Can treatment of pediatric Hodgkin's lymphoma be improved by PET imaging and proton therapy?

BACKGROUND AND PURPOSE: To explore a new positron emission tomography (PET)-based target concept for pediatric Hodgkin's lymphoma (PHL). PATIENTS AND METHODS: For 10 patients, the planning target volume PTV1 was based on initial CT tumor extension and PTV2 on anatomy-related PET-positive lymph node levels after chemotherapy. The treatment techniques investigated (prescribed dose 19.8 Gy) comprised opposed-field (2F), intensity-modulated photon (IMXT), and single-field (PS) proton techniques. Treatment concepts were compared concerning dose-volume histogram (DVH) parameters and organ-equivalent doses (OED). RESULTS: The median PTV1 and PTV2 were 902 ± 555 cm(3) and 281 ± 228 cm(3). When using PTV2 instead of PTV1 for all techniques, the D(2%) of the heart was reduced from 14 to 9 Gy and the D(mean) of the thyroid from 16.6 to 2.7 Gy. Low- (20%), median- (50%), and high-dose volumes (80%) were reduced by 60% for the heart and bones using PTV2. PS reduced the high-dose volume of the lungs and the heart by up to 60%. IMXT increased the low-dose volumes and OED. PTV2 reduced OED by 54 ± 10% for all organs at risk. CONCLUSION: PTV2 has a high impact on the treated volume and on sparing of organs at risk. The combination of an adaptive target volume definition with protons could contribute to future PHL treatment concepts.

Requirements for dose calculation on an active scanned proton beamline for small, shallow fields.

INTRODUCTION: A growing interest in using proton pencil beam scanning in combination with collimators for the treatment of small, shallow targets, such as ocular melanoma or pre-clinical research emerged recently. This study aims at demonstrating that the dose of a synchrotron-based PBS system with a dedicated small, shallow field nozzle can be accurately predicted by a commercial treatment planning system (TPS) following appropriate tuning of both, nozzle and TPS. MATERIALS: A removable extension to the clinical nozzle was developed to modify the beam shape passively. Five circular apertures with diameters between 5 to 34mm, mounted 72cm downstream of a range shifter were used. For each collimator treatment plans with spread-out Bragg peaks (SOBP) with a modulation of 3 to 30mm were measured and calculated with GATE/Geant4 and the research TPS RayStation (RS11B-R). The dose grid, multiple coulomb scattering and block discretization resolution were varied to find the optimal balance between accuracy and performance. RESULTS: For SOBPs deeper than 10mm, the dose in the target agreed within 1% between RS11B-R, GATE/Geant4 and measurements for aperture diameters between 8 to 34mm, but deviated up to 5% for smaller apertures. A plastic taper was introduced reducing scatter contributions to the patient (from the pipe) and improving the dose calculation accuracy of the TPS to a 5% level in the entrance region for large apertures. CONCLUSION: The commercial TPS and GATE/Geant4 can accurately calculate the dose for shallow, small proton fields using a collimator and pencil beam scanning.

Multicenter evaluation of different target volume delineation concepts in pediatric Hodgkin's lymphoma. A case study.

BACKGROUND AND PURPOSE: In pediatric Hodgkin's lymphoma (PHL) improvements in imaging and multiagent chemotherapy have allowed for a reduction in target volume. The involved-node (IN) concept is being tested in several treatment regimens for adult Hodgkin's lymphoma. So far there is no consensus on the definition of the IN. To improve the reproducibility of the IN, we tested a new involved-node-level (INL) concept, using defined anatomical boundaries as basis for target delineation. The aim was to evaluate the feasibility of IN and INL concepts for PHL in terms of interobserver variability. PATIENTS AND METHODS: The INL concept was defined for the neck and mediastinum by the PHL Radiotherapy Group based on accepted concepts for solid tumors. Seven radiation oncologists from six European centers contoured neck and mediastinal clinical target volumes (CTVs) of 2 patients according to the IN and the new INL concepts. The median CTVs, coefficient of variation (COV), and general conformity index (CI) were assessed. The intraclass correlation coefficient (ICC) for reliability of delineations was calculated. RESULTS: All observers agreed that INL is a feasible and practicable delineation concept resulting in stronger interobserver concordance than the IN (mediastinum CI(INL) = 0.39 vs. CI(IN) = 0.28, neck left CI(INL) = 0.33; CI(IN) = 0.18; neck right CI(INL) = 0.24, CI(IN) = 0.14). The COV showed less dispersion and the ICC indicated higher reliability of contouring for INL (ICC(INL) = 0.62, p < 0.05) as for IN (ICC(IN) = 0.40, p < 0.05). CONCLUSION: INL is a practical and feasible alternative to IN resulting in more homogeneous target delineation, and it should be therefore considered as a future target volume concept in PHL.

