Multi-centre real-world validation of automated treatment planning for breast radiotherapy.

PURPOSE: To present the results of the first multi-centre real-world validation of autoplanning for whole breast irradiation after breast-sparing surgery, encompassing high complexity cases (e.g. with a boost or regional lymph nodes) and a wide range of clinical practices. METHODS: The 24 participating centers each included 10 IMRT/VMAT/Tomotherapy patients, previously treated with a manually generated plan ('manplan'). There were no restrictions regarding case complexity, planning aims, plan evaluation parameters and criteria, fractionation, treatment planning system or treatment machine/technique. In addition to dosimetric comparisons of autoplans with manplans, blinded plan scoring/ranking was conducted by a clinician from the treating center. Autoplanning was performed using a single configuration for all patients in all centres. Deliverability was verified through measurements at delivery units. RESULTS: Target dosimetry showed comparability, while reductions in OAR dose parameters were 21.4 % for heart Dmean, 16.7 % for ipsilateral lung Dmean, and 101.9 %, 45.5 %, and 35.7 % for contralateral breast D0.03cc, D5% and Dmean, respectively (all p < 0.001). Among the 240 patients included, the clinicians preferred the autoplan for 119 patients, with manplans preferred for 96 cases (p = 0.01). Per centre there were on average 5.0 ± 2.9 (1SD) patients with a preferred autoplan (range [0-10]), compared to 4.0 ± 2.7 with a preferred manplan ([0,9]). No differences were observed regarding deliverability. CONCLUSION: The automation significantly reduced the hands-on planning workload compared to manual planning, while also achieving an overall superiority. However, fine-tuning of the autoplanning configuration prior to clinical implementation may be necessary in some centres to enhance clinicians' satisfaction with the generated autoplans.

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.

Comparison of volumetric modulated arc therapy and intensity-modulated radiotherapy for left-sided whole-breast irradiation using automated planning.

BACKGROUND: Published treatment technique comparisons for postoperative left-sided whole breast irradiation (WBI) with deep-inspiration breath-hold (DIBH) are scarce, small, and inconclusive. In this study, fully automated multi-criterial plan optimization, generating a single high-quality, Pareto-optimal plan per patient and treatment technique, was used to compare for a large patient cohort 1) intensity modulated radiotherapy (IMRT) with two tangential fields and 2) volumetric modulated arc therapy (VMAT) with two small tangential subarcs. MATERIALS AND METHODS: Forty-eight randomly selected patients recently treated with DIBH and 16â€¯× 2.66 Gy were included. The optimizer was configured for the clinical planning protocol. Comparisons between IMRT and VMAT included dosimetric plan parameters, estimated excess relative risks (ERR) for toxicities, delivery times, MUs, and deliverability accuracy at a linac. RESULTS: The automatically generated IMRT and VMAT plans applied in this study were similar or higher in quality than the manually generated clinical plans. For equal PTVin V95% (98.4 ± 0.9%), VMAT had significant advantages compared to IMRT regarding breast dose homogeneity and doses in heart and ipsilateral lung, at the cost of some minor deteriorations for contralateral breast (few cases with larger deteriorations) and lung. Conformality improved from 1.38 to 1.18 (p < 0.001). With VMAT, ERR for major coronary events and ipsilateral lung tumors were reduced by 3% (range: -1-12%) and 16% (range: -3-38%), respectively. MUs and delivery times were higher for VMAT. There were no statistical differences in γ passing rates. CONCLUSION: For WBI in conservative therapy of left-sided breast patients treated with DIBH, VMAT with two tangential subarcs was generally dosimetrically superior to IMRT with two tangential static fields. Results need confirmation by robustness analyses.

Accurate 3D-dose-based generation of MLC segments for robotic radiotherapy.

