Stereotactic magnetic resonance (MR)-guided adaptive radiotherapy (SMART) for renal cell carcinoma may result in more precise treatment delivery through the capabilities for improved image quality, daily adaptive planning, and accounting for respiratory motion during treatment with real-time MR tracking. In this study, we aimed to characterize the safety and feasibility of SMART for localized kidney cancer. Twenty patients with localized kidney cancer (ten treated in a prospective phase 1 trial and ten in the supplemental cohort) were treated to 40 Gy in five fractions on a 0.35 T MR-guided linear accelerator with daily adaptive planning and a cine MR-guided inspiratory breath hold technique. The median follow-up time was 17 mo (interquartile range: 13-20 months). A single patient developed local failure at 30 mo. No grade ≥3 adverse events were reported. The mean decrease in estimated glomerular filtration rate was -1.8 ml/min/1.73 m2 (95% confidence interval or CI [-6.6 to 3.1 ml/min/1.73 m2]), and the mean decrease in tumor diameter was -0.20 cm (95% CI [-0.6 to 0.2 cm]) at the last follow-up. Anterior location and overlap of the 25 or 28 Gy isodose line with gastrointestinal organs at risk were predictive of the benefit from online adaptive planning. Kidney SMART is feasible and, at the early time point evaluated in this study, was well tolerated with minimal decline in renal function. More studies are warranted to further evaluate the safety and efficacy of this technique. PATIENT SUMMARY: For patients with localized renal cell carcinoma who are not surgical candidates, stereotactic magnetic resonance--guided adaptive radiotherapy is a feasible and safe noninvasive treatment option that results in minimal impact on kidney function.

A method for generating fluoroscopic (time-varying) volumetric images using patient-specific motion models derived from four-dimensional cone-beam CT (4D-CBCT) images was developed. 4D-CBCT images acquired immediately prior to treatment have the potential to accurately represent patient anatomy and respiration during treatment. Fluoroscopic 3D image estimation is performed in two steps: (1) deriving motion models and (2) optimization. To derive motion models, every phase in a 4D-CBCT set is registered to a reference phase chosen from the same set using deformable image registration (DIR). Principal components analysis (PCA) is used to reduce the dimensionality of the displacement vector fields (DVFs) resulting from DIR into a few vectors representing organ motion found in the DVFs. The PCA motion models are optimized iteratively by comparing a cone-beam CT (CBCT) projection to a simulated projection computed from both the motion model and a reference 4D-CBCT phase, resulting in a sequence of fluoroscopic 3D images. Patient datasets were used to evaluate the method by estimating the tumor location in the generated images compared to manually defined ground truth positions. Experimental results showed that the average tumor mean absolute error (MAE) along the superior–inferior (SI) direction and the 95th percentile in two patient datasets were 2.29 and 5.79 mm for patient 1, and 1.89 and 4.82 mm for patient 2. This study demonstrated the feasibility of deriving 4D-CBCT-based PCA motion models that have the potential to account for the 3D non-rigid patient motion and localize tumors and other patient anatomical structures on the day of treatment.

Purpose: Stereotactic magnetic resonance (MR)–guided adaptive radiation therapy (SMART) for prostate cancer allows for MR-based contouring, real-time MR motion management, and daily plan adaptation. The clinical and dosimetric benefits associated with prostate SMART remain largely unknown. Methods and Materials: A phase 1 trial of prostate SMART was conducted with primary endpoints of safety and feasibility. An additional cohort of patients similarly treated with prostate SMART were included in the analysis. SMART was delivered to 36.25 Gy in 5 fractions to the prostate ± seminal vesicles using the MRIdian linear accelerator system (ViewRay, Inc). Rates of urinary and gastrointestinal toxic effects and patient-reported outcome measures were assessed. Dosimetric analyses were conducted to evaluate the specific benefits of daily plan adaptation. Results: The cohort included 22 patients (n = 10 phase 1, n = 12 supplemental) treated in 110 fractions. Median follow-up was 7.9 months. Acute grade 2 urinary and gastrointestinal toxic effects were observed in 22.7% and 4.5%, respectively, and 4.5% and 0%, respectively, at last follow-up. No grade 3+ events were observed. Expanded Prostate Cancer Index-26 urinary obstructive scores decreased during SMART (mean, 9.3 points; P = .03) and returned to baseline by 3 months. No other significant changes in patient-reported outcome measures were observed. One-hundred percent of fractions required plan adaptation owing to exceeding organ-at-risk metrics (68%) or suboptimal target coverage (33%) resulting from anatomic changes. Minimum acceptable planning target volume, rectal, bladder, and urethra/bladder neck metrics were violated in 24%, 20%, 24%, and 33% of predicted plans, respectively; 0% of reoptimized plans violated metrics. Underlying causes for deficient dosimetry before reoptimization included changes in bladder filling, seminal vesicle position, prostate volume (median 4.7% increase by fraction 3; range, 0%-56%), and hotspots shifting into urethra/bladder neck. Conclusions: Prostate SMART results in low risk of acute toxic effects with improvements in target and organ-at-risk dosimetry. The clinical benefits resulting from daily plan adaptation, including urethra/bladder neck protection, warrant further investigation.

