Background and Aims

Recently, the SIOP-RTSG developed a highly-conformal flank target volume definition for children with renal tumors. The aims of this study were to evaluate the inter-clinician delineation variation of this new target volume definition in an international multicenter setting and to explore the necessity of quality assurance.

Methods

Six pediatric renal cancer cases were transferred to ten radiation oncologists from seven European countries (‘participants’). These participants delineated the pre- and postoperative Gross Tumor Volume (GTV_pre/post), and Clinical Target Volume (CTV) during two test phases (case 1-2 and 3-4), followed by guideline refinement and a quality assurance phase (case 5-6). Reference target volumes (TV_ref) were established by three experienced radiation oncologists. The Dice Similarity Coefficient between the reference and participants (DSC_ref/part) was calculated per case. Delineations of case 5-6 were graded by four independent reviewers as ‘per protocol’ (0-4mm), ‘minor deviation’ (5-9mm) or ‘major deviation’ (≥10mm) from the delineation guideline using 18 standardized criteria. Also, a major deviation resulting in underestimation of the CTV_ref was regarded as an unacceptable variation.

Results

A total of 57/60 delineation sets were completed. The median DSC_ref/part for the CTV was 0.55 without improvement after sequential cases (case 3-4 vs. case 5-6: p=0.15). For case 5-6, a major deviation was found for 5/18, 12/17, 18/18 and 4/9 collected delineations of the GTV_pre, GTV_post, CTV-T and CTV-N, respectively. An unacceptable variation from the CTV_ref was found for 7/9 participants for case 5 and 6/9 participants for case 6.

Conclusions

This international multicenter delineation exercise demonstrates that the new consensus for highly-conformal postoperative flank target volume delineation leads to geometrical variation among participants. Moreover, standardized review showed an unacceptable delineation variation in the majority of the participants. These findings strongly suggest the need for additional training and centralized pre-treatment review when this target volume delineation approach is implemented on a larger scale.

Background and Aims

Image guided brachytherapy (IGBT) is an appealing option in the treatment of paediatric solid tumours, with the capability to deliver a high radiation dose to a localised target with rapid dose drop off. IGBT offers an alternative local strategy directed towards the reduction of late side effects and preservation of function. This is a prospective case series of sequentially treated children with pelvic tumours.

Methods

Radiological assessment of tumour response was done after initial chemotherapy and pre-plans created. IGBT implants were performed under general anaesthesia with radiation oncology and surgical team present. Post-operative imaging was acquired and individual adaptive treatment plans created. Dose objectives were adjusted from paediatric protocols and adult BT literature. Quality assurance, safety protocols and workflow were adapted depending on the implant. Children remained sedated and ventilated throughout treatment (twice daily).

A subset of six patients underwent plan comparisons between IGBT and proton therapy to investigate optimal patient selection.

Results

Between 2012 and 2020, 12 children from Australia and New Zealand were treated with IGBT with a median age of 18 months (range 11m–16 yrs). Tumour types comprised 7 rhabdomyosarcoma, 4 undifferentiated sarcoma and 1 recurrence of Wilms tumour. IGBT techniques included transperineal interstitial implants, transabdominal implants and customised 3-dimensional applicators. IGBT as the sole local treatment modality was used in 5 children. Doses of 5-6.5Gy over 5 fractions were delivered to 95% of the target volume. Ten of 12 children are alive without disease at median follow up 31 months (range 3-104 months). Five of six comparative plans had lower growth plate dose using IGBT.

Conclusions

IGBT is an ideal primary local treatment modality option in paediatric patients with pelvic tumours that may preserve function, minimise side effects and is delivered over a shorter time period. It requires a collaborative approach between surgical, paediatric and radiation therapy colleagues.

Background and Aims

Proton therapy is an advantageous radiation modality for children due to its normal tissue-sparing capabilities. However, proton beams are sensitive to density changes, which may lead to beam under/over-ranging. This study used longitudinal imaging to identify patient variables predictive of inter-fractional anatomical variations during abdominal radiotherapy.

