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Background In order to locate an arteriovenous malformation, typically, a digital subtraction angiography (DSA) is carried out. To use the DSA for target definition an accurate image registration between CT and DSA is required. Carrying out a non-invasive, frameless procedure, registration of the 2D-DSA images with the CT is critical. A new software prototype is enabling this frameless procedure. The aim of this work was to evaluate the prototype in terms of targeting accuracy and reliability based on phantom measurements as well as with the aid of patient data. In addition, the user’s ability to recognize registration mismatches and quality was assessed. Methods Targeting accuracy was measured with a simple cubic, as well as with an anthropomorphic head phantom. Clearly defined academic targets within the phantoms were contoured on the CT. These reference structures were compared with the structures generated within the prototype. A similar approach was used with patient data, where the clinically contoured target served as the reference structure. An important error source decreasing the target accuracy comes from registration errors between CT and 2D-DSA. For that reason, the tools in BC provided to the user to check these registrations are very important. In order to check if the user is able to recognize registration errors, a set of different registration errors was introduced to the correctly registered CT and 2D-DSA image data sets of three different patients. Each of six different users rated the whole set of registrations within the prototype. Results The target accuracy of the prototype was found to be below 0.04 cm for the cubic phantom and below 0.05 cm for the anthropomorphic head phantom. The mean target accuracy for the 15 patient cases was found to be below 0.3 cm. In the registration verification part, almost all introduced registration errors above 1° or 0.1 cm were detected by the six users. Nevertheless, in order to quantify and categorize the possibility to detect mismatches in the registration process more data needs to be evaluated. Conclusion Our study shows, that the prototype is a useful tool that has the potential to fill the gap towards a frameless procedure when treating AVMs with the aid of 2D-DSA images in radiosurgery. The target accuracy of the prototype is similar to other systems already established in clinical routine.

Highlight • Dosimetric study suggests cognition sparing optimization with PBS-PT > IMRT > VMAT. • If available, PBS-PT is recommended for WV-RT in intracranial germ cell tumors. • IMRT is dosimetrically superior than VMAT regarding neurofunctional OAR sparing., Background Whole-ventricular radiotherapy (WV-RT) followed by a boost to the tumor bed (WV-RT/TB) is recommended for intracranial germ cell tumors (IGCT). As the critical brain areas are mainly in the target volume vicinity, it is unclear if protons indeed substantially spare neurofunctional organs at risk (NOAR). Therefore, a dosimetric comparison study of WV-RT/TB was conducted to assess whether proton or photon radiotherapy achieves better NOAR sparing. Methods Eleven children with GCT received 24 Gy(RBE) WV-RT and a boost up to 40 Gy(RBE) in 25 fractions of 1.6 Gy(RBE) with pencil beam scanning proton therapy (PBS-PT). Intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) plans were generated for these patients. NOAR were delineated and treatment plans were compared for target volume coverage (TVC), homogeneity index (HI), inhomogeneity coefficient (IC) and (N)OAR sparing. Results TVC was comparable for all three modalities. Compared to IMRT and VMAT, PBS-PT showed statistically significant optimized IC, as well as dose reduction, among others, in mean and integral dose to the: normal brain (−35.2%, −32.7%; −35.2%, −33.0%, respectively), cerebellum (−53.7%, −33.1%; −53.6%, −32.7%) and right temporal lobe (−14.5%, −31.9%; −14.7%, −29.9%). The Willis’ circle was better protected with PBS-PT than IMRT (−7.1%; −7.8%). The left hippocampus sparing was higher with IMRT. Compared to VMAT, the dose to the hippocampi, amygdalae and temporal lobes was significantly decreased in the IMRT plans. Conclusions Dosimetric comparison of WV-RT/TB in IGCT suggests PBS-PT's advantage over photons in conformality and NOAR sparing, whereas IMRT’s superiority over VMAT, thus potentially minimizing long-term sequelae.

