Dose Conformation in Tumor Therapy with External Ionizing Radiation: Physical Possibilities and Limitations

The central problem in tumor irradiation is to deposit a high and spatially uniform dose in the tumor target volume while sparing the surrounding normal tissue as much as possible. The present work investigates how such an adaptation ("conformation") of the spatial dose distribution to arbitrarily shaped target volumes can be achieved, and where the physical limits lie. In particular, the specific possibilities of irradiation with different types of radiation are determined under these aspects, whereby a rough distinction is made between irradiation with charged and uncharged particles. Due to the different mechanisms of radiation-tissue interaction, a conformal dose distribution can be achieved with only one radiation field in the case of heavy charged particles; in the case of uncharged particles, several radiation fields from different directions are required. First, the possibilities and limits of dose conformation are evaluated theoretically. Analytical approximations for modeling dose distributions with uncharged and charged particles are developed. Within the framework of these approximations, the theory of the exponential Radon transform is used to determine the optimal parameters for obtaining a desired dose distribution. It is shown that for an infinite number of radiation fields in the plane, it is possible to adapt the high-dose region to arbitrarily shaped target volumes for both uncharged and charged particles. The dose in a small radiation-sensitive organ at risk in the immediate vicinity of the target volume can be reduced to small scatter contributions. In the case of charged particles, this is also possible for multiple organs at risk. Furthermore, the non-conformal "dose background" is always smaller for charged particles than for uncharged particles. In a more application-oriented chapter, an algorithm is developed for the optimization of dose distributions under practical boundary conditions, i.e. in three dimensions, with finitely many radiation fields and for finite resolutions of the beam shaping devices. To achieve optimal dose distributions, the use of fluence- and (in the case of charged particles) energy-modulated radiation fields is necessary. Especially in the case of uncharged particles, the technical prerequisites for this are not yet available in clinical practice. Therefore, newly developed approaches to fluence modulation for uncharged particles using a dynamically or quasi-dynamically driven "multileaf collimator" are presented. Furthermore, the first phantom experiment is described in which these generalized methods for achieving the best possible conformal dose distribution were realized with high-energy photons (15-MV bremsstrahlung spectrum). The high degree of practically achievable dose conformation is thus verified. Finally, a comparison of the optimized dose distributions achievable with photons and protons is performed for challenging clinical cases where conventional radiotherapy reaches its limits. The most important result is that irradiation with uncharged particles, and in particular with high-energy X-rays, can be optimized in such a way that, in all clinically relevant cases, tumor-conformal dose distributions can be achieved with relatively few (less than ten) radiation fields. The exposure of healthy tissue is naturally higher than for heavy charged particles. However, the tolerance dose values are not exceeded. Exceptions are the rare cases in which the target volume is surrounded on almost all sides by particularly radiation-sensitive risk organs. Only in these cases can a much better result be achieved with the technically more demanding heavy charged particle therapy

New methods for solving the inverse problem of radiotherapy planning

New methods for the automatic determination and optimization of irradiation parameters for percutaneous radiotherapy with high energy photons are developed. The methods are based on an irradiation technique with intensity-modulated radiation fields. The essential problem is therefore to determine the shape of the modulation profiles for the individual fields, based on the specified target dose distribution. This problem is called the inverse problem of radiotherapy planning. It is shown that this is the mirrored version of the problem of reconstructing an image from its projections, such as occurs in computed tomography (CT). Based on this fact, the methods for image reconstruction known from CT are consistently transferred to the optimization of radiotherapy. By appropriate modifications of the methods, special features characteristic for this new field of application are taken into account. This includes in particular the fact that no negative radiation intensities can be realized and that one is limited to a few fields for practical reasons. It is shown that in most cases seven or nine radiation fields are sufficient and that the use of more fields does not lead to clinically significant improvements. The main methods of image reconstruction, namely filtered back projection and iterative reconstruction technique, are used alternatively in CT. In the present application, on the other hand, these methods are used quasi “symbiotically”. The filtered back projection, referred to here as filtered projection is used to quickly determine a starting value for the modulation profiles. These initial profiles are further optimized by an iterative procedure corresponding to the iterative reconstruction technique. The introduction of penalty functions makes it possible for the first time to adequately consider medically indicated constraints. The iterative optimization procedure is based on an algorithm for three-dimensional dose calculation. Therefore, another focus of this work is the development of such an algorithm for intensity modulated radiation fields. Conventional dose calculation algorithms cannot adequately account for modulations. To verify the newly developed method, a first comparison of the dose calculated with it with measured data is carried out. The methods presented here allow the direct determination of the irradiation parameters without the trial and error procedure that is common today. In addition, dose distributions can be generated that are hardly feasible even with the most complex conventional irradiation techniques. These are especially those with extended concave areas. Some examples of this type are presented

