Jürgen Besserer

Secondary neutron dose during proton therapy using spot scanning.

PURPOSE During proton radiotherapy, secondary neutrons are produced by nuclear interactions in the material in the beam line before and after entering the patient. The dose equivalent deposited by these neutrons is usually not considered in routine treatment planning. In this study, we estimated the neutron dose in patients from a spot scanning beam line by performing measurements and Monte Carlo simulations. METHODS AND MATERIALS Measurements of the secondary neutron dose were performed during irradiation of a water phantom with 177-MeV protons using a Bonner sphere and CR39 etch detectors. Additionally, Monte Carlo simulations were performed using the FLUKA code. RESULTS A comparison of our measurements with measurements taken at a beam line using the scatter foil technique shows a dose advantage of at least 10 for the spot scanning technique. In the region of the Bragg peak, the neutron dose equivalent can reach for a medium-sized target volume approximately 1% of the treatment dose. Neutron doses expected in healthy tissues of the patient (in the not-treated volume) are for large and medium target volumes, approximately 0.004 Sv and 0.002 Sv per treatment Gy, respectively. CONCLUSIONS We conclude from the measurements and simulations that the dose deposited by secondary neutrons during proton radiotherapy using the spot scanning technique can be neglected in the treatment region. In the healthy tissue, the dose coming from neutrons (0.002 Sv per treatment Gy) is approximately a factor of two larger than during photon treatment (0.001 Sv). These contributions to the integral dose from neutrons are still very low when compared to the dose sparing that can be achieved by using a proton beam instead of photons.

The Impact of IMRT and Proton Radiotherapy on Secondary Cancer Incidence

Background and Purpose:There is concern about the increase of radiation-induced malignancies with the application of modern radiation treatment techniques such as intensity-modulated radiotherapy (IMRT) and proton radiotherapy. Therefore, X-ray scatter and neutron radiation as well as the impact of the primary dose distribution on secondary cancer incidence are analyzed.Material and Methods:The organ equivalent dose (OED) concept with a linear-exponential and a plateau dose-response curve was applied to dose distributions of 30 patients who received radiation therapy of prostate cancer. Three-dimensional conformal radiotherapy was used in eleven patients, another eleven patients received IMRT with 6-MV photons, and eight patients were treated with spot-scanned protons. The treatment plans were recalculated with 15-MV and 18-MV photons. Secondary cancer risk was estimated based on the OED for the different treatment techniques.Results:A modest increase of 15% radiation-induced cancer results from IMRT using low energies (6 MV), compared to conventional four-field planning with 15-MV photons (plateau dose-response: 1%). The probability to develop a secondary cancer increases with IMRT of higher energies by 20% and 60% for 15 MV and 18 MV, respectively (plateau dose-response: 2% and 30%). The use of spot-scanned protons can reduce secondary cancer incidence as much as 50% (independent of dose-response).Conclusion:By including the primary dose distribution into the analysis of radiation-induced cancer incidence, the resulting increase in risk for secondary cancer using modern treatment techniques such as IMRT is not as dramatic as expected from earlier studies. By using 6-MV photons, only a moderate risk increase is expected. Spot-scanned protons are the treatment of choice in regard to secondary cancer incidence.Hintergrund und Ziel:Durch den Einsatz moderner Bestrahlungstechniken, wie intensitätsmodulierte Strahlentherapie (IMRT) und Protonentherapie, könnte die Anzahl strahleninduzierter Zweittumoren zunehmen. Deswegen wird der Einfluss von Röntgen- und Neutronenstreustrahlung (Tabelle 2) sowie der primären Dosisverteilung auf die Inzidenz von Sekundärtumoren quantifiziert.Material und Methodik:Das Konzept der Organäquivalentdosis (OED) mit einer linear-exponentiellen und einer Plateau-Dosis-Wirkungs-Beziehung wurde auf die Dosisverteilungen von 30 Patienten mit Prostatakarzinom (Tabelle 1) angewendet. Von den 30 Patienten wurden elf mit konformaler Radiotherapie, elf mit 6-MV-IMRT und acht mit Protonentherapie („spot-scanned“) behandelt. Die Bestrahlungspläne wurden für 15-MV- und 18-MV-Photonen neu optimiert. Die OED für die verschiedenen Bestrahlungstechniken (Tabelle 3, Abbildung 1) ist proportional zur Sekundärtumorwahrscheinlichkeit.Ergebnisse:Wird anstatt konventioneller Vier-Felder-Planung (15-MV-Photonen) ein 6-MV-IMRT-Plan verwendet, steigt die Anzahl strahleninduzierten Tumoren um etwa 15% an (Plateau-Dosis-Wirkungs-Beziehung: 1%). Wird allerdings eine höhere Photonenenergie für die IMRT verwendet (Abbildung 1), steigt die Wahrscheinlichkeit, einen Zweittumor zu entwickeln, um 20% für 15 MV bzw. um 60% für 18 MV an (2% bzw. 30% für eine Plateau-Dosis-Wirkungs-Beziehung). Verwendet man Protonentherapie („spot-scanned“) für die Behandlung, kann die Sekundärtumorinzidenz, unabhängig von der Dosis-Wirkungs-Beziehung, um 50% vermindert werden.Schlussfolgerung:Wird neben der Streu- und Neutronenstrahlung auch die primäre Dosisverteilung in die Analyse der Sekundärtumorinzidenz mit einbezogen, steigt das Risiko für einen Zweittumor beim Einsatz der IMRT nicht so dramatisch an, wie in früheren Studien vorhergesagt. Verwendet man ausschließlich 6-MV-Photonen für die IMRT, wird das Sekundärtumorrisiko nur leicht erhöht. Der Einsatz der Protonentherapie kann in Bezug auf die Entstehung von Zweittumoren gegenüber der Photonentherapie von Vorteil sein.

