Search

Abstract Craniospinal irradiation (CSI) is a vital therapeutic approach utilized for young patients suffering from central nervous system disorders such as medulloblastoma. The task of accurately outlining the treatment area is particularly time-consuming due to the presence of several sensitive organs at risk (OAR) that can be affected by radiation. This study aimed to assess two different methods for automating the segmentation process: an atlas technique and a deep learning neural network approach. Additionally, a novel method was devised to prospectively evaluate the accuracy of automated segmentation as a knowledge-based quality assurance (QA) tool. Involving a patient cohort of 100, ranging in ages from 2 to 25 years with a median age of 8, this study employed quantitative metrics centered around overlap and distance calculations to determine the most effective approach for practical clinical application. The contours generated by two distinct methods of atlas and neural network were compared to ground truth contours approved by a radiation oncologist, utilizing 13 distinct metrics. Furthermore, an innovative QA tool was conceptualized, designed for forthcoming cases based on the baseline dataset of 100 patient cases. The calculated metrics indicated that, in the majority of cases (60.58%), the neural network method demonstrated a notably higher alignment with the ground truth. Instances where no difference was observed accounted for 31.25%, while utilization of the atlas method represented 8.17%. The QA tool results showed that the two approaches achieved 100% agreement in 39.4% of instances for the atlas method and in 50.6% of instances for the neural network auto-segmentation. The results indicate that the neural network approach showcases superior performance, and its significantly closer physical alignment to ground truth contours in the majority of cases. The metrics derived from overlap and distance measurements have enabled clinicians to discern the optimal choice for practical clinical application.

Purpose: To develop a novel, monthly quality assurance (QA) regimen for a proton therapy system that uses 2 custom phantoms, each housing a commercial scintillator detector and a charge-coupled device camera. The novel metrology system assessed QA trends at a pediatric proton therapy center from 2018 to 2022. Materials and Methods: The measurement system was designed to accommodate horizontal and vertical positioning of the commercial device and to enable gantry and couch isocentricity measurements (using a star shot procedure), proton spot profile verification, and imaging and radiation congruence tests to be performed simultaneously in the dual-phantom setup. Gantry angles and proton beam energies were varied and alternated each month, using gantry angles of 0°, 30°, 60°, 90°, 120°, 150°, and 180° and discrete beam energies of 69.4, 84.5, 100, 139.1, 180.4, 200.4, and 221.3 MeV after radiographic verification. A total of 1176 individual monthly QA measurements of gantry and couch isocentricity, spot size, and congruence were analyzed. Results: Gantry and couch star shot measurements showed beam isocentricities of 0.3 ± 0.2 mm and 0.2 ± 0.2 mm, respectively, which were within the threshold of 1.0 mm. Spot sizes for each discrete energy were within the threshold of ± 10% of the baseline values for all 3 proton rooms. The imaging and radiation coincidence test results for the 1176 individual monthly QA measurements were 0.5 mm for the 50th percentile and 1.2 mm (the clinical threshold) for the 97.6th percentile. Conclusions: Integrating a commercial device with custom phantoms improved the quality of proton system checks compared with previous methods using radiochromic films, loose ball bearings, and foam. The scheme of alternating beam angles with discrete energies in the monthly QA-enabled, clinically meaningful verification of beam energy and gantry angle combinations while the machine performance and accuracy were being checked.

(1) Background: Proton therapy, a precise form of radiation treatment, can be significantly affected by variations in bowel content. The purpose was to identify the most beneficial gantry angles that minimize deviations from the treatment plan quality, thus enhancing the safety and efficacy of proton therapy for Wilms’ tumor patients. (2) Methods: Thirteen patients with Wilms’ tumor, enrolled in the SJWT21 clinical trial, underwent proton therapy. The variations in bowel gas were systematically monitored using daily Cone Beam Computed Tomography (CBCT) imaging. Air cavities identified in daily CBCT images were analyzed to construct daily verification plans and measure water equivalent path length (WEPL) changes. A worst-case scenario simulation was conducted to identify the safest beam angles. (3) Results: The study revealed a maximum decrease in target dose (ΔD100%) of 8.0%, which corresponded to a WEPL variation (ΔWEPL) of 11.3 mm. The average reduction in target dose, denoted as mean ΔD100%, was found to be 2.8%, with a standard deviation (SD) of 3.2%. The mean ΔWEPL was observed as 3.3 mm, with an SD of 2.7 mm. The worst-case scenario analysis suggested that gantry beam angles oriented toward the patient’s right and posterior aspects from 110° to 310° were associated with minimized WEPL discrepancies. (4) Conclusions: This study comprehensively evaluated the influence of bowel gas variability on treatment plan accuracy and proton range uncertainties in pediatric proton therapy for Wilms’ tumor.

