On the effectiveness of ion range determination from in-beam PET data.

At present, in-beam positron emission tomography (PET) is the only method for in vivo and in situ range verification in ion therapy. At the GSI Helmholtzzentrum für Schwerionenforschung GmbH (GSI) Darmstadt, Germany, a unique in-beam PET installation has been operated from 1997 until the shut down of the carbon ion therapy facility in 2008. Therapeutic irradiation by means of (12)C ion beams of more than 400 patients have been monitored. In this paper a first quantitative study on the accuracy of the in-beam PET method to detect range deviations between planned and applied treatment in clinically relevant situations using simulations based on clinical data is presented. Patient treatment plans were used for performing simulations of positron emitter distributions. For each patient a range difference of + or - 6 mm in water was applied and compared to simulations without any changes. The comparisons were performed manually by six experienced evaluators for data of 81 patients. The number of patients required for the study was calculated using the outcome of a pilot study. The results indicate a sensitivity of (91 + or - 3)% and a specificity of (96 + or - 2)% for detecting an overrange, a reduced range is recognized with a sensitivity of (92 + or - 3)% and a specificity of (96 + or - 2)%. The positive and the negative predictive value of this method are 94% and 87%, respectively. The interobserver coefficient of variation is between 3 and 8%. The in-beam PET method demonstrated a high sensitivity and specificity for the detection of range deviations. As the range is a most indicative factor of deviations in the dose delivery, the promising results shown in this paper confirm the in-beam PET method as an appropriate tool for monitoring ion therapy.

Toward a real-time in vivo dosimetry system using plastic scintillation detectors.

PURPOSE: In the present study, we have presented and validated a plastic scintillation detector (PSD) system designed for real-time multiprobe in vivo measurements. METHODS AND MATERIALS: The PSDs were built with a dose-sensitive volume of 0.4 mm(3). The PSDs were assembled into modular detector patches, each containing five closely packed PSDs. Continuous dose readings were performed every 150 ms, with a gap between consecutive readings of <0.3 ms. We first studied the effect of electron multiplication. We then assessed system performance in acrylic and anthropomorphic pelvic phantoms. RESULTS: The PSDs were compatible with clinical rectal balloons and were easily inserted into the anthropomorphic phantom. With an electron multiplication average gain factor of 40, a twofold increase in the signal/noise ratio was observed, making near real-time dosimetry feasible. Under calibration conditions, the PSDs agreed with the ion chamber measurements to 0.08%. Precision, evaluated as a function of the total dose delivered, ranged from 2.3% at 2 cGy to 0.4% at 200 cGy. CONCLUSION: Real-time PSD measurements are highly accurate and precise. These PSDs can be mounted onto rectal balloons, transforming these clinical devices into in vivo dose detectors without modifying current clinical practice. Real-time monitoring of the dose delivered near the rectum during prostate radiotherapy should help radiation oncologists protect this sensitive normal structure.

Liquid scintillator for 2D dosimetry for high-energy photon beams.

Complex radiation therapy techniques require dosimetric verification of treatment planning and delivery. The authors investigated a liquid scintillator (LS) system for application for real-time high-energy photon beam dosimetry. The system was comprised of a transparent acrylic tank filled with liquid scintillating material, an opaque outer tank, and a CCD camera. A series of images was acquired when the tank with liquid scintillator was irradiated with a 6 MV photon beam, and the light data measured with the CCD camera were filtered to correct for scattering of the optical light inside the liquid scintillator. Depth-dose and lateral profiles as well as two-dimensional (2D) dose distributions were found to agree with results from the treatment planning system. Further, the corrected light output was found to be linear with dose, dose rate independent, and is robust for single or multiple acquisitions. The short time needed for image acquisition and processing could make this system ideal for fast verification of the beam characteristics of the treatment machine. This new detector system shows a potential usefulness of the LS for 2D QA.

In-beam PET measurements of biological half-lives of 12C irradiation induced beta+-activity.

One of the long-standing problems in carbon-ion therapy is the monitoring of the treatment, i.e. of the delivered dose to a given tissue volume within the patient. Over the last 8 years, in-beam positron emission tomography (PET) has been used at the experimental carbon ion treatment facility at the Gesellschaft fur Schwerionenforschung (GSI) Darmstadt and has become a valuable quality assurance tool. In order to determine and evaluate the correct delivery of the patient dose, a simulation of the positron emitter distribution has been compared to the measurement. One particular effect is the blurring as well as the reduction of the measured activity distribution via washout. The objective of this study is the investigation of tissue dependent effective half-lives from patient data. We find no significant dependence of the effective half-life on the Hounsfield unit but on the local dose. The biological half-life within the high dose region is longer than in the low dose region. Furthermore, the influence of the overall treatment time on the kinetics of the positron emitter is reported. There are indications for a metabolic response of the tissue on the irradiation. Taking into account the biological half-life in the simulation leads to an improvement of the quality of the PET-images in some cases.

