A dose-volume histogram based decision-support system for dosimetric comparison of radiotherapy treatment plans

Background: The choice of any radiotherapy treatment plan is usually made after the evaluation of a few preliminary isodose distributions obtained from different beam configurations. Despite considerable advances in planning techniques, such final decision remains a challenging task that would greatly benefit from efficient and reliable assessment tools. Methods: For any dosimetric plan considered, data on dose-volume histograms supplied by treatment planning systems are used to provide estimates on planning target coverage as well as on sparing of organs at risk and the remaining healthy tissue. These partial metrics are then combined into a dose distribution index (DDI), which provides a unified, easy-to-read score for each competing radiotherapy plan. To assess the performance of the proposed scoring system, DDI figures for fifty brain cancer patients were retrospectively evaluated. Patients were divided in three groups depending on tumor location and malignancy. For each patient, three tentative plans were designed and recorded during planning, one of which was eventually selected for treatment. We thus were able to compare the plans with better DDI scores and those actually delivered. Results: When planning target coverage and organs at risk sparing are considered as equally important, the tentative plan with the highest DDI score is shown to coincide with that actually delivered in 32 of the 50 patients considered. In 15 (respectively 3) of the remaining 18 cases, the plan with highest DDI value still coincides with that actually selected, provided that organs at risk sparing is given higher priority (respectively, lower priority) than target coverage. Conclusions: DDI provides a straightforward and non-subjective tool for dosimetric comparison of tentative radiotherapy plans. In particular, DDI readily quantifies differences among competing plans with similar-looking dose-volume histograms and can be easily implemented for any tumor type and localization, irrespective of the planning system and irradiation technique considered. Moreover, DDI permits to estimate the dosimetry impact of different priorities being assigned to sparing of organs at risk or to better target coverag

Integrated scoring approach to assess radiotherapy plan quality for breast cancer treatment

Background: Proposal of an integrated scoring approach assessing the quality of different treatment techniques in a radiotherapy planning comparison. This scoring method incorporates all dosimetric indices of planning target volumes (PTVs) as well as organs at risk (OARs) and provides a single quantitative measure to select an ideal plan. Materials and methods: The radiotherapy planning techniques compared were field-in-field (FinF), intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), hybrid IMRT (H-IMRT), and hybrid VMAT (H-VMAT). These plans were generated for twenty-five locally advanced left-sided breast cancer patients. The PTVs were prescribed a hypofractionation dose of 40.5 Gy in 15 fractions. The integrated score for each planning technique was calculated using the proposed formula. Results: An integrated score value that is close to zero indicates a superior plan. The integrated score that incorporates all dosimetric indices (PTVs and OARs) were 1.37, 1.64, 1.72, 1.18, and 1.24 for FinF, IMRT, VMAT, H-IMRT, and H-VMAT plans, respectively. Conclusion: The proposed integrated scoring approach is scientific to select a better plan and flexible to incorporate the patient-specific clinical demands. This simple tool is useful to quantify the treatment techniques and able to differentiate the acceptable and unacceptable plans

Improvements on the planning and delivery of intensity-modulated arc therapy

In the past decade, intensity-modulated radiation therapy (IMRT) has taken a significant step towards dose conformality and has now become a standard radiotherapy technique in the clinic. In this era, a rotational IMRT technique called intensity-modulated arc therapy (IMAT) was also proposed to possibly further reduce normal tissue toxicity and compete with conventional IMRT. However, clinical implementation of IMAT had been stagnant primarily due to the lack of mature planning and delivery systems. In this study, various aspects of treatment planning and delivery of IMAT have been investigated and improved. The dosimetric accuracy and computational efficiency of IMAT planning has been greatly augmented by the use of Monte Carlo technique which is immune to the large number of discrete beams in approximating a continuous rotation as compared with traditional arc calculation methods. An efficient single-arc form of IMAT delivery has also been explored and extended in contrast to the original multi-arc IMAT. Here the clinical feasibility of single-arc IMAT was established by comparing to multi-arc IMAT and conventional IMRT. It was demonstrated that when using multiple arcs, the requirements on aperture shape connectivity incurred fewer constraints on the optimisation so that the plan quality became the best among the three methods studied although the dosimetric differences among them were generally small and considered clinically insignificant. Nevertheless, single-arc IMAT was able to provide a plan quality in between multi-arc IMAT and fixed-field IMRT with a significant delivery efficiency advantage. Single-arc IMAT may require dose-rate variation for delivery, which is only available with the new treatment machines. To expand the clinical utilisation, an alternative planning and delivery approach was developed such that single-arc IMAT can be delivered using constant dose-rate with the existing machines, sparing the expensive and time-consuming upgrades

