Paediatric CBCT protocols for image-guided radiotherapy; outcome of a survey across SIOP Europe affiliated countries and literature review.

BACKGROUND: Implementation of daily cone-beam CT (CBCT) into clinical practice in paediatric image-guided radiotherapy (IGRT) lags behind compared to adults. Surveys report wide variation in practice for paediatric IGRT and technical information remains unreported. In this study we report on technical settings from applied paediatric CBCT protocols and review the literature for paediatric CBCT protocols. METHODS: From September to October 2022, a survey was conducted among 246 SIOPE-affiliated centres across 35 countries. The survey consisted of 3 parts: 1) baseline information; technical CBCT exposure settings and patient set-up procedure for 2) brain/head, and 3) abdomen. Descriptive statistics was used to summarise current practice. The literature was reviewed systematically with two reviewers obtaining consensus RESULTS: The literature search revealed 22 papers concerning paediatric CBCT protocols. Seven papers focused on dose-optimisation. Responses from 50/246 centres in 25/35 countries were collected: 44/50 treated with photons and 10/50 with protons. In total, 48 brain/head and 53 abdominal protocols were reported. 42/50 centres used kV-CBCT for brain/head and 35/50 for abdomen; daily CBCT was used for brain/head = 28/48 (58%) and abdomen = 33/53 62%. Greater consistency was seen in brain/head protocols (dose range 0.32 - 67.7 mGy) compared to abdominal (dose range 0.27 - 119.7 mGy). CONCLUSION: Although daily CBCT is now widely used in paediatric IGRT, our survey demonstrates a wide range of technical settings, suggesting an unmet need to optimise paediatric IGRT protocols. This is in accordance with the literature. However, there are only few paediatric optimisation studies suggesting that dose reduction is possible while maintaining image quality.

The need for consensus on delineation and dose constraints of dentofacial structures in paediatric radiotherapy: Outcomes of a SIOP Europe survey.

Background and purpose: Children receiving radiotherapy for head-and-neck tumours often experience severe dentofacial side effects. Despite this, recommendations for contouring and dose constraints to dentofacial structures are lacking in clinical practice. We report on a survey aiming to understand current practice in contouring and dose assessment to dentofacial structures. Methods: A digital survey was distributed to European Society for Paediatric Oncology members of the Radiation Oncology Working Group, and member-affiliated centres in Europe, Australia, and New Zealand. The questions focused on clinical practice and aimed to establish areas for future development. Results: Results from 52 paediatric radiotherapy centres across 27 countries are reported. Only 29/52 centres routinely delineated some dentofacial structures, with the most common being the mandible (25 centres), temporo-mandibular joint (22), dentition (13), orbit (10) and maxillary bone (eight). For most bones contoured, an 'As Low As Reasonably Achievable' dose objective was implemented. Only four centres reported age-adapted dose constraints.The largest barrier to clinical implementation of dose constraints was firstly, the lack of contouring guidance (49/52, 94%) and secondly, that delineation is time-consuming (33/52, 63%). Most respondents who routinely contour dentofacial structures (25/27, 90%) agreed a contouring atlas would aid delineation. Conclusion: Routine delineation of dentofacial structures is infrequent in paediatric radiotherapy. Based on survey findings, we aim to 1) define a consensus-contouring atlas for dentofacial structures, 2) develop auto-contouring solutions for dentofacial structures to aid clinical implementation, and 3) carry out treatment planning studies to investigate the importance of delineation of these structures for planning optimisation.

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.

Machine intelligence for radiation science: summary of the Radiation Research Society 67th annual meeting symposium.

The era of high-throughput techniques created big data in the medical field and research disciplines. Machine intelligence (MI) approaches can overcome critical limitations on how those large-scale data sets are processed, analyzed, and interpreted. The 67th Annual Meeting of the Radiation Research Society featured a symposium on MI approaches to highlight recent advancements in the radiation sciences and their clinical applications. This article summarizes three of those presentations regarding recent developments for metadata processing and ontological formalization, data mining for radiation outcomes in pediatric oncology, and imaging in lung cancer.