First proton radiography of an animal patient.

The purpose of this work is to show the feasibility of proton radiography in terms of radiation dose, imaging speed, image quality (density and spatial resolution), and image content under clinical conditions. Protons with 214 MeV energy can penetrate through most patients and were used for imaging. The measured residual range (or energy) of the protons behind the patient was subtracted from the range without an object in the beam path and used to create a projected image. The image content is therefore proportional to the range that protons have lost in the patient. We took proton images of the head of a dog after it received proton radiotherapy treatment of a nasal tumor. The spatial resolution by measuring for each proton separately its coordinate in front of and behind the patient was approximately 1 mm. The acquisition time was on the order of several seconds and was limited by the patient table movement. The range sensitivity of the images was approximately 0.6 mm, which is good enough to use the images for therapy range verification. The dose that the dog received during exposure was 0.03 mGy, which is approximately a factor 50-100 smaller than for a comparable x-ray image. The potential to obtain quantitative images of proton ranges with satisfying spatial and range resolution and low dose to the patient suggests that proton radiography should be applied to patients who are under proton radiotherapy treatment.

Patient specific optimization of the relation between CT‐Hounsfield units and proton stopping power with proton radiography

The purpose of this work is to show the feasibility of using in vivo proton radiography of a radiotherapy patient for the patient individual optimization of the calibration from CT-Hounsfield units to relative proton stopping power. Water equivalent tissue (WET) calibrated proton radiographs of a dog patient treated for a nasal tumor were used as baseline in comparison with integrated proton stopping power through the calibrated CT of the dog. In an optimization procedure starting with a stoichiometric calibration curve, the calibration was modified randomly. The result of this iteration is an optimized calibration curve which was used to recalculate the dose distribution of the patient. One result of this experiment was that the mean value of the deviations between WET calculations based on the stoichiometric calibration curve and the measurements was shifted systematically away from zero. The calibration produced by the optimization procedure reduced this shift to around 0.4 mm. Another result was that the precision of the calibration, reflected as the standard deviation of the normally distributed deviations between WET calculation and measurement, could be reduced from 7.9 to 6.7 mm with the optimized calibration. The dose distributions based on the two calibration curves showed major deviations at the distal end of the target volume.

Influence of respiration-induced organ motion on dose distributions in treatments using enhanced dynamic wedges

The mean velocity of respiration-induced organ motion in cranio-caudal direction is of the same magnitude as the velocity of the moving jaw during a treatment with an enhanced dynamic wedge. Therefore, if organ motion is present during collimator movement, the resulting dose distribution in wedge direction may differ from that obtained for the static case, i.e., without organ motion. The position as a function of time of the moving jaw has been derived from a log-file generated during each treatment. Parameters for the respiratory cycle and information about respiration-induced motion for organs in the upper abdomen were taken from the literature. Both movements were superimposed and the resulting monitor unit distribution has been calculated in the intrinsic coordinate system of the organ. The deviations from the static case have been studied as a function of wedge angle, amplitude of organ motion, respiratory rate, asymmetry of the respiratory cycle, beam energy, and the dose rate. If an amplitude of 30 mm and a respiratory rate of 10 min(-1) are assumed, the maximum deviation in monitor units is 2.5% for a 10 degees wedge, 7% for a 30 degrees wedge, and 16% for a 60 degrees wedge. Furthermore, a dose distribution for an organ undergoing respiration-induced motion has been generated and we found dose deviations of the same magnitude as calculated with the monitor unit distribution.