Intensity modulated radiation therapy and arc therapy: validation and evolution as applied to tumours of the head and neck, abdominal and pelvic regions

Intensiteitsgemoduleerde radiotherapie (IMRT) laat een betere controle over de dosisdistributie (DD) toe dan meer conventionele bestralingstechnieken. Zo is het met IMRT mogelijk om concave DDs te bereiken en om de risico-organen conformeel uit te sparen. IMRT werd in het UZG klinisch toegepast voor een hele waaier van tumorlocalisaties. De toepassing van IMRT voor de bestraling van hoofd- en halstumoren (HHT) vormt het onderwerp van het eerste deel van deze thesis. De planningsstrategie voor herbestralingen en bestraling van HHT, uitgaande van de keel en de mondholte wordt beschreven, evenals de eerste klinische resultaten hiervan. IMRT voor tumoren van de neus(bij)holten leidt tot minstens even goede lokale controle (LC) en overleving als conventionele bestralingstechnieken, en dit zonder stralingsgeïnduceerde blindheid. IMRT leidt dus tot een gunstiger toxiciteitprofiel maar heeft nog geen bewijs kunnen leveren van een gunstig effect op LC of overleving. De meeste hervallen van HHT worden gezien in het gebied dat tot een hoge dosis bestraald werd, wat erop wijst dat deze “hoge dosis” niet volstaat om alle clonogene tumorcellen uit te schakelen. We startten een studie op, om de mogelijkheid van dosisescalatie op geleide van biologische beeldvorming uit te testen. Naast de toepassing en klinische validatie van IMRT bestond het werk in het kader van deze thesis ook uit de ontwikkeling en het klinisch opstarten van intensiteitgemoduleerde arc therapie (IMAT). IMAT is een rotationele vorm van IMRT (d.w.z. de gantry draait rond tijdens de bestraling), waarbij de modulatie van de intensiteit bereikt wordt door overlappende arcs. IMAT heeft enkele duidelijke voordelen ten opzichte van IMRT in bepaalde situaties. Als het doelvolume concaaf rond een risico-orgaan ligt met een grote diameter, biedt IMAT eigenlijk een oneindig aantal bundelrichtingen aan. Een planningsstrategie voor IMAT werd ontwikkeld, en type-oplossingen voor totaal abdominale bestraling en rectumbestraling werden onderzocht en klinisch toegepast

Impact of using different radiation therapy techniques in breat cancer: contralateral breast dose