Methods

Body contour and gastrointestinal gas were semi-automatically segmented on 21 planning computed-tomography (CT) and 77 weekly cone-beam CT (CBCT) scans for 21 patients treated with intensity modulated arc therapy for abdominal high-risk neuroblastoma (median age 4, range 2-19 years). Sex, age, feeding tube and general anaesthesia (GA) were explored as predictive variables for inter-patient variability in gas volume (ΔV_gas) and body contour shape (d_avg) throughout radiotherapy. ΔV_gas was defined as the standard deviation of the gas volume over all scans available per subject; d_avg was defined as the mean value (over all CBCTs per subject) of the average three-dimensional separation between CT and CBCT body contours. All analyses considered only common field-of-views between rigidly-aligned CT/CBCTs.

Results

We found a ΔV_gas and d_avg of 71.0±51.6ml and 1.10±0.40mm, respectively. Most patients exhibited in-room reduction in gastrointestinal gas and body contour compared to planning (81% and 86%, respectively). ΔV_gas was greater for subjects ≤4y (P<0.01) and under GA (P<0.01); multivariate analysis identified GA as the strongest predictor for ΔV_gas (P=0.01). d_avg was greater in patients without feeding tubes (P=0.04). No other variables predicted for ΔV_gas and d_avg. A moderate correlation between reduction (from planning) in gastrointestinal gas and body contour (R=0.50) suggests that, whilst body contour changes are affected by abdominal distension, weight fluctuations and setup variations may contribute to some degree.

Conclusions

Age, GA and feeding tubes were identified as potential predictors of inter-fractional anatomical variations. Our findings may help identify patients who benefit from adaptive/robust planning pathways and more frequent surface and/or image-guided protocols to monitor changes.

Background and Aims

This study explored the use of low dose Cone-Beam Computed Tomography (CBCT_LD) in Image-Guided Radiotherapy (IGRT) for children with an abdominal and/or pelvic planning target volume (PTV). The aim was to compare CBCT_LD with standard dose CBCT (CBCT_SD) using qualitative assessment of relevant IGRT aspects. The study also aimed to determine optimal patient separation in the left-right direction (L-Rsep) where CBCT_LD could be implemented without compromise on image usability.

Methods

Thirty-Five CBCT’s were acquired on 10 children. (Abdomen PTV n=7, Abdomen + Pelvis PTV n=3) CBCT_SD was acquired on the first fraction of each course; remaining acquired images were CBCT_LD. CBCT dose was measured using clinical phantoms. Five clinicians (2x therapeutic radiographers, 2x clinical oncologists, 1x dosimetrist) assessed each CBCT for seven clinically relevant aspects. These included kidney, bladder, bowel/rectum, tumour-insitu, external contour and bone visibility. Comparison between clinician feedback and lateral patient separation (L-Rsep) was used to determine optimal indications for CBCT_LD in IGRT analysis.

Results

All clinicians reported that both external contour and bone could be clearly visualised in all CBCT_LD. Kidneys were reported to be clearly seen in 40.7% of CBCT_LD (61.3% if L-Rsep≤18.5cm), compared to 77.7% on CBCT_SD. Bowel gas was reported to be clearly visible in 73.3% of CBCT_LD (85.7% if L-Rsep≤18.5cm), and 87.7% for CBCT_SD. Bladder and rectum were visualised clearly on CBCT_LD in 48.4% and 55.8% cases respectively (83.3% and 61.1% if L-Rsep≤18.5cm), compared to 28.5% and 57.2% for CBCT_SD. Tumour-insitu was not seen on included CBCT’s due to small residual volume.

Conclusions

CBCT_LD is an excellent IGRT tool for use in assessing external contour and bone position, whilst kidney, bladder and bowel/rectum assessment was most suitable for patients with a L-Rsep≤18.5cm at level of PTV. CBCT_LD can account for up to 4.3mSv dose reduction per image when compared to CBCT_SD.