Radiotherapy treatment planning requires accurate modeling of the delivered patient dose, including radiation scatter effects, multi-leaf collimator (MLC) leaf transmission, interleaf-leakage, etc. In fluence map optimization (FMO), a simple dose model is used to first generate an intermediate plan based on pencil-beams. In a second step (segmentation phase), this intermediate plan is then converted into a deliverable treatment plan with MLC segments. In this paper, we investigate novel approaches for the use of a clinical dose engine (CDE) for segmentation of FMO plans in robotic radiotherapy. Segments are sequentially added to the plan. Generation of each next segment is based on the total 3D dose distribution, resulting from already selected segments and the desired FMO dose, considering all treatment beams as candidates for delivery of the new segment. Three versions of the segmentation algorithm were investigated with differences in the integration of the CDE. The combined use of pencil-beams and segments in a segmentation method is non-trivial. Therefore, new methods were developed for the use of segment doses calculated with the CDE in combination with pencil-beams, used for the selection of new segments. For 20 patients with prostate cancer and 12 with liver cancer, segmented plans were compared with FMO plans. All three versions of the proposed segmentation algorithm could well mimic FMO dose distributions. Segmentation with a fully integrated CDE provided the best plan quality and lowest numbers of monitor units and segments at the cost of increased calculation time.

Automated prioritised 3D dose-based MLC segment generation for step-and-shoot IMRT.

Segmentation can degrade a high-quality dose distribution obtained by fluence map optimisation (FMO). A novel algorithm is proposed for generation of MLC segments to deliver an FMO plan with step-and-shoot IMRT while minimising quality loss. All beams are considered simultaneously while generating MLC segments for reproducing the 3D FMO dose distribution. Segment generation is only steered by the 3D FMO dose distribution, i.e. underlying FMO fluence profiles are not considered. The algorithm features prioritised generation of segments, focusing on accurate reproduction of clinical objectives with the highest priorities. The performance of the segmentation algorithm was evaluated for 20 prostate patients, 15 head-and-neck patients, and 12 liver patients. FMO dose distributions were generated by automated multi-criteria treatment planning (Pareto-optimal plans) and subsequently segmented using the proposed method. Various segmentation strategies were investigated regarding prioritisation of objectives and limitation of the number of segments. Segmented plans were dosimetrically similar to FMO plans and for all patients a clinically acceptable segmented plan could be generated. Substantial differences between FMO and segmented fluence profiles were observed. Avoidance of the usual reconstruction of 2D FMO fluence profiles for segment generation, and instead simultaneously generating segments for all beams to directly reproduce the 3D FMO dose distribution is a likely explanation for the obtained results. For the strategies of limiting the number of segments large reductions in number of segments were observed with minimal impact on plan quality.

Progression of hearing loss after LINAC-based stereotactic radiotherapy for vestibular schwannoma is associated with cochlear dose, not with pre-treatment hearing level.

BACKGROUND: Although stereotactic radiotherapy (SRT) for vestibular schwannoma has demonstrated excellent local control rates, hearing deterioration is often reported after treatment. We therefore wished to assess the change in hearing loss after SRT and to determine which patient, tumor and treatment-related factors influence deterioration. METHODS: We retrospectively analyzed progression of hearing loss in patients with vestibular schwannoma who had received stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) as a primary treatment between 2000 and 2014. SRS had been delivered as a single fraction of 12 Gy, and patients treated with FSRT had received 30 fractions of 1.8 Gy. To compare the effects of SRS and FSRT, we converted cochlear doses into EQD2. Primary outcomes were loss of functional hearing, Gardner Robertson (GR) classes I and II, and loss of baseline hearing class. These events were used in Kaplan Meier plots and Cox regression. We also calculated the rate of change in Pure Tone Average (PTA) in dB per month elapsed after radiation-a measure we use in linear regression-to assess the associations between the rate of change in PTA and age, pre-treatment hearing level, tumor size, dose scheme, cochlear dose, and time elapsed after treatment (time-to-first-audiogram). RESULTS: The median follow-up was 36 months for 67 SRS patients and 63 months for 27 FSRT patients. Multivariate Cox regression and in linear regression both showed that the cochlear V90 was significantly associated with the progression of hearing loss. But although pre-treatment PTA correlated with rate of change in Cox regression, it did not correlate in linear regression. The time-to-first-audiogram was also significantly associated, indicating time dependency of the rate of change. None of the analysis showed a significant difference between dose schemes. CONCLUSIONS: We found no significant difference between SRS and FSRT. As the deterioration in hearing after radiotherapy for vestibular schwannoma was associated with the cochlea V90, restricting the V90 may reduce progression of hearing loss. The association between loss of functional hearing and baseline PTA seems to be biased by the use of a categorized variable for hearing loss.

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.

Dose and Volume of the Irradiated Main Bronchi and Related Side Effects in the Treatment of Central Lung Tumors With Stereotactic Radiotherapy.

High radiation dose to the main bronchi can result in stenosis, occlusion or fistula formation, and death. Only 8 articles have reported side effects to the main bronchi from stereotactic body radiation therapy (SBRT), mostly with only one symptomatic complication per article. Therefore, we calculated the dose to the bronchial structures, such as trachea; mainstem bronchi; intermediate bronchus; upper-, middle-, and lower-lobe bronchus; and the segmental bronchi in 134 patients with central tumors and calculated the normal tissue complication probability (NTCP) for each of these structures, with toxicity determination based upon computed tomography imaging. No side effects were found in the trachea, and only stenosis occurred in the main bronchus and bronchus intermedius. Higher grades of side effects, such as occlusion and atelectasis, were only seen in the upper-, middle-, and lower bronchi and the segmental bronchi. When 0.5cc of a segmental bronchi was irradiated to 50Gy in 5 fractions, it was about 50% likely to be occluded radiographically. For grade 1 radiographically evident side effects, the 50% risk level for a 5-fraction Dmax was 55Gy for mid-bronchi and 65Gy for mainstem bronchi. To assure the relationship between clinical toxicity and side effects to the bronchi, further investigation is needed.

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.

Individualized nonadaptive and online-adaptive intensity-modulated radiotherapy treatment strategies for cervical cancer patients based on pretreatment acquired variable bladder filling computed tomography scans.

PURPOSE: To design and evaluate individualized nonadaptive and online-adaptive strategies based on a pretreatment established motion model for the highly deformable target volume in cervical cancer patients. METHODS AND MATERIALS: For 14 patients, nine to ten variable bladder filling computed tomography (CT) scans were acquired at pretreatment and after 40 Gy. Individualized model-based internal target volumes (mbITVs) accounting for the cervix and uterus motion due to bladder volume changes were generated by using a motion-model constructed from two pretreatment CT scans (full and empty bladder). Two individualized strategies were designed: a nonadaptive strategy, using an mbITV accounting for the full-range of bladder volume changes throughout the treatment; and an online-adaptive strategy, using mbITVs of bladder volume subranges to construct a library of plans. The latter adapts the treatment online by selecting the plan-of-the-day from the library based on the measured bladder volume. The individualized strategies were evaluated by the seven to eight CT scans not used for mbITVs construction, and compared with a population-based approach. Geometric uniform margins around planning cervix-uterus and mbITVs were determined to ensure adequate coverage. For each strategy, the percentage of the cervix-uterus, bladder, and rectum volumes inside the planning target volume (PTV), and the clinical target volume (CTV)-to-PTV volume (volume difference between PTV and CTV) were calculated. RESULTS: The margin for the population-based approach was 38 mm and for the individualized strategies was 7 to 10 mm. Compared with the population-based approach, the individualized nonadaptive strategy decreased the CTV-to-PTV volume by 48% ± 6% and the percentage of bladder and rectum inside the PTV by 5% to 45% and 26% to 74% (p < 0.001), respectively. Replacing the individualized nonadaptive strategy by an online-adaptive, two-plan library further decreased the percentage of bladder and rectum inside the PTV (0% to 10% and -1% to 9%; p < 0.004) and the CTV-to-PTV volume (4-96 ml). CONCLUSIONS: Compared with population-based margins, an individualized PTV results in better organ-at-risk sparing. Online-adaptive radiotherapy further improves organ-at-risk sparing.

SU-E-T-617: Towards Fully Automated Multi-Criterial Plan Generation: A Prospective Clinical Study.

PURPOSE: To prospectively compare plans generated with iCycle, an in-house developed algorithm for fully automated multi-criterial IMRT beam profile and beam orientation optimization (Breedveld, Med. Phys. 2012), and plans manually generated by dosimetrists with the clinical treatment planning system. METHODS: For 20 randomly selected head-and-neck cancer patients with various tumour locations (of whom 13 received sequential boost treatments) we offered the treating physician the choice between an automatically generated iCycle plan and a manually optimized plan following standard clinical procedures. While iCycle used a fixed'wish-list' with hard constraints and prioritised objectives, the dosimetrists manually selected the beam configuration and fine-tuned the constraints and objectives for each IMRT plan. Dosimetrists and treating physicians were not informed in advance whether a competing iCycle plan was made or not. The two plans were simultaneously presented to the physician who then selected the plan to be used for treatment. For the patient group, we quantified differences in PTV coverage and sparing of critical tissues. RESULTS: In 32/33 plan comparisons the physician selected the iCycle plan for treatment. This highly consistent preference for automatically generated plans was mainly caused by improved sparing for the large majority of critical structures. With iCycle, the NTCPs for parotid and submandibular glands were reduced by 2.4% ± 4.9% (maximum: 18.5%, p=0.001) and 6.5% ± 8.3% (maximum: 27%, p=0.005), respectively. The reduction in mean oral cavity dose was 2.8 Gy ± 2.8 Gy (maximum: 8.1 Gy, p=0.005). For swallowing muscles, esophagus and larynx, the mean dose reduction was 3.3 Gy ± 1.1Gy (maximum: 9.2 Gy, p<0.001). Moreover, for 15 patients, the target coverage was improved as well. CONCLUSIONS: In 97% of cases, the automatically generated plan was selected for treatment because of superior quality. Apart from improved plan quality, automatic plan generation is economically attractive because of reduced workload.

SU-E-T-647: Plan Quality in Computerized Non-Coplanar IMRT Beam Angle Optimization is Highly Dependent on the Extent of the Beam direction Search Space.

PURPOSE: To investigate the relationship between plan quality and the extent of the beam direction search space in computerized beam angle selection for generating optimal (non-coplanar) IMRT plans for prostate SBRT with dose distributions simulating HDR brachytherapy. METHODS: iCycle (1) was used to investigate the relationship between plan quality and the extent of the set of beam directions available for plan generation. For a group of 10 prostate patients, optimal plans were generated for 5 direction search spaces. For coplanar treatments (CP set), 72 orientations were available for selection (separation 5°). The fully non-coplanar set (F-NCP) included the CP directions plus 430 directions spread over the sphere. The CK set contained the directions available at the robotic Cyberknife unit. CK+ and CK++ were extensions of CK to investigate some of its characteristics. Generated plans were in accordance with our clinical SBRT protocol for Cyberknife treatment, delivering 4 fractions of 9.5 Gy. Adequate PTV coverage had the highest priority. Reduction of rectum dose was the highest OAR priority. RESULTS: The mean PTV coverage (V95) of all SBRT plans was 99% ï,± 0.9% (1 SD). F-NCP plans had most favorable OAR dose parameters, while for coplanar plans OAR doses were highest. Compared to coplanar treatment, rectum Dmean/V60 were 25% / 37% and 19% / 21% lower in F-NCP and CK plans. Higher rectum dose for the Cyberknife set compared to F-NCP was not caused by a lack of posterior beams for Cyberknife. For all search spaces, reduction in OAR dose only leveled off with > 20 beams in the plans (for CP, rectum V60 in 25 beam plans was reduced by 64% compared to 11 beams). In the non-coplanar set-ups, there was a preference for beams with a (large) lateral component. CONCLUSIONS: Plan quality clearly improved with the extent of the beam direction search space (coplanar worst), and the number of beam directions in the plan (25 clearly better than 11).(1) Breedveld S, Storchi P, Voet P, Heijmen B, Med Phys 2012; DOI: 10.1118/1.3676689.

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.

Stereotactic body radiation therapy for colorectal liver metastases.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is a treatment option for colorectal liver metastases. Local control, patient survival and toxicity were assessed in an experience of SBRT for colorectal liver metastases. METHODS: SBRT was delivered with curative intent to 20 consecutively treated patients with colorectal hepatic metastases who were candidates for neither resection nor radiofrequency ablation (RFA). The median number of metastases was 1 (range 1-3) and median size was 2.3 (range 0.7-6.2) cm. Toxicity was scored according to the Common Toxicity Criteria version 3.0. Local control rates were derived on tumour-based analysis. RESULTS: Median follow-up was 26 (range 6-57) months. Local failure was observed in nine of 31 lesions after a median interval of 22 (range 12-52) months. Actuarial 2-year local control and survival rates were 74 and 83 per cent respectively. Hepatic toxicity grade 2 or less was reported in 18 patients. Two patients had an episode of hepatic toxicity grade 3. CONCLUSION: SBRT is a treatment option for patients with colorectal liver metastases who are not candidates for resection or RFA.

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.