Reducing the lateral dose penumbra in IMPT by incorporating transmission pencil beams.

OBJECTIVE: In intensity-modulated proton therapy (IMPT), Bragg peaks result in steep distal dose fall-offs, while the lateral IMPT dose fall-off is often less steep than in photon therapy. High-energy pristine transmission ('shoot through') pencil beams have no Bragg peak in the patient, but show a sharp lateral penumbra at the target level. We investigated whether combining Bragg peaks with Transmission pencil beams ('IMPT&TPB') could improve head-and-neck plans by exploiting the steep lateral dose fall-off of transmission pencil beams. APPROACH: Our system for automated multi-criteria IMPT plan optimisation was extended for combined optimisation of BPs and TPBs. The system generates for each patient a Pareto-optimal plan using a generic 'wish-list' with prioritised planning objectives and hard constraints. For eight nasopharynx cancer patients (NPC) and eight oropharynx cancer (OPC) patients, the IMPT&TPB plan was compared to the competing conventional IMPT plan with only Bragg peaks, which was generated with the same optimiser, but without transmission pencil beams. MAIN RESULTS: Clinical OAR and target constraints were met in all plans. By allowing transmission pencil beams in the optimisation, on average 14 of the 25 investigated OAR plan parameters significantly improved for NPC, and 9 of the 17 for OPC, while only one OPC parameter showed small but significant deterioration. Non-significant differences were found in the remaining parameters. In NPC, cochlea Dmean reduced by up to 17.5 Gy and optic nerve D2% by up to 11.1 Gy. CONCLUSION: Compared to IMPT, IMPT&TPB resulted in comparable target coverage with overall superior OAR sparing, the latter originating from steeper dose fall-offs close to OARs.

SISS-MCO: large scale sparsity-induced spot selection for fast and fully-automated robust multi-criteria optimisation of proton plans.

Objective.Intensity modulated proton therapy (IMPT) is an emerging treatment modality for cancer. However, treatment planning for IMPT is labour-intensive and time-consuming. We have developed a novel approach for multi-criteria optimisation (MCO) of robust IMPT plans (SISS-MCO) that is fully automated and fast, and we compare it for head and neck, cervix, and prostate tumours to a previously published method for automated robust MCO (IPBR-MCO, van de Water 2013).Approach.In both auto-planning approaches, the applied automated MCO of spot weights was performed with wish-list driven prioritised optimisation (Breedveld 2012). In SISS-MCO, spot weight MCO was applied once for every patient after sparsity-induced spot selection (SISS) for pre-selection of the most relevant spots from a large input set of candidate spots. IPBR-MCO had several iterations of spot re-sampling, each followed by MCO of the weights of the current spots.Main results.Compared to the published IPBR-MCO, the novel SISS-MCO resulted in similar or slightly superior plan quality. Optimisation times were reduced by a factor of 6 i.e. from 287 to 47 min. Numbers of spots and energy layers in the final plans were similar.Significance.The novel SISS-MCO automatically generated high-quality robust IMPT plans. Compared to a published algorithm for automated robust IMPT planning, optimisation times were reduced on average by a factor of 6. Moreover, SISS-MCO is a large scale approach; this enables optimisation of more complex wish-lists, and novel research opportunities in proton therapy.

TBS-BAO: fully automated beam angle optimization for IMRT guided by a total-beam-space reference plan.

Properly selected beam angles contribute to the quality of radiotherapy treatment plans. However, the beam angle optimization (BAO) problem is difficult to solve to optimality due to its non-convex discrete nature with many local minima. In this study, we propose TBS-BAO, a novel approach for solving the BAO problem, and test it for non-coplanar robotic CyberKnife radiotherapy for prostate cancer. First, an ideal Pareto-optimal reference dose distribution is automatically generated usinga priorimulti-criterial fluence map optimization (FMO) to generate a plan that includes all candidate beams (total-beam-space, TBS). Then, this ideal dose distribution is reproduced as closely as possible in a subsequent segmentation/beam angle optimization step (SEG/BAO), while limiting the number of allowed beams to a user-selectable preset value. SEG/BAO aims at a close reproduction of the ideal dose distribution. For each of 33 prostate SBRT patients, 18 treatment plans with different pre-set numbers of allowed beams were automatically generated with the proposed TBS-BAO. For each patient, the TBS-BAO plans were then compared to a plan that was automatically generated with an alternative BAO method (Erasmus-iCycle) and to a high-quality manually generated plan. TBS-BAO was able to automatically generate plans with clinically feasible numbers of beams (∼25), with a quality highly similar to corresponding 91-beam ideal reference plans. Compared to the alternative Erasmus-iCycle BAO approach, similar plan quality was obtained for 25-beam segmented plans, while computation times were reduced from 10.7 hours to 4.8/1.5 hours, depending on the applied pencil-beam resolution in TBS-BAO. 25-beam TBS-BAO plans had similar quality as manually generated plans with on average 48 beams, while delivery times reduced from 22.3 to 18.4/18.1 min. TBS reference plans could effectively steer the discrete non-convex BAO.

