Unraveling Mill-Rearranged Pedriatic Acute Myeloid Leukemia

Blood cells are derived from hematopoietic stem cells (HSC) that reside in the bone marrow. HSC’s are multipotent and have the capacity to diff erentiate into the cells of all blood lineages, i.e. erythrocytes, platelets, neutrophils, eosinophils, basophils, monocytes, T and B lymphocytes, natural killer cells, and dendritic cells. Leukemia is cancer of the blood in which the normal population of blood cells in the bone marrow is replaced by immature blood cells (blasts). Th ese immature cells occur due to an imbalance in diff erentiation and proliferation. Accumulation of these malignant cells in the bone marrow results in decrease of normal mature blood cells, like white blood and red blood cells and platelets

Non-invasive stereotactic arrhythmia radiotherapy for ventricular tachycardia: results of the prospective STARNL-1 trial

Aims: Stereotactic arrhythmia radiotherapy (STAR) is suggested as potentially effective and safe treatment for patients with therapy-refractory ventricular tachycardia (VT). However, the current prospective knowledge base and experience with STAR is limited. In this study we aimed to prospectively evaluate the efficacy and safety of STAR. Methods and results: The StereoTactic Arrhythmia Radiotherapy in the Netherlands no.1 was a pre-post intervention study to prospectively evaluate efficacy and safety of STAR. In patients with therapy-refractory VT, the pro-arrhythmic region was treated with a 25 Gy single radiotherapy fraction. The main efficacy measure was a reduction in the number of treated VT-episodes by >= 50%, comparing the 12 months before and after treatment (or end of follow-up, excluding a 6-week blanking period). The study was deemed positive when >= 50% of patients would meet this criterion. Safety evaluation included left ventricular ejection fraction, pulmonary function, and adverse events. Six male patients with an ischaemic cardiomyopathy were enrolled, and median age was 73 years (range 54-83). Median left ventricular ejection fraction was 38% (range 24-52). The median planning target volume was 187 mL (range 93-372). Four (67%) patients completed the 12-month follow-up, and two patients died (not STAR related) during follow-up. The main efficacy measure of >= 50% reduction in treated VT-episodes at the end of follow-up was achieved in four patients (67%). The median number of treated VT-episodes was reduced by 87%. No reduction in left ventricular ejection fraction or pulmonary function was observed. No treatment related serious adverse events occurred. Conclusions: STAR resulted in a >= 50% reduction in treated VT-episodes in 4/6 (67%) patients. No reduction in cardiac and pulmonary function nor treatment-related serious adverse events were observed during follow-up.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Surrogate-free machine learning-based organ dose reconstruction for pediatric abdominal radiotherapy

To study radiotherapy-related adverse effects, detailed dose information (3D distribution) is needed for accurate dose-effect modeling. For childhood cancer survivors who underwent radiotherapy in the pre-CT era, only 2D radiographs were acquired, thus 3D dose distributions must be reconstructed. State-of-the-art methods achieve this by using 3D surrogate anatomies. These can however lack personalization and lead to coarse reconstructions. We present and validate a surrogate-free dose reconstruction method based on Machine Learning (ML). Abdominal planning CTs (n=142) of recently-treated childhood cancer patients were gathered, their organs at risk were segmented, and 300 artificial Wilms' tumor plans were sampled automatically. Each artificial plan was automatically emulated on the 142 CTs, resulting in 42,600 3D dose distributions from which dose-volume metrics were derived. Anatomical features were extracted from digitally reconstructed radiographs simulated from the CTs to resemble historical radiographs. Further, patient and radiotherapy plan features typically available from historical treatment records were collected. An evolutionary ML algorithm was then used to link features to dose-volume metrics. Besides 5-fold cross validation, a further evaluation was done on an independent dataset of five CTs each associated with two clinical plans. Cross-validation resulted in mean absolute errors ≤0.6 Gy for organs completely inside or outside the field. For organs positioned at the edge of the field, mean absolute errors ≤1.7 Gy for Dmean, ≤2.9 Gy for D2cc, and ≤13% for V5Gy and V10Gy, were obtained, without systematic bias. Similar results were found for the independent dataset. To conclude, our novel organ dose reconstruction method is not only accurate, but also efficient, as the setup of a surrogate is no longer needed

