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BACKGROUND: In pediatric radiotherapy treatment planning of abdominal tumors, dose constraints to the pancreatic tail/spleen are applied to reduce late toxicity. In this study, an analysis of inter- and intrafraction motion of the pancreatic tail/spleen is performed to estimate the potential benefits of online MRI-guided radiotherapy (MRgRT). MATERIALS AND METHODS: Ten randomly selected neuroblastoma patients (median age: 3.4 years), irradiated with intensity-modulated arc therapy at our department (prescription dose: 21.6/1.8 Gy), were retrospectively evaluated for inter- and intrafraction motion of the pancreatic tail/spleen. Three follow-up MRIs (T2- and T1-weighted ± gadolinium) were rigidly registered to a planning CT (pCT), on the vertebrae around the target volume. The pancreatic tail/spleen were delineated on all MRIs and pCT. Interfraction motion was defined as a center of gravity change between pCT and T2-weighted images in left-right (LR), anterior-posterior (AP) and cranial-caudal (CC) direction. For intrafraction motion analysis, organ position on T1-weighted ± gadolinium was compared to T2-weighted. The clinical radiation plan was used to estimate the dose received by the pancreatic tail/spleen for each position. RESULTS: The median (IQR) interfraction motion was minimal in LR/AP, and largest in CC direction; pancreatic tail 2.5 mm (8.9), and spleen 0.9 mm (3.9). Intrafraction motion was smaller, but showed a similar motion pattern (pancreatic tail, CC: 0.4 mm (1.6); spleen, CC: 0.9 mm (2.8)). The differences of Dmean associated with inter- and intrafraction motions ranged from - 3.5 to 5.8 Gy for the pancreatic tail and - 1.2 to 3.0 Gy for the spleen. In 6 out of 10 patients, movements of the pancreatic tail and spleen were highlighted as potentially clinically significant because of ≥ 1 Gy dose constraint violation. CONCLUSION: Inter- and intrafraction organ motion results into unexpected constrain violations in 60% of a randomly selected neuroblastoma cohort, supporting further prospective exploration of MRgRT.

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BACKGROUND: Herein, the authors describe the successful utilization of 5-aminolevulinic acid (5-ALA) and the first case of GammaTile cesium-131 therapy in a pediatric patient with recurrent high-grade glioma. 5-ALA was utilized to optimize gross-total resection prior to GammaTile implantation. After conversion to an equivalent dose in 2-Gy fractions (EQD2), a composite was made of the GammaTile dose with the initial external beam radiotherapy. Two hypothetical plans consisting of a standard hypofractionated strategy for glioma reirradiation and a CyberKnife plan using GammaTile's planning target volume were developed and likewise underwent EQD2 conversion and composite plan generation with the initial radiotherapy. OBSERVATIONS: 5-ALA was useful in achieving gross-total resection with no acute toxicity from the surgery or GammaTile irradiation. When compared with the hypothetical composite doses, GammaTile's composite, axium point dose (D0.03cc) to the brainstem was 32.9 Gy less than the hypofractionated and the CyberKnife composite plans at 38.7 Gy and 40.2 Gy, respectively. The right hippocampus demonstrated a substantially reduced composite plan dose with GammaTile with a D0.03cc of 62.4 Gy versus 71.7 and 80.7 Gy for the hypofractionated and CyberKnife composite plans, respectively. LESSONS: Utilization of 5-ALA and GammaTile therapy yielded clinically superior tumor debulking and effective radiotherapy dose localization with sparing of organs at risk, respectively.

