Clinical Dosimetry in Photon Radiotherapy – a Monte Carlo Based Investigation

Die klinische Dosimetrie ist ein fundamentaler Schritt im Rahmen der Strahlentherapie und zielt auf eine Quantifizierung der absorbierten Energiedosis innerhalb einer Unsicherheit von 1-2%. Um eine entsprechende Genauigkeit zu erreichen, müssen Korrektionen bei Messungen mit luft-gefüllten, kalibrierten Ionisationskammern angewendet werden. Die Anwendung der Korrektionen basiert auf der Hohlraumtheorie nach Spencer-Attix und wird in den jeweiligen, aktuellen Dosimetrieprotokollen definiert. Energieabhängige Korrektionen berücksichtigen die Abweichung von Kalibrierbedingungen und die damit verbundene Änderung des Ansprechvermögens von Ionisationskammern im Therapiestrahl. Die üblicherweise angewendeten Korrektionen basieren auf semi-analytischen Modellen oder auf Vergleichsmessungen und sind auf Grund der Größenordnung von einigen Prozent oder weniger schwierig zu quantifizieren. Weiterhin werden die Korrektionen für feste geometrische Referenzbedingungen definiert, die nicht zwangsläufig mit den Bedingungen in den modernen Strahlentherapie-Anwendungen übereinstimmen. Das stochastische Monte-Carlo Verfahren zur Simulation von Strahlungstransport gewinnt zunehmend Bedeutung in der Medizinischen Physik. Es stellt ein geeignetes Werkzeug zur Berechnung dieser Korrektionen mit einer prinzipiell hohen Genauigkeit dar und erlaubt die Untersuchung von Ionisationskammern unter verschiedensten Bedingungen. Ziel der vorliegenden Arbeit ist die konsistente Untersuchung der gängigen Ionisationskammer-Dosimetrie in der Strahlentherapie mit Photonen unter Anwendung von Monte-Carlo Simulationen. Heutzutage existieren Monte-Carlo Algorithmen, die die präzise Berechnung des Ansprechvermögens von Ionisationskammern prinzipiell erlauben. Dem Ergebnis einer Monte Carlo Simulation haftet allerdings immer eine statistische Unsicherheit an. Untersuchungen dieser Art sind damit durch lange Berechnungszeiten, die für ein signifikantes Ergebnis innerhalb kleiner statistischen Unsicherheiten entstehen, nur begrenzt möglich. Neben der Verwendung großer Rechnerkapazitäten, lassen sich so genannte Varianzreduktions-Verfahren anwenden, die die benötigte Simulationszeit verringern. Entsprechende Methoden zur Steigerung der Recheneffizienz um mehrere Größenordnungen wurden im Rahmen der Arbeit entwickelt und in ein modernes und etabliertes Monte-Carlo Simulationspaket implementiert. Mit Hilfe der entwickelten Methoden wurden Daten aktueller klinischer Dosimetrieprotokolle zur Bestimmung der Wasserenergiedosis unter Referenzbedingungen in Photonenstrahlung untersucht. Korrektionsfaktoren wurden berechnet und mit den existierenden Daten in der Literatur verglichen. Es konnte gezeigt werden, dass berechnete Daten in guter Übereinstimmung mit aktuellen Messdaten liegen, allerdings teilweise von den in Dosimetrieprotokollen genutzten Daten um _1% abweichen. Ursache hierfür sind z.T. überholte Theorien und jahrzehnte alte Messungen zu einzelnen Störungsfaktoren. Quellen von Unsicherheiten in den durch Monte-Carlo Simulationen berechneten Daten wurden untersucht, auch unter Berücksichtigung von Unsicherheiten in den Wirkungsquerschnitten, die den Simulationen zu Grunde liegen. Im Sinne einer konservativen Abschätzung zeigten sich dabei systematische (Typ B) Unsicherheiten von ~1%. Ionisationskammern unter Nicht-Referenzbedingungen wurden mit Hilfe eines virtuellen Linearbeschleuniger-Modells untersucht. Neben der Entwicklung einer Methodik zur Kommissionierung, d.h. dem Anpassen des Modells an Messungen hinsichtlich der Eigenschaften des primären Elektronenstrahls, war das Ziel dieser Berechnungen eine Untersuchung des Verhaltens von Ionisationskammern unter geometrischen Nicht-Referenzbedingungen. Es konnte gezeigt werden, dass die üblicherweise eingesetzten Ionisationskammertypen nur kleine Abweichungen in ihrem Ansprechvermögen zeigen, solange Sekundärelektronen-Gleichgewicht vorausgesetzt werden kann. Demgegenüber zeigen Detektoren eine starke Änderung ihres Ansprechvermögens in Regionen, in denen kein Sekundärelektronen-Gleichgewicht und damit ein hoher Dosisgradient vorliegt, wie etwa im Feldrand. Die Anwendbarkeit der Spencer-Attix Theorie unter diesen Bedingungen wurde überprüft und es konnte gezeigt werden, dass innerhalb von ~1% die Bestimmung der Wasserenergiedosis mit Hilfe der Korrektionsfaktoren möglich ist. Eine weitere Untersuchung dieser Bedingungen bei der Messung von Profilen wurde genutzt, um einen Detektortyp zu bestimmen, der die geringsten Abweichungen in seinem Ansprechvermögen in Regionen mit Sekundärelektronen-Ungleichgewicht und hohen Dosisgradienten zeigt. Hinsichtlich der Verbreiterung des Feldrands zeigt die Filmdosimetrie die geringsten Abweichungen zu einem idealen Profil. Langfristig werden Monte-Carlo Simulationen die Daten in klinischen Dosimetrieprotokollen ersetzen oder zumindest erweitern, um eine Verringerung der Unsicherheiten bei der Strahlenanwendung am Menschen zu erreichen. Für Korrektionen in Nicht-Referenzbedingungen wie sie in modernen strahlentherapeutischen Anwendungen auftreten, werden Monte-Carlo Simulationen eine entscheidende Rolle spielen. Die in dieser Arbeit entwickelten Methoden stellen dementsprechend einen wichtigen Schritt zur Verringerung der Unsicherheiten in der Strahlentherapie dar

