Stereotactic body radiation therapy (SBRT) for prostate cancer: Improving treatment delivery efficiency and accuracy.

Purpose: In stereotactic body radiation therapy (SBRT) for prostate cancer, intrafraction motion is an important source of treatment uncertainty as it could not be completely smoothed through fractionation. Herein, we compared different arrangements and beam qualities for extreme hypofractionated treatments to minimize beam delivery time and so intrafractional errors. Methods: A retrospective dataset of 11 patients was used. Three volumetric modulated arc therapy (VMAT) beam arrangements were compared for a prescription dose of 40 Gy/5 fractions: two full arcs, 6 MV flattening filter free (FFF); one full arc, 6 MV FFF; one full arc, 10 MV FFF. A plan quality index was defined to compare achievement of the planning goals. Plan complexity was evaluated with the modulation factor. Dose delivery accuracy and efficiency were measured with patient-specific quality assurance plans. Results: All treatment plans fulfilled all dose objectives. No statistical differences were found both in plan quality and complexity. Very accurate dose delivery was achieved with the three arrangements, with mean γ passing rates >96.5 % (2 %/2 mm criteria). Slightly but significantly higher γ passing rates were observed with single-arc 6 MV FFF. Contrariwise, statistically significant reductions of the delivery time were obtained with single-arc geometries: the average delivery times were 1.6 min (-46.1 %) and 1.3 min (-56.2 %) for 6 and 10 MV FFF respectively. Conclusions: The high-quality, very fast and accurate dose delivery of single-arc plans confirmed the suitability of this arrangement for prostate SBRT. In particular, the significant reduction of delivery time would improve treatment robustness against intrafraction prostate motion.

Full-Dose Intraoperative Electron Radiotherapy for Early Breast Cancer: Evidence from a Single Center's Experience.

To evaluate the clinical response rate and cosmetic outcome after full-dose intraoperative electron radiotherapy (IOERT) in early breast cancer (BC) treated with conserving surgery. Inclusion criteria were: >60 years old, clinical tumor size ≤2 cm, luminal A carcinoma, patological negative lymph nodes, excluded lobular carcinoma histology. IOERT was delivered with a dose of 21 Gy at 90% isodose. Clinical, cosmetic and/or instrumental follow-up were performed 45 days after IOERT, 6 months after the first check, and every 12 months thereafter. Acute and late toxicities were assessed with the CTCAE v.4.03 and EORTC-RTOG scales, respectively. Cosmetic outcome was evaluated using the Harvard/NSABO/RTOG Breast Cosmesis Grading Scale. Overall, 162 consecutive patients were included in this analysis (median follow-up: 54 months, range: 1-98 months). The overall response rate was 97.5% (CI 95%: 0.93-0.99%). Locoragional relapse occurred in 2.5% of patients. No patient showed distant metastases. No patient showed radiation-related acute complications, with 3.7% showing late G2-3 toxicity. Only 3.7% of patients showed poor cosmetic results. Our data confirmed that IOERT is a feasible and valid therapeutic option in low-risk BC patients treated with lumpectomy. A low local recurrence rate combined with good cosmetic results validates the settings of our operative method in routinely clinical practice.

Dosimetric characterization of a mobile accelerator dedicated for intraoperative radiation therapy: Monte Carlo simulations and experimental validation.