Interobserver variability in target definition for stereotactic arrhythmia radioablation

Background: Stereotactic arrhythmia radioablation (STAR) is a potential new therapy for patients with refractory ventricular tachycardia (VT). The arrhythmogenic substrate (target) is synthesized from clinical and electro-anatomical information. This study was designed to evaluate the baseline interobserver variability in target delineation for STAR. Methods: Delineation software designed for research purposes was used. The study was split into three phases. Firstly, electrophysiologists delineated a well-defined structure in three patients (spinal canal). Secondly, observers delineated the VT-target in three patients based on case descriptions. To evaluate baseline performance, a basic workflow approach was used, no advanced techniques were allowed. Thirdly, observers delineated three predefined segments from the 17-segment model. Interobserver variability was evaluated by assessing volumes, variation in distance to the median volume expressed by the root-mean-square of the standard deviation (RMS-SD) over the target volume, and the Dice-coefficient. Results: Ten electrophysiologists completed the study. For the first phase interobserver variability was low as indicated by low variation in distance to the median volume (RMS-SD range: 0.02–0.02 cm) and high Dice-coefficients (mean: 0.97 ± 0.01). In the second phase distance to the median volume was large (RMS-SD range: 0.52–1.02 cm) and the Dice-coefficients low (mean: 0.40 ± 0.15). In the third phase, similar results were observed (RMS-SD range: 0.51–1.55 cm, Dice-coefficient mean: 0.31 ± 0.21). Conclusions: Interobserver variability is high for manual delineation of the VT-target and ventricular segments. This evaluation of the baseline observer variation shows that there is a need for methods and tools to improve variability and allows for future comparison of interventions aiming to reduce observer variation, for STAR but possibly also for catheter ablation

A review of the clinical experience in pulsed dose rate brachytherapy

Pulsed dose rate (PDR) brachytherapy is a treatment modality that combines physical advantages of high dose rate (HDR) brachytherapy with the radiobiological advantages of low dose rate brachytherapy. The aim of this review was to describe the effective clinical use of PDR brachytherapy worldwide in different tumour locations. We found 66 articles reporting on clinical PDR brachytherapy including the treatment procedure and outcome. Moreover, PDR brachytherapy has been applied in almost all tumour sites for which brachytherapy is indicated and with good local control and low toxicity. The main advantage of PDR is, because of the small pulse sizes used, the ability to spare normal tissue. In certain cases, HDR resembles PDR brachytherapy by the use of multifractionated low-fraction dos

Automatic generation of three-dimensional dose reconstruction data for two-dimensional radiotherapy plans for historically treated patients

Performing large-scale three-dimensional radiation dose reconstruction for patients requires a large amount of manual work. We present an image processing-based pipeline to automatically reconstruct radiation dose. The pipeline was designed for childhood cancer survivors that received abdominal radiotherapy with anterior-to-posterior and posterior-to-anterior field set-up. First, anatomical landmarks are automatically identified on two-dimensional radiographs. Second, these landmarks are used to derive parameters to emulate the geometry of the plan on a surrogate computed tomography. Finally, the plan is emulated and used as input for dose calculation. For qualitative evaluation, 100 cases of automatic and manual plan emulations were assessed by two experienced radiation dosimetrists in a blinded comparison. The two radiation dosimetrists approved 100%/100% and 92%/91% of the automatic/manual plan emulations, respectively. Similar approval rates of 100% and 94% hold when the automatic pipeline is applied on another 50 cases. Further, quantitative comparisons resulted in on average <5 mm difference in plan isocenter/borders, and <0.9 Gy in organ mean dose (prescribed dose: 14.4 Gy) calculated from the automatic and manual plan emulations. No statistically significant difference in terms of dose reconstruction accuracy was found for most organs at risk. Ultimately, our automatic pipeline results are of sufficient quality to enable effortless scaling of dose reconstruction data generation. (C) 2020 Society of Photo-Optical Instrumentation Engineers (SPIE)Biological, physical and clinical aspects of cancer treatment with ionising radiatio