Monte Carlo calculated ionization chamber correction factors in clinical proton beams – deriving uncertainties from published data

For the update of the IAEA TRS-398 Code of Practice (CoP), global ionization chamber factors (fQ) and beam quality correction factors (kQ) for air-filled ionization chambers in clinical proton beams have been calculated with different Monte Carlo codes. In this study, average Monte Carlo calculated fQ and kQ factors are provided and the uncertainty of these factors is estimated. Average fQ factors in monoenergetic proton beams with energies between 60 MeV and 250 MeV were derived from Monte Carlo calculated fQ factors published in the literature. Altogether, 195 fQ factors for six plane-parallel and three cylindrical ionization chambers calculated with PENH, FLUKA and GEANT4 were incorporated. Additionally, a weighted standard deviation of fQ factors was calculated, where the same weight was assigned to each Monte Carlo code. From average fQ factors, kQ factors were derived and compared to the values from the IAEA TRS-398 CoP published in 2000 as well as to the values of the upcoming version. Average Monte Carlo calculated fQ factors are constant within 0.6% over the energy range investigated. In general, the different Monte Carlo codes agree within 1% for low energies and show larger differences up to 2% for high energies. As a result, the standard deviation of fQ factors increases with energy and is ∼0.3% for low energies and ∼0.8% for high energies. kQ factors derived from average Monte Carlo calculated fQ factors differ from the values presented in the IAEA TRS-398 CoP by up to 2.4%. The overall estimated uncertainty of Monte Carlo calculated kQ factors is ∼0.5%–1% smaller than the uncertainties estimated in IAEA TRS-398 CoP since the individual ionization chamber characteristics (e.g. fluence perturbations) are considered in detail in Monte Carlo calculations. The agreement between Monte Carlo calculated kQ factors and the values of the upcoming version of IAEA TRS-398 CoP is better with deviations smaller than 1%.</p