PURPOSE: This Technical Note validates previously published data about the dosimetry of the electron beams produced by a mobile accelerator dedicated for intraoperative radiation therapy (IORT). The evaluation of the directional response of a PTW microDiamond detector is presented together with a detailed analysis of the output factors (OFs) for bevelled applicators. METHODS: The OFs of the 6, 8, 10 and 12 MeV electron beams produced by a light intraoperative accelerator (LIAC, SIT, Italy) were measured in a commercial water phantom using the microDiamond. A set of flat and bevelled applicators with sizes ranging from 4 to 10 cm was characterized. For bevelled applicators, a correction for the angular dependence of the microDiamond was calculated using a home-made spherical phantom. Correction factors were obtained through measurements performed rotating the accelerator treatment head at 0°, 15°, 30° and 45°. RESULTS: For flat applicators, the average deviation between measured and simulated OFs was (-1.1 ± 0.7)%. The microDiamond showed a higher angular dependence for the 6 MeV beam (∼8% for angles up to 45°, range 92 % ÷ 100 %), while the variations for 8, 10 and 12 MeV beams were âˆ¼ 4 % (range 97 % ÷ 101 %). Correcting for this dependence, the average deviation of the OFs for bevelled applicators was (-0.9 ± 1.6)%. CONCLUSIONS: The presented results were in very good agreement with those reported in literature. Very similar deviations were found between flat and bevelled applicators confirming the suitability of our method to determine the angular dependence correction factors of the microDiamond detector.

Time-resolved MRI for off-line treatment robustness evaluation in carbon-ion radiotherapy of pancreatic cancer.

PURPOSE: In this study, we investigate the use of magnetic resonance imaging (MRI) for the clinical evaluation of gating treatment robustness in carbon-ion radiotherapy (CIRT) of pancreatic cancer. Indeed, MRI allows radiation-free repeated scans and fast dynamic sequences for time-resolved (TR) imaging (cine-MRI), providing information on inter- and intra-fraction cycle-to-cycle variations of respiratory motion. MRI can therefore support treatment planning and verification, overcoming the limitations of the current clinical standard, that is, four-dimensional computed tomography (4DCT), which describes an "average" breathing cycle neglecting breathing motion variability. METHODS: We integrated a technique to generate a virtual CT (vCT) from 3D MRI with a method for 3D reconstruction from 2D cine-MRI, to produce TR vCTs for dose recalculations. For eight patients, the method allowed evaluating inter-fraction variations at end-exhale and intra-fraction cycle-to-cycle variability within the gating window in terms of tumor displacement and dose to the target and organs at risk. RESULTS: The median inter-fraction tumor motion was in the range 3.33-12.16 mm, but the target coverage was robust (-0.4% median D95% variation). Concerning cycle-to-cycle variations, the gating technique was effective in limiting tumor displacement (1.35 mm median gating motion) and corresponding dose variations (-3.9% median D95% variation). The larger exposure of organs at risk (duodenum and stomach) was caused by inter-fraction motion, whereas intra-fraction cycle-to-cycle dose variations were limited. CONCLUSIONS: This study proposed a method for the generation of TR vCTs from MRI, which enabled an off-line evaluation of gating treatment robustness and suggested its feasibility to support treatment planning of pancreatic tumors in CIRT.

In Silico Feasibility Study of Carbon Ion Radiotherapy With Simultaneous Integrated Boost for Head and Neck Adenoid Cystic Carcinoma.

PURPOSE: In carbon ion radiotherapy (CIRT), a simultaneous integrated boost (SIB) approach has not been fully exploited so far. The feasibility of a CIRT-SIB strategy for head and neck adenoid cystic carcinoma (ACC) patients was investigated in order to improve treatment planning dose distributions. METHODS AND MATERIALS: CIRT plans of 10 ACC patients treated at the National Center for Oncological Hadrontherapy (CNAO, Pavia, Italy) with sequential boost (SEQ) irradiation and prescription doses of 41.0 Gy [relative biological effectiveness (RBE)]/10 fractions to low-risk (LR) clinical target volume (CTV) plus 24.6 Gy(RBE)/6 fractions to the high-risk (HR) CTV were re-planned with two SIB dose levels to the LR-CTV, namely, 48.0 Gy(RBE) and 54.4 Gy(RBE). While planning with SIB, the HR-CTV coverage had higher priority, with fixed organ-at-risk dose constraints among the SIB and SEQ plans. The homogeneity and conformity indexes were selected for CTV coverage comparison. The biologically effective dose (BED) was calculated to compare the different fractionation schemes. RESULTS: Comparable HR-CTV coverage was achieved with the treatment approaches, while superior conformality and homogeneity were obtained with the SIB technique in both CTVs. With the SEQ, SIB48.0, and SIB54.4, the LR-CTV median doses were respectively 50.3%, 11.9%, and 6.0% higher than the prescriptions. Significant reductions of the median and near-maximum BEDs were achieved with both SIB dose levels in the LR-CTV. CONCLUSIONS: The SIB approach resulted in highly conformal dose distributions with the reduction of the unintended dose to the LR-CTV. A prescription dose range for the LR-CTV will be clinically defined to offer tailored personalized treatments, according to the clinical and imaging characteristics of the patients.