RESUMO: O cancro de mama e o mais frequente diagnoticado a indiv duos do sexo feminino. O conhecimento cientifico e a tecnologia tem permitido a cria ção de muitas e diferentes estrat egias para tratar esta patologia. A Radioterapia (RT) est a entre as diretrizes atuais para a maioria dos tratamentos de cancro de mama. No entanto, a radia ção e como uma arma de dois canos: apesar de tratar, pode ser indutora de neoplasias secund arias. A mama contralateral (CLB) e um orgão susceptivel de absorver doses com o tratamento da outra mama, potenciando o risco de desenvolver um tumor secund ario. Nos departamentos de radioterapia tem sido implementadas novas tecnicas relacionadas com a radia ção, com complexas estrat egias de administra ção da dose e resultados promissores. No entanto, algumas questões precisam de ser devidamente colocadas, tais como: E seguro avançar para tecnicas complexas para obter melhores indices de conformidade nos volumes alvo, em radioterapia de mama? O que acontece aos volumes alvo e aos tecidos saudaveis adjacentes? Quão exata e a administração de dose? Quais são as limitações e vantagens das técnicas e algoritmos atualmente usados? A resposta a estas questões e conseguida recorrendo a m etodos de Monte Carlo para modelar com precisão os diferentes componentes do equipamento produtor de radia ção(alvos, ltros, colimadores, etc), a m de obter uma descri cão apropriada dos campos de radia cão usados, bem como uma representa ção geometrica detalhada e a composição dos materiais que constituem os orgãos e os tecidos envolvidos. Este trabalho visa investigar o impacto de tratar cancro de mama esquerda usando diferentes tecnicas de radioterapia f-IMRT (intensidade modulada por planeamento direto), IMRT por planeamento inverso (IMRT2, usando 2 feixes; IMRT5, com 5 feixes) e DCART (arco conformacional dinamico) e os seus impactos em irradia ção da mama e na irradia ção indesejada dos tecidos saud aveis adjacentes. Dois algoritmos do sistema de planeamento iPlan da BrainLAB foram usados: Pencil Beam Convolution (PBC) e Monte Carlo comercial iMC. Foi ainda usado um modelo de Monte Carlo criado para o acelerador usado (Trilogy da VARIAN Medical Systems), no c odigo EGSnrc MC, para determinar as doses depositadas na mama contralateral. Para atingir este objetivo foi necess ario modelar o novo colimador multi-laminas High- De nition que nunca antes havia sido simulado. O modelo desenvolvido est a agora disponí vel no pacote do c odigo EGSnrc MC do National Research Council Canada (NRC). O acelerador simulado foi validado com medidas realizadas em agua e posteriormente com c alculos realizados no sistema de planeamento (TPS).As distribui ções de dose no volume alvo (PTV) e a dose nos orgãos de risco (OAR) foram comparadas atrav es da an alise de histogramas de dose-volume; an alise estati stica complementar foi realizadas usando o software IBM SPSS v20. Para o algoritmo PBC, todas as tecnicas proporcionaram uma cobertura adequada do PTV. No entanto, foram encontradas diferen cas estatisticamente significativas entre as t ecnicas, no PTV, nos OAR e ainda no padrão da distribui ção de dose pelos tecidos sãos. IMRT5 e DCART contribuem para maior dispersão de doses baixas pelos tecidos normais, mama direita, pulmão direito, cora cão e at e pelo pulmão esquerdo, quando comparados com as tecnicas tangenciais (f-IMRT e IMRT2). No entanto, os planos de IMRT5 melhoram a distribuição de dose no PTV apresentando melhor conformidade e homogeneidade no volume alvo e percentagens de dose mais baixas nos orgãos do mesmo lado. A t ecnica de DCART não apresenta vantagens comparativamente com as restantes t ecnicas investigadas. Foram tamb em identi cadas diferen cas entre os algoritmos de c alculos: em geral, o PBC estimou doses mais elevadas para o PTV, pulmão esquerdo e cora ção, do que os algoritmos de MC. Os algoritmos de MC, entre si, apresentaram resultados semelhantes (com dferen cas at e 2%). Considera-se que o PBC não e preciso na determina ção de dose em meios homog eneos e na região de build-up. Nesse sentido, atualmente na cl nica, a equipa da F sica realiza medi ções para adquirir dados para outro algoritmo de c alculo. Apesar de melhor homogeneidade e conformidade no PTV considera-se que h a um aumento de risco de cancro na mama contralateral quando se utilizam t ecnicas não-tangenciais. Os resultados globais dos estudos apresentados confirmam o excelente poder de previsão com precisão na determinação e c alculo das distribui ções de dose nos orgãos e tecidos das tecnicas de simulação de Monte Carlo usados.