Diaphragm and abdominal organ motion during radiotherapy: a comprehensive multicenter study in 189 children.

BACKGROUND: For accurate thoracic and abdominal radiotherapy, inter- and intrafractional geometrical uncertainties need to be considered to enable accurate margin sizes. We aim to quantify interfractional diaphragm and abdominal organ position variations, and intrafractional diaphragm motion in a large multicenter cohort of pediatric cancer patients (< 18 years). We investigated the correlation of interfractional position variations and intrafractional motion with age, and with general anesthesia (GA). METHODS: In 189 children (mean age 8.1; range 0.4-17.9 years) from six institutes, interfractional position variation of both hemidiaphragms, spleen, liver, left and right kidneys was quantified using a two-step registration. CBCTs were registered to the reference CT relative to the bony anatomy, followed by organ registration. We calculated the group mean, systematic and random errors (standard deviations Σ and σ, respectively) in cranial-caudal (CC), left-right and anterior-posterior directions. Intrafractional right hemidiaphragm motion was quantified using CBCTs on which the breathing amplitude, defined as the difference between end-inspiration and end-expiration peaks, was assessed (N = 79). We investigated correlations with age (Spearman's ρ), and differences in motion between patients treated with and without GA (N = 75; all < 5.5 years). RESULTS: Interfractional group means were largest in CC direction and varied widely between patients, with largest variations in the right hemidiaphragm (range -13.0-17.5 mm). Interfractional group mean of the left kidney showed a borderline significant correlation with age (p = 0.047; ρ = 0.17). Intrafractional right hemidiaphragm motion in patients ≥ 5.5 years (mean 10.3 mm) was significantly larger compared to patients < 5.5 years treated without GA (mean 8.3 mm) (p = 0.02), with smaller Σ and σ values. We found a significant correlation between breathing amplitude and age (p < 0.001; ρ = 0.43). Interfractional right hemidiaphragm position variations were significantly smaller in patients < 5.5 years treated with GA than without GA (p = 0.004), but intrafractional motion showed no significant difference. CONCLUSION: In this large multicenter cohort of children undergoing thoracic and abdominal radiotherapy, we found that interfractional position variation does not depend on age, but the use of GA in patients < 5.5 years showed smaller systematic and random errors. Furthermore, our results showed that breathing amplitude increases with age. Moreover, variations between patients advocate the need for a patient-specific margin approach.

Pediatric radiotherapy for thoracic and abdominal targets: Organ motion, reported margin sizes, and delineation variations - A systematic review.

For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and delineation variability. For pediatric patients no standardized margins are defined. Moreover, studies on these geometrical uncertainties are relatively scarce. Therefore, this systematic review presents an overview of organ motion, applied margin sizes and delineation variability in patients <18 years. A search from January 2000 to March 2021 in Medline, Embase, Web of Science, ClinicalTrials.gov and the International Trials Registry Platform resulted in the inclusion of 117 studies reporting on organ motion, margin sizes and/or delineation variability. Studies were heterogeneous concerning age, tumor types, the use of general anesthesia, imaging modalities; image guidance techniques were reported in 39% of the studies. Inter- and intrafractional motion as reported for different organs was largest in cranio-caudal direction and ranged from -9.1 to 10.0 mm and -4.4 to 19.5 mm, respectively. Motion quantification methodologies differed between studies regarding measures of displacement and definitions of motion direction. Reported CTV-PTV margins varied from 3 to 20 mm for both thoracic and abdominal targets, and for spinal and pelvic from 3to 15 mm and 3 to 10 mm, respectively. Studies reported wide variation in interobserver variability of target volume delineation, which may affect dose distributions to both target volumes and organs at risk. Results of this review indicate possible reduction of margin sizes for children, however, wide variation in organ motion and delineation variability caused by differences in methodologies and outcomes hamper the use of standardized margins.

Design and evaluation of a modular multimodality imaging phantom to simulate heterogeneous uptake and enhancement patterns for radiomic quantification in hybrid imaging: A feasibility study.