Dosimetric Impact of Inter-Fraction Anatomical Changes in Carbon Ion Boost Treatment for High-Risk Prostate Cancer (AIRC IG 14300).

Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session. Planning target volume (PTV) together with rectum and bladder volume variation was evaluated with sCT dose-volume histogram (DVH) metric deviations from the planning values. The correlations between the bladder and rectum volumes, and the corresponding DVH metrics, were also assessed. No significant difference in the bladder, rectum, and PTV median volumes between the planning computed tomography (pCT) and the sCT was found. In addition, no significant difference was assessed when comparing the average DVHs and median DVH metrics between pCT and sCT. Dose deviations determined by bladder and rectum filling variations demonstrated that dose distributions were reproducible in terms of both target coverage and organs at risk (OARs) sparing.

FRoG dose computation meets Monte Carlo accuracy for proton therapy dose calculation in lung.

PURPOSE: To benchmark and evaluate the clinical viability of novel analytical GPU-accelerated and CPU-based Monte Carlo (MC) dose-engines for spot-scanning intensity-modulated-proton-therapy (IMPT) towards the improvement of lung cancer treatment. METHODS: Nine patient cases were collected from the CNAO clinical experience and The Cancer Imaging Archive-4D-Lung-Database for in-silico study. All plans were optimized with 2 orthogonal beams in RayStation (RS) v.8. Forward calculations were performed with FRoG, an independent dose calculation system using a fast robust approach to the pencil beam algorithm (PBA), RS-MC (CPU for v.8) and general-purpose MC (gp-MC). Dosimetric benchmarks were acquired via irradiation of a lung-like phantom and ionization chambers for both a single-field-uniform-dose (SFUD) and IMPT plans. Dose-volume-histograms, dose-difference and γ-analyses were conducted. RESULTS: With respect to reference gp-MC, the average dose to the GTV was 1.8% and 2.3% larger for FRoG and the RS-MC treatment planning system (TPS). FRoG and RS-MC showed a local γ-passing rate of ~96% and ~93%. Phantom measurements confirmed FRoG's high accuracywith a deviation < 0.1%. CONCLUSIONS: Dose calculation performance using the GPU-accelerated analytical PBA, MC-TPS and gp-MC code were well within clinical tolerances. FRoG predictions were in good agreement with both the full gp-MC and experimental data for proton beams optimized for thoracic dose calculations. GPU-accelerated dose-engines like FRoG may alleviate current issues related to deficiencies in current commercial analytical proton beam models. The novel approach to the PBA implemented in FRoG is suitable for either clinical TPS or as an auxiliary dose-engine to support clinical activity for lung patients.

High-dose hypofractionated pencil beam scanning carbon ion radiotherapy for lung tumors: Dosimetric impact of different spot sizes and robustness to interfractional uncertainties.