Predictive value of pediatric respiratory-induced diaphragm motion quantified using pre-treatment 4DCT and CBCTs

Background: In adults, a single pre-treatment four-dimensional CT (4D-CT) acquisition is often used to account for respiratory-induced target motion during radiotherapy. However, studies have indicated that a 4D-CT is not always representative for respiratory motion. Our aim was to investigate whether respiratory-induced diaphragm motion in children on a single pre-treatment 4DCT can accurately predict respiratory-induced diaphragm motion as observed on cone beam CTs (CBCTs).Methods: Twelve patients (mean age 14.5 yrs.; range 8.6-17.9 yrs) were retrospectively included based on visibility of the diaphragm on abdominal or thoracic imaging data acquired during free breathing. A 4DCT for planning purposes and daily/weekly CBCTs (total 125; range 4-29 per patient) acquired prior to dose delivery were available. The amplitude, corresponding to the difference in position of the diaphragm in cranial-caudal direction in end-inspiration and end-expiration phases, was extracted from the 4DCT (A(4DCT)). The amplitude in CBCTs (A(CBCT)) was defined as displacement between averaged in- and expiration diaphragm positions on corresponding projection images, and the distribution of A(CBCT) was compared to A(4DCT) (one-sample t-test, significance level p3 mm were found in 69/125 CBCTs (55%), with A(4DCT) mostly underestimating A(CBCT). For 7/12 patients, diaphragm positions differed significantly from the baseline position.Conclusion: Respiratory-induced diaphragm motion determined on 4DCT does not accurately predict the daily respiratory-induced diaphragm motion observed on CBCTs, as the amplitude and baseline position differed statistically significantly in the majority of patients. Regular monitoring of respiratory motion during the treatment course using CBCTs could yield a higher accuracy when a daily adaptation to the actual breathing amplitude takes place.Biological, physical and clinical aspects of cancer treatment with ionising radiatio

An overview of radiological manifestations of acquired dental developmental disturbances in paediatric head and neck cancer survivors

Objectives: In paediatric cancer survivors treated with chemotherapy and radiotherapy therapy, late effects on dental development are quite common. Oral radiologists are not familiar with the radiographic images of these specific dental consequences of chemotherapy and radiotherapy. With the goal of educating colleagues, to raise awareness of the needs of survivors, and to identify directions for future research, we present dental radiographs of survivors treated for head and neck rhabdomyosarcoma with chemotherapy and radiotherapy. Also, based on the survivors reviewed, a radiographic inventory of commonly found late dental developmental effects seen in conjunction with treatment is presented. Methods: Panoramic radiographic findings of five illustrative cases are presented, from a group of 42 survivors of head and neck rhabdomyosarcoma treated at the Academic Medical Center Amsterdam, The Netherlands over the past 25 years. Results: Five cases showing dental developmental disorders are presented. These cases show an association of the location of the radiation field and the developmental stage of the teeth with the severity of the effect on dental development. We also report an inventory of severe and moderate effects of chemotherapy and radiotherapy on the development of molars and anterior teeth. conclusions: This paper presents five cases and a radiographic inventory to illustrate disturbances of dental development associated with chemotherapy and radiotherapy in children. Medical and dental professionals involved in the treatment of cancer survivors are relatively unaware of the dental consequences of radiation therapy and the age dependency of specific regional effects. These effects can be severe, with great impact on quality of life. Further research in this area could help improve planning of radiation therapy for children, potentially preventing or limiting dental or maxillofacial sequelae