Why we need systematic reviews and meta-analyses in the testing and assessment literature

Multivariate analysis of psychological dat

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment

The Influence of Dosimetric Parameters on Quality of Life for Early Stage Non-small Cell Lung Cancer Patients Treated with Stereotactic Body Radiation Therapy

Background: Lung stereotactic body radiotherapy (SBRT) has become a standard treatment option for early stage non-small cell lung cancer (NSCLC) patients who are medically inoperable. The influence of radiation dose/volume parameters on quality of life is not known. Our hypothesis is that clinically meaningful declines in quality of life over time will be associated with increased radiation lung dose/volume parameters. Objectives: To investigate clinical toxicity and quality of life (QOL) outcomes of stage I NSCLC patients after SBRT as a function of radiation dose/volume parameters. Methods: In this IRB-approved study, 55 stage I NSCLC patients who received SBRT (12 Gy x 4) and completed QOL forms were analyzed. Clinical symptoms and QOL were measured at baseline and at 3, 6, 12, 18, 24, and 36 months post-SBRT. Clinical toxicity was graded using the common terminology criteria for adverse effects (CTCAE v4.0). Quality of life was followed using the validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) instrument. Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving \u3e 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were measured from the radiation treatment plan. Student\u27s t-test and Pearson correlation analyses were used to examine the relationships between radiation lung metrics and clinically meaningful changes in QOL and/or clinical toxicities. Kaplan-Meier method was used to estimate rates of local control (LC), disease free survival (DFS), and overall survival (OS). Results: With a median follow-up of 24 months, the 3 year LC, DFS, and OS were 93%, 65% and 84%, respectively, with 5.5% grade 3 toxicity and no grade 4 or 5 toxicities. Clinically meaningful declines in patient reported QOL (FACT-TOI, lung cancer subscale, physical well-being, and/or functional well-being) post-treatment significantly correlated with increased dosimetric parameters, such as V10, V13, and V20. Conclusions: While lung SBRT is associated with excellent LC and minimal clinical toxicity for early stage NSCLC, clinically meaningful declines in QOL significantly correlated with increasing lung dose/volume parameters. This suggests that further improvements in the techniques of lung SBRT have the potential to further enhance patients\u27 QOL following this treatment

Indoor robot gardening: design and implementation

This paper describes the architecture and implementation of a distributed autonomous gardening system with applications in urban/indoor precision agriculture. The garden is a mesh network of robots and plants. The gardening robots are mobile manipulators with an eye-in-hand camera. They are capable of locating plants in the garden, watering them, and locating and grasping fruit. The plants are potted cherry tomatoes enhanced with sensors and computation to monitor their well-being (e.g. soil humidity, state of fruits) and with networking to communicate servicing requests to the robots. By embedding sensing, computation, and communication into the pots, task allocation in the system is de-centrally coordinated, which makes the system scalable and robust against the failure of a centralized agent. We describe the architecture of this system and present experimental results for navigation, object recognition, and manipulation as well as challenges that lie ahead toward autonomous precision agriculture with multi-robot teams.Swiss National Science Foundation (contract number PBEL2118737)United States. Army Research Office. Multidisciplinary University Research Initiative (MURI SWARMS project W911NF-05-1-0219)National Science Foundation (U.S.) (NSF IIS-0426838)Intel Corporation (EFRI 0735953 Intel)Massachusetts Institute of Technology (UROP program)Massachusetts Institute of Technology (MSRP program

Learn2Reg: comprehensive multi-task medical image registration challenge, dataset and evaluation in the era of deep learning

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Benchmarking of 4D CBCT Based Dose Calculation Against Measurements in a Lung Phantom

Purpose To quantify 4DCBCT dose calculation accuracy of lung SBRT plans by comparing the calculated dose to the measured dose on an anthropomorphic phantom. Methods: 4DCBCTs were taken of a CIRS lung phantom using the RPM system (Varian). Scans were acquired with our clinical lung scan protocol, which compromises between SNR and imaging dose (gantry rotation speed of 3 degrees/s). Images were binned into 10 phases, and dose was calculated on each phase using the AAA algorithm in Eclipse v15.5(Varian). Computed dose for each phase was summed to give the total dose per beam. Breathing motion was simulated by moving the couch 1.5 cm superior/inferior and 0.5 cm anterior/posterior. Developer mode was used to transpose the couch while the beams were delivered. For comparison, 4DCBCTs and measurements were acquired without couch motion to determine if motion affects the dose accuracy. Doses were measured with an IBA CC01 chamber. Patient plan prescriptions ranged from 48 to 56 Gy in 4 fractions. Results: Mean measured versus calculated dose differences were-1.0 ± 1.6% for deliveries with motion and-0.1 ± 1.0% for static deliveries. For each plan, dose calculations were within 3% of measurement. The overall mean coefficient of variation of calculated dose over the 10 phases was 3.8 ± 1.4% per beam, which gives insight into the dose uncertainty caused by limited projection data per phase. Conclusion: This study demonstrated the overall 4DCBCT dose calculation accuracy on an anthropomorphic phantom is within 4.1% (95% CI), with per phase dose calculation uncertainty of 6.5% (95% CI). Calculation and measurement dose differences between the phantom moving and static were within delivery uncertainty. Future work will examine using iterative CBCT (iCBCT) reconstruction to decrease noise and artifacts, with the hypothesized goal of decreasing calculation uncertainty