This study quantifies setup uncertainty in brain tumor patients who received image-guided proton therapy. Patients analyzed include 165 children, adolescents, and young adults (median age at radiotherapy: 9 years (range: 10 months to 24 years); 80 anesthetized and 85 awake) enrolled in a single-institution prospective study from 2020 to 2023. Cone-beam computed tomography (CBCT) was performed daily to calculate and correct manual setup errors, once per course after setup correction to measure residual errors, and weekly after treatments to assess intrafractional motion. Orthogonal radiographs were acquired consecutively with CBCT for paired comparisons of 40 patients. Translational and rotational errors were converted from 6 degrees of freedom to a scalar by a statistical approach that considers the distance from the target to the isocenter. The 95th percentile of setup uncertainty was reduced by daily CBCT from 10 mm (manual positioning) to 1–1.5 mm (after correction) and increased to 2 mm by the end of fractional treatment. A larger variation existed between the roll corrections reported by radiographs vs. CBCT than for pitch and yaw, while there was no statistically significant difference in translational variation. A quantile mixed regression model showed that the 95th percentile of intrafractional motion was 0.40 mm lower for anesthetized patients (p=0.0016). Considering additional uncertainty in radiation-imaging isocentricity, the commonly used total plan robustness of 3 mm against positional uncertainty would be appropriate for our study cohort.

We introduce a custom-made silicone-filled vaginal spacer for use during treatment of female patients receiving pelvic proton radiation therapy. Commercially available vaginal dilators can be purchased as hollow objects; when filled with a media, they can act as a beam stopper and/or tissue spacer while pushing uninvolved vaginal wall away from a high-dose region. Dosimetric advantages of these specifically constructed silicone-filled vaginal spacers were investigated when compared to the unaltered commercially available product or no vaginal spacer in pediatric proton therapy.

(1) Background: The most significant cause of an unacceptable deviation from the planned dose during respiratory motion is the interplay effect. We examined the correlation between the magnitude of splenic motion and its impact on plan quality for total lymphoid irradiation (TLI); (2) Methods: Static and 4D CT images from ten patients were used for interplay effect simulations. Patients’ original plans were optimized based on the average CT extracted from the 4D CT and planned with two posterior beams using scenario-based optimization (±3 mm of setup and ±3% of range uncertainty) and gradient matching at the level of mid-spleen. Dynamically accumulated 4D doses (interplay effect dose) were calculated based on the time-dependent delivery sequence of radiation fluence across all phases of the 4D CT. Dose volume parameters for each simulated treatment delivery were evaluated for plan quality; (3) Results: Peak-to-peak splenic motion (≤12 mm) was measured from the 4D CT of ten patients. Interplay effect simulations revealed that the ITV coverage of the spleen remained within the protocol tolerance for splenic motion, ≤8 mm. The D100% coverage for ITV spleen decreased from 95.0% (nominal plan) to 89.3% with 10 mm and 87.2% with 12 mm of splenic motion; (4) Conclusions: 4D plan evaluation and robust optimization may overcome problems associated with respiratory motion in proton TLI treatments. Patient-specific respiratory motion evaluations are essential to confirming adequate dosimetric coverage when proton therapy is utilized.