What is the optimal number of library plans in ART for locally advanced cervical cancer?

PURPOSE: Library-of-plans ART is used to manage daily anatomy changes in locally advanced cervical cancer. In our institute, the library contains 2 VMAT plans for patients with large cervix-uterus motion. Increasing this number could be beneficial for tissue sparing, but is burdensome while the dosimetric gain is yet unclear. This study's aim is to determine the optimal number of plans at an individual patient level. MATERIAL AND METHODS: Data of 14 treated patients were analyzed. Plan libraries were created containing 1-4 VMAT plans. Pre-treatment extent of uterus motion was defined by the 99th percentile of the Hausdorff distance (HD99). For dosimetric evaluations, OARs were contoured in daily CBCT scans, plan selection was simulated, and the V45Gy and V40Gy parameters were recorded. RESULTS: Moderate to strong correlations were found between HD99 and the volume of spared OARs. All patients benefitted from adding a 2nd plan, as is the clinical practice. For patients with a HD99 between 30 and 50mm, a 3-plan library reduced the composite V40Gy with 11-21ml compared to a 2-plan library. CONCLUSION: Patients with large uterus motion (HD99>30mm) would benefit from an extension of the plan library to 3. HD99 is an easy-to-implement criteria to select those patients pre-treatment.

Dynamics of patient reported quality of life and symptoms in the acute phase of online adaptive external beam radiation therapy for locally advanced cervical cancer.

OBJECTIVE: For locally advanced cervical cancer patients, treated with External Beam Radiotherapy (EBRT), Quality of Life (QoL) questionnaires arefrequently used to evaluate treatment-related symptoms and functioning scales. Currently, it is unknown how those evolve during the radiation treatment course. In this prospective study we report on weekly-captured patient-reported QoL and symptoms during image-guided adaptive radiotherapy (IGART) of cervical cancer patients. MATERIAL AND METHODS: Between January 2012 and September 2016, all locally advanced cervical cancer patients treated with IGART and brachytherapy with or without chemotherapy or hyperthermia, were eligible. QoL was assessed at baseline; weekly during the first five weeks of treatment; 1week, 1 and 3months after treatment, using the EORTC QLQ-C30 and the QLQ-CX24 questionnaires. Comparisons were made with an age-matched norm population. RESULTS: Among the 138 (70%) responders, most symptoms showed a moderate-to-large increase, reaching a maximum at the end of treatment, or first week after treatment with return to baseline value at 3months after treatment. While most symptoms gradually increased during the first five weeks, diarrhea and bowel cramps already markedly increased within the first three weeks to reach a plateau at the 5th week of treatment. Global health and functioning were temporarily decreased and returned to a plateau at baseline level 3months after treatment, except for cognitive functioning. CONCLUSION: A profound impact on QoL was observed during the radiation treatment course, temporarily affecting functioning. The maximum impaired was reached at the end of EBRT.

Computation of mean and variance of the radiotherapy dose for PCA-modeled random shape and position variations of the target.

Radiotherapy dose delivery in the tumor and surrounding healthy tissues is affected by movements and deformations of the corresponding organs between fractions. The random variations may be characterized by non-rigid, anisotropic principal component analysis (PCA) modes. In this article new dynamic dose deposition matrices, based on established PCA modes, are introduced as a tool to evaluate the mean and the variance of the dose at each target point resulting from any given set of fluence profiles. The method is tested for a simple cubic geometry and for a prostate case. The movements spread out the distributions of the mean dose and cause the variance of the dose to be highest near the edges of the beams. The non-rigidity and anisotropy of the movements are reflected in both quantities. The dynamic dose deposition matrices facilitate the inclusion of the mean and the variance of the dose in the existing fluence-profile optimizer for radiotherapy planning, to ensure robust plans with respect to the movements.

Improved efficiency of multi-criteria IMPT treatment planning using iterative resampling of randomly placed pencil beams.

This study investigates whether 'pencil beam resampling', i.e. iterative selection and weight optimization of randomly placed pencil beams (PBs), reduces optimization time and improves plan quality for multi-criteria optimization in intensity-modulated proton therapy, compared with traditional modes in which PBs are distributed over a regular grid. Resampling consisted of repeatedly performing: (1) random selection of candidate PBs from a very fine grid, (2) inverse multi-criteria optimization, and (3) exclusion of low-weight PBs. The newly selected candidate PBs were added to the PBs in the existing solution, causing the solution to improve with each iteration. Resampling and traditional regular grid planning were implemented into our in-house developed multi-criteria treatment planning system 'Erasmus iCycle'. The system optimizes objectives successively according to their priorities as defined in the so-called 'wish-list'. For five head-and-neck cancer patients and two PB widths (3 and 6 mm sigma at 230 MeV), treatment plans were generated using: (1) resampling, (2) anisotropic regular grids and (3) isotropic regular grids, while using varying sample sizes (resampling) or grid spacings (regular grid). We assessed differences in optimization time (for comparable plan quality) and in plan quality parameters (for comparable optimization time). Resampling reduced optimization time by a factor of 2.8 and 5.6 on average (7.8 and 17.0 at maximum) compared with the use of anisotropic and isotropic grids, respectively. Doses to organs-at-risk were generally reduced when using resampling, with median dose reductions ranging from 0.0 to 3.0 Gy (maximum: 14.3 Gy, relative: 0%-42%) compared with anisotropic grids and from -0.3 to 2.6 Gy (maximum: 11.4 Gy, relative: -4%-19%) compared with isotropic grids. Resampling was especially effective when using thin PBs (3 mm sigma). Resampling plans contained on average fewer PBs, energy layers and protons than anisotropic grid plans and more energy layers and protons than isotropic grid plans. In conclusion, resampling resulted in improved plan quality and in considerable optimization time reduction compared with traditional regular grid planning.

Treatment precision of image-guided liver SBRT using implanted fiducial markers depends on marker-tumour distance.

The purpose of this study is to assess the accuracy of day-to-day predictions of liver tumour position using implanted gold markers as surrogates and to compare the method with alternative set-up strategies, i.e. no correction, vertebrae and 3D diaphragm-based set-up. Twenty patients undergoing stereotactic body radiation therapy (SBRT) with abdominal compression for primary or metastatic liver cancer were analysed. We determined the day-to-day correlation between gold marker and tumour positions in contrast-enhanced CT scans acquired at treatment preparation and before each treatment session. The influence of marker-tumour distance on the accuracy of prediction was estimated by introducing a method extension of the set-up error paradigm. The distance between gold markers and the centre of the tumour varied between 5 and 96 mm. Marker-guidance was superior to guiding treatment using other surrogates, although both the random and systematic components of the prediction error SD depended on the tumour-marker distance. For a marker-tumour distance of 4 cm, we observed σ = 1.3 mm and Σ = 1.6 mm. The 3D position of the diaphragm dome was the second best predictor. In conclusion, the tumour position can be predicted accurately using implanted markers, but marker-guided set-up accuracy decreases with increasing distance between implanted markers and the tumour.

Optically stimulated luminescence (OSL) of carbon-doped aluminum oxide (Al2O3:C) for film dosimetry in radiotherapy.

INTRODUCTION AND PURPOSE: Conventional x-ray films and radiochromic films have inherent challenges for high precision radiotherapy dosimetry. Here we have investigated basic characteristics of optically stimulated luminescence (OSL) of irradiated films containing carbon-doped aluminum oxide (Al2O3:C) for dosimetry in therapeutic photon and electron beams. MATERIALS AND METHODS: The OSL films consist of a polystyrene sheet, with a top layer of a mixture of single crystals of Al2O3:C, ground into a powder, and a polyester base. The total thickness of the films is 0.3 mm. Measurements have been performed in a water equivalent phantom, using 4, 6, 10, and 18 MV photon beams, and 6-22 MeV electron beams. The studies include assessment of the film response (acquired OSL signal/delivered dose) on delivered dose (linearity), dose rate (1-6 Gy/min), beam quality, field size and depth (6 MV, ranges 4 x 4-30 x 30 cm2, dmax-35 cm). Doses have been derived from ionization chamber measurements. OSL films have also been compared with conventional x-ray and GafChromic films for dosimetry outside the high dose area, with a high proportion of low dose scattered photons. In total, 787 OSL films have been irradiated. RESULTS: Overall, the OSL response for electron beams was 3.6% lower than for photon beams. Differences between the various electron beam energies were not significant. The 6 and 18 MV photon beams differed in response by 4%. No response dependencies on dose rate were observed. For the 6 MV beam, the field size and depth dependencies of the OSL response were within +/-2.5%. The observed inter-film response variation for films irradiated with the same dose varied from 1% to 3.2% (1 SD), depending on the measurement day. At a depth of 20 cm, 5 cm outside the 20 x 20 cm2 6 and 18 MV beams, an over response of 17% was observed. In contrast to GafChromic and conventional x-ray films, the response of the Al2O3:C films is linear in the clinically relevant dose range 0-200 cGy. CONCLUSIONS: Measurement of the OSL signal of irradiated films containing Al2O3:C is a promising technique for film dosimetry in radiotherapy with no or small response variations with dose rate, beam quality, field size and depth, and a linear response from 0 to 200 cGy.

Improvement of radiotherapy treatment delivery accuracy using an electronic portal imaging device.

Reliable application of advanced external beam techniques for the treatment of patients with cancer, such as intensity modulated radiotherapy, requires an adequate quality assurance programme for the verification of the dose delivery. Accurate patient positioning is mandatory because of the steep dose gradients outside the tumour volume. Owing to the increased complexity of the treatment planning and delivery techniques, verification of the dose delivery before and during the actual patient treatment is equally important. For this purpose, a quality assurance programme has been established in our clinic that is primarily based on measurements with electronic portal imaging devices. To minimise systematic set-up errors, the patient positioning is measured in the first few treatment fractions and a set-up correction is applied in the subsequent ones. Before the first treatment fraction, portal dose measurements are performed for each treatment field with the electronic portal imaging device to verify that the planned fluence distribution is correctly delivered at the treatment unit. Dosimetric measurements are also performed during patient treatment to derive the actually delivered fluence maps. By combining this information with knowledge on the patient set-up, the delivered 3-D dose distribution to both the tumour and sensitive organs may be assessed. However, for the highest accuracy, exact knowledge on the (internal) patient geometry during treatment, e.g. using a cone-beam CT, is required.

A novel approach to accurate portal dosimetry using CCD-camera based EPIDs.

A new method for portal dosimetry using CCD camera-based electronic portal imaging devices (CEPIDs) is demonstrated. Unlike previous approaches, it is not based on a priori assumptions concerning CEPID cross-talk characteristics. In this method, the nonsymmetrical and position-dependent cross-talk is determined by directly imaging a set of cross-talk kernels generated by small fields ("pencil beams") exploiting the high signal-to-noise ratio of a cooled CCD camera. Signal calibration is achieved by imaging two reference fields. Next, portal dose images (PDIs) can be derived from electronic portal dose images (EPIs), in a fast forward-calculating iterative deconvolution. To test the accuracy of these EPI-based PDIs, a comparison is made to PDIs obtained by scanning diode measurements. The method proved accurate to within 0.2+/-0.7% (1 SD), for on-axis symmetrical and asymmetrical fields with different field widths and homogeneous phantom thicknesses, off-axis Alderson thorax fields and a strongly modulated IMRT field. Hence, the proposed method allows for fast, accurate portal dosimetry. In addition, it is demonstrated that the CEPID cross-talk signal is not only induced by optical photon reflection and scatter within the CEPID structure, but also by high-energy back-scattered radiation from CEPID elements (mirror and housing) towards the fluorescent screen.

Characteristics relevant to portal dosimetry of a cooled CCD camera-based EPID.

Our EPIDs have recently been equipped with Peltier-cooled CCD cameras. The CCD cooling dramatically reduced deteriorating effects of radiation damage on image quality. Over more than 600 days of clinical operation, the radiation induced noise contribution has remained stable at a very low level (1 SD < or = 0.15% of the camera dynamic range), in marked contrast with the previously used noncooled cameras. The camera response (output signal versus incident EPID radiation exposure) can be accurately described with a quadratic function. This response reproduced well, both in short and long term (variation < 0.2% respectively < 0.4% (1 SD)), rendering the cooled camera well-suited for EPID dosimetry applications.

Stereotactic arc therapy for small elongated tumors using cones and collimator jaws; dosimetric and planning aspects.

Stereotactic arc treatment of small intracranial tumors is usually performed with arcs collimated by circular cones, resulting in treatment volumes which are basically spherical. For nonspherical lesions this results in a suboptimal dose distribution. Multiple isocenters may improve the dose conformity for these lesions, at the cost of large overdosages in the target volume. To achieve improved dose conformity as well as dose homogeneity, the linac jaws (with a minimum distance of 1.0 cm to the central beam axis) can routinely be used to block part of the circular beams. The purpose of this study was to investigate the feasibility of blocking cones with diameters as small as 1.0 cm and a minimum distance between the jaw and the central beam axis of 0.3 cm. First, the reproducibility in jaw positioning and resulting dose delivery on the treatment unit were assessed. Second, the accuracy of the TPS dose calculation for these small fields was established. Finally, clinically applied treatment plans using nonblocked cones were compared with plans using the partially blocked cones for several treatment sites. The reproducibility in dose delivery on our Varian Clinac 2300 C/D machines on the central beam axis is 0.8% (1 SD). The accuracy of the treatment planning system dose calculation algorithm is critically dependent on the used fits for the penumbra and the phantom scatter. The average deviation of calculated from measured dose on the central beam axis is -1.0%+/-1.4% (1 SD), which is clinically acceptable. Partial cone blocking results in improved dose distributions for elongated tumors, such as vestibular schwannoma and uveal melanoma. Multiple isocenters may be avoided. The technique is easy to implement and requires no additional workload.

Dosimetric verification of x-ray fields with steep dose gradients using an electronic portal imaging device.

Regions with steep dose gradients are often encountered in clinical x-ray beams, especially with the growing use of intensity modulated radiotherapy (IMRT). Such regions are present both at field edges and, for IMRT, in the vicinity of the projection of sensitive anatomical structures in the treatment field. Dose measurements in these regions are often difficult and labour intensive, while dose prediction may be inaccurate. A dedicated algorithm developed in our institution for conversion of pixel values, measured with a charged coupled device camera based fluoroscopic electronic portal imaging device (EPID), into absolute absorbed doses at the EPID plane has an accuracy of 1-2% for flat and smoothly modulated fields. However, in the current algorithm there is no mechanism to correct for the (short-range) differences in lateral electron transport between water and the metal plate with the fluorescent layer in the EPID. Moreover, lateral optical photon transport in the fluorescent layer is not taken into account. This results in large deviations (>10%) in the penumbra region of these fields. We have investigated the differences between dose profiles measured in water and with the EPID for small heavily peaked fields. A convolution kernel has been developed to empirically describe these differences. After applying the derived kernel to raw EPID images, a general agreement within 2% was obtained with the water measurements in the central region of the fields, and within 0.03 cm in the penumbra region. These results indicate that the EPID is well suited for accurate dosimetric verification of steep gradient x-ray fields.

A new approach to off-line setup corrections: combining safety with minimum workload.

Off-line patient setup correction protocols based on electronic portal images are an effective tool to reduce systematic patient setup errors. Recently, we have introduced the no action level (NAL) protocol which establishes a significant error reduction at a very small workload. However, this protocol did not include an explicit verification of the applied setup corrections. Systematic mistakes in the execution of setup corrections (e.g., a setup correction is always executed in the +X direction whereas a correction in the -X direction was prescribed) may introduce large systematic setup errors (irrespective of the setup protocol) and may seriously impair treatment outcome. We have therefore extended the NAL protocol with a correction verification (COVER) stage, solely aimed at detecting such mistakes. In short, COVER tests the magnitude of the postcorrection setup error in each relevant direction. If these residue errors are below the acceptance threshold T, no more electronic portal images are required and the protocol has finished. If not, the origin of this result should be investigated; if no obvious mistakes are present, the procedure is repeated for one more treatment fraction. If the residue setup errors are confirmed to be larger than T, the entire protocol is restarted. Using both Monte Carlo simulations and analytical calculations, we performed a risk analysis and evaluated the workload for various choices of T. A threshold T = 3 x sigma(r), where sigma(r) is the mean standard deviation of the random setup errors, ensured that (1) COVER introduces only a small additional workload (1.05 measurement per patient, while the absolute minimum is 1.0) and (2) serious correction mistakes are detected with high probability. Even if setup corrections are wrongly applied in each patient (worst case scenario), COVER ensures that the final distribution of systematic errors is not wider than the precorrection distribution of systematic errors; for realistic frequencies of correction mistakes (<< 1 per patient) this distribution becomes much more narrow. The combination of NAL and COVER thus provides a highly efficient as well as safe method to reduce systematic setup errors.