---------ABSTRACT:Breast cancer is the most frequent in women. Scienti c knowledge and technology have created many and di erent strategies to treat this pathology. Radiotherapy (RT) is in the actual standard guidelines for most of breast cancer treatments. However, radiation is a two-sword weapon: although it may heal cancer, it may also induce secondary cancer. The contralateral breast (CLB) is a susceptible organ to absorb doses with the treatment of the other breast, being at signi cant risk to develop a secondary tumor. New radiation related techniques, with more complex delivery strategies and promising results are being implemented and used in radiotherapy departments. However some questions have to be properly addressed, such as: Is it safe to move to complex techniques to achieve better conformation in the target volumes, in breast radiotherapy? What happens to the target volumes and surrounding healthy tissues? How accurate is dose delivery? What are the shortcomings and limitations of currently used treatment planning systems (TPS)? The answers to these questions largely rely in the use of Monte Carlo (MC) simulations using state-of-the-art computer programs to accurately model the di erent components of the equipment (target, lters, collimators, etc.) and obtain an adequate description of the radiation elds used, as well as the detailed geometric representation and material composition of organs and tissues. This work aims at investigating the impact of treating left breast cancer using di erent radiation therapy (RT) techniques f-IMRT (forwardly-planned intensity-modulated), inversely-planned IMRT (IMRT2, using 2 beams; IMRT5, using 5 beams) and dynamic conformal arc (DCART) RT and their e ects on the whole-breast irradiation and in the undesirable irradiation of the surrounding healthy tissues. Two algorithms of iPlan BrainLAB TPS were used: Pencil Beam Convolution (PBC)and commercial Monte Carlo (iMC). Furthermore, an accurate Monte Carlo (MC) model of the linear accelerator used (a Trilogy R VARIANR) was done with the EGSnrc MC code, to accurately determine the doses that reach the CLB. For this purpose it was necessary to model the new High De nition multileaf collimator that had never before been simulated. The model developed was then included on the EGSnrc MC package of National Research Council Canada (NRC). The linac was benchmarked with water measurements and later on validated against the TPS calculations. The dose distributions in the planning target volume (PTV) and the dose to the organs at risk (OAR) were compared analyzing dose-volume histograms; further statistical analysis was performed using IBM SPSS v20 software. For PBC, all the techniques provided adequate coverage of the PTV. However, statistically significant dose di erences were observed between the techniques, in the PTV, OAR and also in the pattern of dose distribution spreading into normal tissues. IMRT5 and DCART spread low doses into greater volumes of normal tissue, right breast, right lung, heart and even the left lung than tangential techniques (f-IMRT and IMRT2). However,IMRT5 plans improved distributions for the PTV, exhibiting better conformity and homogeneity in target and reduced high dose percentages in ipsilateral OAR. DCART did not present advantages over any of the techniques investigated. Di erences were also found comparing the calculation algorithms: PBC estimated higher doses for the PTV, ipsilateral lung and heart than the MC algorithms predicted. The MC algorithms presented similar results (within 2% di erences). The PBC algorithm was considered not accurate in determining the dose in heterogeneous media and in build-up regions. Therefore, a major e ort is being done at the clinic to acquire data to move from PBC to another calculation algorithm. Despite better PTV homogeneity and conformity there is an increased risk of CLB cancer development, when using non-tangential techniques. The overall results of the studies performed con rm the outstanding predictive power and accuracy in the assessment and calculation of dose distributions in organs and tissues rendered possible by the utilization and implementation of MC simulation techniques in RT TPS