Background Stereotactic radiosurgery (SRS) has been recognized as a first-line treatment option for small to moderate sized vestibular schwannoma (VS). Our aim is to evaluate the impact of SRS doses and other patient and disease characteristics on vestibular function in patients with VS. Methods Data on VS patients treated with single-fraction SRS to 12 Gy were retrospectively reviewed. No dose constraints were given to the vestibule during optimization in treatment planning. Patient and tumor characteristics, pre- and post-SRS vestibular examination results and patient-reported dizziness were assessed from patient records. Results Fifty-three patients were analyzed. Median follow-up was 32 months (range, 6–79). The median minimum, mean and maximum vestibular doses were 2.6 ± 1.6 Gy, 6.7 ± 2.8 Gy, and 11 ± 3.6 Gy, respectively. On univariate analysis, Koos grade (p = 0.04; OR: 3.45; 95% CI 1.01–11.81), tumor volume (median 6.1 cm3; range, 0.8–38; p = 0.01; OR: 4.85; 95% CI 1.43–16.49), presence of pre-SRS dizziness (p = 0.02; OR: 3.98; 95% CI 1.19–13.24) and minimum vestibular dose (p = 0.033; OR: 1.55; 95% CI 1.03–2.32) showed a significant association with patient-reported dizziness. On multivariate analysis, minimum vestibular dose remained significant (p = 0.02; OR: 1.75; 95% CI 1.05–2.89). Patients with improved caloric function had received significantly lower mean (1.5 ± 0.7 Gy, p = 0.01) and maximum doses (4 ± 1.5 Gy, p = 0.01) to the vestibule. Conclusions Our results reveal that 5 Gy and above minimum vestibular doses significantly worsened dizziness. Additionally, mean and maximum doses received by the vestibule were significantly lower in patients who had improved caloric function. Further investigations are needed to determine dose-volume parameters and their effects on vestibular toxicity.

Background Automated brain tumor segmentation methods are computational algorithms that yield tumor delineation from, in this case, multimodal magnetic resonance imaging (MRI). We present an automated segmentation method and its results for resection cavity (RC) in glioblastoma multiforme (GBM) patients using deep learning (DL) technologies. Methods Post-operative, T1w with and without contrast, T2w and fluid attenuated inversion recovery MRI studies of 30 GBM patients were included. Three radiation oncologists manually delineated the RC to obtain a reference segmentation. We developed a DL cavity segmentation method, which utilizes all four MRI sequences and the reference segmentation to learn to perform RC delineations. We evaluated the segmentation method in terms of Dice coefficient (DC) and estimated volume measurements. Results Median DC of the three radiation oncologist were 0.85 (interquartile range [IQR]: 0.08), 0.84 (IQR: 0.07), and 0.86 (IQR: 0.07). The results of the automatic segmentation compared to the three different raters were 0.83 (IQR: 0.14), 0.81 (IQR: 0.12), and 0.81 (IQR: 0.13) which was significantly lower compared to the DC among raters (chi-square = 11.63, p = 0.04). We did not detect a statistically significant difference of the measured RC volumes for the different raters and the automated method (Kruskal-Wallis test: chi-square = 1.46, p = 0.69). The main sources of error were due to signal inhomogeneity and similar intensity patterns between cavity and brain tissues. Conclusions The proposed DL approach yields promising results for automated RC segmentation in this proof of concept study. Compared to human experts, the DC are still subpar.

Purpose To provide fast and accurate dose calculation in voxelized geometries for proton radiation therapy by implementing an adaptive step size algorithm in the proton macro Monte Carlo (pMMC) method. Methods The in-house developed local-to-global MMC method for proton dose calculation is extended with an adaptive step size algorithm for efficient proton transport through a voxelized geometry by sampling transport parameters from a pre-simulated database. Adaptive choice of an adequate slab size in dependence of material interfaces in the proton’s longitudinal and lateral vicinity is investigated. The dose calculation algorithm is validated against the non-adaptive pMMC and full MC simulation for pencil and broad beams with various energies impinging on academic phantoms as well as a head and neck patient CT. Results For material interfaces perpendicular to a proton’s direction, choice of nearest neighbor slab thickness shows best trade-off between dosimetric accuracy and calculation efficiency. Adaptive reduction of chosen slab size is shown to be required for material interfaces closer than 0.5 mm in lateral direction. For the academic phantoms, dose differences of within 1% or 1 mm compared to full Geant4 MC simulation are found, while achieving an efficiency gain of up to a factor of 5.6 compared to the non-adaptive algorithm and 284 compared to Geant4. For the head and neck patient CT, dose differences are within 1% or 1 mm with an efficiency gain factor of up to 3.4 compared to the non-adaptive algorithm and 145 compared to Geant4. Conclusion An adaptive step size algorithm for proton macro Monte Carlo was implemented and evaluated. The dose calculation provides the accuracy of full MC simulations, while achieving an efficiency gain factor of three compared to the non-adaptive algorithm and two orders of magnitude compared to full MC for a complex patient CT., Radiation Oncology, 14 (1)