Background and Aims

Pediatric radiotherapy comprises a plethora of diagnoses and challenges for radiotherapy departments. The rare incidence of pediatric malignancies infers difficulties in securing and maintaining state-of-the-art competence among radiation oncologists and for providing adequate training for young physicians. In Sweden, only six centers give pediatric radiotherapy, each center treating 10-30 children annually. With the intention to secure competence, the Swedish Pediatric Radiotherapy Group was formed in the year 2000. We report on the lessons learnt and the utility and benefits from these 20 years of work.

Methods

The group has become an established basis for pediatric radiotherapy with bi-monthly telemedicine conferences. In 2008, we started a registry (dosimetric and follow-up data) for Swedish children receiving radiotherapy. A national monitor secures a 100% enrollment.

Results

During these first 20 years almost all children due for radiotherapy have been reviewed in the teleconferences. Treatment recommendations for challenging clinical situations have been formulated, and selection of optimal treatment techniques, as proton treatment was introduced as an alternative to photon techniques, have been facilitated.

Dummy-runs were conducted on new treatment protocols for rhabdomyosarcoma, Hodgkin’s lymphoma and cranial tumors in order to discern ambiguities or possible risks of misinterpretation for radiotherapy guidelines before implementation. Treatment guidelines for re-irradiation of intracranial tumors have been developed, and the experience of introducing proton treatment in 2015 continuously evaluated. Also, guidelines for delivering CSI, ependymomas and craniopharyngiomas have been formulated. On a case-by-case basis, also children from neighboring countries lacking similar groups have been discussed. A core-curriculum for pediatric radiotherapy is being developed.

Conclusions

The experiences strongly support the benefits of regular telemedicine collaboration between radiotherapy centers providing pediatric radiotherapy. It may enhance treatment quality in centers with few pediatric cases and provides an excellent tool for education and further training in radiotherapy.

Background and Aims

Idiopathic pneumonitis is a treatment-related morbidity that emerges after total body irradiation (TBI). A reduced intensity conditioning (RIC) regimen with low-dose irradiation has been recently applied for the treatment for both malignant and non-malignant diseases, to support engraftment with minimized toxicity. This study analysed the risk of pulmonary complications, including idiopathic pneumonitis after low dose TBI (LDTBI), in RIC.

Methods

We performed a retrospective analysis of patients who underwent LDTBI and 3 Gy single-fraction as a conditioning regimen in a children’s hospital between 2010 and 2020. Any respiratory symptoms that emerged 120 days after transplantation and having been subjected to radiological examination were listed as pulmonary complications. These pulmonary complications were classified into three categories according to American Thoracic Society Research Statement : group 1, idiopathic pneumonia syndrome group; group 2, infection group; and group 3, respiratory disorder caused by other specific aetiologies. The factors causing idiopathic pneumonia, including disease status, graft versus host disease (GVHD), and radiotherapeutic parameters were explored.

Results

LDTBI was introduced in a total of 57 patients, with median age of 4.4 (0.3-20.9) years.. The primary diseases for stem cell transplantation were: malignant disease (n=8), non-malignant disease (n=44). Pulmonary complications were observed in nine patients. Among those with the idiopathic pneumonitis, group 1 accounted for 2 patients (3.5%). Acute GVHD was observed in 26 patients. All two idiopathic pneumonia patients suffered from acute GVHD.

Conclusions

The incidence of pulmonary complications after LDTBI was lower than 15% that reported for TBI in myeloablative conditioning, and most events were caused by infection or other organ failure. The relationship between idiopathic pneumonia and acute GVHD predicted that idiopathic pneumonia after LDTBI is attributed not only to pulmonary damage by irradiation, but also to immunological hyperreaction after stem cell transplantation.