Although finished genomes have become more common, there is still a need for assemblies of individual genes or chromosomal regions when only unassembled reads are available. slag (Seeded Local Assembly of Genes) fulfils this need by performing iterative local assembly based on cycles of matching-read retrieval with blast and assembly with cap3, phrap, spades, canu or unicycler. The target sequence can be nucleotide or protein. Read fragmentation allows slag to use phrap or cap3 to assemble long reads at lower coverage (e.g., 5×) than is possible with canu or unicycler. In simple, nonrepetitive genomes, a slag assembly can cover a whole chromosome, but in complex genomes the growth of target-matching contigs is limited as additional reads are consumed by consensus contigs consisting of repetitive elements. Apart from genomic complexity, contig length and correctness depend on read length and accuracy. With pyrosequencing or Illumina reads, slag-assembled contigs are accurate enough to allow design of PCR primers, while contigs assembled from Oxford Nanopore or pre-HiFi Pacific Biosciences long reads are generally only accurate enough to design baiting sequences for further targeted sequencing. In an application with real reads, slag successfully extended sequences for four wheat genes, which were verified by cloning and Sanger sequencing of overlapping amplicons. slag is a robust alternative to atram2 for local assemblies, especially for read sets with less than 20× coverage. slag is freely available at https://github.com/cfcrane/SLAG.

Simultaneous acquisition of cone beam CT (CBCT) projections using both the kV and MV imagers of an image guided radiotherapy system reduces set-up scan times-a benefit to lung cancer radiation oncology patients-but increases noise in the 3D reconstruction. In this article, we present a kV-MV scan time reduction technique that uses two noise-reducing measures to achieve superior performance. The first is a high-DQE multi-layer MV imager prototype. The second is a beam hardening correction algorithm which combines poly-energetic modeling with edge-preserving, regularized smoothing of the projections. Performance was tested in real acquisitions of the Catphan 604 and a thorax phantom. Percent noise was quantified from voxel values in a soft tissue volume of interest (VOI) while edge blur was quantified from a VOI straddling a boundary between air and soft material. Comparisons in noise/resolution performance trade-off were made between our proposed approach, a dose-equivalent kV-only scan, and a kV-MV reconstruction technique previously published by Yin et al (2005 Med. Phys. 32 9). The proposed technique demonstrated lower noise as a function of spatial resolution than the baseline kV-MV method, notably a 50% noise reduction at typical edge blur levels. Our proposed method also exhibited fainter non-uniformity artifacts and in some cases superior contrast. Overall, we find that the combination of a multi-layer MV imager, acquiring at a LINAC source energy of 2.5 MV, and a denoised beam hardening correction algorithm enables noise, resolution, and dose performance comparable to standard kV-imager only set-up CBCT, but with nearly half the gantry rotation time.

STUDY OBJECTIVE:Adolescent menstrual dysfunction (AMD) is a common cause of iron deficiency anemia and absences from school. The management of AMD with single- and double-dose desogestrel is largely on the basis of anecdotal evidence. Our aim was to describe the effectiveness and safety of both dosing strategies in our clinic cohort to help guide future management.DESIGN:Local service evaluation with retrospective analysis of clinic notes.SETTING:Adolescent gynecology clinic in a tertiary pediatric center in the North West of England.PARTICIPANTS:Adolescent girls (10-18 years of age) with AMD (n = 129).INTERVENTIONS:Single-dose (75 µg) desogestrel vs double-dose (150 µg) desogestrel.MAIN OUTCOME MEASURES:Prevalence of amenorrhea and light spotting, side effects, and discontinuation rates of both dosing regimens.RESULTS:Forty-three of 87 (49%) adolescent girls who started treatment with a double dose of desogestrel were amenorrheic/experienced light spotting, compared with 7/40 (18%) of girls who started treatment with a single dose (P = .001). Patients taking a double dose of desogestrel were less likely to discontinue overall (double: 45/89 [51%]; vs single: 35/40 [88%]; P < .001) and there was no evidence of an increase in nonbleeding side effects (double: 30/89 [34%]; vs single: 15/40 [38%]; P = .68).CONCLUSION:Our findings provide evidence that a double dose of desogestrel is associated with a higher prevalence of amenorrhea and light spotting compared with a single dose in adolescent girls with AMD. However, larger studies are needed to further inform clinical guidelines.

