radiation-planning-assistant-streamlined-fully-automated-radiotherapy

Radiation Planning Assistant - A Streamlined, Fully Automated Radiotherapy Treatment Planning System

The Radiation Planning Assistant (RPA) is a system developed for the fully automated creation of radiotherapy treatment plans, including volume-modulated ...

Respiratory motion causes movement of internal structures in the thorax and abdomen, making accurate delivery of radiation therapy to tumors in those areas a challenge. To reduce the uncertainties caused by this motion, we have developed feedback-guided breath hold (FGBH), a novel delivery technique in which radiation is delivered only during a voluntary breath hold that is sustained for as long as the patient feels comfortable. Here we present the technical aspects of FGBH, which involve (1) fabricating the hardware so the respiratory trace can be displayed to the patient, (2) assembling a delay box to be used as a breath-hold detector, and (3) performing quality control tests to ensure that FGBH can be delivered accurately and safely. A commercial respiratory tracking system that uses an external fiducial to monitor abdominal wall motion generates and displays the breathing trace and specific positions in the breathing cycle where a breath hold needs to occur. Hardware was developed to present this display to the patient in the treatment position. Patients view the presentation either on a liquid crystal display or through a pair of virtual reality goggles. Using the respiratory trace as a visual aid, the patient performs a breath hold so that the position representing the location of a fiducial is held within a specified gating window. A delay box was fabricated to differentiate between gating signals received during free breathing and those received during breath hold, allowing radiation delivery only when the fiducial was within the breath-hold gating window. A quality control analysis of the gating delay box and the integrated system was performed to ensure that all of the hardware and components were ready for clinical use.

Respiration-correlated treatment delivery using feedback-guided breath hold: a technical study.

The purpose of this work was to assess the magnitude of setup uncertainties and respiratory-induced motion of lung tumors by monitoring the location of fiducials implanted in the vicinity of the tumors.

Assessment of lung tumor motion and setup uncertainties using implanted fiducials.

This study aimed to validate and implement a methodology in which fiducials implanted in the periphery of lung tumors can be used to reduce uncertainties in tumor location. Alignment software that matches marker positions on two-dimensional (2D) kilovoltage portal images to positions on three-dimensional (3D) computed tomography data sets was validated using static and moving phantoms. This software also was used to reduce uncertainties in tumor location in a patient with fiducials implanted in the periphery of a lung tumor. Alignment of fiducial locations in orthogonal projection images with corresponding fiducial locations in 3D data sets can position both static and moving phantoms with an accuracy of 1 mm. In a patient, alignment based on fiducial locations reduced systematic errors in the left-right direction by 3 mm and random errors by 2 mm, and random errors in the superior-inferior direction by 3 mm as measured by anterior-posterior cine images. Software that matches fiducial markers on 2D and 3D images is effective for aligning both static and moving fiducials before treatment and can be implemented to reduce patient setup uncertainties.

A technique for reducing patient setup uncertainties by aligning and verifying daily positioning of a moving tumor using implanted fiducials.

To evaluate the margins currently used to generate the planning target volume for lung tumors and to determine whether image-guided patient setup or respiratory gating is more effective in reducing uncertainties in tumor position.

Evaluation of tumor position and PTV margins using image guidance and respiratory gating.

A dose calculation verification system (VS) was acquired and commissioned as a second check on the treatment planning system (TPS). This system reads DICOM CT datasets, RT plans, RT structures, and RT dose from the TPS and automatically, using its own collapsed cone superposition/convolution algorithm, computes dose on the same CT dataset. The system was commissioned by extracting basic beam parameters for simple field geometries and dose verification for complex treatments. Percent depth doses (PDD) and profiles were extracted for field sizes using jaw settings 3 × 3 cm2 - 40 × 40 cm2 and compared to measured data, as well as our TPS model. Smaller fields of 1 × 1 cm2 and 2 × 2 cm2 generated using the multileaf collimator (MLC) were analyzed in the same fashion as the open fields. In addition, 40 patient plans consisting of both IMRT and VMAT were computed and the following comparisons were made: 1) TPS to the VS, 2) VS to measured data, and 3) TPS to measured data where measured data is both ion chamber (IC) and film measurements. Our results indicated for all field sizes using jaw settings PDD errors for the VS on average were less than 0.87%, 1.38%, and 1.07% for 6x, 15x, and 18x, respectively, relative to measured data. PDD errors for MLC field sizes were less than 2.28%, 1.02%, and 2.23% for 6x, 15x, and 18x, respectively. The infield profile analysis yielded results less than 0.58% for 6x, 0.61% for 15x, and 0.77% for 18x for the VS relative to measured data. Analysis of the penumbra region yields results ranging from 66.5% points, meeting the DTA criteria to 100% of the points for smaller field sizes for all energies. Analysis of profile data for field sizes generated using the MLC saw agreement with infield DTA analysis ranging from 68.8%-100% points passing the 1.5%/1.5 mm criteria. Results from the dose verification for IMRT and VMAT beams indicated that, on average, the ratio of TPS to IC and VS to IC measurements was 100.5 ± 1.9% and 100.4 ± 1.3%, respectively, while our TPS to VS was 100.1 ± 1.0%. When comparing the TPS and VS to film measurements, the average percentage pixels passing a 3%/3mm criteria based gamma analysis were 96.6 ± 4.2% and 97 ± 5.6%, respectively. When the VS was compared to the TPS, on average 98.1 ± 5.3% of pixels passed the gamma analysis. Based upon these preliminary results, the VS system should be able to calculate dose adequately as a verification tool of our TPS.

Commissioning results of an automated treatment planning verification system.

For left-sided breast cancer, radiation to the heart is a concern. We present a comparison of mean heart and coronary artery biologically effective dose (BED) between accelerated partial breast irradiation (APBI) and whole breast irradiation with deep inspiration breath-hold technique (DIBH-WBI).

Lower mean heart dose with deep inspiration breath hold-whole breast irradiation compared with brachytherapy-based accelerated partial breast irradiation for women with left-sided tumors.

Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.

Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.

Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.

In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.

Article	Year
Respiration-correlated treatment delivery using feedback-guided breath hold: a technical study. Medical physics\| PubMed ID: 15719968	2005
Assessment of lung tumor motion and setup uncertainties using implanted fiducials. International journal of radiation oncology, biology, physics\| PubMed ID: 17293241	2007
A technique for reducing patient setup uncertainties by aligning and verifying daily positioning of a moving tumor using implanted fiducials. Journal of applied clinical medical physics\| PubMed ID: 19020478	2008
Evaluation of tumor position and PTV margins using image guidance and respiratory gating. International journal of radiation oncology, biology, physics\| PubMed ID: 20137865	2010
Commissioning results of an automated treatment planning verification system. Journal of applied clinical medical physics\| PubMed ID: 25207567	2014
Lower mean heart dose with deep inspiration breath hold-whole breast irradiation compared with brachytherapy-based accelerated partial breast irradiation for women with left-sided tumors. Practical radiation oncology\| PubMed ID: 28274398	2017
Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nature genetics\| PubMed ID: 29273807	2018
Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nature genetics\| PubMed ID: 29549329	2018
Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity. Nature genetics\| PubMed ID: 29549330	2018

Christopher Nelson

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