Background and Aims

4D CT is often used for the evaluating the extent of respiratory motion in the thoracic and abdominal region for use in radiation treatment. However, improved image contrast and lack of ionizing radiation makes MRI an attractive alternative. The aim of this study was to evaluate the use of movie-like 2D cine MRI sequences to measure the extent of respiratory motion for radiotherapy planning in pediatric patients treated with proton therapy for abdominal tumors.

Methods

Sagittal and coronal cine MRI sequences were added to an MRI acquired in general anaesthesia for target delineation for five pediatric patients with abdominal tumors. The median age was 3 years (7 months - 4 years). Cine MRI sequences were acquired at 4Hz for 16 seconds with 2-3 coronal and 2-7 sagittal images. The displacement length (d) between expiration and inspiration was visually assessed in three directions (AP, CC, LR) as maximal (d_v) in CTV near structures that were easy to visualize. This was compared to deformable registration between the inspiration and expiration respiratory phase and d was measured at 90% (d_90%) and at maximum (d_max).

Results

Visual evaluation resulted across all patient in median(range) of d_v,AP=1mm (0mm 1mm), d_v,LR=1mm (0mm 2mm), and d_v,CC=2mm (2mm 5mm). Similarly, deformable registration resulted in a median(range) 90% displacement of d_90%,AP=1.6mm (1.3mm 2.3mm), d_90%,LR=1.7mm (1.3mm 3.7mm), and d_90%,CC=2.8mm (2mm 3.4mm). The maximal deformation length was d_max,AP=3.3mm (2.7mm 12.0mm), d_max,LR=3.9mm (3.7mm 6.4mm), and d_max,CC=5.3mm (3.7mm 6.0mm).

Conclusions

Visual evaluation was closer to the 90% central range than to the maximal deformation vector length. However, further validation using a 4D MRI phantom to establish a ground truth is needed as well as direct comparison to 4D CT. Cine MR may be used as an alternative to 4DCT for evaluation on abdominal motion with the largest motion found in the CC direction.

Background and Aims

Background :

Splenectomy in young children has long been associated with a risk of bacterial infections. Radiation may also cause long-term splenic dysfunction, risking potentially fatal late sepsis.

Purpose:

To assess the doses received to the spleen in pediatric patient who receive abdominal radiation.

Methods

A retrospective dosimetric analysis of 3D radiotherapy plans of 29 pediatric patients treated from 2014 to 2020, in our department. Those patients has received abdominal irradiation. Radiotherapy plans were reviewed to assess spleen dosimetry. Mean doses to the spleen were considered.

Results

The mean patient age was 5,4 years (range from 2 to 14 years old). Patients were treated for medulloblastoma (20.7%) with a total dose of 54 Gy, wilm’s tumor (37.9%) with a dose of 14.4 Gy, neuroblastoma (13.8%) with a dose of 36 Gy , synovial sarcoma(3.4%) with a dose of 45 Gy, Rhabdomyosarcoma (3.4%) with a dose of 54 Gy, ewing sarcoma of the spinal epidural (3.4%) with a dose of 45 Gy, pinealoblastoma (3.4%) with a dose of 54 Gy, primary neuroendocrine tumor (10.3%) with a dose of 54 Gy and embryonal tumor (3.4%) with a dose of 54 Gy.

The median mean dose to the spleen was 1.328 Gy (range: 0.138 - 45.897 Gy). 6 patients (20.7%) received a mean spleen dose >10 Gy, but only one patient received a dose >40 Gy.

This patient had a primary left renal synovial sarcoma receiving postoperative radiotherapy with a dose of 45 Gy in 25 fractions.

No cases of septicemia or bacterial meningitis were noted in this study;

Conclusions

The spleen may receive some incidental dose when the target volume is in the abdomen. SIOP-Europe Radiation Oncology Working Group recommend routine delineation of the spleen and advocate antibiotic prophylaxis and/or (re)vaccination, to prevent « overwhelming post-splenectomy infection » if the mean spleen dose is >10 Gy.