Background Vendor-independent Monte Carlo (MC) dose calculation (IDC) for patient-specific quality assurance of multi-leaf collimator (MLC) based CyberKnife treatments is used to benchmark and validate the commercial MC dose calculation engine for MLC based treatments built into the CyberKnife treatment planning system (Precision MC). Methods The benchmark included dose profiles in water in 15 mm depth and depth dose curves of rectangular MLC shaped fields ranging from 7.6 mm × 7.7 mm to 115.0 mm × 100.1 mm, which were compared between IDC, Precision MC and measurements in terms of dose difference and distance to agreement. Dose distributions of three phantom cases and seven clinical lung cases were calculated using both IDC and Precision MC. The lung PTVs ranged from 14 cm3 to 93 cm3. Quantitative comparison of these dose distributions was performed using dose-volume parameters and 3D gamma analysis with 2% global dose difference and 1 mm distance criteria and a global 10% dose threshold. Time to calculate dose distributions was recorded and efficiency was assessed. Results Absolute dose profiles in 15 mm depth in water showed agreement between Precision MC and IDC within 3.1% or 1 mm. Depth dose curves agreed within 2.3% / 1 mm. For the phantom and clinical lung cases, mean PTV doses differed from − 1.0 to + 2.3% between IDC and Precision MC and gamma passing rates were > =98.1% for all multiple beam treatment plans. For the lung cases, lung V20 agreed within ±1.5%. Calculation times ranged from 2.2 min (for 39 cm3 PTV at 1.0 × 1.0 × 2.5 mm3 native CT resolution) to 8.1 min (93 cm3 at 1.1 × 1.1 × 1.0 mm3), at 2% uncertainty for Precision MC for the 7 examined lung cases and 4–6 h for IDC, which, however, is not optimized for efficiency but used as a gold standard for accuracy. Conclusions Both accuracy and efficiency of Precision MC in the context of MLC based planning for the CyberKnife M6 system were benchmarked against MC based IDC framework. Precision MC is used in clinical practice at our institute.

For patients with inoperable liver metastases, intra-operative liver high dose-rate brachytherapy (HDR-BT) is a promising technology enabling delivery of a high radiation dose to the tumor, while sparing healthy tissue. Liver brachytherapy has been described in the literature as safe and effective for the treatment of primary or secondary hepatic malignancies. It is preferred over other ablative techniques for lesions that are either larger than 4 cm or located in close proximity to large vessels or the common bile duct. In contrast to external beam radiation techniques, organ movements do not affect the size of the irradiated volume in intra-operative HDR-BT and new technical solutions exist to support image guidance for intra-operative HDR-BT. We have retrospectively analyzed anonymized CT datasets of 5 patients who underwent open liver surgery (resection and/or ablation) in order to test whether the accuracy of a new image-guidance method specifically adapted for intra-operative HDR-BT is high enough to use it in similar situations and whether patients could potentially benefit from navigation-guided intra-operative needle placement for liver HDR-BT.