Gender-related and geographic trends in interactions between radiotherapy professionals on Twitter.

Background and purpose: Twitter presence in academia has been linked to greater research impact which influences career progression. The purpose of this study was to analyse Twitter activity of the radiotherapy community around ESTRO congresses with a focus on gender-related and geographic trends. Materials and methods: Tweets, re-tweets and replies, here designated as interactions, around the ESTRO congresses held in 2012-2021 were collected. Twitter activity was analysed temporally and, for the period 2016-2021, the geographical span of the ESTRO Twitter network was studied. Tweets and Twitter users collated during the 10 years analysed were ranked based on number of 'likes', 're-tweets' and followers, considered as indicators of leadership/influence. Gender representation was assessed for the top-end percentiles. Results: Twitter activity around ESTRO congresses was multiplied by 60 in 6 years growing from 150 interactions in 2012 to a peak of 9097 in 2018. In 2020, during the SARS-CoV-2 pandemic, activity dropped by 60 % to reach 2945 interactions and recovered to half the pre-pandemic level in 2021. Europe, North America and Oceania were strongly connected and remained the main contributors. While overall, 58 % of accounts were owned by men, this proportion increased towards top liked/re-tweeted tweets and most-followed profiles to reach up to 84 % in the top-percentiles. Conclusion: During the SARS-CoV-2 pandemic, Twitter activity around ESTRO congresses substantially decreased. Men were over-represented on the platform and in most popular tweets and influential accounts. Given the increasing importance of social media presence in academia the gender-based biases observed may help in understanding the gender gap in career progression.

The late effects of cranial irradiation in childhood on the hypothalamic-pituitary axis: a radiotherapist's perspective.

Brain tumours make up nearly one-third of paediatric malignancies. Over time, advancements in oncological treatments like radiotherapy have helped reduce normal-tissue toxicity when treating cancers in the brain. However, clinicians are still facing a trade-off between treatment efficacy and potential side effects. The aim of this review is to address the late effects of cranial irradiation on the neuroendocrine system and to identify factors that make patients more vulnerable to radiation-induced endocrine sequelae. Radiation damage to the hypothalamic-pituitary axis, which orchestrates hormone release, can lead to endocrinopathy; up to 48.8% of children who have undergone cranial irradiation develop a hormone deficiency. This may lead to further health complications that can appear up to decades after the last treatment, lowering the patients' quality of life and increasing long-term costs as lifelong hormone replacement therapy may be required. Growth hormone deficiency is the most common sequelae, followed by either thyroid or gonadotropic hormone deficiency. Adrenocorticotropic hormone deficiency tends to be the least common. Identified factors that increase the risk of late endocrine deficiency include total radiation dose, age at treatment, and time since last treatment. However, as there are various other factors that may potentiate the damage, a universal solution proven to be most effective in sparing the endocrine tissues is yet to be identified. Until then, accounting for the identified risk factors during treatment planning may in some cases help reduce the development of endocrine sequelae in childhood cancer survivors.

Image-based data mining applies to data collected from children.

PURPOSE: Image-based data mining (IBDM) is a novel voxel-based method for analyzing radiation dose responses that has been successfully applied in adult data. Because anatomic variability and side effects of interest differ for children compared to adults, we investigated the feasibility of IBDM for pediatric analyses. METHODS: We tested IBDM with CT images and dose distributions collected from 167 children (aged 10 months to 20 years) who received proton radiotherapy for primary brain tumors. We used data from four reference patients to assess IBDM sensitivity to reference selection. We quantified spatial-normalization accuracy via contour distances and deviations of the centers-of-mass of brain substructures. We performed dose comparisons with simplified and modified clinical dose distributions with a simulated effect, assessing their accuracy via sensitivity, positive predictive value (PPV) and Dice similarity coefficient (DSC). RESULTS: Spatial normalizations and dose comparisons were insensitive to reference selection. Normalization discrepancies were small (average contour distance < 2.5 mm, average center-of-mass deviation < 6 mm). Dose comparisons identified differences (p < 0.01) in 81% of simplified and all modified clinical dose distributions. The DSCs for simplified doses were high (peak frequency magnitudes of 0.9-1.0). However, the PPVs and DSCs were low (maximum 0.3 and 0.4, respectively) in the modified clinical tests. CONCLUSIONS: IBDM is feasible for childhood late-effects research. Our findings may inform cohort selection in future studies of pediatric radiotherapy dose responses and facilitate treatment planning to reduce treatment-related toxicities and improve quality of life among childhood cancer survivors.