A Prospective Analysis of Quality of Life Data and Clinical Toxicity as a Function of Radiation Dose and Volume in Stage I Lung Cancer Patients after SBRT

Background: Stereotactic body radiation therapy (SBRT) is an appropriate treatment option for patients with stage I non-small cell lung cancer (NSCLC) who are not surgical candidates. As these patients often present with significant co-morbidities, quality of life (QOL) outcomes are especially important. Objectives: To use a validated patient reported quality of life (QOL) assessment tool to measure clinical toxicity and patient reported quality of life (QOL) outcomes up to 36 months after SBRT in stage I NSCLC patients based on pre-treatment dosimetric parameters and tumor volumes. Methods: Fifty-six stage I NSCLC patients treated with SBRT (12 Gy x 4) were prospectively monitored for symptoms including cough, dyspnea, fatigue, and pneumonitis. Symptoms were measured at baseline (before treatment), immediately after treatment and 3, 6, 12, 18, 24, and 36 months post-treatment. Toxicity was graded from zero to five following the Charlson comorbidity and toxicity index. Quality of life was determined using the previously-validated Functional Assessment of Cancer Therapy-Trial Outcome Index (FACT-TOI) Lung questionnaire which incorporated three subscale endpoints: lung subscale (LSC), physical well-being (PWB) and functional well-being (FWB). Dosimetric parameters, including the mean lung radiation dose (MLD), and the volume of normal lung receiving at least 5, 10, 13 or 20 Gy (V5, V10, V13, and V20) were obtained from the treatment plan. Pearson correlation and student t-test analyses were used to measure correlations and distinguish between lung metrics with QOL and clinical toxicities. Results: SBRT produced minimal toxicities. QOL (TOI, LSC, PWB, or FWB) at 3, 6, 12 and 24 months post-treatment were significantly correlated with V5, V10, V13, V20, or MLD. Radiation pneumonitis showed mild positive but statistically significant (P \u3c 0.05) correlation with V20. Moreover, FWB at 3 months showed mild negative correlation with dyspnea. Conclusions: Lung SBRT treatment for patients with NSCLC, using a 12 Gy x 4 dose regimen, was well tolerated with minimal toxicity observed. A validated patient related quality of life assessment tool was used to identify the dosimetric parameters most crucial for treatment planning. Further follow-up is recommended

Characterization of the Response of 9L and U-251N Orthotopic Brain Tumors to 3D Conformal Radiation Therapy

In a study employing MRI-guided stereotactic radiotherapy (SRS) in two orthotopic rodent brain tumor models, the radiation dose yielding 50% survival (the TCD50) was sought. Syngeneic 9L cells, or human U-251N cells, were implanted stereotactically in 136 Fischer 344 rats or 98 RNU athymic rats, respectively. At approximately 7 days after implantation for 9L, and 18 days for U-251N, rats were imaged with contrast-enhanced MRI (CE-MRI) and then irradiated using a Small Animal Radiation Research Platform (SARRP) operating at 220 kV and 13 mA with an effective energy of ∼70 keV and dose rate of ∼2.5 Gy per min. Radiation doses were delivered as single fractions. Cone-beam CT images were acquired before irradiation, and tumor volumes were defined using co-registered CE-MRI images. Treatment planning using MuriPlan software defined four non-coplanar arcs with an identical isocenter, subsequently accomplished by the SARRP. Thus, the treatment workflow emulated that of current clinical practice. The study endpoint was animal survival to 200 days. The TCD50 inferred from Kaplan-Meier survival estimation was approximately 25 Gy for 9L tumors and below 20 Gy, but within the 95% confidence interval in U-251N tumors. Cox proportional-hazards modeling did not suggest an effect of sex, with the caveat of wide confidence intervals. Having identified the radiation dose at which approximately half of a group of animals was cured, the biological parameters that accompany radiation response can be examined