inconclusive results of other imaging examinations were enrolled in the study. In all patients GLP-1 receptor imaging was performed to localise potential pancreatic lesions. Results: Positive results of GLP-1 scintigraphy were observed in 28 patients. In 18 patients postsurgical histopathological examination confirmed diagnosis of insulinoma. Two patients had contraindications to the surgery, one patient did not want to be operated. One patient, who presented with postprandial hypoglycemia, with positive result of GLP-1 imaging was not qualified for surgery and is in the observational group. Eight patients were lost for follow up, among them 6 patients with positive GLP-1 scintigraphy result. One patient with negative scintigraphy was diagnosed with malignant insulinoma. In two patients with negative scintigraphy Munchausen syndrome was diagnosed (patients were taking insulin). Other seven patients with negative results of 99mTcGLP-1 scintigraphy and postprandial hypoglycemia with C-peptide and insulin levels within the limits of normal ranges are in the observational group. We would like to mention that 99mTc-GLP1-SPECT/CT was also performed in 3 pts with nesidioblastosis (revealing diffuse tracer uptake in two and a focal lesion in one case) and in two patients with malignant insulinoma (with the a focal uptake in the localization of a removed pancreatic headin one case and negative GLP-1 1 scintigraphy in the other patient). Conclusions: 99mTc-GLP1-SPECT/CT could be helpful examination in the management of patients with hypoglycemia enabling proper localization of the pancreatic lesion and effective surgical treatment. This imaging technique may eliminate the need to perform invasive procedures in case of occult insulinoma. [ABSTRACT FROM AUTHOR]

This study aimed to identify the computed tomography characteristics of treatment-naïve patients with lung adenocarcinoma and known driver mutations in EGFR, KRAS, or ALK. Patients with advanced lung adenocarcinoma (stage IIIB–IV) and known mutations in EGFR, KRAS, or ALK were assessed. The radiological findings for the main tumor and intra-thoracic status were retrospectively analyzed in each group, and the groups’ characteristics were compared. We identified 265 treatment-naïve patients with non-small-cell carcinoma, who had EGFR mutations (n = 159), KRAS mutations (n = 55), or ALK rearrangements (n = 51). Among the three groups, we evaluated only patients with stage IIIB–IV lung adenocarcinoma who had EGFR mutations (n = 126), KRAS mutations (n = 35), or ALK rearrangements (n = 47). We found that ground-glass opacity at the main tumor was significantly more common among EGFR-positive patients, compared to ALK-positive patients (p = 0.009). Lymphadenopathy was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.003). Extranodal invasion was significantly more common among ALK-positive patients, compared to EGFR-positive patients and KRAS-positive patients (p = 0.001 and p = 0.049, respectively). Lymphangitis was significantly more common among ALK-positive patients, compared to EGFR-positive patients (p = 0.049). Pleural effusion was significantly less common among KRAS-positive patients, compared to EGFR-positive patients and ALK-positive patients (p = 0.046 and p = 0.026, respectively). Lung metastases were significantly more common among EGFR-positive patients, compared to KRAS-positive patients and ALK-positive patients (p = 0.007 and p = 0.04, respectively). In conclusion, EGFR mutations were associated with ground-glass opacity, KRAS-positive tumors were generally solid and less likely to metastasize to the lung and pleura, and ALK-positive tumors tended to present with lymphadenopathy, extranodal invasion, and lymphangitis. These mutation-specific imaging characteristics may be related to the biological differences between these cancers. [ABSTRACT FROM AUTHOR]