Additional PET/CT in week 5-6 of radiotherapy for patients with stage III non-small cell lung cancer as a means of dose escalation planning?

BACKGROUND AND PURPOSE: Loco-regional failure after radiotherapy with total doses of 60-70 Gy for non-small cell lung cancer (NSCLC) remains a major clinical problem. Escalation of radiation dose is often limited because of exceeding normal tissue constraints. The present study was designed to test the hypothesis that a reduction in disease volume during radiotherapy detected by FDG PET/CT would facilitate radiation dose escalation, whilst remaining within normal tissue constraints. MATERIALS AND METHODS: Ten patients with localised inoperable NSCLC were prospectively enrolled. Each received standard 3D-conformally planned radiotherapy to a dose of 66 Gy in 33 fractions over 6.5 weeks. FDG PET/CT imaging in the treatment position was performed prior to treatment and repeated following 50 or 60 Gy. CT and PET-delineated gross tumour volumes were generated and a composite created. A margin of 15mm was added in all planes to form the planning target volume (PTV). Treatment planning was performed to compare two dose escalation strategies: 78 Gy delivered to the initial PTV with treatment in two phases (shrinking field), i.e., 66 Gy to the initial PTV with a 12 Gy-boost to the PTV after 50/60 Gy. As an alternative planning approach the maximal dose without exceeding normal tissue constraints was evaluated for each patient (individualized dose prescription). RESULTS: There was a median PTV reduction after 50/60 Gy of 20%. Delivering 78 Gy to the initial PTV could have been achieved in 4/10 patients. Of the remaining 6, delivering 78 Gy to the initial PTV would have exceeded normal tissue constraints and no benefit was seen when delivered in two phases. The results from the individualized dose prescription indicated a higher median maximal dose when treatment would be given in two phases compared to one phase resulting in a modest increase of calculated tumour control probability. CONCLUSIONS: Our data suggest that despite tumour shrinkage determined by subsequent FDG PET/CT during treatment the tested adaptive targeting strategy would result only in a modest improvement in the context of dose escalation. Further studies on the optimal use of FDG PET/CT and other approaches for dose escalation in loco-regionally advanced NSCLC are warranted.

Attenuation correction of four dimensional (4D) PET using phase-correlated 4D-computed tomography.

The image quality in a conventional positron emission tomography (PET)/computed tomography (CT) scanner is degraded by respiratory motion because of erroneous attenuation correction when three-dimensional image acquisition is used. To overcome this problem, time-resolved data acquisition (4D) is required. For this, a Siemens Biograph 16 PET/CT scanner has been modified and its normal capability has been extended to a true 4D-PET/4D-CT imaging device including phase-correlated attenuation correction. To verify the correct functionality of this device, experiments on a respiratory motion phantom that allowed movement in two dimensions have been performed. The measurements showed good spatial correlation as well as good time synchronization between the PET and CT data. Furthermore, the motion pattern of the phantom and the shape of the activity distribution have been examined, and the volume of the reconstructed PET images has been analyzed. The results demonstrate the feasibility of such a procedure, and we therefore recommend that 4D-PET data should be reconstructed using 4D-CT data, which can be acquired on the same machine.

A Monte Carlo model for out-of-field dose calculation from high-energy photon therapy.

As cancer therapy becomes more efficacious and patients survive longer, the potential for late effects increases, including effects induced by radiation dose delivered away from the treatment site. This out-of-field radiation is of particular concern with high-energy radiotherapy, as neutrons are produced in the accelerator head. We recently developed an accurate Monte Carlo model of a Varian 2100 accelerator using MCNPX for calculating the dose away from the treatment field resulting from low-energy therapy. In this study, we expanded and validated our Monte Carlo model for high-energy (18 MV) photon therapy, including both photons and neutrons. Simulated out-of-field photon doses were compared with measurements made with thermoluminescent dosimeters in an acrylic phantom up to 55 cm from the central axis. Simulated neutron fluences and energy spectra were compared with measurements using moderated gold foil activation in moderators and data from the literature. The average local difference between the calculated and measured photon dose was 17%, including doses as low as 0.01% of the central axis dose. The out-of-field photon dose varied substantially with field size and distance from the edge of the field but varied little with depth in the phantom, except at depths shallower than 3 cm, where the dose sharply increased. On average, the difference between the simulated and measured neutron fluences was 19% and good agreement was observed with the neutron spectra. The neutron dose equivalent varied little with field size or distance from the central axis but decreased with depth in the phantom. Neutrons were the dominant component of the out-of-field dose equivalent for shallow depths and large distances from the edge of the treatment field. This Monte Carlo model is useful to both physicists and clinicians when evaluating out-of-field doses and associated potential risks.