Comprehensive investigation of lateral dose profile and output factor measurements in small proton fields from different delivery techniques

Background and purpose: As a part of the commissioning and quality assurance in proton beam therapy, lateral dose profiles and output factors have to be acquired. Such measurements can be performed with point detectors and are especially challenging in small fields or steep lateral penumbra regions as the detector's volume effect may lead to perturbations. To address this issue, this work aims to quantify and correct for such perturbations of six point detectors in small proton fields created via three different delivery techniques. Methods: Lateral dose profile and output measurements of three proton beam delivery techniques (pencil beam scanning, pencil beam scanning combined with collimators, passive scattering with collimators) were performed using high-resolution EBT3 films, a PinPoint 3D 31022 ionization chamber, a microSilicon diode 60023 and a microDiamond detector 60019 (all PTW Freiburg, Germany). Detector specific lateral dose response functions K(x,y) acting as the convolution kernel transforming the undisturbed dose distribution D(x,y) into the measured signal profiles M(x,y) were applied to quantify perturbations of the six investigated detectors in the proton fields and correct the measurements. A signal theoretical analysis in Fourier space of the dose distributions and detector's K(x,y) was performed to aid the understanding of the measurement process with regard to the combination of detector choice and delivery technique. Results: Quantification of the lateral penumbra broadening and signal reduction at the fields center revealed that measurements in the pencil beam scanning fields are only compromised slightly even by large volume ionization chambers with maximum differences in the lateral penumbra of 0.25 mm and 4% signal reduction at the field center. In contrast, radiation techniques with collimation are not accurately represented by the investigated detectors as indicated by a penumbra broadening up to 1.6 mm for passive scattering with collimators and 2.2 mm for pencil beam scanning with collimators. For a 3 mm diameter collimator field, a signal reduction at field center between 7.6% and 60.7% was asserted. Lateral dose profile measurements have been corrected via deconvolution with the corresponding K(x,y) to obtain the undisturbed D(x,y). Corrected output ratios of the passively scattered collimated fields obtained for the microDiamond, microSilicon and PinPoint 3D show agreement better than 0.9% (one standard deviation) for the smallest field size of 3 mm. Conclusion: Point detector perturbations in small proton fields created with three delivery techniques were quantified and found to be especially pronounced for collimated small proton fields with steep dose gradients. Among all investigated detectors, the microSilicon diode showed the smallest perturbations. The correction strategies based on detector's K(x,y) were found suitable for obtaining unperturbed lateral dose profiles and output factors. Approximation of K(x,y) by considering only the geometrical averaging effect has been shown to provide reasonable prediction of the detector's volume effect. The findings of this work may be used to guide the choice of point detectors in various proton fields and to contribute toward the development of a code of practice for small field proton dosimetry.</p

Validating a double Gaussian source model for small proton fields in a commercial Monte-Carlo dose calculation engine