Background: Image texture analysis is a noninvasive technique for quantifying intratumoral heterogeneity, with derived texture features reported to be closely related to the treatment outcome of tumors. Gastric cancer is one of the most common tumors and the third leading cause of cancer-related deaths worldwide. Although trastuzumab is associated with a survival gain among patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer, optimal patient selection is challenging. The purpose of this study was to determine whether CT texture features of HER2-positive gastric cancer were related to the survival rate after trastuzumab treatment. Methods and Findings: Patients diagnosed with HER2-positive advanced gastric cancer from February 2007 to August 2014 were retrospectively selected. Using in-house built software, histogram features (kurtosis and skewness) and gray-level co-occurrence matrices (GLCM) features (angular second moment [ASM], contrast, entropy, variance, and correlation) were derived from the CT images of HER2-positive advanced gastric cancer in 26 patients. All the patients were followed up for more than 6 months, with no confirmed deaths. The patients were dichotomized into a good and poor survival group based on cutoff points of overall survival of 12 months. A receiver-operating characteristics (ROC) analysis was performed to test the ability of each texture parameter to identify the good survival group. Kaplan–Meier curves for patients above and below each threshold were constructed. Using a threshold of >265.8480 for contrast, >488.3150 for variance, and ≤0.1319×10−3. for correlation, all of the area under the ROC curves showed fair accuracy (>0.7). Kaplan–Meier analysis showed statistically significant survival difference between two groups according to optimal cutoff values of contrast, variance, correlation and ASM. However, as this study had a small number of patients, a further study with a larger population will be needed to validate the results. Conclusions: Heterogeneous texture features on CT images were associated with better survival in patients with HER2-positive advanced gastric cancer who received trastuzumab-based treatment. Therefore, texture analysis shows potential to be a clinically useful imaging biomarker providing additional prognostic information for patient selection. [ABSTRACT FROM AUTHOR]

Purpose: This is a clinical study to compare noninvasive hypoxia imaging using 18F-fluoroerythronitroimidazole (18F-FETNIM) and 18F-fluoromisonidazole (18F-FMISO) positron emission tomography/computed tomography (PET/CT) in patients with inoperable stages III–IV lung cancer. Methods: A total of forty-two patients with inoperable stages III–IV lung cancer underwent 18F-FETNIM PET/CT (n = 18) and 18F-FMISO PET/CT (n = 24) before chemo/radiation therapy. The standard uptake values (SUVs) of malignant and normal tissues depict 18F-FETNIM PET/CT and 18F-FMISO PET/CT uptake. Tumor-to-blood ratios (T/B) were used to quantify hypoxia. Results: All patients with lung cancer underwent 18F-FETNIM PET/CT and 18F-FMISO PET/CT successfully. Compared to 18F-FMISO, 18F-FETNIM showed similar uptake in muscle, thyroid, spleen, pancreas, heart, lung and different uptake in blood, liver, and kidney. Significantly higher SUV and T/B ratio with 18F-FMISO (2.56±0.77, 1.98±0.54), as compared to 18F-FETNIM (2.12±0.56, 1.42±0.33) were seen in tumor, P = 0.022, <0.001. For the patients with different histopathological subtypes, no significant difference of SUV (or T/B ratio) was observed both in 18F-FMISO and 18F-FETNIM in tumor. A significantly different SUV (or T/B ratio) was detected between < = 2cm, 2~5cm, and >5cm groups in 18F-FMISO PET/CT, P = 0.015 (or P = 0.029), whereas no difference was detected in 18F-FMISO PET/CT, P = 0.446 (or P = 0.707). Both 18F-FETNIM and 18F-FMISO showed significantly higher SUVs (or T/B ratios) in stage IV than stage III, P = 0.021, 0.013 (or P = 0.032, 0.02). Conclusion: 18F-FMISO showed significantly higher uptake than 18F-FETNIM in tumor/non-tumor ratio and might be a better hypoxia tracer in lung cancer. [ABSTRACT FROM AUTHOR]