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BACKGROUND: Health-related quality of life (HRQOL) measurement has become an important health care outcome even in oncological pediatric scenario. During radiation therapy care path, pediatric patients and their relatives may suffer from emotional and psychosocial distress not only related to cancer diagnosis, but also due to the procedure and the required daily routine. Despite the high prevalence of psychosocial consequences in this setting, instruments that inquire pediatric HRQOL and healthcare satisfaction have rarely been studied in Italy. Purpose of this study was to investigate reliability and linguistic validation of the PedsQL™ healthcare satisfaction Hematology/Oncology module from its original English version to Italian language. METHODS: Three phases standard procedure of cross-culture adaptation were used to create Italian version of PedsQL™ healthcare satisfaction Hematology/Oncology module. Forward translations and backward translations were performed. Finally, a pilot-testing for understandability of the 'pre-final' version was conducted with parents of children attending our Radiotherapy Center using two methodologies of Cognitive Interviewing ("Think-aloud Interviews" and "Respondent Debriefing"), in order to obtain the final Italian version of the PedsQL™ healthcare satisfaction Hematology/Oncology module. RESULTS: Twenty-five parents (2 father, 23 mothers) were recruited during their children's radiotherapy treatment and the grammatically and conceptually acceptable pre-final version of the PedsQL™ Healthcare Satisfaction Hematology/Oncology Module was administered. The questionnaire was well understood reflecting its linguistic adaptation. Compliance with questionnaire administration was optimal. All subjects stated that the questions were interesting to express their opinion, most of them reported that all the questions of each section were clearly comprehensible and easy to understand, suggesting minimal changes that were double-checked with back translation. Furthermore, six of them spontaneously asked to complete the questionnaire in order to review the assistance received during radiotherapy. CONCLUSION: Our Italian version of the PedsQL™ 3.0 Healthcare Satisfaction Hematology/Oncology Module seems to be a valid and functional instrument to indagate Healthcare Satisfaction.

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Purpose: To report our design, manufacturing, commissioning and initial clinical experience with a table-mounted range shifter board (RSB) intended to replace the machine-mounted range shifter (MRS) in a synchrotron-based pencil beam scanning (PBS) system to reduce penumbra and normal tissue dose for image-guided pediatric craniospinal irradiation (CSI). Methods: A custom RSB was designed and manufactured from a 3.5 cm thick slab of polymethyl methacrylate (PMMA) to be placed directly under patients, on top of our existing couch top. The relative linear stopping power (RLSP) of the RSB was measured using a multi-layer ionization chamber, and output constancy was measured using an ion chamber. End-to-end tests were performed using the MRS and RSB approaches using an anthropomorphic phantom and radiochromic film measurements. Cone beam CT (CBCT) and 2D planar kV X-ray image quality were compared with and without the RSB present using image quality phantoms. CSI plans were produced using MRS and RSB approaches for two retrospective pediatric patients, and the resultant normal tissue doses were compared. Results: The RLSP of the RSB was found to be 1.163 and provided computed penumbra of 6.9 mm in the phantom compared to 11.8 mm using the MRS. Phantom measurements using the RSB demonstrated errors in output constancy, range, and penumbra of 0.3%, -0.8%, and 0.6 mm, respectively. The RSB reduced mean kidney and lung dose compared to the MRS by 57.7% and 46.3%, respectively. The RSB decreased mean CBCT image intensities by 86.8 HU but did not significantly impact CBCT or kV spatial resolution providing acceptable image quality for patient setup. Conclusions: A custom RSB for pediatric proton CSI was designed, manufactured, modeled in our TPS, and found to significantly reduce lateral proton beam penumbra compared to a standard MRS while maintaining CBCT and kV image-quality and is in routine use at our center.

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BACKGROUND: Adverse late health outcomes after multimodal treatment for pediatric cancer are diverse and of prime interest. Currently available evidence and survivorship care guidelines are largely based on studies addressing side-effects of two dimensional planned radiotherapy. AIMS: The Dutch pediatric 3D-planned radiotherapy (3D-RT) study aims to gain insight in the long-term health outcomes among children who had radiotherapy in the 3D era. Here, we describe the study design, data-collection methods, and baseline cohort characteristics. METHODS AND RESULTS: The 3D-RT study represents an expansion of the Dutch Childhood Cancer Survivor study (DCCSS) LATER cohort, including pediatric cancer patients diagnosed during 2000-2012, who survived at least 5 years after initial diagnosis and 2 years post external beam radiotherapy. Individual cancer treatment parameters were obtained from medical files. A national infrastructure for uniform collection and archival of digital radiotherapy files (Computed Tomography [CT]-scans, delineations, plan, and dose files) was established. Health outcome information, including subsequent tumors, originated from medical records at the LATER outpatient clinics, and national registry-linkage. With a median follow-up of 10.9 (interquartile range [IQR]: 7.9-14.3) years after childhood cancer diagnosis, 711 eligible survivors were identified. The most common cancer types were Hodgkin lymphoma, medulloblastoma, and nephroblastoma. Most survivors received radiotherapy directed to the head/cranium only, the craniospinal axis, or the abdominopelvic region. CONCLUSION: The 3D-RT study will provide knowledge on the risk of adverse late health outcomes and radiation-associated dose-effect relationships. This information is valuable to guide follow-up care of childhood cancer survivors and to refine future treatment protocols.