PURPOSE: The robustness against setup and motion uncertainties of gated four-dimensional restricted robust optimization (4DRRO) was investigated for hypofractionated carbon ion radiotherapy (CIRT) of lung tumors. METHODS: CIRT plans of 9 patients were optimized using 4DRRO strategy with 3 mm setup errors, 3% density errors and 3 breathing phases related to the gate window. The prescription was 60 Gy(RBE) in 4 fractions. Standard spots (SS) were compared to big spots (BS). Plans were recalculated on multiple 4DCTs acquired within 3 weeks from treatment simulation and rigidly registered with planning images using bone matching. Warped dose distributions were generated using deformable image registration and accumulated on the planning 4DCTs. Target coverage (D98%, D95% and V95%) and dose to lung were evaluated in the recalculated and accumulated dose distributions. RESULTS: Comparable target coverage was obtained with both spot sizes (p = 0.53 for D95%). The mean lung dose increased of 0.6 Gy(RBE) with BS (p = 0.0078), still respecting the dose constraint of a 4-fraction stereotactic treatment for the risk of radiation pneumonitis. Statistically significant differences were found in the recalculated and accumulated D95% (p = 0.048 and p = 0.024), with BS showing to be more robust. Using BS, the average degradations of the D98%, D95% and V95% in the accumulated doses were -2.7%, -1.6% and -1.5%. CONCLUSIONS: Gated 4DRRO was highly robust against setup and motion uncertainties. BS increased the dose to healthy tissues but were more robust than SS. The selected optimization settings guaranteed adequate target coverage during the simulated treatment course with acceptable risk of toxicity.

Therapeutic challenges in radiation-induced salivary gland cancers.

PURPOSE OF REVIEW: To give an overview of recent advances in therapeutic approaches of radiation-induced salivary gland cancers (ri-SGCs). RECENT FINDINGS: Reirradiation with protons and carbon ions demonstrated to be feasible, safe and to offer good local control rates, with the possibility of overcoming radioresistance and dosimetric issues in previously irradiated cancer patients. Chromosomal rearrangements, gene fusions and expression profiles are important to identify specific cancer subtypes and can guide tailored systemic therapy. SUMMARY: Ri-SGCs are rare and heterogeneous. Patients are often heavily pretreated and at risk of toxicities, and their management remain challenging. A multidisciplinary approach in referral centers is mandatory. Knowledge about SGCs cellular and molecular mechanisms is constantly evolving. In the last years, novel advances in therapeutic approaches, such as carbon ion radiotherapy, are emerging as safe and effective options in active treatment, but further efforts are needed to offer tailored personalized treatments and to improve survival.

Proton and carbon ion radiotherapy in skull base chordomas: a prospective study based on a dual particle and a patient-customized treatment strategy.

BACKGROUND: The aim of this study is to evaluate results in terms of local control (LC), overall survival (OS), and toxicity profile and to better identify factors influencing clinical outcome of skull base chordoma treated with proton therapy (PT) and carbon ion radiotherapy (CIRT). METHODS: We prospectively collected and analyzed data of 135 patients treated between November 2011 and December 2018. Total prescription dose in the PT group (70 patients) and CIRT group (65 patients) was 74 Gy relative biological effectiveness (RBE) delivered in 37 fractions and 70.4 Gy(RBE) delivered in 16 fractions, respectively (CIRT in unfavorable patients). LC and OS were evaluated using the Kaplan-Meier method. Univariate and multivariate analyses were performed, to identify prognostic factors on clinical outcomes. RESULTS: After a median follow-up of 44 (range, 6-87) months, 14 (21%) and 8 (11%) local failures were observed in CIRT and PT group, respectively. Five-year LC rate was 71% in CIRT cohort and 84% in PT cohort. The estimated 5-year OS rate in the CIRT and PT group was 82% and 83%, respectively. On multivariate analysis, gross tumor volume (GTV), optic pathways, and/or brainstem compression and dose coverage are independent prognostic factors of local failure risk. High rate toxicity grade ≥3 was reported in 11% of patients. CONCLUSIONS: Particle radiotherapy is an effective treatment for skull base chordoma with acceptable late toxicity. GTV, optic pathways, and/or brainstem compression and target coverage were independent prognostic factors for LC. KEY POINTS: • Proton and carbon ion therapy are effective and safe in skull base chordoma.• Prognostic factors are GTV, organs at risk compression, and dose coverage.• Dual particle therapy and customized strategy was adopted.

4D strategies for lung tumors treated with hypofractionated scanning proton beam therapy: Dosimetric impact and robustness to interplay effects.

PURPOSE: To investigate the impact of four-dimensional robust optimization (4DRO) on dose delivered to lung cancer patients in pencil beam scanning proton therapy. METHODS AND MATERIALS: 2 strategies were compared for 20 lung cancer patients, using a different number of breathing phases of the reconstructed 4D computed tomography (CT) included in the plan optimization problem. In the restricted approach combined with gating, only 3 phases close to reference end-exhale were considered instead of the whole breathing cycle. The prescribed dose was 60 Gy(RBE) in 10 fractions. Target coverage (D98%) and dose to healthy tissues were evaluated using Wilcoxon signed-rank test. To assess the robustness against interfractional anatomical and respiratory variations, the optimized plans were recalculated on re-evaluation 4DCTs. To compare the sensitivity of both strategies to interplay effects, we implemented an end-to-end test with a home-made heterogeneous moving phantom and ionization chambers measurements. Robustly optimized plans with prescription doses of 6 Gy(RBE) were delivered in different dynamic conditions. RESULTS: Both 4D robustly optimized plans reached the same target coverage (p = 0.56), while a statistically significant decrease of the homolateral lung dose was observed using the restricted approach (p < 0.0001). Plan recalculations within 15 days from the treatment simulation showed the same robustness of target D98% against interfractional variations (p = 0.48), with an average decrease of approximately 3 Gy(RBE). Phantom measurements confirmed the delivery accuracy of the restricted approach (mean dose deviations <5%). Higher deviations were found for ungated full 4DRO and larger motion amplitude. CONCLUSION: The restricted approach combined with gating improved normal tissue sparing and was shown to be more robust to single fraction deliveries and large motion amplitude.

Mixed-beam approach in locally advanced nasopharyngeal carcinoma: IMRT followed by proton therapy boost versus IMRT-only. Evaluation of toxicity and efficacy.

Objective: To compare radiation-induced toxicity and dosimetry parameters in patients with locally advanced nasopharyngeal cancer (LANPC) treated with a mixed-beam (MB) approach (IMRT followed by proton therapy boost) with an historic cohort of patients treated with a full course of IMRT-only.Material and methods: Twenty-seven patients with LANPC treated with the MB approach were compared to a similar cohort of 17 patients treated with IMRT-only. The MB approach consisted in a first phase of IMRT up to 54-60 Gy followed by a second phase delivered with a proton therapy boost up to 70-74 Gy (RBE). The total dose for patients treated with IMRT-only was 69.96 Gy. Induction chemotherapy was administrated to 59 and 88% and concurrent chemoradiotherapy to 88 and 100% of the MB and IMRT-only patients, respectively. The worst toxicity occurring during the entire course of treatment (acute toxicity) and early-late toxicity were registered according to the Common Terminology Criteria Adverse Events V4.03.Results: The two cohorts were comparable. Patients treated with MB received a significantly higher median total dose to target volumes (p = .02). Acute grade 3 mucositis was found in 11 and 76% (p = .0002) of patients treated with MB and IMRT-only approach, respectively, while grade 2 xerostomia was found in 7 and 35% (p = .02) of patients treated with MB and IMRT-only, respectively. There was no statistical difference in late toxicity. Local progression-free survival (PFS) and progression-free survival curves were similar between the two cohorts of patients (p = .17 and p = .40, respectively). Local control rate was 96% and 81% for patients treated with MB approach and IMRT-only, respectively.Conclusions: Sequential MB approach for LANPC patients provides a significantly lower acute toxicity profile compared to full course of IMRT. There were no differences in early-late morbidities and disease-related outcomes (censored at two-years) but a longer follow-up is required to achieve conclusive results.

Microdosimetric characterization of clinical carbon-ion beams using synthetic diamond detectors and spectral conversion methods.