Purpose: To study the dosimetric difference between fixed-jaw volumetric modulated radiotherapy (FJ-VMAT) and large-field volumetric modulated radiotherapy (LF-VMAT) for nasopharyngeal carcinoma (NPC) with cervical lymph node metastasis. Methods: Computed tomography (CT) datasets of 10 NPC patients undergoing chemoradiotherapy were used to generate LF-VMAT and FJ-VMAT plans in the Eclipse version 10.0 treatment planning system. These two kinds of plans were then compared with respect to planning-target-volume (PTV) coverage, conformity index (CI), homogeneity index (HI), organ-at-risk sparing, monitor units (MUs) and treatment time (TT). Results: The FJ-VMAT plans provided lower D2% of PGTVnd (PTV of lymph nodes), PTV1 (high-risk PTV) and PTV2 (low-risk PTV) than did the LF-VMAT plans, whereas no significant differences were observed in PGTVnx (PTV of primary nasopharyngeal tumor). The FJ-VMAT plans provided lower doses delivered to the planning organ at risk (OAR) volumes (PRVs) of both brainstem and spinal cord, both parotid glands and normal tissue than did the LF-VMAT plans, whereas no significant differences were observed with respect to the oral cavity and larynx. The MUs of the FJ-VMAT plans (683 ± 87) were increased by 22% ± 12% compared with the LF-VMAT plans (559 ± 62). In terms of the TT, no significant difference was found between the two kinds of plans. Conclusions: FJ-VMAT was similar or slightly superior to LF-VMAT in terms of PTV coverage and was significantly superior in terms of OAR sparing, at the expense of increased MUs. [ABSTRACT FROM AUTHOR]

Purpose: Lung cancer screening with CT has been recently recommended for decreasing lung cancer mortality. The radiation dose of CT, however, must be kept as low as reasonably achievable for reducing potential stochastic risks from ionizing radiation. The purpose of this study was to calculate individual patients’ lung doses and to estimate cancer risks in low-dose CT (LDCT) in comparison with a standard dose CT (SDCT) protocol. Materials and Methods: This study included 47 adult patients (mean age 63.0 ± 5.7 years) undergoing chest CT on a third-generation dual-source scanner. 23/47 patients (49%) had a non-enhanced chest SDCT, 24 patients (51%) underwent LDCT at 100 kVp with spectral shaping at a dose equivalent to a chest x-ray. 3D-dose distributions were obtained from Monte Carlo simulations for each patient, taking into account their body size and individual CT protocol. Based on the dose distributions, patient-specific lung doses were calculated and relative cancer risk was estimated according to BEIR VII recommendations. Results: As compared to SDCT, the LDCT protocol allowed for significant organ dose and cancer risk reductions (p<0.001). On average, lung dose was reduced from 7.7 mGy to 0.3 mGy when using LDCT, which was associated with lowering of the cancer risk from 8.6 to 0.35 per 100’000 cases. A strong linear correlation between lung dose and patient effective diameter was found for both protocols (R2 = 0.72 and R2 = 0.75 for SDCT and LDCT, respectively). Conclusion: Use of a LDCT protocol for chest CT with a dose equivalent to a chest x-ray allows for significant lung dose and cancer risk reduction from ionizing radiation. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association between image characteristics on preoperative chest CT and severe pleural adhesion during surgery in lung cancer patients. We included consecutive 124 patients who underwent lung cancer surgeries. Preoperative chest CT was retrospectively reviewed to assess pleural thickening or calcification, pulmonary calcified nodules, active pulmonary inflammation, extent of emphysema, interstitial pneumonitis, and bronchiectasis in the operated thorax. The extent of pleural thickening or calcification was visually estimated and categorized into two groups: localized and diffuse. We measured total size of pulmonary calcified nodules. The extent of emphysema, interstitial pneumonitis, and bronchiectasis was also evaluated with a visual scoring system. The occurrence of severe pleural adhesion during lung cancer surgery was retrospectively investigated from the electrical medical records. We performed logistic regression analysis to determine the association of image characteristic on chest CT with severe pleural adhesion. Localized pleural thickening was found in 8 patients (6.5%), localized pleural calcification in 8 (6.5%), pulmonary calcified nodules in 28 (22.6%), and active pulmonary inflammation in 22 (17.7%). There was no patient with diffuse pleural thickening or calcification in this study. Trivial, mild, and moderate emphysema was found in 31 (25.0%), 21 (16.9%), and 12 (9.7%) patients, respectively. Severe pleural adhesion was found in 31 (25.0%) patients. The association of localized pleural thickening or calcification on CT with severe pleural adhesion was not found (P = 0.405 and 0.107, respectively). Size of pulmonary calcified nodules and extent of emphysema were significant variables in a univariate analysis (P = 0.045 and 0.005, respectively). In a multivariate analysis, moderate emphysema was significantly associated with severe pleural adhesion (odds ratio of 11.202, P = 0.001). In conclusion, severe pleural adhesion might be found during lung cancer surgery, provided that preoperative chest CT shows substantial pulmonary calcified nodules or emphysema. [ABSTRACT FROM AUTHOR]