Purpose: The primary fluence of a proton pencil beam exiting the accelerator is enveloped by a region of secondaries, commonly called “spray”. Although small in magnitude, this spray may affect dose distributions in pencil beam scanning mode e.g., in the calculation of the small field output, if not modelled properly in a treatment planning system (TPS). The purpose of this study was to dosimetrically benchmark the Monte Carlo (MC) dose engine of the RayStation TPS (v.10A) in small proton fields and systematically compare single Gaussian (SG) and double Gaussian (DG) modeling of initial proton fluence providing a more accurate representation of the nozzle spray. Methods: The initial proton fluence distribution for SG/DG beam modeling was deduced from two-dimensional measurements in air with a scintillation screen with electronic readout. The DG model was either based on direct fits of the two Gaussians to the measured profiles, or by an iterative optimization procedure, which uses the measured profiles to mimic in-air scan-field factor (SF) measurements. To validate the DG beam models SFs, i.e. relative doses to a 10 × 10 cm2 field, were measured in water for three different initial proton energies (100MeV, 160MeV, 226.7MeV) and square field sizes from 1×1cm2 to 10×10cm2 using a small field ionization chamber (IBA CC01) and an IBA ProteusPlus system (universal nozzle). Furthermore, the dose to the center of spherical target volumes (diameters: 1cm to 10cm) was determined using the same small volume ionization chamber (IC). A comprehensive uncertainty analysis was performed, including estimates of influence factors typical for small field dosimetry deduced from a simple two-dimensional analytical model of the relative fluence distribution. Measurements were compared to the predictions of the RayStation TPS. Results: SFs deviated by more than 2% from TPS predictions in all fields <4×4cm2 with a maximum deviation of 5.8% for SG modeling. In contrast, deviations were smaller than 2% for all field-sizes and proton energies when using the directly fitted DG model. The optimized DG model performed similarly except for slightly larger deviations in the 1×1cm2 scan-fields. The uncertainty estimates showed a significant impact of pencil beam size variations (±5%) resulting in up to 5.0% standard uncertainty. The point doses within spherical irradiation volumes deviated from calculations by up to 3.3% for the SG model and 2.0% for the DG model. Conclusion: Properly representing nozzle spray in RayStation's MC-based dose engine using a DG beam model was found to reduce the deviation to measurements in small spherical targets to below 2%. A thorough uncertainty analysis shows a similar magnitude for the combined standard uncertainty of such measurements

Complete patient exposure during paediatric brain cancer treatment for photon and proton therapy techniques including imaging procedures

BackgroundIn radiotherapy, especially when treating children, minimising exposure of healthy tissue can prevent the development of adverse outcomes, including second cancers. In this study we propose a validated Monte Carlo framework to evaluate the complete patient exposure during paediatric brain cancer treatment.Materials and methodsOrgan doses were calculated for treatment of a diffuse midline glioma (50.4 Gy with 1.8 Gy per fraction) on a 5-year-old anthropomorphic phantom with 3D-conformal radiotherapy, intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and intensity modulated pencil beam scanning (PBS) proton therapy. Doses from computed tomography (CT) for planning and on-board imaging for positioning (kV-cone beam CT and X-ray imaging) accounted for the estimate of the exposure of the patient including imaging therapeutic dose. For dose calculations we used validated Monte Carlo-based tools (PRIMO, TOPAS, PENELOPE), while lifetime attributable risk (LAR) was estimated from dose-response relationships for cancer induction, proposed by Schneider et al.ResultsOut-of-field organ dose equivalent data of proton therapy are lower, with doses between 0.6 mSv (testes) and 120 mSv (thyroid), when compared to photon therapy revealing the highest out-of-field doses for IMRT ranging between 43 mSv (testes) and 575 mSv (thyroid). Dose delivered by CT ranged between 0.01 mSv (testes) and 72 mSv (scapula) while a single imaging positioning ranged between 2 μSv (testes) and 1.3 mSv (thyroid) for CBCT and 0.03 μSv (testes) and 48 μSv (scapula) for X-ray. Adding imaging dose from CT and daily CBCT to the therapeutic demonstrated an important contribution of imaging to the overall radiation burden in the course of treatment, which is subsequently used to predict the LAR, for selected organs.ConclusionThe complete patient exposure during paediatric brain cancer treatment was estimated by combining the results from different Monte Carlo-based dosimetry tools, showing that proton therapy allows significant reduction of the out-of-field doses and secondary cancer risk in selected organs

The Concise guide to pharmacology 2019/20: Ion channels

The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide represents approximately 400 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.14749. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2019, and supersedes data presented in the 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Ion channels

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15539. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate

The Concise Guide to PHARMACOLOGY 2023/24: Ion channels

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and over 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (https://www.guidetopharmacology.org/), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point‐in‐time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16178. Ion channels are one of the six major pharmacological targets into which the Guide is divided, with the others being: G protein‐coupled receptors, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid‐2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC‐IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate