Use of radiobiological modeling in treatment plan evaluation and optimization of prostate cancer radiotherapy

There are many tools available that are used to evaluate a radiotherapy treatment plan, such as isodose distribution charts, dose volume histograms (DVH), maximum, minimum and mean doses of the dose distributions as well as DVH point dose constraints. All the already mentioned evaluation tools are dosimetric only without taking into account the radiobiological characteristics of tumors or OARs. It has been demonstrated that although competing treatment plans might have similar mean, maximum or minimum doses they may have significantly different clinical outcomes (Mavroidis et al. 2001). For performing a more complete treatment plan evaluation and comparison the complication-free tumor control probability (P+) and the biologically effective uniform dose (D ) have been proposed (Källman et al. 1992a, Mavroidis et al. 2000). The D concept denotes that any two dose distributions within a target or OAR are equivalent if they produce the same probability for tumor control or normal tissue complication, respectively (Mavroidis et al. 2001)..

A Hierachical Evolutionary Algorithm for Multiobjective Optimization in IMRT

Purpose: Current inverse planning methods for IMRT are limited because they are not designed to explore the trade-offs between the competing objectives between the tumor and normal tissues. Our goal was to develop an efficient multiobjective optimization algorithm that was flexible enough to handle any form of objective function and that resulted in a set of Pareto optimal plans. Methods: We developed a hierarchical evolutionary multiobjective algorithm designed to quickly generate a diverse Pareto optimal set of IMRT plans that meet all clinical constraints and reflect the trade-offs in the plans. The top level of the hierarchical algorithm is a multiobjective evolutionary algorithm (MOEA). The genes of the individuals generated in the MOEA are the parameters that define the penalty function minimized during an accelerated deterministic IMRT optimization that represents the bottom level of the hierarchy. The MOEA incorporates clinical criteria to restrict the search space through protocol objectives and then uses Pareto optimality among the fitness objectives to select individuals. Results: Acceleration techniques implemented on both levels of the hierarchical algorithm resulted in short, practical runtimes for optimizations. The MOEA improvements were evaluated for example prostate cases with one target and two OARs. The modified MOEA dominated 11.3% of plans using a standard genetic algorithm package. By implementing domination advantage and protocol objectives, small diverse populations of clinically acceptable plans that were only dominated 0.2% by the Pareto front could be generated in a fraction of an hour. Conclusions: Our MOEA produces a diverse Pareto optimal set of plans that meet all dosimetric protocol criteria in a feasible amount of time. It optimizes not only beamlet intensities but also objective function parameters on a patient-specific basis

Viability of Non-Coplanar VMAT for Liver SBRT as Compared to Coplanar VMAT and Beam Orientation Optimized 4π IMRT.

PurposeThe 4π static non-coplanar radiotherapy delivery technique has demonstrated better normal tissue sparing and dose conformity than the clinically used volumetric modulated arc therapy (VMAT). It is unclear whether this is a fundamental limitation of VMAT delivery or the coplanar nature of its typical clinical plans. The dosimetry and the limits of normal tissue toxicity constrained dose escalation of coplanar VMAT, non-coplanar VMAT and 4π radiotherapy are quantified in this study.Methods and materialsClinical stereotactic body radiation therapy plans for 20 liver patients receiving 30-60 Gy using coplanar VMAT (cVMAT) were re-planned using 3-4 partial non-coplanar arcs (nVMAT) and 4π with 20 intensity-modulated non-coplanar fields. The conformity number (CN), homogeneity index (HI), 50% dose spillage volume (R50), normal liver volume receiving >15 Gy (VL>15), dose to organs at risk (OARs), and tumor control probability (TCP) were compared for all three treatment plans. The maximum tolerable dose (MTD) yielding a normal liver normal tissue control probability (NTCP) below 1%, 5%, and 10% was calculated with the Lyman-Kutcher-Burman model for each plan, as well as the resulting survival fractions at one, two, three, and four years.ResultsCompared to cVMAT, the nVMAT and 4π plans reduced VL>15 by an average of 5 cm3 and 80 cm3, respectively. 4π reduced the 50% dose spillage volume by ~23% compared to both VMAT plans, and either significantly decreased or maintained OAR doses. The 4π MTDs and survival fractions were significantly higher than both cVMAT and nVMAT (p<0.05) for all normal liver NTCP limits used in this study.ConclusionsThe 4π technique provides significantly better OAR sparing than both cVMAT and vMAT and enables more clinically relevant dose escalation for tumor local control. Therefore, despite the current accessibility of nVMAT, it is not a viable alternative to 4π for liver SBRT

IMRT QA using machine learning: A multi-institutional validation.

PurposeTo validate a machine learning approach to Virtual intensity-modulated radiation therapy (IMRT) quality assurance (QA) for accurately predicting gamma passing rates using different measurement approaches at different institutions.MethodsA Virtual IMRT QA framework was previously developed using a machine learning algorithm based on 498 IMRT plans, in which QA measurements were performed using diode-array detectors and a 3%local/3 mm with 10% threshold at Institution 1. An independent set of 139 IMRT measurements from a different institution, Institution 2, with QA data based on portal dosimetry using the same gamma index, was used to test the mathematical framework. Only pixels with ≥10% of the maximum calibrated units (CU) or dose were included in the comparison. Plans were characterized by 90 different complexity metrics. A weighted poison regression with Lasso regularization was trained to predict passing rates using the complexity metrics as input.ResultsThe methodology predicted passing rates within 3% accuracy for all composite plans measured using diode-array detectors at Institution 1, and within 3.5% for 120 of 139 plans using portal dosimetry measurements performed on a per-beam basis at Institution 2. The remaining measurements (19) had large areas of low CU, where portal dosimetry has a larger disagreement with the calculated dose and as such, the failure was expected. These beams need further modeling in the treatment planning system to correct the under-response in low-dose regions. Important features selected by Lasso to predict gamma passing rates were as follows: complete irradiated area outline (CIAO), jaw position, fraction of MLC leafs with gaps smaller than 20 or 5 mm, fraction of area receiving less than 50% of the total CU, fraction of the area receiving dose from penumbra, weighted average irregularity factor, and duty cycle.ConclusionsWe have demonstrated that Virtual IMRT QA can predict passing rates using different measurement techniques and across multiple institutions. Prediction of QA passing rates can have profound implications on the current IMRT process

An Automated Treatment Plan Quality Control Tool for Intensity-Modulated Radiation Therapy Using a Voxel-Weighting Factor-Based Re-Optimization Algorithm.

Intensity-modulated radiation therapy (IMRT) currently plays an important role in radiotherapy, but its treatment plan quality can vary significantly among institutions and planners. Treatment plan quality control (QC) is a necessary component for individual clinics to ensure that patients receive treatments with high therapeutic gain ratios. The voxel-weighting factor-based plan re-optimization mechanism has been proved able to explore a larger Pareto surface (solution domain) and therefore increase the possibility of finding an optimal treatment plan. In this study, we incorporated additional modules into an in-house developed voxel weighting factor-based re-optimization algorithm, which was enhanced as a highly automated and accurate IMRT plan QC tool (TPS-QC tool). After importing an under-assessment plan, the TPS-QC tool was able to generate a QC report within 2 minutes. This QC report contains the plan quality determination as well as information supporting the determination. Finally, the IMRT plan quality can be controlled by approving quality-passed plans and replacing quality-failed plans using the TPS-QC tool. The feasibility and accuracy of the proposed TPS-QC tool were evaluated using 25 clinically approved cervical cancer patient IMRT plans and 5 manually created poor-quality IMRT plans. The results showed high consistency between the QC report quality determinations and the actual plan quality. In the 25 clinically approved cases that the TPS-QC tool identified as passed, a greater difference could be observed for dosimetric endpoints for organs at risk (OAR) than for planning target volume (PTV), implying that better dose sparing could be achieved in OAR than in PTV. In addition, the dose-volume histogram (DVH) curves of the TPS-QC tool re-optimized plans satisfied the dosimetric criteria more frequently than did the under-assessment plans. In addition, the criteria for unsatisfied dosimetric endpoints in the 5 poor-quality plans could typically be satisfied when the TPS-QC tool generated re-optimized plans without sacrificing other dosimetric endpoints. In addition to its feasibility and accuracy, the proposed TPS-QC tool is also user-friendly and easy to operate, both of which are necessary characteristics for clinical use

When is Better Best? A multiobjective perspective

Purpose: To identify the most informative methods for reporting results of treatment planning comparisons. Methods: Seven papers from the past year of International Journal of Radiation Oncology Biology Physics reported on comparisons of treatment plans for IMRT and IMAT. The papers were reviewed to identify methods of comparisons. Decision theoretical concepts were used to evaluate the study methods and highlight those that provide the most information. Results: None of the studies examined the correlation between objectives. Statistical comparisons provided some information but not enough to make provide support for a robust decision analysis. Conclusion: The increased use of treatment planning studies to evaluate different methods in radiation therapy requires improved standards for designing the studies and reporting the results

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

Comparative evaluation of a novel, moderately hypofractionated radiation protocol in 56 dogs with symptomatic intracranial neoplasia

BACKGROUND: Use of strongly hypofractionated radiation treatments in dogs with intracranial neoplasia did not improve outcomes and yielded increased rates of toxicosis. OBJECTIVES: To evaluate safety and efficacy of a new, moderately hypofractionated radiation protocol of 10 × 4 Gy compared to a standard protocol. ANIMALS: Convenience sample of 56 client-owned dogs with primary symptomatic brain tumors. METHODS: Retrospective observational study. Twenty-six dogs were assigned to the control standard protocol of 20 × 2.5 Gy (group A) and 30 dogs to the new protocol of 10 × 4 Gy (group B), assigned on owners' informed consent. Statistical analysis was conducted under the "as treated" regime, using Kaplan-Meier and Cox-regression analysis. Treatment was delivered with technically advanced image-guided radiation therapy. The 2 treatment groups were compared in terms of outcome and signs of toxicosis. RESULTS: Overall progression-free interval (PFI) and overall survival (OS) time were favorable, with 663 (95%CI: 497;828) and 637 (95%CI: 403;870) days, respectively. We found no significant difference between the two groups: PFI for dogs in group A vs B was 608 (95%CI: 437;779) days and mean (median not reached) 863 (95%CI: 644;1083) days, respectively (P = .89), and OS for dogs in group A vs B 610 (95%CI: 404;816) and mean (median not reached) 796 (95%CI: 586;1007) days (P = .83). CONCLUSION AND CLINICAL IMPORTANCE: In conclusion, 10 × 4 Gy is a safe and efficient protocol for treatment of primary intracranial neoplasia and future dose escalation can be considered