The aim of this paper is to quantify the day-to-day variations of motion models derived from pre-treatment 4-dimensional cone beam CT (4DCBCT) fractions for lung cancer stereotactic body radiotherapy (SBRT) patients. Motion models are built by (1) applying deformable image registration (DIR) on each 4DCBCT image with respect to a reference image from that day, resulting in a set of displacement vector fields (DVFs), and (2) applying principal component analysis (PCA) on the DVFs to obtain principal components representing a motion model. Variations were quantified by comparing the PCA eigenvectors of the motion model built from the first day of treatment to the corresponding eigenvectors of the other motion models built from each successive day of treatment. Three metrics were used to quantify the variations: root mean squared (RMS) difference in the vectors, directional similarity, and an introduced metric called the Euclidean Model Norm (EMN). EMN quantifies the degree to which a motion model derived from the first fraction can represent the motion models of subsequent fractions. Twenty-one 4DCBCT scans from five SBRT patient treatments were used in this retrospective study. Experimental results demonstrated that the first two eigenvectors of motion models across all fractions have smaller RMS (0.00017), larger directional similarity (0.528), and larger EMN (0.678) than the last three eigenvectors (RMS: 0.00025, directional similarity: 0.041, and EMN: 0.212). The study concluded that, while the motion model eigenvectors varied from fraction to fraction, the first few eigenvectors were shown to be more stable across treatment fractions than others. This supports the notion that a pre-treatment motion model built from the first few PCA eigenvectors may remain valid throughout a treatment course. Future work is necessary to quantify how day-to-day variations in these models will affect motion reconstruction accuracy for specific clinical tasks.

Hessian fly is among the major pests of wheat (Triticum spp.) around the world. We evaluated 18 tetraploid (4X) or durum accessions [Triticum turgidum L. ssp. durum (Desf.) van Slageren], which were sourced from the USDA-ARS National Small Grains Collection. Two of the most virulent strains of Hessian fly, vH9 and Biotype L, were used to assess the reaction of germplasm to larval attack. A susceptible hexaploid wheat accession (CItr 17790, also known as 'Len') and a resistant tetraploid wheat accession (PI 134942, which is a donor of resistance gene H33), were included as controls during the test. We confirmed previously reported resistant germplasm and identified two novel germplasm accessions that exhibited a clear resistance against vH9 and Biotype L infestation. The data showed that Trigo 87 (Reg. no. GP-1046, PI 519832, a durum accession from Lebanon) and Iumillo (Reg. no. GP-1047, PI 519716, a durum accession from India) are both resistant to vH9 infestation. In addition, Trigo 87 is also resistant to Biotype L infestation, while the resistance of Iumillo to Biotype L was inconclusive. These wheat lines can be used directly in durum breeding programs. Moreover, the resistance genes can be transferred to hexaploid wheat backgrounds for use especially in the eastern and southeastern United States, where few options for resistance are available.

Tumor tracking during radiotherapy treatment can improve dose accuracy, conformity and sparing of healthy tissue. Many methods have been introduced to tackle this challenge utilizing multiple imaging modalities, including a template matching based approach using the megavoltage (MV) on-board portal imager demonstrated on 3D conformal treatments. However, the complexity of treatments is evolving with the introduction of VMAT and IMRT, and successful motion management is becoming more important due to a trend towards hypofractionation. We have developed a markerless lung tumor tracking algorithm, utilizing the electronic portal imager (EPID) of the treatment machine. The algorithm has been specifically adapted to track during complex treatment deliveries with gantry and MLC motion. The core of the algorithm is an adaptive template matching method that relies on template stability metrics and local relative orientations to perform multiple feature tracking simultaneously. Only a single image is required to initialize the algorithm and features are automatically added, modified or removed in response to the input images. This algorithm was evaluated against images collected during VMAT arcs of a dynamic thorax phantom. Dynamic phantom images were collected during radiation delivery for multiple lung SBRT breathing traces and an example patient data set. The tracking error was 1.34 mm for the phantom data and 0.68 mm for the patient data. A multi-region, markerless tracking algorithm has been developed, capable of tracking multiple features simultaneously without requiring any other a priori information. This novel approach delivers robust target localization during complex treatment delivery. The reported tracking error is similar to previous reports for 3D conformal treatments.