Reduced neutron production through use of a flattening-filter-free accelerator.

PURPOSE: To measure and compare neutron fluence around an accelerator operating at 18 MV, both with the flattening filter present (FF mode) and absent (flattening-filter-free [FFF] mode). METHODS AND MATERIALS: The neutron fluence was measured at several locations in the patient plane using gold foil activation in neutron moderators. Differences in neutron fluence between the FF and FFF mode were assessed in three frameworks: (1) measured per monitor unit of machine-on time, (2) determined per dose on the central axis, and (3) determined for a complete course of prostate intensity-modulated radiotherapy. RESULTS: Neutron fluence per monitor unit was approximately 20% lower when the accelerator was operated in the FFF mode than when it was in FF mode. The total amount of neutron fluence that would be obtained during the entire course of prostate intensity-modulate radiotherapy was 69% lower when the accelerator was operated in the FFF mode than when it was in the FF mode. This reduction in neutron fluence would correspond to a drastic reduction in the neutron dose equivalent received by the patient as a byproduct of high-energy radiotherapy. It would also correspond to a reduction in activation within the treatment vault and subsequent exposure to radiation therapists. CONCLUSION: When feasible, operating the accelerator without a FF will benefit both patients and radiation therapists by reducing the number of unwanted neutrons and resultant exposure. This reduces the risk of negative effects from such exposure (e.g., second cancers).

A Monte Carlo model for calculating out-of-field dose from a varian 6 MV beam.

Dose to the patient outside of the treatment field is important when evaluating the outcome of radiotherapy treatments. However, determining out-of-field doses for any particular treatment plan currently requires either time-consuming measurements or calculated estimations that may be highly uncertain. A Monte Carlo model may allow these doses to be determined quickly, accurately, and with a great degree of flexibility. MCNPX was used to create a Monte Carlo model of a Varian Clinac 2100 accelerator head operated at 6 MV. Simulations of the dose out-of-field were made and measurements were taken with thermoluminescent dosimeters in an acrylic phantom and with an ion chamber in a water tank to validate the Monte Carlo model. Although local differences between the out-of-field doses calculated by the model and those measured did exceed 50% at some points far from the treatment field, the average local difference was only 16%. This included a range of doses as low as 0.01% of the central axis dose, and at distances in excess of 50 cm from the central axis of the treatment field. The out-of-field dose was found to vary with field size and distance from the central axis, but was almost independent of the depth in the phantom except where the dose increased substantially at depths less than dmax. The relationship between dose and kerma was also investigated, and kerma was found to be a good estimate of dose (within 3% on average) except near the surface and in the field penumbra. Our Monte Carlo model was found to well represent typical Varian 2100 accelerators operated at 6 MV.

Properties of unflattened photon beams shaped by a multileaf collimator.

Several studies have shown that removal of the flattening filter from the treatment head of a clinical accelerator increases the dose rate and changes the lateral profile in radiation therapy with photons. However, the multileaf collimator (MLC) used to shape the field was not taken into consideration in these studies. We therefore investigated the effect of the MLC on flattened and unflattened beams. To do this, we performed measurements on a Varian Clinac 21EX and MCNPX Monte Carlo simulations to analyze the physical properties of the photon beam. We compared lateral profiles, depth dose curves, MLC leakages, and total scatter factors for two energies (6 and 18 MV) of MLC-shaped fields and jaw-shaped fields. Our study showed that flattening filter-free beams shaped by a MLC differ from the jaw-shaped beams. Similar differences were also observed for flattened beams. Although both collimating methods produced identical depth dose curves, the penumbra size and the MLC leakage were reduced in the softer, unflattened beam and the total scatter factors showed a smaller field size dependence.

Monte Carlo study of photon fields from a flattening filter-free clinical accelerator.

