Peter Pemler

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.

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).

Evaluation des Elektronendichte-Phantoms CIRS Model 62

Zusammenfassung Die Eigenschaften des Elektronendichte-Phantoms CIRS M62 und dessen Verwendbarkeit zur routinemasigen Qualitatskontrolle und zur Kalibrierung von 3D- Bestrahlungsplanungssystemen (BPS) wurden untersucht. Physikalische Dichten und Elektronendichten der einzelnen Proben wurden berechnet und mit den Herstellerangaben sowie den Empfehlungen im ICRU-Report 44 verglichen. Das Phantom wurde zur Evaluation sowohl im Standard-CT als auch im Spiral-CT-Modus mit verschiedenen Parametern gescannt. Speziell angefertigte Proben fur dichten Knochen wurden in Bezug auf Artefaktverhalten analysiert. Die Aufnahmen wurden zur Ermittlung der Hounsfieldwerte der einzelnen Proben mit dem BPS Cadplan ® ausgewertet. Es wurden Kalibrierkurven berechnet und mit einer stochiometrischen Kalibrierung fur echtes Gewebe verglichen. Die Untersuchungen ergaben eine gute Ubereinstimmung der berechneten physikalischen Daten mit denen des Herstellers. Die Proben sind nur naherungsweise gewebeaquivalent. Die speziell angefertigten Proben fur dichten Knochen zeigen geringfugig Artefakte. Die berechnete Kalibrierkurve stimmt gut mit der stochiometrischen Kalibrierkurve uberein.

On small angle multiple coulomb scattering of protons in the gaussian approximation.

Experimental data from the literature on small-angle multiple Coulomb scattering of protons in various materials were analysed in order to device an equation for the scattering angle in the Gaussian approximation. In comparison to Highlands well-known formula, the present approximation can be integrated to take into account energy loss in the scattering media. In addition, it is more precise than Highlands formulation for thin and thick scatterers consisting of elements with low atomic number. The simple equation obtained in this study can be used to obtain prompt answers for scattering problems which can occur, for example, in proton therapy or proton radiography.

SU‐FF‐T‐85: Radiation Induced Cancer After Radiotherapy: The Impact of IMRT and Proton Radiotherapy

Purpose: There is concern about the increase of radiation induced malignancies with the application of modern radiotherapytreatment techniques such as IMRT and protonradiotherapy. In this work we analyze not only x‐ray scatter and neutronradiation , but also the impact of the primary dose distribution on secondary cancer incidence. Method and Materials: The organ equivalent dose (OED) concept with a linear‐exponential dose‐response curve was applied to 3D dose distributions of 30 patients who received radiotherapytreatment of prostate cancer. From the 30 patients 11 received 3D conformal radiotherapy, 11 IMRT with 6MV photons and 8 spot scanned protonradiotherapy. The IMRTtreatment plans were re‐calculated with 15 MV photons. For 18 MV photons the OED was approximately calculated. From the OED of the different treatment techniques secondary cancer risk was estimated. Results:IMRT prostate treatments using low energies result in a modest increase of around 15% of radiation induced cancer compared to conventional four field planning with 15 MV photons. Using energies larger than 10 MV for IMRT could increase the probability to develop a secondary cancer by more than 20% (15MV) and 60% (18MV). The use spot scanned protons for treatment can reduce the secondary cancer incidence significantly by about 50%. 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 an energy of 6 MV only a moderate risk increase can be expected. Spot scanned protons are the treatment of choice in regard to secondary cancer incidence.

Quantitative proton radiography of an animal patient

Images (with a spatial resolution of 1 mm x 1mm) were produced both, with range and range dilution information of the protons passing through a dog. The radiographies were taken prior to a proton radiotherapy treatment of a nasal tumor, while the dog patient was under anesthetics. The first image was created by calculating the mean range of the protons detected in each pixel. This image was compared to calculations of the treatment planning system based on a CT-scan of the dog. Errors in the calculated range could be detected. The second image was produced by calculating the width of the range spectrum in each pixel. This value is a measure of the dilution of the range due to tissue inhomogeneities. The dilution image can be used to indicate critical situations during proton therapy, to determine the safety margin around the tumor volume, or to optimise treatment. In a preliminary analysis of the radiography data we found range uncertainty and range dilution effects in the order of up to 10 mm.