Investigation of the Bragg peak degradation caused by homogeneous and heterogeneous lung tissue substitutes: proton beam experiments and comparison to current clinical dose calculation.

Submillimetre structures of lung tissue are not represented in computed tomography images used for radiotherapeutic dose calculation. In order to study the effect experimentally, lung substitutes with properties similar to lung tissue were chosen, namely two types of commercial lung tissue equivalent plates (LTEPs) (CIRS, USA), two types of cork, balsawood, floral foam and konjac sponge. Laterally integrated dose profiles were measured as a function of depth for proton pencil beams (PBs) with an initial nominal energy of 97.4 and 148.2 MeV, respectively. The obtained dose profiles were investigated for their shifting and degradation of the Bragg peak (BP) caused by the materials, expressed as water equivalent thickness (WET) and full width half maximum. The set-up was simulated in the treatment planning system (TPS) RayStation using the Monte Carlo (MC) dose calculation algorithm. While the WET between experiment and dose calculation agreed within 0.5 mm, except for floral foam, the full width half maximum was underestimated in the TPS by up to 2.3 mm. Normalisation to the same mass thickness of the lung substitutes allowed to classify LTEPs and balsawood as homogeneous and cork, floral foam and konjac sponge as heterogeneous materials. The material specific BP degradation was up to 3.4 times higher for the heterogeneous samples. The modulation power as a measure for the heterogeneity was compared to the spectrum of Hounsfield units (HU) of the materials. A clear correlation was not found, but with further improvements the HU spectrum may serve as an indicator for the material heterogeneity. Further, MC simulations of binary voxel models using GATE/Geant4 were performed to investigate the influence of grain size and mass density. For mass densities similar to lung tissue the BP degradation had a maximum at 3 and 7 mm grain size.

Time-resolved dosimetry for validation of 4D dose calculation in PBS proton therapy.

Four-dimensional dose calculation (4D-DC) is crucial for predicting the dosimetric outcome in the presence of intra-fractional organ motion. Time-resolved dosimetry can provide significant insights into 4D pencil beam scanning dose accumulation and is therefore irreplaceable for benchmarking 4D-DC. In this study a novel approach of time-resolved dosimetry using five PinPoint ionization chambers (ICs) embedded in an anthropomorphic dynamic phantom was employed and validated against beam delivery details. Beam intensity variations as well as the beam delivery time structure were well reflected with an accuracy comparable to the temporal resolution of the IC measurements. The 4D dosimetry approach was further applied for benchmarking the 4D-DC implemented in the RayStation 6.99 treatment planning system. Agreement between computed values and measurements was investigated for (i) partial doses based on individual breathing phases, and (ii) temporally distributed cumulative doses. For varied beam delivery and patient-related parameters the average unsigned dose difference for (i) was 0.04 ± 0.03 Gy over all considered IC measurement values, while the prescribed physical dose was 2 Gy. By implementing (ii), a strong effect of the dose gradient on measurement accuracy was observed. The gradient originated from scanned beam energy modulation and target motion transversal to the beam. Excluding measurements in the high gradient the relative dose difference between measurements and 4D-DCs for a given treatment plan at the end of delivery was 3.5% on average and 6.6% at maximum over measurement points inside the target. Overall, the agreement between 4D dose measurements in the moving phantom and retrospective 4D-DC was found to be comparable to the static dose differences for all delivery scenarios. The presented 4D-DC has been proven to be suitable for simulating treatment deliveries with various beam- as well as patient-specific parameters and can therefore be employed for dosimetric validation of different motion mitigation techniques.