Compact Method for Proton Range Verification Based on Coaxial Prompt Gamma-Ray Monitoring: a Theoretical Study

Range uncertainties in proton therapy hamper treatment precision. Prompt gamma-rays were suggested 16 years ago for real-time range verification, and have already shown promising results in clinical studies with collimated cameras. Simultaneously, alternative imaging concepts without collimation are investigated to reduce the footprint and price of current prototypes. In this paper, a compact range verification method is presented. It monitors prompt gamma-rays with a single scintillation detector positioned coaxially to the beam and behind the patient. Thanks to the solid angle effect, proton range deviations can be derived from changes in the number of gamma-rays detected per proton, provided that the number of incident protons is well known. A theoretical background is formulated and the requirements for a future proof-of-principle experiment are identified. The potential benefits and disadvantages of the method are discussed, and the prospects and potential obstacles for its use during patient treatments are assessed. The final milestone is to monitor proton range differences in clinical cases with a statistical precision of 1 mm, a material cost of 25000 USD and a weight below 10 kg. This technique could facilitate the widespread application of in vivo range verification in proton therapy and eventually the improvement of treatment quality

Dosiskonformation in der Tumortherapie mit externer ionisierender Strahlung: Physikalische Möglichkeiten und Grenzen

Das zentrale Problem bei der Strahlenbehandlung von Tumoren besteht darin, eine hohe und räumlich homogen verteilte Energiedosis im zu bestrahlenden Zielvolumen zu deponieren und gleichzeitig das umliegende Normalgewebe so weit wie möglich zu schonen. In der vorliegenden Arbeit wird untersucht, wie eine solche Anpassung (”Kon-formation“) der räumlichen Dosisverteilung an beliebig geformte Zielvolumina erreicht werden kann und wo die physikalischen Grenzen liegen. Insbesondere werden die spezifischen Möglichkeiten von Bestrahlungen mit verschiedenen Strahlenarten unter diesen Gesichtspunkten ermittelt, wobei eine grobe Einteilung in Bestrahlungen mit geladenen und ungeladenen Teilchen vorgenommen wird. Aufgrund der unterschiedlichen Wechselwirkungsprinzipien kann eine konformierende Dosisverteilung im Fall von schweren geladenen Teilchen bereits mit nur einem Strahlungsfeld erreicht werden; bei ungeladenen Teilchen sind dazu mehrere Strahlungsfelder aus verschiedenen Richtungen erforderlich. Zunächst werden die Möglichkeiten und Grenzen der Dosiskonformation theoretisch abgeschätzt. Es werden analytische Näherungsverfahren zur Modellierung von Dosisverteilungen mit ungeladenen und geladenen Teilchen entwickelt. Im Rahmen dieser Näherungen wird die Theorie der exponentiellen Radontransformation zur Bestimmung der optimalen Parameter für die Erzielung einer gewünschten Dosisverteilung herangezogen. Damit wird für den Fall unendlich vieler Strahlungsfelder in der Ebene gezeigt, daß sowohl mit ungeladenen als auch mit geladenen Teilchen eine Anpassung des Hochdosisbereichs an beliebig geformte Zielvolumina möglich ist. Die Dosis in einem kleinen strahlensensiblen Risikoorgan in unmittelbarer Nachbarschaft des Zielvolumens kann bis auf Streubeiträge reduziert werden. Bei geladenen Teilchen ist dies auch für mehrere Risikoorgane möglich. Ferner ist der nicht-konforme ”Dosisuntergrund“ bei geladenen Teilchen stets kleiner als bei ungeladenen. In einem mehr anwendungsbezogenen Kapitel wird ein Algorithmus zur Optimierung von Dosisverteilungen unter praktischen Randbedingungen, d. h. im Dreidimensionalen, mit endlich vielen