Background The aim was to evaluate the geometric and corresponding dosimetric differences between two delineation strategies for head and neck tumors neighboring air cavities. Methods Primary gross and clinical tumor volumes (GTV and CTV) of 14 patients with oropharynx or larynx tumors were contoured using a soft tissue window (S). In a second strategy, the same volumes were contoured with an extension to include the parts which became visible on lung window (L). For the calculation of Hausdorff-distances (HD) between contoured volumes of the two strategies, triangular meshes were exported. Two radiotherapy plans with identical goals and optimization parameters were generated for each case. Plan_S were optimized on CTV_S, and Plan_L on CTV_L. The dose coverages of CTV_L and CTV_Δ (CTV_L minus CTV_S) were evaluated in Plan_S. OAR doses were compared among Plan_S and Plan_L. Results Median three-dimensional HD for GTVs and CTVs were 5.7 (±2.6) and 9.3 (±2.8) mm, respectively. The median volume differences between structures contoured using L and S windows were 9% (±5%) and 9% (±4%) for GTV and CTV, respectively. In 13 out of 14 cases, Plan_S met the plan acceptance criteria for CTV_L. In 8 cases CTV_Δ was covered insufficiently in Plan_S. Mean and median differences in OAR dose-volume histogram parameters between Plan_S and Plan_L were within 3%. Conclusion For the current practice in radiotherapy planning for head and neck cancer, the delineation of L-based volumes seems unnecessary. However, in special settings, where smaller or no PTV margins are used, this approach may play an important role for local control. Electronic supplementary material The online version of this article (doi:10.1186/s13014-017-0838-4) contains supplementary material, which is available to authorized users.

Purpose Different international target volume delineation guidelines exist and different treatment techniques are available for salvage radiation therapy (RT) for recurrent prostate cancer, but less is known regarding their respective applicability in clinical practice. Methods and Materials A randomized phase III trial testing 64 Gy vs 70 Gy salvage RT was accompanied by an intense quality assurance program including a site-specific and study-specific questionnaire and a dummy run (DR). Target volume delineation was performed according to the European Organisation for the Research and Treatment of Cancer guidelines, and a DR-based treatment plan was established for 70 Gy. Major and minor protocol deviations were noted, interobserver agreement of delineated target contours was assessed, and dose-volume histogram (DVH) parameters of different treatment techniques were compared. Results Thirty European centers participated, 43% of which were using 3-dimensional conformal RT (3D-CRT), with the remaining centers using intensity modulated RT (IMRT) or volumetric modulated arc technique (VMAT). The first submitted version of the DR contained major deviations in 21 of 30 (70%) centers, mostly caused by inappropriately defined or lack of prostate bed (PB). All but 5 centers completed the DR successfully with their second submitted version. The interobserver agreement of the PB was moderate and was improved by the DR review, as indicated by an increased κ value (0.59 vs 0.55), mean sensitivity (0.64 vs 0.58), volume of total agreement (3.9 vs 3.3 cm 3 ), and decrease in the union volume (79.3 vs 84.2 cm 3 ). Rectal and bladder wall DVH parameters of IMRT and VMAT vs 3D-CRT plans were not significantly different. Conclusions The interobserver agreement of PB delineation was moderate but was improved by the DR. Major deviations could be identified for the majority of centers. The DR has improved the acquaintance of the participating centers with the trial protocol.

Background To determine the outcome and patterns of failure in oral cavity cancer (OCC) patients after postoperative intensity modulated radiotherapy (IMRT) with concomitant systemic therapy. Methods All patients with locally advanced (AJCC stage III/IV) or high-risk OCC (AJCC stage II) who underwent postoperative IMRT at our institution between December 2006 and July 2010 were retrospectively analyzed. The primary endpoint was locoregional recurrence-free survival (LRRFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), acute and late toxicities. Results Overall 53 patients were analyzed. Twenty-three patients (43%) underwent concomitant chemotherapy with cisplatin, two patients with carboplatin (4%) and four patients were treated with the monoclonal antibody cetuximab (8%). At a median follow-up of 2.3 (range, 1.1–4.6) years the 3-year LRRFS, DMFS and OS estimates were 79%, 90%, and 73% respectively. Twelve patients experienced a locoregional recurrence. Eight patients, 5 of which had both a flap reconstruction and extracapsular extension (ECE), showed an unusual multifocal pattern of recurrence. Ten locoregional recurrences occurred marginally or outside of the high-risk target volumes. Acute toxicity grades of 2 (27%) and 3 (66%) and late toxicity grades of 2 (34%) and 3 (11%) were observed. Conclusion LRRFS after postoperative IMRT is satisfying and toxicity is acceptable. The majority of locoregional recurrences occurred marginally or outside of the high-risk target volumes. Improvement of high-risk target volume definition especially in patients with flap reconstruction and ECE might transfer into better locoregional control.