BACKGROUND: Accuracy and precision assessment in radiomic features is important for the determination of their potential to characterize cancer lesions. In this regard, simulation of different imaging conditions using specialized phantoms is increasingly being investigated. In this study, the design and evaluation of a modular multimodality imaging phantom to simulate heterogeneous uptake and enhancement patterns for radiomics quantification in hybrid imaging is presented. METHODS: A modular multimodality imaging phantom was constructed that could simulate different patterns of heterogeneous uptake and enhancement patterns in positron emission tomography (PET), single-photon emission computed tomography (SPECT), computed tomography (CT), and magnetic resonance (MR) imaging. The phantom was designed to be used as an insert in the standard NEMA-NU2 IEC body phantom casing. The entire phantom insert is composed of three segments, each containing three separately fillable compartments. The fillable compartments between segments had different sizes in order to simulate heterogeneous patterns at different spatial scales. The compartments were separately filled with different ratios of 99m Tc-pertechnetate, 18 F-fluorodeoxyglucose ([18 F]FDG), iodine- and gadolinium-based contrast agents for SPECT, PET, CT, and T1 -weighted MR imaging respectively. Image acquisition was performed using standard oncological protocols on all modalities and repeated five times for repeatability assessment. A total of 93 radiomic features were calculated. Variability was assessed by determining the coefficient of quartile variation (CQV) of the features. Comparison of feature repeatability at different modalities and spatial scales was performed using Kruskal-Wallis-, Mann-Whitney U-, one-way ANOVA- and independent t-tests. RESULTS: Heterogeneous uptake and enhancement could be simulated on all four imaging modalities. Radiomic features in SPECT were significantly less stable than in all other modalities. Features in PET were significantly less stable than in MR and CT. A total of 20 features, particularly in the gray-level co-occurrence matrix (GLCM) and gray-level run-length matrix (GLRLM) class, were found to be relatively stable in all four modalities for all three spatial scales of heterogeneous patterns (with CQV < 10%). CONCLUSION: The phantom was suitable for simulating heterogeneous uptake and enhancement patterns in [18 F]FDG-PET, 99m Tc-SPECT, CT, and T1 -weighted MR images. The results of this work indicate that the phantom might be useful for the further development and optimization of imaging protocols for radiomic quantification in hybrid imaging modalities.

Associations of herd- and cow-level factors, cow lying behavior, and risk of elevated somatic cell count in free-stall housed lactating dairy cows.

Recent evidence suggests that the risk of intramammary infection in dairy cows is related to lying patterns. The objectives of this study were to quantify the standing and lying behavior of dairy cows milked 3×/d, determine the cow- and herd-level factors associated with these behaviors, and relate these findings to the risk of an elevated somatic cell count (SCC). Five commercial free-stall dairy herds in Eastern Ontario, milking 3×/d, were enrolled in a longitudinal study. Forty Holstein-Friesian cows/herd were randomly selected as focal animals based on days in milk (<200 d) and SCC (<100,000 cells/mL). Farms were followed for 4, 5-week periods. Individual-cow SCC was recorded at the beginning of each period and end of the final period. Elevated SCC (eSCC) was used as an indicator of subclinical mastitis. A new incident eSCC was defined as an individual cow that started the period with a SCC <100,000 cells/mL but whose next SCC exceeded 200,000 cells/mL. Lying behavior was recorded 5d after each milk sampling using data loggers. For these 5d, individual milking times and feeding times were also recorded. On d1 of each recording period 2 trained observers scored focal cows for hygiene and lameness. Throughout the course of the study, cows averaged 11.2h/d of lying time, split into 8.6 lying bouts/d that were on average 84.6 min in length. Later lactation cows had longer daily lying times that were split into fewer lying bouts of longer duration than cows earlier in lactation. Lame cows had longer daily lying times and lying bout durations than non-lame cows. Cows with greater milk yield had lower lying times than lower producing cows. Average post-milking standing time across the study herds was 103 min. Manipulation of feed (feed delivery or push-up) by the stockperson, in the hour before milking or shortly thereafter, resulted in the longest post-milking standing times. Over the study period, 48 new eSCC were detected, resulting in a mean herd incidence rate of 0.91 eSCC/cow-year at risk for all study herds. A non-linear relationship between post-milking standing time and eSCC incidence was found; compared to those cows that lie down <90 min after milking, cows that lie down for the first time >90 min after milking had a lower risk of acquiring a new eSCC. The risk of experiencing an eSCC was also increased in multiparous cows, and in those cows with a higher SCC at the beginning of the study. These results indicate that management practices that promote post-milking standing time, such as the manipulation of feed delivery around milking times, should be encouraged to reduce the risk of cows experiencing new eSCC.