A. Bazani

3D-printed applicators for high dose rate brachytherapy: Dosimetric assessment at different infill percentage

PURPOSE Dosimetric assessment of high dose rate (HDR) brachytherapy applicators, printed in 3D with acrylonitrile butadiene styrene (ABS) at different infill percentage. MATERIALS AND METHODS A low-cost, desktop, 3D printer (Hamlet 3DX100, Hamlet, Dublin, IE) was used for manufacturing simple HDR applicators, reproducing typical geometries in brachytherapy: cylindrical (common in vaginal treatment) and flat configurations (generally used to treat superficial lesions). Printer accuracy was investigated through physical measurements. The dosimetric consequences of varying the applicators density by tuning the printing infill percentage were analysed experimentally by measuring depth dose profiles and superficial dose distribution with Gafchromic EBT3 films (International Specialty Products, Wayne, NJ). Dose distributions were compared to those obtained with a commercial superficial applicator. RESULTS Measured printing accuracy was within 0.5mm. Dose attenuation was not sensitive to the density of the material. Surface dose distribution comparison of the 3D printed flat applicators with respect to the commercial superficial applicator showed an overall passing rate greater than 94% for gamma analysis with 3% dose difference criteria, 3mm distance-to-agreement criteria and 10% dose threshold. CONCLUSION Low-cost 3D printers are a promising solution for the customization of the HDR brachytherapy applicators. However, further assessment of 3D printing techniques and regulatory materials approval are required for clinical application.

Translational and rotational localization errors in cone-beam CT based image-guided lung stereotactic radiotherapy

PURPOSE Accurate localization is crucial in delivering safe and effective stereotactic body radiation therapy (SBRT). The aim of this study was to analyse the accuracy of image-guidance using the cone-beam computed tomography (CBCT) of the VERO system in 57 patients treated for lung SBRT and to calculate the treatment margins. MATERIALS AND METHODS The internal target volume (ITV) was obtained by contouring the tumor on maximum and mean intensity projection CT images reconstructed from a respiration correlated 4D-CT. Translational and rotational tumor localization errors were identified by comparing the manual registration of the ITV to the motion-blurred tumor on the CBCT and they were corrected by means of the robotic couch and the ring rotation. A verification CBCT was acquired after correction in order to evaluate residual errors. RESULTS The mean 3D vector at initial set-up was 6.6±2.3mm, which was significantly reduced to 1.6±0.8mm after 6D automatic correction. 94% of the rotational errors were within 3°. The PTV margins used to compensate for residual tumor localization errors were 3.1, 3.5 and 3.3mm in the LR, SI and AP directions, respectively. CONCLUSIONS On-line image guidance with the ITV-CBCT matching technique and automatic 6D correction of the VERO system allowed a very accurate tumor localization in lung SBRT.

Rationale and protocol of AIRC IG-13218, short-term radiotherapy for early prostate cancer with concomitant boost to the dominant lesion.

Introduction Of the different treatments for early prostate cancer, hypofractionated external-beam radiotherapy is one of the most interesting and studied options. Methods The main objective of this phase II clinical study is to evaluate the feasibility, in terms of the incidence of acute side effects, of a new ultra-hypofractionated scheme for low- or intermediate-risk prostate cancer patients treated with the latest imaging and radiotherapy technology, allowing dose escalation to the dominant intraprostatic lesion identified by multiparametric magnetic resonance imaging. Secondary endpoints of the study are the evaluation of the long-term tolerability of the treatment in terms of late side effects, quality of life, and efficacy (oncological outcome). Results The study is ongoing, and we expect to complete recruitment by the end of 2016. Conclusions Like in previous studies, we expect ultra-hypofractionated radiation treatment for prostate cancer to be well tolerated and effective. Trial registration ClinicalTrials.gov identifier: NCT01913717.

Geometric and dosimetric accuracy and imaging dose of the real-time tumour tracking system of a gimbal mounted linac