Purpose: : To report acute and late toxicity in prostate cancer patients treated by high-dose intensity-modulated radiation therapy (IMRT) with daily image-guidance. Patients and Methods: : From 06/2004-03/2008, 102 men were treated with 80 Gy IMRT with daily image-guidance. The risk groups were as follows: low, intermediate, and high risk in 21%, 27%, and 52% of patients, respectively. Hormone therapy was given to 65% of patients. Toxicity was scored according to the CTC scale version 3.0. Results: : Median age was 69 years and median follow-up was 39 months (range, 16-61 months). Acute and late grade 2 gastrointestinal (GI) toxicity occurred in 2% and 5% of patients, respectively, while acute and late grade 3 GI toxicity was absent. Grade 2 and 3 pretreatment genitourinary (GU) morbidity (PGUM) were 15% and 2%, respectively. Acute grade 2 and 3 GU toxicity were 43% and 5% and late grade 2 and 3 GU toxicity were 21% and 1%, respectively. After multiple Cox regression analysis, PGUM was an independent predictor of decreased late ≥ grade 2 GU toxicity-free survival (hazard ratio = 9.4 (95% confidence interval: 4.1, 22.0), p < 0.001). At the end of follow-up, the incidence of late grade 2 and 3 GU toxicity decreased to 7% and 1%, respectively. Conclusion: : GI toxicity rates after IMRT with daily image-guidance were excellent. GU toxicity rates were acceptable and strongly related to PGUM

Background To report acute and late toxicity in prostate cancer patients treated by dose escalated intensity-modulated radiation therapy (IMRT) and organ tracking. Methods From 06/2004 to 12/2005 39 men were treated by 80 Gy IMRT along with organ tracking. Median age was 69 years, risk of recurrence was low 18%, intermediate 21% and high in 61% patients. Hormone therapy (HT) was received by 74% of patients. Toxicity was scored according to the CTC scale version 3.0. Median follow-up (FU) was 29 months. Results Acute and maximal late grade 2 gastrointestinal (GI) toxicity was 3% and 8%, late grade 2 GI toxicity dropped to 0% at the end of FU. No acute or late grade 3 GI toxicity was observed. Grade 2 and 3 pre-treatment genitourinary (GU) morbidity (PGUM) was 20% and 5%. Acute and maximal late grade 2 GU toxicity was 56% and 28% and late grade 2 GU toxicity decreased to 15% of patients at the end of FU. Acute and maximal late grade 3 GU toxicity was 8% and 3%, respectively. Decreased late ≥ grade 2 GU toxicity free survival was associated with higher age (P = .025), absence of HT (P = .016) and higher PGUM (P < .001). Discussion GI toxicity rates after IMRT and organ tracking are excellent, GU toxicity rates are strongly related to PGUM.