Background: Transcatheter aortic valve implantation (TAVI) has become the treatment of choice in patients with severe aortic valve stenosis who are not eligible for operative replacement and an alternative for those with high surgical risk. Due to high age and smoking history in a high proportion of TAVI patients, suspicious findings are frequently observed in pre-procedural chest computer tomography (CCT). Methods: CCT scans of 484 consecutive patients undergoing TAVI were evaluated for incidentally discovered solitary pulmonary nodules (SPN). Results: In the entire study population, SPN ≥ 5 mm were found in 87 patients (18%). These patients were compared to 150 patients who were incidentally collected from the 397 patients without SPN or with SPN < 5 mm (control group). After a median follow-up of 455 days, lung cancer was diagnosed in only two patients. Neither SPN ≥ 5 mm (p = 0.579) nor SPN > 8 mm (p = 0.328) were significant predictors of overall survival. Conclusions: Despite the high prevalence of SPNs in this single center TAVI cohort lung cancer incidence at midterm follow-up seems to be low. Thus, aggressive diagnostic approaches for incidentally discovered SPN during TAVI evaluation should not delay the treatment of aortic stenosis. Unless advanced thoracic malignancy is obvious, the well documented reduction of morbidity and mortality by TAVI outweighs potentially harmful delays regarding further diagnostics. Standard guideline-approved procedure for SPN can be safely performed after TAVI. [ABSTRACT FROM AUTHOR]

Objectives: To investigate fused multiparametric positron emission tomography/magnetic resonance imaging (MP PET/MRI) at 3T in patients with locally advanced cervical cancer, using high-resolution T2-weighted, contrast-enhanced MRI (CE-MRI), diffusion-weighted imaging (DWI), and the radiotracers [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoromisonidazol ([18F]FMISO) for the non-invasive detection of tumor heterogeneity for an improved planning of chemo-radiation therapy (CRT). Materials and Methods: Sixteen patients with locally advanced cervix were enrolled in this IRB approved and were examined with fused MP [18F]FDG/ [18F]FMISO PET/MRI and in eleven patients complete data sets were acquired. MP PET/MRI was assessed for tumor volume, enhancement (EH)-kinetics, diffusivity, and [18F]FDG/ [18F]FMISO-avidity. Descriptive statistics and voxel-by-voxel analysis of MRI and PET parameters were performed. Correlations were assessed using multiple correlation analysis. Results: All tumors displayed imaging parameters concordant with cervix cancer, i.e. type II/III EH-kinetics, restricted diffusivity (median ADC 0.80x10-3mm2/sec), [18F]FDG- (median SUVmax16.2) and [18F]FMISO-avidity (median SUVmax3.1). In all patients, [18F]FMISO PET identified the hypoxic tumor subvolume, which was independent of tumor volume. A voxel-by-voxel analysis revealed only weak correlations between the MRI and PET parameters (0.05–0.22), indicating that each individual parameter yields independent information and the presence of tumor heterogeneity. Conclusion: MP [18F]FDG/ [18F]FMISO PET/MRI in patients with cervical cancer facilitates the acquisition of independent predictive and prognostic imaging parameters. MP [18F]FDG/ [18F]FMISO PET/MRI enables insights into tumor biology on multiple levels and provides information on tumor heterogeneity, which has the potential to improve the planning of CRT. [ABSTRACT FROM AUTHOR]