Dynamic lung phantom commissioning for 4D dose assessment in proton therapy.

Anthropomorphic phantoms mimicking organ and tumor motion of patients are essential for end-to-end testing of motion mitigation techniques in ion beam therapy. In this work a commissioning procedure developed with the in-house designed respiratory phantom ARDOS (Advanced Radiation DOSimetry system) is presented. The phantom was tested and benchmarked for 4D dose verification in proton therapy, which included: characterization of the tissue equivalent materials from computed tomography (CT) imaging, assessment of dose calculation accuracy in critical structures of the phantom, and testing various detectors for proton dosimetry in the ARDOS phantom. To prove the validity of the CT calibration curve, measured relative stopping powers (RSP) of the ARDOS materials were compared with values from CTs: original and overwritten with known material parameters. Override of rib- and soft-tissue phantom components improved RSP accuracy while inhomogeneous lung tissue, represented by the balsa wood, was better modelled by the CT Hounsfield units. Monte Carlo (MC) dose calculations were benchmarked against measurements with a reference Farmer chamber embedded in ARDOS material samples showing less than 3% relative dose difference. Differences between MC calculated dose distributions and those calculated by analytical algorithms for the ARDOS geometry were higher than 20% of the prescribed dose, depending on the position in the phantom. Pinpoint ionization chambers and thermoluminescence dosimeters showed differences of up to 5.5% compared to MC dose calculations for all lung setups in the static phantom. They were also able to detect dose distortions due to motion. EBT3 film dosimetry was shown to be suitable for 2D relative dose characterization, which could provide extended information on dose distributions in the penumbra area. The presented methodology and results can be used for drafting general recommendations for dynamic phantom commissioning, which is an essential step towards end-to-end evaluation of motion mitigation techniques in ion beam therapy.

Influence of PET reconstruction parameters on the TrueX algorithm. A combined phantom and patient study.

UNLABELLED: With the increasing use of functional imaging in modern radiotherapy (RT) and the envisaged automated integration of PET into target definition, the need for reliable quantification of PET is growing. Reconstruction algorithms in new PET scanners employ point-spread-function (PSF) based resolution recovery, however, their impact on PET quantification still requires thorough investigation. PATIENTS, MATERIAL, METHODS: Measurements were performed on a Siemens PET/CT using an IEC phantom filled with varying activity. Data were reconstructed using the OSEM (Gauss filter) and the PSF TrueX (Gauss and Allpass filter) algorithm with all available products of iterations (i) and subsets (ss). The recovery coeffcient (RC) and threshold defining the real sphere volume were determined for all settings and compared to the clinical standard (4i21ss). PET acquisitions of eight lung patients were reconstructed using all algorithms with 4i21ss. Volume size and tracer uptake were determined with different segmentation methods. RESULTS: The threshold for the TrueX was lower (up to 40%) than for the OSEM. The RC for the different algorithms and filters varied. TrueX was more sensitive to permutations of i and ss and only the RC of the OSEM stabilised with increasing number. For patient scans the difference of the volume and activity between TrueX and OSEM could be reduced by applying an adapted threshold and activity correction. CONCLUSION: The TrueX algorithm results in excellent diagnostic image quality, however, guidelines for native algorithms have to be extended for PSF based reconstruction methods. For appropriate tumour delineation, for the TrueX a lower threshold than the 42% recommended for the OSEM is necessary. These filter dependent thresholds have to be verified for different scanners prior to using them in multicenter trials.

"Label and go"--a fast and easy radiolabelling method for pellets.

For the development and process optimization of pharmaceutical equipment, it is important to investigate the underlying processes. Taking the fluidized bed technology as an example, the study of particle flow pattern and convection of the particles within the functional unity is essential for construction and process improvement. With positron emission particle tracking (PEPT) it is possible to study the real-time particle motion with radiolabelled particles. We established a fast and simple labelling technique with [(18)F]fluoride for pellets composed of Avicel and anion exchange resin. The uptake of activity ranged from 1.3% to 1.7% per mg and 8.6% to 16.3% per pellet. A specific binding of [(18)F]fluoride with increasing degree of anion exchange resin in the pellets could be observed.