A novel voxel based homogeneity index: rationale and clinical implications for whole-brain radiation therapy

A homogeneity index (HI) is an objective measure for the uniformity of a dose distribution within a given target volume in radiotherapy (RT). The calculation of conventional HIs is based on a limited number of dose volume histogram (DVH) data points which leads to assignment of the same score to RT plans with different homogeneity. This implies a fundamental drawback of DVH-based indices. A voxel-based homogeneity index (VHI) is proposed which aims to improve the sensitivity for homogeneity by utilizing the entire information present in the three-dimensional dose distribution. Properties of conventional HIs are conserved by the VHI. The score is dimensionless; its value is 0 for ideal homogeneity and increases continuously with higher inhomogeneity, therefore allowing for objective comparison of RT plans of different patients. At the same time it has novel properties like the ability to decide to which extent under- or overdosage contribute to inhomogeneity. Sensitivity of VHI was compared with conventional HIs by evaluating whole brain radiation therapy (WBRT) (n=770) RT treatment plans. A mathematical proof was formulated demonstrating the connection between VHI and tumor control probability. For clinical validation radiation underdosage as assessed by the new index was correlated with treatment outcomes of patients who underwent therapeutic WBRT (n=430). Kaplan-Meier-methods and multivariable Cox-regression analysis were used to compare overall survival (OS) and central nervous system progression free survival (CNS PFS) for different levels of underdosage (Low/Intermediate/High Underdosage). A significantly lower OS and CNS PFS were observed for higher levels of VHI_Underdosage, particularly in patients with good performance status (Karnofsky-Index > 70%). In this patient group median OS was 7.63 months in the Low Underdosage group, 7.76 months in the Intermediate Underdosage group and 3.78 months in the High Underdosage group (n=142, unadjusted HR=1.369 95%CI [1.089,1.721], Log rank test for trend P=0.007). VHI has a higher sensitivity to assess inhomogeneity than conventional HIs. First clinical implications were found in terms of compromised OS and CNS PFS for WBRT with higher levels of underdosage in the target volume as assessed by the new index.Ein Homogenitätsindex (HI) ist ein objektives Maß für die Dosishomogenität im Zielvolumen eines Bestrahlungsplans. Bei der Berechnung von konventionellen HIs werden nur wenige Datenpunkte des Dosis-Volumen-Histogramms (DVH) herangezogen, was dazu führt, dass Bestrahlungspläne mit unterschiedlicher Homogenität einen identischen Score erhalten. Dies weist auf einen fundamentalen Nachteil von DVH-basierten Indices hin. In dieser Arbeit wird ein voxel-basierter Homogenitätsindex (VHI) vorgestellt, welcher darauf abzielt, eine höhere Sensitivität bezüglich von Dosis-Inhomogenität aufzuweisen, indem die gesamte Information in der dreidimensionalen Dosisverteilung analysiert wird. Der VHI behält wesentliche Eigenschaften konventioneller HIs bei. Der Score ist eine dimensionslose Größe, hat den Wert 0 bei idealer Homogenität und steigt kontinuierlich mit höherer Inhomogenität an. Auf diese Weise wird es ermöglicht, Bestrahlungspläne verschiedener Patienten miteinander objektiv zu vergleichen. Gleichermaßen weißt er neuartige Eigenschaften auf. So kann das Ausmaß bestimmt werden, inwiefern Unter- und Überdosierungen zur Inhomogenität beitragen. Die Sensitivität des VHI wurde mit der von konventionellen HIs durch die Evaluation von Ganzhirnbestrahlungsplänen (n=770) verglichen. Es wurde ein mathematischer Beweis erbracht, der den Zusammenhang zwischen dem VHI und der Tumorkontrollwahrscheinlichkeit offenbart. Zur klinischen Validierung wurde das Outcome von Patienten mit therapeutischer Ganzhirn-Radiatio (WBRT) mit der Unterdosierung erfasst durch den VHI korreliert. Die Kaplan-Meier-Methoden und eine multivariable Cox-Regression wurden verwendet, um das Gesamtüberleben (OS) und das intrakranielle progressionsfreie Überleben (CNS PFS) von Patienten mit unterschiedlichen Leveln der Unterdosierung (niedrige/mittlere/hohe Unterdosierung) zu analysieren. Ein signifikant erniedrigtes OS und CNS PFS konnte für höhere Level von VHI_Underdosage beobachtet werden, insbesondere bei Patienten in gutem Allgemeinzustand (Karnofsky-Index > 70%). In dieser Patientengruppe lag das mediane OS bei 7.63 Monaten bei niedriger Unterdosierung, bei 7.76 Monaten bei mittlerer Unterdosierung und 3.78 Monaten bei hoher Unterdosierung (n=142, unadjustierter HR=1.369 95%CI [1.089,1.721], Log Rank Test für Trend P=0.007). Der VHI weist eine höhere Sensitivität zur Erfassung von Inhomogenitäten im Zielvolumen als konventionelle HIs auf. Eine erste klinische Relevanz konnte durch ein erniedrigtes OS und CNS PFS bei Patienten gezeigt werden, die eine therapeutische WBRT erhielten und höhere Level an Unterdosierungen im Zielvolumen aufwiesen