Purpose/Objective: We present a Fluka Monte Carlo (MC) simulation study for proton treatments based on Varian Eclipse proton plans for left breast cancers including the internal mammary chain. Doses calculated in TPSs are usually accurate within the primary field, but less accurate outside. With the MC treatment verification we can not only find possible inaccuracies in the delivered dose to the regions of main interest (PTV and OAR like heart and left lung) mainly due to body inhomogeneities close to the PTV (i.e., ribs and lung), but also find the accurate dose deposited in other healthy tissues not included in the TPS optimisation (contra lateral lung, contra lateral breast). Doses deposited by other particles not generated in the TPS, but usually created during a real treatment, such as neutrons and light ions, are also accounded for in the MC. All of this allows us to more accurately determine toxicity to healthy tissues and risk of secondary malignancies. Materials and Methods: Before starting any comparison between the MC and the TPS, the virtual CAP GENERAL machine used in the proton Eclipse TPS had to be accurately characterised. In this context studies were performed using virtual water phantoms to determine the beam characteristics (energy, energy spread, spatial spread) and so to prove the equivalence of Eclipse plans in Fluka. Eighteen different patient plans for breast treatments were then performed using Eclipse and the information about the used beams included in the TPS RTPLAN files were extracted and converted to plans in Fluka. This allowed us to perform dose comparisons between plans and simulations in the entire upper body of the patient. Results: In this work we developed a method of performing treatment verification of Eclipse breast plans with the Monte Carlo Fluka and show that dose differences up to 4% in the PTV and up to 70% in other healthy tissues (i.e., contra lateral breast) can be observed when the TPS plans are compared with Fluka simulations of the same plans. Conclusions: While the Varian TPS for conventional radiotherapy is widely used, the proton Eclipse TPS is only used in a few facilities, resulting in a dearth of comparison studies. In particular breast treatments with protons are in the early stages of investigation and not many groups so far have demonstrated the accuracy of TPSs with respect to this treatment site. With this study we demonstrate that treatment verification with Monte Carlo simulations is essential to better determine the dose deposited in the entire patient body, and in particular to the healthy tissues. EP-1459 Dosimetric evaluation of arc-based modulated electron radiation therapy A. Joosten, D. Henzen, W. Volken, D. Frei, K. Lossl, P. Manser, M.K. Fix Inselspital Bern University, Division of Medical Radiation Physics and Department of Radiation Oncology, Bern, Switzerland

Conclusions: VMAT SBRT for lung presents particular challenges for accurate dosimetry as it involves very small fields rapidly changing in shape within tissue where there are large density inhomogeneities. There are many factors that influence the accuracy of the dose measured compared to calculated, including MLC leaf calibration, accuracy of chamber positioning, and phantom constituents. The results presented here indicate that when simple, small phantoms are used then the dosimetric results obtained are within tolerance but as the measurements are moved to larger more complex phantoms the results move beyond acceptable limits. The semiflex chamber gave very similar results to the much smaller A16 chamber. Further work is required to understand and resolve the remaining uncertainties before this technique is used clinically.

BACKGROUND: We present results of an automated segmentation method for resection cavity in Glioblastoma (GBM) patients using deep learning technologies. The approach fully segments the resection cavity and yields estimates of uncertainty. We compare the approach to a previously reported machine learning method and show the superiority in performance of the deep learning approach while yielding estimates of segmentation uncertainty, which can be used by an operator to monitor computer’s results. MATERIAL AND METHODS: We included post-OP, pre- and post-contrast T1, T2 and FLAIR MRI datasets of 30 patients with newly diagnosed, surgically resected and histologically confirmed GBM. Radiation Cavity (RC) were defined as surgical cavity plus blood products. Three radiation oncologists manually delineated the RC using all four MRI sequences. For fully automatic segmentation, we developed a deep learning cavity segmentation method, which was trained on a subset of 25 cases, and utilizes all four MRI sequences to learn RC delineations. We evaluated the segmentation method in terms of Dice coefficient (DC) (volumetric overlap) and estimated volume measurements using the Kruskal-Wallis test followed by a 6-fold cross-validation using the imaging data. RESULTS: Median DC and interquartile range (IQR) of the different pairings of expert raters (reported as tuples) were (0.85, 0.08), (0.84, 0.07), and (0.86, 0.07). The results of the automatic segmentation compared to the three different raters were (0.83, 0.14), (0.81, 0.12), and (0.81, 0.13). We did not detect a statistically significant difference regarding the distribution of the measured volumes for the different raters and methods (Kruskal-Wallis test: chi-square=1.46, p=0.69). The main sources of error consisted in over- or under-segmentation of the RC due to signal inhomogeneity (especially in T2 and FLAIR sequences) and over-segmentation due to similar intensity patterns (edema, subarachnoid space, or ventricles). Uncertainty maps generated by the deep learning approach were visually compared against the segmentation errors, and a good spatial overlap was found between uncertainty and RC delineation errors. This allow us to conclude on the reliability and good calibration properties of the deep learning approach. CONCLUSION: The proposed deep learning approach yields good results for the segmentation of the RC. However, blood products and air can affect its performance. Compared to human experts, the computer-generated results are still subpar but outperform previously presented approaches, while providing estimates of segmentation uncertainty, which can leverage the interactions between these systems and human experts.