PURPOSE: To investigate for the first time the potentialities of obtaining microdosimetric measurements in scanned clinical carbon-ion beams using synthetic single crystal diamond detector and to verify the spectral conversion methods. METHODS: Microdosimetric measurements were performed at different depths in a water phantom at the therapeutic scanned carbon-ion beam of the National Center of Oncological Hadrontherapy (CNAO) in Pavia, using waterproof encapsulated diamond microdosimeter developed at "Tor Vergata" University. A monoenergetic carbon-ion beam of 195 MeV/µ scanned over a square field of 2 × 2 cm2 was used. Experimental microdosimetric spectra were compared with those obtained with a propane-filled Tissue Equivalent Proportional Counters (TEPCs) microdosimeter in the same facility at the same conditions. To this purpose, the spectra in diamond were converted to the spectra that would have been collected with a propane-filled cylindrical sensitive volume by means of a novel analytic methodology, recently developed at MedAustron. RESULTS: The microdosimetric spectra acquired by the diamond microdosimeter show different shapes in the 10 keV µm-1  ÷ 103  keV µm-1 lineal-energy range at different water depths. In spite of the high counting rate, no spectral distortion, due to pile-up events and polarization effects, were observed. The experimental spectra have a low detection threshold of about 6 keV µm-1 due to the electronic noise in the irradiation room. The comparison between the spectra converted to propane from diamond detector and the spectra collected directly with propane-filled TEPC shows a good agreement in the whole lineal-energy range. Furthermore this comparison confirms that diamond detector response is LET independent. The frequency- and dose-mean lineal energy values were also assessed for all spectra. The frequency-mean values obtained with diamond microdosimeter at different depths scales rather well with the absorbed dose values. CONCLUSIONS: Microdosimetric characterization of a synthetic single crystal diamond detector in high-energy scanned carbon-ion beams was performed. The results of the present study showed that this detector is suitable for microdosimetry of clinical carbon ion beams. In addition, the good agreement between the converted diamond spectra and those obtained with TEPC provides the first experimental validation of the spectra conversion methodologies as valuable tools for the comparison of spectra collected with different detectors.

A platform for patient positioning and motion monitoring in ocular proton therapy with a non-dedicated beamline.

PURPOSE: At Centro Nazionale di Adroterapia Oncologica (CNAO, Pavia, Italy) ocular proton therapy (OPT) is delivered using a non-dedicated beamline. This paper describes the novel clinical workflow as well as technologies and methods adopted to achieve accurate target positioning and verification during ocular proton therapy at CNAO. METHOD: The OPT clinical protocol at CNAO prescribes a treatment simulation and a delivery phase, performed in the CT and treatment rooms, respectively. The patient gaze direction is controlled and monitored during the entire workflow by means of an eye tracking system (ETS) featuring two optical cameras and an embedded fixation diode light. Thus, the accurate alignment of the fixation light provided to the patient to the prescribed gazed direction is required for an effective treatment. As such, a technological platform based on active robotic manipulators and IR optical tracking-based guidance was developed and tested. The effectiveness of patient positioning strategies was evaluated on a clinical dataset comprising twenty patients treated at CNAO. RESULTS: According to experimental testing, the developed technologies guarantee uncertainties lower than one degree in gaze direction definition by means of ETS-guided positioning. Patient positioning and monitoring strategies during treatment effectively mitigated set-up uncertainties and exhibited sub-millimetric accuracy in radiopaque markers alignment. CONCLUSION: Ocular proton therapy is currently delivered at CNAO with a non-dedicated beamline. The technologies developed for patient positioning and motion monitoring have proven to be compliant with the high geometrical accuracy required for the treatment of intraocular tumors.

Impact of TPS calculation algorithms on dose delivered to the patient in proton therapy treatments.