PURPOSE To suggest a comprehensive testing scheme to evaluate the geometric and dosimetric accuracy and the imaging dose of the VERO dynamic tumour tracking (DTT) for its clinical implementation. METHODS Geometric accuracy was evaluated for gantry 0° and 90° in terms of prediction (EP), mechanical (EM) and tracking (ET) errors for sinusoidal patterns with 10 and 20 mm amplitudes, 2-6 s periods and phase shift up to 1 s and for 3 patient patterns. The automatic 4D model update was investigated simulating changes in the breathing pattern during treatment. Dosimetric accuracy was evaluated with gafchromic films irradiated in static and moving phantom with and without DTT. The entrance skin dose (ESD) was assessed using a solid state detector and gafchromic films. RESULTS The RMS of EP, EM, and ET were up to 0.8, 0.5 and 0.9 mm for all non phased-shifted motion patterns while for the phased-shifted ones, EP and ET increased to 2.2 and 2.6 mm. Up to 4 updates are necessary to restore a good correlation model, according to type of change. For 100 kVp and 1 mA s X-ray beam, the ESD per portal due to 20 s fluoroscopy was 16.6 mGy, while treatment verification at a frequency of 1 Hz contributed with 4.2 mGy/min. CONCLUSIONS The proposed testing scheme highlighted that the VERO DTT system tracks a moving target with high accuracy. The automatic update of the 4D model is a powerful tool to guarantee the accuracy of tracking without increasing the imaging dose.

Dosimetric characterization of 3D printed bolus at different infill percentage for external photon beam radiotherapy

BACKGROUND AND PURPOSE 3D printing is rapidly evolving and further assessment of materials and technique is required for clinical applications. We evaluated 3D printed boluses with acrylonitrile butadiene styrene (ABS) and polylactide (PLA) at different infill percentage. MATERIAL AND METHODS A low-cost 3D printer was used. The influence of the air inclusion within the 3D printed boluses was assessed thoroughly both with treatment planning system (TPS) and with physical measurements. For each bolus, two treatment plans were calculated with Monte Carlo algorithm, considering the computed tomography (CT) scan of the 3D printed bolus or modelling the 3D printed bolus as a virtual bolus structure with a homogeneous density. Depth dose measurements were performed with Gafchromic films. RESULTS High infill percentage corresponds to high density and high homogeneity within bolus material. The approximation of the bolus in the TPS as a homogeneous material is satisfying for infill percentages greater than 20%. Measurements performed with PLA boluses are more comparable to the TPS calculated profiles. For boluses printed at 40% and 60% infill, the discrepancies between calculated and measured dose distribution are within 5%. CONCLUSIONS 3D printing technology allows modulating the shift of the build-up region by tuning the infill percentage of the 3D printed bolus in order to improve superficial target coverage.

Multimodal image registration for the identification of dominant intraprostatic lesion in high-precision radiotherapy treatments

PURPOSE The integration of CT and multiparametric MRI (mpMRI) is a challenging task in high-precision radiotherapy for prostate cancer. A simple methodology for multimodal deformable image registration (DIR) of prostate cancer patients is presented. METHODS CT and mpMRI of 10 patients were considered. Organs at risk and prostate were contoured on both scans. The dominant intraprostatic lesion was additionally delineated on MRI. After a preliminary rigid image registration, the voxel intensity of all the segmented structures in both scans except the prostate was increased by a specific amount (a constant additional value, A), in order to enhance the contrast of the main organs influencing its position and shape. 70 couples of scans were obtained by varying A from 0 to 800 and they were subsequently non-rigidly registered. Quantities derived from image analysis and contour statistics were considered for the tuning of the best performing A. RESULTS A = 200 resulted the minimum enhancement value required to obtain statistically significant superior registration results. Mean centre of mass distance between corresponding structures decreases from 7.4 mm in rigid registration to 5.3 mm in DIR without enhancement (DIR-0) and to 2.7 mm in DIR with A = 200 (DIR-200). Mean contour distance was 2.5, 1.9 and 0.67 mm in rigid registration, DIR-0 and DIR-200, respectively. In DIR-200 mean contours overlap increases of +13 and +24% with respect to DIR-0 and rigid registration, respectively. CONCLUSION Contour propagation according to the vector field resulting from DIR-200 allows the delineation of dominant intraprostatic lesion on CT scan and its use for high-precision radiotherapy treatment planning. Advances in knowledge: We investigated the application of a B-spline, mutual information-based multimodal DIR coupled with a simple, patient-unspecific but efficient contrast enhancement procedure in the pelvic body area, thus obtaining a robust and accurate methodology to transfer the functional information deriving from mpMRI onto a planning CT reference volume.