(1) Background: Synthetic CT images of the pelvis were generated from daily CBCT images to monitor changes in water equivalent path length (WEPL) and determine the dosimetric impact of anatomy changes along the proton beam’s path; (2) Methods: Ten pediatric patients with pelvic tumors treated using proton therapy with daily CBCT were included. The original planning CT was deformed to the same-day CBCT to generate synthetic CT images for WEPL comparison and dosimetric evaluation; (3) Results: WEPL changes of 20 proton fields at the distal edge of the CTV ranged from 0.1 to 12 mm with a median of 2.5 mm, and 75th percentile of 5.1 mm for (the original CT—rescanned CT) and ranged from 0.3 to 10.1 mm with a median of 2.45 mm and 75th percentile of 4.8 mm for (the original CT—synthetic CT). The dosimetric impact was due to proton range pullback or overshoot, which led to reduced coverage in CTV Dmin averaging 12.1% and 11.3% in the rescanned and synthetic CT verification plans, respectively; (4) Conclusions: The study demonstrated that synthetic CT generated by deforming the original planning CT to daily CBCT can be used to quantify proton range changes and predict adverse dosimetric scenarios without the need for excessive rescanned CT scans during large interfractional variations in adaptive proton therapy of pediatric pelvic tumors.

Purpose: To determine whether self-attention cycle-generative adversarial networks (cycle-GANs), a novel deep-learning method, can generate accurate synthetic computed tomography (sCT) to facilitate adaptive proton therapy in children with brain tumors. Materials and Methods: Both CT and T1-weighted magnetic resonance imaging (MRI) of 125 children (ages 1-20 years) with brain tumors were included in the training dataset. A model introducing a self-attention mechanism into the conventional cycle-GAN was created to enhance tissue interfaces and reduce noise. The test dataset consisted of 7 patients (ages 2-14 years) who underwent adaptive planning because of changes in anatomy discovered on MRI during proton therapy. The MRI during proton therapy-based sCT was compared with replanning CT (ground truth). Results: The Hounsfield unit-mean absolute error was significantly reduced with self-attention cycle-GAN, as compared with conventional cycle-GAN (65.3 ± 13.9 versus 88.9 ± 19.3, P < .01). The average 3-dimensional gamma passing rates (2%/2 mm criteria) for the original plan on the anatomy of the day and for the adapted plan were high (97.6% ± 1.2% and 98.9 ± 0.9%, respectively) when using sCT generated by self-attention cycle-GAN. The mean absolute differences in clinical target volume (CTV) receiving 95% of the prescription dose and 80% distal falloff along the beam axis were 1.1% ± 0.8% and 1.1 ± 0.9 mm, respectively. Areas of greatest dose difference were distal to the CTV and corresponded to shifts in distal falloff. Plan adaptation was appropriately triggered in all test patients when using sCT. Conclusion: The novel cycle-GAN model with self-attention outperforms conventional cycle-GAN for children with brain tumors. Encouraging dosimetric results suggest that sCT generation can be used to identify patients who would benefit from adaptive replanning.

Radiation to the female pelvis as part of treatment for cancer predisposes young women to develop Premature Ovarian Insufficiency (POI). As the human female is born with their full complement of non-growing follicles which decline in an exponential fashion until the menopause, the age at which POI occurs is dependent on the age of the patient at treatment and the dose received by the ovary. A model that predicts the age at which POI occurs for a known dose at a known age will aid counselling patients on their fertility risk. Patients deemed to be at high risk of POI may be considered to be good candidates for established fertility preservation techniques. An updated and externally validated model of the age-related decline in human ovarian reserve was combined with the best available estimate of the median lethal dose LD50 for the human ovary. Using known age at diagnosis and posited radiotherapy treatment plan to estimate the dose to the least-affected ovary, we use an age-related model of the decline in ovarian reserve to generate a personalized age prediction of premature ovarian insufficiency. Our algorithm is available as an online calculator which graphs model outputs to inform discussions around survivor fertility. We report four example cases across different ages and diagnoses, each with two carefully designed photon and proton treatment plans. The treatment options are compared in terms of remaining fertile lifespan for the survivor. International oncology guidelines now mandate the consideration of later fertility when reviewing treatment options for children diagnosed with cancer. Our calculator (https://sites.cs.st-andrews.ac.uk/radiosensitivity), and the underlying algorithm and models, allow detailed predictions of the impact of various radiotherapy plans on fertility. These patient-specific data enhance pre-treatment discussions around post-treatment fertility and fertility preservation.