The water equivalence of solid materials used for dosimetry with small proton beams

Various solid materials are used instead of water for absolute dosimetry with small proton beams. This may result in a dose measurement different to that in water, even when the range of protons in the phantom material is considered correctly. This dose difference is caused by the diverse cross sections for inelastic nuclear scattering in water and in the phantom materials respectively. To estimate the magnitude of this effect, flux and dose measurements with a 177 MeV proton pencil beam having a width of 0.6 cm (FWHM) were performed. The proton flux and the deposited dose in the beam path were determined behind water, lucite, polyethylene, teflon, and aluminum of diverse thicknesses. The number of out-scattered protons due to inelastic nuclear scattering was determined for water and the different materials. The ratios of the number of scattered protons in the materials relative to that in water were found to be 1.20 for lucite, 1.16 for polyethylene, 1.22 for teflon, and 1.03 for aluminum. The difference between the deposited dose in water and in the phantom materials taken in the center of the proton pencil beam, was estimated from the flux measurements, always taking the different ranges of protons in the materials into account. The estimated dose difference relative to water in 15 cm water equivalent thickness was -2.3% for lucite, -1.7% for polyethylene, -2.5% for teflon, and -0.4% for aluminum. The dose deviation was verified by a measurement using an ionization chamber. It should be noted that the dose error is larger when the effective point of measurement in the material is deeper or when the energy is higher.

Systematic measurements of whole-body dose distributions for various treatment machines and delivery techniques in radiation therapy

PURPOSE Contemporary radiotherapy treatment techniques, such as intensity-modulated radiation therapy and volumetric modulated arc therapy, could increase the radiation-induced malignancies because of the increased beam-on time, i.e., number of monitor units needed to deliver the same dose to the target and the larger volume irradiated with low doses. In this study, whole-body dose distributions from typical radiotherapy patient plans using different treatment techniques and therapy machines were measured using the same measurement setup and irradiation intention. METHODS Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from 6 MV beams were compared in terms of treatment technique (3D-conformal, intensity-modulated radiation therapy, volumetric modulated arc therapy, helical TomoTherapy, stereotactic radiotherapy, hard wedges, and flattening filter-free radiotherapy) and therapy machine (Elekta, Siemens and Varian linear accelerators, Accuray CyberKnife and TomoTherapy). RESULTS Close to the target, the doses from intensity-modulated treatments (including flattening filter-free) were below the dose from a static treatment plan, whereas the CyberKnife showed a larger dose by a factor of two. Far away from the treatment field, the dose from intensity-modulated treatments showed an increase in dose from stray radiation of about 50% compared to the 3D-conformal treatment. For the flattening filter-free photon beams, the dose from stray radiation far away from the target was slightly lower than the dose from a static treatment. The CyberKnife irradiation and the treatment using hard wedges increased the dose from stray radiation by nearly a factor of three compared to the 3D-conformal treatment. CONCLUSIONS This study showed that the dose outside of the treated volume is influenced by several sources. Therefore, when comparing different treatment techniques, the dose ratios vary with distance to the isocenter. The effective dose outside the treated volume of intensity-modulated treatments with or without flattening filter was 10%-30% larger when compared to 3D-conformal radiotherapy. This dose increase is much lower than the monitor unit scaled effective dose from a static treatment.

Evaluation of a commercial electron treatment planning system based on Monte Carlo techniques (eMC)