Background: In ALK-positive advanced NSCLC, crizotinib has a high response rate and effectively increases quality of life and survival. CT measurement of the tumor may insufficiently reflect the actual tumor load changes during targeted therapy with crizotinib. We explored whether 18F-FDG PET measured metabolic changes are different from CT based changes and studied the impact of these changes on disease progression. Methods: 18F-FDG PET/CT was performed prior to and after 6 weeks of crizotinib treatment. Tumor response on CT was classified with RECIST 1.1, while 18F-FDG PET response was assessed according to the 1999 EORTC recommendations and PERCIST criteria. Agreement was assessed using McNemars test. During follow-up, patients received additional PET/CT during crizotinib treatment and second generation ALK inhibition. We assessed whether PET was able to detect progression earlier then CT. Results: In this exploratory study 15 patients were analyzed who were treated with crizotinib. There was a good agreement in the applicability of CT and 18F-FDG PET/CT using the EORTC recommendations. During first line crizotinib and subsequent second line ALK inhibitors, PET was able to detect progression earlier then CT in 10/22 (45%) events of progression and in the others disease progression was detected simultaneously. Conclusion: In advanced ALK positive NSCLC PET was able to detect progressive disease earlier than with CT in nearly half of the assessments while both imaging tests performed similar in the others. [ABSTRACT FROM AUTHOR]

Aim: The aim of this retrospective study was to determine whether glucose metabolism assessed by using Fluorine-18 (F-18) fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) provides prognostic information independent of established prognostic factors in patients with Ewing sarcoma. Methods: We retrospectively reviewed the medical records of 34 patients (men, 19; women, 15; mean age, 14.5 ± 9.7 years) with pathologically proven Ewing sarcoma. They had undergone F-18 FDG PET/CT as part of a pretreatment workup between September 2006 and April 2012. In this analysis, patients were classified by age, sex, initial location, size, and maximum standardized uptake value (SUVmax). The relationship between FDG uptake and survival was analyzed using the Kaplan-Meier method with the log-rank test and Cox’s proportional hazards regression model. Results: The median survival time for all 34 subjects was 999 days and the median SUV by using PET/CT was 5.8 (range, 2–18.1). Patients with a SUVmax ≤ 5.8 survived significantly longer than those with a SUVmax > 5.8 (median survival time, 1265 vs. 656 days; p = 0.002). Survival was also found to be significantly related to age (p = 0.024), size (p = 0.03), and initial tumor location (p = 0.036). Multivariate analysis revealed that a higher SUVmax (p = 0.003; confidence interval [CI], 3.63–508.26; hazard ratio [HR], 42.98), older age (p = 0.023; CI, 1.34–54.80; HR, 8.59), and higher stage (p = 0.03; CI, 1.21–43.95; HR, 7.3) were associated with worse overall survival. Conclusions: SUVmax measured by pretreatment F-18-FDG PET/CT can predict overall survival in patients with Ewing sarcoma. [ABSTRACT FROM AUTHOR]

Objectives: We have developed a relevant preclinical model associated with a specific imaging protocol dedicated to onco-pharmacology studies in mice. Materials and Methods: We optimized both the animal model and an ultrasound imaging procedure to follow up longitudinally the lung tumor growth in mice. Moreover we proposed to measure by photoacoustic imaging the intratumoral hypoxia, which is a crucial parameter responsible for resistance to therapies. Finally, we compared ultrasound data to x-ray micro computed tomography and volumetric measurements to validate the relevance of this approach on the NCI-H460 human orthotopic lung tumor. Results: This study demonstrates the ability of ultrasound imaging to detect and monitor the in vivo orthotopic lung tumor growth by high resolution ultrasound imaging. This approach enabled us to characterize key biological parameters such as oxygenation, perfusion status and vascularization of tumors. Conclusion: Such an experimental approach has never been reported previously and it would provide a nonradiative tool for assessment of anticancer therapeutic efficacy in mice. Considering the absence of ultrasound propagation through the lung parenchyma, this strategy requires the implantation of tumors strictly located in the superficial posterior part of the lung. [ABSTRACT FROM AUTHOR]