Low dose cone beam CT for paediatric image-guided radiotherapy: Image quality and practical recommendations.

PURPOSE: Cone beam CT (CBCT) is used in paediatric image-guided radiotherapy (IGRT) for patient setup and internal anatomy assessment. Adult CBCT protocols lead to excessive doses in children, increasing the risk of radiation-induced malignancies. Reducing imaging dose increases quantum noise, degrading image quality. Patient CBCTs also include 'anatomical noise' (e.g. motion artefacts), further degrading quality. We determine noise contributions in paediatric CBCT, recommending practical imaging protocols and thresholds above which increasing dose yields no improvement in image quality. METHODS AND MATERIALS: Sixty CBCTs including the thorax or abdomen/pelvis from 7 paediatric patients (aged 6-13 years) were acquired at a range of doses and used to simulate lower dose scans, totalling 192 scans (0.5-12.8 mGy). Noise measured in corresponding regions of each patient and a 10-year-old phantom were compared, modelling total (including anatomical) noise, and quantum noise contributions as a function of dose. Contrast-to-noise ratio (CNR) was measured between fat/muscle. Soft tissue registration was performed on the kidneys, comparing accuracy to the highest dose scans. RESULTS: Quantum noise contributed <20% to total noise in all cases, suggesting anatomical noise is the largest determinant of image quality in the abdominal/pelvic region. CNR exceeded 3 in over 90% of cases ≥ 1 mGy, and 57% of cases at 0.5 mGy. Soft tissue registration was accurate for doses > 1 mGy. CONCLUSION: Anatomical noise dominates quantum noise in paediatric CBCT. Appropriate soft tissue contrast and registration accuracy can be achieved for doses as low as 1 mGy. Increasing dose above 1 mGy holds no benefit in improving image quality or registration accuracy due to the presence of anatomical noise.

Quantitative evaluation of 4D Cone beam CT scans with reduced scan time in lung cancer patients.

PURPOSE: Image guided radiotherapy (IGRT) based on respiration correlated cone-beam CT (4D-CBCT) provides accurate tumour localisation in lung cancer patients by taking into account respiratory motion when deriving setup correction. However, 4D-CBCT scan times are typically longer than for acquisition of 3D-CBCT scans, e.g. 4 min. This work aims to quantitatively evaluate the effect of reduced scan times on 4D-CBCT image quality and registration accuracy in lung cancer patients. METHODS AND MATERIALS: Scan times down to 1 min were simulated by retaining only projection images corresponding to every second, third or fourth respiratory cycle in forty-four 4D-CBCTs from 15 lung cancer patients. In addition twenty 2-minute scans were acquired for 12 lung cancer patients. Image quality was quantified by assessing registration accuracy in the shorter scan times, comparing to the 4-minute scan registration result where available as reference. RESULTS: Use of 2-minute scans had little impact on registration accuracy or ability to detect tumour motion: automatic registration accuracy was within 2 mm in 6/8 scans analysed with 2-minute acquisitions, and 96.6% of registration discrepancies were within 2 mm for the simulated scans. When the scan time simulated was below 2 min, automatic registration results still agreed within 2 mm for 84.7% of scans, however visual image quality was considerably degraded. CONCLUSION: A 4D-CBCT acquisition time of 2 min produces scans of sufficient image quality for IGRT in most lung cancer patients, as demonstrated quantitatively by assessing the impact on automatic registration accuracy in simulated and real acquisitions.