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PURPOSE: Pediatric radiotherapy (RT) is a highly specialized field, requiring great experience to delineate correctly tumor targets and organs at risk. To reduce treatment failures related to planning inaccuracies and to obtain robust clinical results despite the limited numbers of enrolled pediatric patients, the SIOP PNET5MB clinical trial on medulloblastoma requires a real-time, pre-radiation review of the RT treatment (craniospinal irradiation and boost plan) under the direct responsibility of the national coordinator center. Here we describe the centralized radiotherapy quality assurance (QA) program developed in Italy for this purpose. METHODS: Using the software package VODCA (MSS, Hagendorn, Switzerland, www.vodca.ch ), we developed a cloud platform able to handle computed tomography (CT) images and RT objects and to support the complete workflow required by the review process in the context of the SIOP PNET5 trial. RESULTS: All Italian centers participating in the PNET5 trial adopted the proposed QA system. 24 patients were successfully enrolled and reviewed. For 15 patients (62.5%), one or more plan revisions were requested for the craniospinal irradiation plan and for 11 patients (45.8%) plan revisions were requested for the boost. RT was delivered after the plan was centrally approved for all enrolled patients. So far, in Italy, no patients have been excluded from PNET5 due to dosimetric incompliance to the protocol or for exceeding the RT starting time limit. CONCLUSION: The cloud platform successfully supported the trial workflow, producing official review documents. This efficient QA was crucial to guarantee optimized treatments and protocol compliance for all pediatric patients enrolled in the SIOP protocol.

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BACKROUND AND PURPOSE: To investigate the incidence of complications related to propofol-based anesthesia and the factors associated with complications in children with radiotherapy. MATERIALS AND METHODS: Patients who underwent anesthesia for external beam radiotherapy between May 2013 and November 2017 were included in the study. We assessed the age/weight, sex, oncologic diagnosis, type of radiotherapy procedure, duration of anesthesia, applied agents, and complications related to anesthesia. Complications were evaluated between group I (only propofol group) and group II (propofol plus adjuvant drugs) as respiratory and cardiac. RESULTS: In 130 patients, sedation was given for 1376 radiotherapy procedures. Of these, 1274 (1140 radiation treatment sessions and 134 computed tomography simulations) in 126 patients were propofol-based and were included in the analysis. Although respiratory complications are the most common in both groups, there were no episodes of laryngospasm, broncospasm, and no use of advanced airway intervention. The rate of complication was significantly higher in only propofol anesthesia group than in patients treated with propofol plus adjuvant drugs. In the multivariate analysis, we found three factors that were significantly associated with the risk of complications: total dose of propofol (mg/kg) (p < 0.001), anesthesia with propofol alone (as compared to propofol plus adjunct agents) (p = 0.001), and diagnosis of neuroblastoma (as compared to other diagnosis) (p = 0.043). CONCLUSION: Propofol-based anesthesia is preferred in order to minimize the rate of complications in radiotherapy anesthesia applications. The use of non-opioid adjuvants in combination with propofol to achieve a balanced anesthesia will also reduce the complications that may be encountered.

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PURPOSE: A form of lung functional imaging has been developed that uses 4DCT data to calculate ventilation (4DCT-ventilation). Because 4DCTs are acquired as standard-of-care to manage breathing motion during radiotherapy, 4DCT-ventilation provides functional information at no extra dosimetric or monetary cost. 4DCT-ventilation has yet to be described in children. 4DCT-ventilation can be used as a tool to help assess post-treatment lung function and predict for future clinical thoracic toxicities for pediatric patients receiving radiotherapy to the chest. The purpose of this work was to perform a preliminary evaluation of 4DCT-ventilation-based lung function changes for pediatric patients receiving radiotherapy to the lungs. METHODS: The study used four patients with pre and postradiotherapy 4DCTs. The 4DCTs, deformable image registration, and a density-change-based algorithm were used to compute pre and post-treatment 4DCT-ventilation images. The post-treatment 4DCT-ventilation images were compared to the pretreatment 4DCT-ventilation images for a global lung response and for an intrapatient dose-response (providing an assessment for dose-dependent regional dose-response). RESULTS: For three of the four patients, a global ventilation decline of 7-37% was observed, while one patient did not demonstrate a global functional decline. Dose-response analysis did not reveal an intrapatient dose-response from 0 to 20 Gy for three patients while one patient demonstrated increased 4DCT-ventilation decline as a function of increasing lung doses up to 50 Gy. CONCLUSIONS: Compared to adults, pediatric patients have unique lung function, dosimetric, and toxicity profiles. The presented work is the first to evaluate spatial lung function changes in pediatric patients using 4DCT-ventilation and showed lung function changes for three of the four patients. The early changes demonstrated with lung function imaging warrant further longitudinal work to determine whether the imaging-based early changes can be predicted for long-term clinical toxicity.