Background: Inter-observer delineation variation has been detailed for many years in almost every tumor location. Inadequate delineation can impair the chance of cure and/or increase toxicity. The aim of our original work was to prospectively improve the homogeneity of delineation among all of the senior radiation oncologists in the Nord-Pas de Calais region, irrespective of the conditions of practice. Methods: All 11 centers were involved. The first studied cancer was prostate cancer. Three clinical cases were studied: a low-risk prostate cancer case (case 1), a high-risk prostate cancer case (pelvic nodes, case 2) and a case of post-operative biochemical elevated PSA (case 3). All of the involved physicians delineated characteristically the clinical target volume (CTV) and organs at risk. The volumes were compared using validated indexes: the volume ratio (VR), common and additional volumes (CV and AV), volume overlap (VO) and Dice similarity coefficient (DSC). A second delineation of the same three cases was performed after discussion of the slice results and the choice of shared guidelines to evaluate homogenization. A comparative analysis of the indexes before and after discussion was conducted using the Wilcoxon test for paired samples. A p-value less than 0.05 was considered to indicate statistical significance. Results: The indexes were not improved in case 1, for which the inter-observer agreement was considered good after the first comparison (DSC = 0.83±0.06). In case 2, the second comparison showed homogenization of the CTV delineation with a significant improvement in CV (81.4±11.7 vs. 88.6±10.26, respectively, p = 0.048), VO (0.41±0.09 vs. 0.47±0.07, respectively; p = 0.009) and DSC (0.58±0.09 vs. 0.63±0.07, respectively; p = 0.0098). In case 3, VR and AV were significantly improved: VR: 1.71(±0.6) vs. 1.34(±0.46), respectively, p = 0.0034; AV: 46.58(±14.50) vs. 38.08(±15.10), respectively, p = 0.0024. DSC was not improved, but it was already superior to 0.6 in the first comparison. Conclusion: Our prospective work showed that a collaborative discussion about clinical cases and the choice of shared guidelines within an established framework improved the homogeneity of CTV delineation among the senior radiation oncologists in our region. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate whether early reductions in CT perfusion parameters predict response to pre-operative chemotherapy prior to surgery for gastroesophageal junction (GEJ) and gastric cancer. Materials and Methods: Twenty-eight patients with adenocarcinoma of the gastro-esophageal junction (GEJ) and stomach were included. Patients received three series of chemotherapy before surgery, each consisting of a 3-week cycle of intravenous epirubicin, cisplatin or oxaliplatin, concomitant with capecitabine peroral. The patients were evaluated with a CT perfusion scan prior to, after the first series of, and after three series of chemotherapy. The CT perfusion scans were performed using a 320-detector row scanner. Tumour volume and perfusion parameters (arterial flow, blood volume and permeability) were computed on a dedicated workstation with a consensus between two radiologists. Response to chemotherapy was evaluated by two measures. Clinical response was defined as a tumour size reduction of more than 50%. Histological response was evaluated based on residual tumour cells in the surgical specimen using the standardized Mandard Score 1 to 5, in which values of 1 and 2 were classified as responders, and 3 to 5 were classified as nonresponders. Results: A decrease in tumour permeability after one series of chemotherapy was positively correlated with clinical response after three series of chemotherapy. Significant changes in permeability and tumour volume were apparent after three series of chemotherapy in both clinical and histological responders. A cut-off value of more than 25% reduction in tumour permeability yielded a sensitivity of 69% and a specificity of 58% for predicting clinical response. Conclusion: Early decrease in permeability is correlated with the likelihood of clinical response to pre-operative chemotherapy in GEJ and gastric cancer. As a single diagnostic test, CT Perfusion only has moderate sensitivity and specificity in response assessment of pre-operative chemotherapy making it insufficient for clinical decision purposes. [ABSTRACT FROM AUTHOR]