To estimate the impact of dose calculation approaches adopted in different treatment planning systems (TPSs) on proton therapy dose delivered with pencil beam scanning (PBS). Treatment plans for six regular volumes in water and 15 clinical cases were optimized with Syngo-VC13 and exported for forward recalculation with Raystation-V7.0 pencil beam (RS-PBA) and Monte Carlo (RS-MC) algorithms and with the independent Fluka-MC engine. To verify clinical consistency between the two TPS dosimetric outcomes, the average percentage variations of clinical target volume (CTV) D 98%, D 50% and D 2%, adopted for plan prescription and evaluation, were considered. Ionization chamber measurements served as a further reference for comparison in homogeneous conditions. CTV dose volume histogram (DVH) analysis and gamma evaluation with 3 mm-3% agreement criteria quantified the dose deviation of TPS calculation algorithms, in heterogeneous conditions, against the Fluka-MC code. CTV D 50%, representing the plan dose prescription goal, was higher on average over H&N cases of (3.9 ± 0.9)% and (2.3 ± 0.6)% as calculated with RS-PBA and RS-MC, respectively, compared to Syngo. For tumors located in the pelvis district, average D 50% variations of (1.6 ± 0.7)% and (1.2 ± 0.7)% were found. Syngo underestimated target near maximum doses with respect to all computation systems. Calculation accuracy in heterogeneous conditions of RS-PBA H&N plans resulted poor when a range shifter was required. Target DVH and γ-analysis showed excellent agreement between RS-MC and Fluka-MC, with γ-pass rates >98% for all patient groups. Different TPS dose calculation approaches mainly affected dose delivered in H&N proton treatments, while minor deviations were found for pelvic tumors. RS-MC proved to be the most accurate TPS dose calculation algorithm when compared to an independent MC simulation code.

Design and commissioning of the non-dedicated scanning proton beamline for ocular treatment at the synchrotron-based CNAO facility.

PURPOSE: Only few centers worldwide treat intraocular tumors with proton therapy, all of them with a dedicated beamline, except in one case in the USA. The Italian National Center for Oncological Hadrontherapy (CNAO) is a synchrotron-based hadrontherapy facility equipped with fixed beamlines and pencil beam scanning modality. Recently, a general-purpose horizontal proton beamline was adapted to treat also ocular diseases. In this work, the conceptual design and main dosimetric properties of this new proton eyeline are presented. METHODS: A 28 mm thick water-equivalent range shifter (RS) was placed along the proton beamline to shift the minimum beam penetration at shallower depths. FLUKA Monte Carlo (MC) simulations were performed to optimize the position of the RS and patient-specific collimator, in order to achieve sharp lateral dose gradients. Lateral dose profiles were then measured with radiochromic EBT3 films to evaluate the dose uniformity and lateral penumbra width at several depths. Different beam scanning patterns were tested. Discrete energy levels with 1 mm water-equivalent step within the whole ocular energy range (62.7-89.8 MeV) were used, while fine adjustment of beam range was achieved using thin polymethylmethacrylate additional sheets. Depth-dose distributions (DDDs) were measured with the Peakfinder system. Monoenergetic beam weights to achieve flat spread-out Bragg Peaks (SOBPs) were numerically determined. Absorbed dose to water under reference conditions was measured with an Advanced Markus chamber, following International Atomic Energy Agency (IAEA) Technical Report Series (TRS)-398 Code of Practice. Neutron dose at the contralateral eye was evaluated with passive bubble dosimeters. RESULTS: Monte Carlo simulations and experimental results confirmed that maximizing the air gap between RS and aperture reduces the lateral dose penumbra width of the collimated beam and increases the field transversal dose homogeneity. Therefore, RS and brass collimator were placed at about 98 cm (upstream of the beam monitors) and 7 cm from the isocenter, respectively. The lateral 80%-20% penumbra at middle-SOBP ranged between 1.4 and 1.7 mm depending on field size, while 90%-10% distal fall-off of the DDDs ranged between 1.0 and 1.5 mm, as a function of range. Such values are comparable to those reported for most existing eye-dedicated facilities. Measured SOBP doses were in very good agreement with MC simulations. Mean neutron dose at the contralateral eye was 68 µSv/Gy. Beam delivery time, for 60 Gy relative biological effectiveness (RBE) prescription dose in four fractions, was around 3 min per session. CONCLUSIONS: Our adapted scanning proton beamline satisfied the requirements for intraocular tumor treatment. The first ocular treatment was delivered in August 2016 and more than 100 patients successfully completed their treatment in these 2 yr.

Characterization of a MLIC Detector for QA in Scanned Proton and Carbon Ion Beams.