Short-term high precision radiotherapy for early prostate cancer with concomitant boost to the dominant lesion: ad interim analysis and preliminary results of Phase II trial AIRC-IG-13218

OBJECTIVE To report preliminary results of a cutting edge extreme hypofractionated treatment with concomitant boost to the dominant lesion for patients with early stage prostate cancer (PCa). METHODS AIRC-IG-13218 is a prospective Phase II trial started in June 2015. Patients with low and intermediate risk PCa who met the inclusion criteria underwent extreme hypofractionated radiotherapy to the prostate (36.25 Gy in 5 fractions) and a simultaneous integrated boost to the dominant intraprostatic lesion (DIL) to 37.5 Gy. The DIL was identified by a multiparamentric MRI (mpMRI) co-registered with planning CT. Toxicity was assessed according to CTCAE v4.0 and RTOG/EORTC criteria. The preliminary evaluation of the first 13 patients was required to confirm the feasibility of the treatment before completing the enrollment of 65 patients. RESULTS The first 13 patients completed the treatment between June 2015 and February 2016. With a median clinical follow-up of 17 months (range 11-26), no Grade 3 or 4 early toxicity was reported. CONCLUSIONS Our preliminary data about early toxicity of an extreme hypofractionated schedule with concomitant boost on the DIL are encouraging. The higher number of patients expected for the trial and a longer follow-up are needed to confirm these results. Advances in knowledge: The use of mpMRI to identify and boost the DIL is an innovative and interesting approach to PCa. Our preliminary findings suggest that dose escalation using DIL boost and extremely hypofractionated radiotherapy regimens might be a safe approach, allowing for short and effective treatment of organ-confined PCa.

Abstract P1-15-07: Simultaneous integrated boost incorporated into a hypofractionated regimen using tomoDirect: Acute toxicity assessment

Aim: We report on acute toxicity, which is the secondary endpoint of a phase II clinical trial specifically addressed to assess the chronic toxicity of a hypofractionated scheme including a simultaneous integrated boost, with intensity modulated radiotherapy. Materials and methods: From 2/2012 to 12/2013 194 patients with early breast cancer entered a phase II study on hypofractionated radiotherapy including a boost dose to the tumor bed. All patients were operated on conservatively. The whole breast and the tumor bed are planned to receive a dose of 45 Gy and 50 Gy, respectively, in 20 fractions, over 4 weeks. Treatment plans are generated using the TomoDirect modality,which is available on Tomotherapy Hi-Art System (Madison,WI). Acute toxicity was evaluated according to the RTOG acute toxicity scale, up to 6 months after the treatment. Afterwards, chronic toxicity is evaluated using LENT/SOMA scale. Results: 95% of the volume of the breast and boost PTVs received 99% and 100% of the planned dose, as median values, respectively and 0.1% (median value) of the entire breast volume received 100% of the boost dose. The median maximum dose to the breast and to the boost PTVs was 113% and 103.3 %, respectively. At the end of treatment, the acute toxicity, was distributed as follows. As far as erythema was concerned, at the end of treatment, 58% of the patients experienced grade 1 erythema, which dropped to 23% one month later. Grade 2 erythema affected 37% of the cases, and after one month, it decreased to 2%.Only 1 patient (0.5%) complained of Grade 3 erythema at the end of the treatment, which rapidly disappeared afterwards. With regard to breast oedema, at the end of treatment grade 1 was observed in 16% of the cases, for whom it tended to remain stable after one month, while grade 2 oedema was noted in 4% of the cases, decreasing to 1.5% on the first month- follow-up visit. Regarding desquamation, dry desquamation ( grade 1) was observed in less than 10% of cases at the end of treatment, but it tended to increase to 17% one month later. Patchy moist desquamation (grade 2) was present in 1.9% of the patients at the end of radiotherapy, and in 1% of them, one month afterwards. Confluent desquamation (grade 3) was noted only in 1 patient (0.5%), who was receiving concomitant chemotherapy with cyclophospamide, methotrexate and fluoruracil: it was still present 1 month after the radiotherapy completion, as the patient continued to be on chemotherapy. No significantly different side effects were observed between the whole breast and the boost area. No patients experienced any lung and cardiac symptoms. Conclusion : The clinical results of this SIB hypofractionated scheme showed low acute toxicity. In spite of the high dose per fraction, with the tumor bed receiving an even higher dose /per fraction, acute toxicity was within the limit acknowledged by literature for conventional fractionation. This non-rotational treatment option allows us to deliver treatment with a traditional tangent-like dose, without spreading low doses to the adjacent structures. Chronic toxicity will be assessed after 2 years. Therefore, a longer follow-up is needed to assess the effective tolerance to the SIB schedule. Citation Format: Maria Cristina Leonardi, Anna Morra, Federica Cattani, Luigi Santoro, Samantha Dicuonzo, Raffaella Cambria, Rosa Luraschi, Alessia Bazani, Roberta Lazzari, Veronica Dell9Acqua, Roberto Orecchia. Simultaneous integrated boost incorporated into a hypofractionated regimen using tomoDirect: Acute toxicity assessment [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-15-07.