A commercial electron beam treatment planning system on the basis of a Monte Carlo algorithm (Varian Eclipse, eMC V7.2.35) was evaluated. Measured dose distributions were used for comparison with dose distributions predicted by eMC calculations. Tests were carried out for various applicators and field sizes, irregular shaped cut outs and an inhomogeneity phantom for energies between 6 Me V and 22 MeV Monitor units were calculated for all applicator/energy combinations and field sizes down to 3 cm diameter and source-to-surface distances of 100 cm and 110 cm. A mass-density-to-Hounsfield-Units calibration was performed to compare dose distributions calculated with a default and an individual calibration. The relationship between calculation parameters of the eMC and the resulting dose distribution was studied in detail. Finally, the algorithm was also applied to a clinical case (boost treatment of the breast) to reveal possible problems in the implementation. For standard geometries there was a good agreement between measurements and calculations, except for profiles for low energies (6 MeV) and high energies (18 Me V 22 MeV), in which cases the algorithm overestimated the dose off-axis in the high-dose region. For energies of 12 MeV and higher there were oscillations in the plateau region of the corresponding depth dose curves calculated with a grid size of 1 mm. With irregular cut outs, an overestimation of the dose was observed for small slits and low energies (4% for 6 MeV), as well as for asymmetric cases and extended source-to-surface distances (12% for SSD = 120 cm). While all monitor unit calculations for SSD = 100 cm were within 3% compared to measure-ments, there were large deviations for small cut outs and source-to-surface distances larger than 100 cm (7%for a 3 cm diameter cut-out and a source-to-surface distance of 10 cm).

Systematic measurements of whole-body imaging dose distributions in image-guided radiation therapy

PURPOSE The full benefit of the increased precision of contemporary treatment techniques can only be exploited if the accuracy of the patient positioning is guaranteed. Therefore, more and more imaging modalities are used in the process of the patient setup in clinical routine of radiation therapy. The improved accuracy in patient positioning, however, results in additional dose contributions to the integral patient dose. To quantify this, absorbed dose measurements from typical imaging procedures involved in an image-guided radiation therapy treatment were measured in an anthropomorphic phantom for a complete course of treatment. The experimental setup, including the measurement positions in the phantom, was exactly the same as in a preceding study of radiotherapy stray dose measurements. This allows a direct combination of imaging dose distributions with the therapy dose distribution. METHODS Individually calibrated thermoluminescent dosimeters were used to measure absorbed dose in an anthropomorphic phantom at 184 locations. The dose distributions from imaging devices used with treatment machines from the manufacturers Accuray, Elekta, Siemens, and Varian and from computed tomography scanners from GE Healthcare were determined and the resulting effective dose was calculated. The list of investigated imaging techniques consisted of cone beam computed tomography (kilo- and megavoltage), megavoltage fan beam computed tomography, kilo- and megavoltage planar imaging, planning computed tomography with and without gating methods and planar scout views. RESULTS A conventional 3D planning CT resulted in an effective dose additional to the treatment stray dose of less than 1 mSv outside of the treated volume, whereas a 4D planning CT resulted in a 10 times larger dose. For a daily setup of the patient with two planar kilovoltage images or with a fan beam CT at the TomoTherapy unit, an additional effective dose outside of the treated volume of less than 0.4 mSv and 1.4 mSv was measured, respectively. Using kilovoltage or megavoltage radiation to obtain cone beam computed tomography scans led to an additional dose of 8-46 mSv. For treatment verification images performed once per week using double exposure technique, an additional effective dose of up to 18 mSv was measured. CONCLUSIONS Daily setup imaging using kilovoltage planar images or TomoTherapy megavoltage fan beam CT imaging can be used as a standard procedure in clinical routine. Daily kilovoltage and megavoltage cone beam computed tomography setup imaging should be applied on an individual or indication based protocol. Depending on the imaging scheme applied, image-guided radiation therapy can be administered without increasing the dose outside of the treated volume compared to therapies without image guidance.

Dose-response relationship for lung cancer induction at radiotherapy dose

Cancer induction after radiation therapy is a severe side effect. It is therefore of interest to predict the probability of second cancer appearance for the treated patient. Currently there is large uncertainty about the shape of the dose-response relationship for carcinogenesis for most cancer types at high dose levels. In this work a dose-response relationship for lung cancer is derived based on (i) the analysis of lung cancer induction after Hodgkins disease, (ii) a cancer risk model developed for high doses including fractionation based on the linear quadratic model, and (iii) the reconstruction of treatment plans for Hodgkins patients treated with radiotherapy. The fitted model parameters for an α/β=3 Gy were α=0.061Gy(-1) and R=0.84. The value for α is in agreement with analysis of normal tissue complications of the lung after radiation therapy. The repopulation/repair parameter R is large, but seems to be characteristic for lung tissue which is sensitive with regard to fractionation. Lung cancer risk is according to this model for small doses consistent with the finding of the A-bomb survivors, has a maximum at doses of around 15 Gy and drops off only slightly at larger doses. The predicted EAR for lung after radiotherapy of Hodgkins disease is 18.4/10000PY which can be compared to the findings of several epidemiological studies were EAR for lung varies between 9.7 and 21.5/10000PY.