In conventional clinical linear accelerators, the flattening filter scatters and absorbs a large fraction of primary photons. Increasing the beam-on time, which also increases the out-of-field exposure to patients, compensates for the reduction in photon fluence. In recent years, intensity modulated radiation therapy has been introduced, yielding better dose distributions than conventional three-dimensional conformal therapy. The drawback of this method is the further increase in beam-on time. An accelerator with the flattening filter removed, which would increase photon fluence greatly, could deliver considerably higher dose rates. The objective of the present study is to investigate the dosimetric properties of 6 and 18 MV photon beams from an accelerator without a flattening filter. The dosimetric data were generated using the Monte Carlo programs BEAMnrc and DOSXYZnrc. The accelerator model was based on the Varian Clinac 2100 design. We compared depth doses, dose rates, lateral profiles, doses outside collimation, total and collimator scatter factors for an accelerator with and without a flatteneing filter. The study showed that removing the filter increased the dose rate on the central axis by a factor of 2.31 (6 MV) and 5.45 (18 MV) at a given target current. Because the flattening filter is a major source of head scatter photons, its removal from the beam line could reduce the out-of-field dose.

MCNPX simulation of a multileaf collimator.

Our purpose in this work was to validate a very detailed Monte Carlo model, developed in MCNPX, of a Millennium 120 multileaf collimator integrated into a Varian Clinac 21EX treatment head. The Monte Carlo results were compared with measurements for both the 6-MV and 18-MV photon modes. The following comparisons were performed: depth-dose curves, lateral profiles, multileaf collimator leakage, the tongue-and-grove test, and the round leaf-end test. The good agreement between the Monte Carlo simulations and measurements showed that our model is accurate. Consequently, the benchmarks provided by our study can be used in future Monte Carlo studies.

Dosimetric properties of photon beams from a flattening filter free clinical accelerator.

Basic dosimetric properties of 6 MV and 18 MV photon beams from a Varian Clinac 21EX accelerator operating without the flattening filter have been measured. These include dose rate data, depth dose dependencies and lateral profiles in a water phantom, total scatter factors and transmission factors of a multileaf collimator. The data are reviewed and compared with measurements for the flattened beams. The unflattened beams have the following: a higher dose rate by factors of 2.3 (6 MV) and 5.5 (18 MV) on the central axis; lower out-of-field dose due to reduced head scatter and softer spectra; less variation of the total scatter factor with field size; and less variation of the shape of lateral dose profiles with depth. The findings suggest that with a flattening filter free accelerator better radiation treatments can be developed, with shorter delivery times and lower doses to normal tissues and organs.

The modelling of positron emitter production and PET imaging during carbon ion therapy.

At the carbon ion therapy facility of GSI Darmstadt in-beam positron emission tomography (PET) is used for imaging the beta+-activity distributions which are produced via nuclear fragmentation reactions between the carbon ions and the atomic nuclei of the irradiated tissue. On the basis of these PET images the quality of the irradiation, i.e. the position of the field, the particle range in vivo and even local deviations between the planned and the applied dose distribution, can be evaluated. However, for such an evaluation the measured beta+-activity distributions have to be compared with those predicted from the treatment plan. The predictions are calculated as follows: a Monte Carlo event generator produces list mode data files of the same format as the PET scanner in order to be processed like the measured ones for tomographic reconstruction. The event generator models the whole chain from the interaction of the projectiles with the target, i.e. their stopping and nuclear reactions, the production and the decay of positron emitters, the motion of the positrons as well as the propagation and the detection of the annihilation photons. The steps of the modelling, the experimental validation and clinical implementation are presented.

Attenuation and scatter correction for in-beam positron emission tomography monitoring of tumour irradiations with heavy ions.

An in-beam dual-head positron camera is used to monitor the dose application in situ during the tumour irradiation with carbon ion beams at the experimental heavy ion therapy facility at GSI Darmstadt. Therefore, a positron emission tomograph has been mounted directly at the treatment site. A fully 3D reconstruction algorithm based on the maximum likelihood expectation maximization (MLEM) algorithm has been developed and adapted to this spatially varying imaging situation. The scatter and attenuation correction are included in the forward projection step of the maximum likelihood image reconstruction. This requires an attenuation map containing the information on the material composition and densities. This information is derived from the x-ray computed tomograms of the patient and the patient fixation system including the head-rest. The normalization of scattered events relative to the unscattered events is done by a global scatter fraction factor which is estimated by means of a Monte Carlo simulation. The feasibility of the proposed algorithm is shown by means of computer simulations, phantom measurements as well as patient data.