Strahlungsfeldern und für endliche Auflösungen der Strahlformungssysteme entwickelt. Um optimale Dosisverteilungen erzielen zu können, ist der Einsatz von fluenz- und (bei geladenen Teilchen) energiemodulierten Strahlungsfeldern erforderlich. Speziell im Fall von ungeladenen Teilchen sind die technischen Voraussetzungen dazu bisher noch nicht gegeben. Es werden daher neuentwickelte Ansätze zur Fluenzmodulation für ungeladene Teilchen unter Verwendung eines dynamisch oder quasi-dynamisch angesteuerten ”Multileaf-Kollimators“ vorgestellt. Des weiteren wird das erste Phantomexperiment beschrieben, bei dem diese verallgemeinerten Methoden zur Erzielung der bestmöglichen konformierenden Dosisverteilung mit hochenergetischen Photonen (15-MV-Bremsstrahlungsspektrum) realisiert wurden. Der hohe Grad der praktisch erreichbaren Dosiskonformation wird damit verifiziert. Schließlich wird ein Vergleich der mit Photonen und Protonen erzielbaren optimierten Dosisverteilungen für komplizierte klinische Fälle durchgeführt, bei denen die konventionelle Strahlentherapie an ihre Grenzen stößt. Das wichtigste Ergebnis: Bestrahlungen mit ungeladenen Teilchen und speziell mit hochenergetischer Röntgenstrahlung können so optimiert werden, daß mit relativ wenigen (weniger als zehn) Strahlungsfeldern in allen klinisch auftretenden Fällen konformierende Dosisverteilungen zu erzielen sind. Die Belastung des gesunden Gewebes ist naturgemäß höher als bei schweren geladenen Teilchen. Die Toleranzwerte können jedoch stets eingehalten werden. Eine Ausnahme stellen die seltenen Fälle dar, bei denen das Zielvolumen auf fast allen Seiten von besonders strahlenempfindlichen Risikoorganen umgeben ist. Nur in diesen Fällen kann durch die technisch aufwendigere Therapie mit schweren geladenen Teilchen ein wesentlich besseres Ergebnis erzielt werden

Range uncertainty reductions in proton therapy may lead to the feasibility of novel beam arrangements which improve organ-at-risk sparing

Purpose In proton therapy, dose distributions are currently often conformed to organs at risk (OARs) using the less sharp dose fall-off at the lateral beam edge to reduce the effects of uncertainties in the in vivo proton range. However, range uncertainty reductions may make greater use of the sharper dose fall-off at the distal beam edge feasible, potentially improving OAR sparing. We quantified the benefits of such novel beam arrangements. Methods For each of 10 brain or skull base cases, five treatment plans robust to 2 mm setup and 0%-4% range uncertainty were created for the traditional clinical beam arrangement and a novel beam arrangement making greater use of the distal beam edge to conform the dose distribution to the brainstem. Metrics including the brainstem normal tissue complication probability (NTCP) with the endpoint of necrosis were determined for all plans and all setup and range uncertainty scenarios. Results For the traditional beam arrangement, reducing the range uncertainty from the current level of approximately 4% to a potentially achievable level of 1% reduced the brainstem NTCP by up to 0.9 percentage points in the nominal and up to 1.5 percentage points in the worst-case scenario. Switching to the novel beam arrangement at 1% range uncertainty improved these values by a factor of 2, that is, to 1.8 percentage points and 3.2 percentage points, respectively. The novel beam arrangement achieved a lower brainstem NTCP in all cases starting at a range uncertainty of 2%. Conclusion The benefits of novel beam arrangements may be of the same magnitude or even exceed the direct benefits of range uncertainty reductions. Indirect effects may therefore contribute markedly to the benefits of reducing proton range uncertainties