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BACKGROUND AND PURPOSE: Substantial inter-observer variations in target delineation have been presented previously. Target delineation for paediatric cases is difficult due to the small number of children, the variation in paediatric targets, the number of study protocols, and the individual patient's specific needs and demands. Uncertainties in target delineation might lead to under-dosage or over-dosage. The aim of this work is to apply the concept of a consensus volume and good quality treatment plans to visualise and quantify inter-observer target delineation variations in dosimetric terms in addition to conventional geometrically based volume concordance indices. MATERIAL AND METHODS: Two paediatric cases were used to demonstrate the potential of adding dose metrics when evaluating target delineation diversity; Hodgkin's disease (case 1) and rhabdomyosarcoma of the parotid gland (case 2). The variability in target delineation (PTV delineations) between six centres was quantified using the generalised conformity index, CIgen, generated for volume overlap. The STAPLE algorithm, as implemented in CERR, was used for both cases to derive a consensus volumes. STAPLE is a probabilistic estimate of the true volume generated from all observers. Dose distributions created by each centre for the original target volumes were then applied to this consensus volume. RESULTS: A considerable variation in target segmentation was seen in both cases. For case 1 the variation was 374-960 cm3 (average 669 cm3) and for case 2; 65-126 cm3 (average 109 cm3). CIgen were 0.53 and 0.70, respectively. The DVHs in absolute volume displayed for the delineated target volume as well as for the consensus volume adds information on both "compliant" target volumes as well as outliers which are hidden with just the use of concordance indices. CONCLUSIONS: The DVHs in absolute volume add valuable and easily understood information to various indices for evaluating uniformity in target delineation.

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Pediatric radiotherapy is a critical part of pediatric oncology protocols and the quality of the radiotherapy may determine the future quality of life for long-term survivors. Multidisciplinary team decision making provides the basis for high-quality care. However, delivery of high-quality radiotherapy is dependent on resources. This article provides guidelines for delivery of good quality radiation therapy in resource-limited countries based on rational procurement and maintenance planning, protocol development, three-dimensional planning, quality assurance, and adequate staff numbers and training.

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Squamous cell carcinoma in children and adolescents is extremely rare. Less than 80 case reports have been reported in the literature since it was first reported in 1868. In this article, we intend to report a case where a 16-year-old girl who presented with complaints of change in voice was found to have early-stage vocal cord carcinoma on evaluation.

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When standard conformal x-ray technique for craniospinal irradiation is used, it is a challenge to achieve satisfactory dose coverage of the target including the area of the cribriform plate, while sparing organs at risk. We present a new intensity-modulated radiation therapy (IMRT), noncoplanar technique, for delivering irradiation to the cranial part and compare it with 3 other techniques and previously published results. A total of 13 patients who had previously received craniospinal irradiation with standard conformal x-ray technique were reviewed. New treatment plans were generated for each patient using the noncoplanar IMRT-based technique, a coplanar IMRT-based technique, and a coplanar volumetric-modulated arch therapy (VMAT) technique. Dosimetry data for all patients were compared with the corresponding data from the conventional treatment plans. The new noncoplanar IMRT technique substantially reduced the mean dose to organs at risk compared with the standard radiation technique. The 2 other coplanar techniques also reduced the mean dose to some of the critical organs. However, this reduction was not as substantial as the reduction obtained by the noncoplanar technique. Furthermore, compared with the standard technique, the IMRT techniques reduced the total calculated radiation dose that was delivered to the normal tissue, whereas the VMAT technique increased this dose. Additionally, the coverage of the target was significantly improved by the noncoplanar IMRT technique. Compared with the standard technique, the coplanar IMRT and the VMAT technique did not improve the coverage of the target significantly. All the new planning techniques increased the number of monitor units (MU) used-the noncoplanar IMRT technique by 99%, the coplanar IMRT technique by 122%, and the VMAT technique by 26%-causing concern for leak radiation. The noncoplanar IMRT technique covered the target better and decreased doses to organs at risk compared with the other techniques. All the new techniques increased the number of MU compared with the standard technique.

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