IntroductionTotal body irradiation is an effective conditioning regimen for allogeneic stem cell transplantation in pediatric and adult patients with high risk or relapsed/refractory leukemia. The most common adverse effect is pulmonary toxicity including idiopathic pneumonia syndrome (IPS). As centers adopt more advanced treatment planning techniques for TBI, total marrow irradiation (TMI), or total marrow and lymphoid irradiation (TMLI) there is a greater need to understand treatment-related risks for IPS for patients treated with conventional TBI. However, definitions of IPS as well as risk factors for IPS remain poorly characterized. In this study, we perform a critical review to further evaluate the literature describing pulmonary outcomes after TBI.Materials and MethodsA search of publications from 1960-2020 was undertaken in PubMed, Embase, and Cochrane Library. Search terms included “total body irradiation”, “whole body radiation”, “radiation pneumonias”, “interstitial pneumonia”, and “bone marrow transplantation”. Demographic and treatment-related data was abstracted and evidence quality supporting risk factors for pulmonary toxicity was evaluated.ResultsOf an initial 119,686 publications, 118 met inclusion criteria. Forty-six (39%) studies included a definition for pulmonary toxicity. A grading scale was provided in 20 studies (17%). In 42% of studies the lungs were shielded to a set mean dose of 800cGy. Fourteen (12%) reported toxicity outcomes by patient age. Reported pulmonary toxicity ranged from 0-71% of patients treated with TBI, and IPS ranged from 1-60%. The most common risk factors for IPS were receipt of a TBI containing regimen, increasing dose rate, and lack of pulmonary shielding. Four studies found an increasing risk of pulmonary toxicity with increasing age.ConclusionsDefinitions of IPS as well as demographic and treatment-related risk factors remain poorly characterized in the literature. We recommend routine adoption of the diagnostic workup and the definition of IPS proposed by the American Thoracic Society. Additional study is required to determine differences in clinical and treatment-related risk between pediatric and adult patients. Further study using 3D treatment planning is warranted to enhance dosimetric precision and correlation of dose volume histograms with toxicities.

Background and purpose: Four-dimensional magnetic resonance imaging (4D MRI) has advanced recently by incorporating prospective gating, but its performance on pediatric populations has not been investigated. This study aimed to determine the age-related performance of prospective gating, as compared with retrospective sorting. Materials and methods: Prospectively gated 4D MRI scans were acquired on a motion phantom driven by real respiratory waveforms obtained from 23 pediatric and young adult patients (aged 5–24 years). The correlations between patient-specific breathing characteristics and the performance of 4D MRI were comparatively evaluated against retrospective sorting for the same scan time. For six patients who underwent both 4D MRI and 4D CT, the internal target volumes (ITVs) determined by the two modalities were compared. Results: Longer scan time and greater sorting error were most highly correlated (P 30%). The ITVs of 4D MRI and 4D CT were comparable (Dice similarity: >90%) unless the breathing characteristics changed between the two imaging sessions. Conclusions: For most patients analyzed in this study, prospective gating provided more accurate 4D MRI (95th percentile of deviation:

Background: Proton radiotherapy produces superior dose distributions compared to photon radiotherapy, reducing side effects. Differences between the two modalities are not fully quantified in paediatric patients for various intracranial tumour sites or age. Understanding these differences may help clinicians estimate the benefit and improve referral across available centres. Our aim was to compare intensity-modulated proton therapy (IMPT) and intensity-modulated photon radiotherapy (IMRT) radiation doses for select paediatric intracranial tumours. Methods: IMPT and IMRT dose distributions for gender-matched paediatric cranial CT-datasets (ages 5, 9 and 13 years) were retrospectively calculated to simulate irradiation of supratentorial (ependymoma) and infratentorial (medulloblastoma) target volumes diameters (1–3 cm) and position (central and 1–2 cm shifts). Results: Clinical dosimetric objectives were achieved for all 216 treatment plans. Whilst infratentorial IMPT plans achieved greater maximum dose sparing to optic structures (4.8–12.6 Gy optic chiasm), brainstem sparing was limited (~0.5 Gy). Mean dose difference for optic chiasm was associated with medulloblastoma target position (p < 0.0197). Supratentorial IMPT plans demonstrated greater dose reduction for the youngest patients (pituitary gland p < 0.001). Conclusions: Normal tissue sparing was achieved regardless of patient age for infratentorial tumours. However, for supratentorial tumours, there was a dosimetric advantage of IMPT across 9 vs. 13-year-old patients.