PURPOSE: Beam energy validation is a fundamental aspect of the routine quality assurance (QA) protocol of a particle therapy facility. A multilayer ionization chamber (MLIC) detector provides the optimal tradeoff between achieving accuracy in particle range determination and saving operational time in measurements and analysis procedures. We propose the characterization of a commercial MLIC as a suitable QA tool for a clinical environment with proton and carbon-ion scanning beams. MATERIALS AND METHODS: Commercial MLIC Giraffe (IBA Dosimetry, Schwarzenbruck, Germany) was primarily evaluated in terms of short-term and long-term stability, linearity with dose, and dose-rate independence. Accuracy was tested by analyzing range of integrated depth-dose curves for a set of representative energies against reference acquisitions in water for proton and carbon ion beams; in addition, 2 modulated proton spread-out Bragg peaks were also measured. Possible methods to increase the native spatial resolution of the detector were also investigated. RESULTS: Measurements showed a high repeatability: mean relative standard deviation was within 0.5% for all channels and both particle types. The long-term stability of the gain calibration showed discrepancies less than 1% at different times. The detector response was linear with dose (R 2 > 0.99) and independent on the dose rate. Measurements of integrated depth-dose curve ranges revealed a mean deviation from reference measurements in water of 0.1 ± 0.3 mm for protons with a maximum difference of 0.4 mm and 0.2 ± 0.6 mm with maximum difference of 0.85 mm for carbon ion beams. For the 2 modulated proton spread-out Bragg peaks, measured differences in distal dose falloff were ≤0.5 mm against calculated values. CONCLUSIONS: The detector is stable, linearly responding with dose, precise, and easy to handle for QA beam energy checks of proton and carbon ion beams.

Characterization of a multilayer ionization chamber prototype for fast verification of relative depth ionization curves and spread-out-Bragg-peaks in light ion beam therapy.

PURPOSE: To dosimetrically characterize a multilayer ionization chamber (MLIC) prototype for quality assurance (QA) of pristine integral ionization curves (ICs) and spread-out-Bragg-peaks (SOBPs) for scanning light ion beams. METHODS: QUBE (De.Tec.Tor., Torino, Italy) is a modular detector designed for QA in particle therapy (PT). Its main module is a MLIC detector, able to evaluate particle beam relative depth ionization distributions at different beam energies and modulations. The charge collecting electrodes are made of aluminum, for a nominal water equivalent thickness (WET) of ~75 mm. The detector prototype was calibrated by acquiring the signals in the initial plateau region of a pristine BP and in terms of WET. Successively, it was characterized in terms of repeatability response, linearity, short-term stability and dose rate dependence. Beam-induced measurements of activation in terms of ambient dose equivalent rate were also performed. To increase the detector coarse native spatial resolution (~2.3 mm), several consecutive acquisitions with a set of certified 0.175-mm-thick PMMA sheets (Goodfellow, Cambridge Limited, UK), placed in front of the QUBE mylar entrance window, were performed. The ICs/SOBPs were achieved as the result of the sum of the set of measurements, made up of a one-by-one PMMA layer acquisition. The newly obtained detector spatial resolution allowed the experimental measurements to be properly comparable against the reference curves acquired in water with the PTW Peakfinder. Furthermore, QUBE detector was modeled in the FLUKA Monte Carlo (MC) code following the technical design details and ICs/SOBPs were calculated. RESULTS: Measurements showed a high repeatability: mean relative standard deviation within ±0.5% for all channels and both particle types. Moreover, the detector response was linear with dose (R2  > 0.998) and independent on the dose rate. The mean deviation over the channel-by-channel readout respect to the reference beam flux (100%) was equal to 0.7% (1.9%) for the 50% (20%) beam flux level. The short-term stability of the gain calibration was very satisfying for both particle types: the channel mean relative standard deviation was within ±1% for all the acquisitions performed at different times. The ICs obtained with the MLIC QUBE at improved resolution satisfactorily matched both the MC simulations and the reference curves acquired with Peakfinder. Deviations from the reference values in terms of BP position, peak width and distal fall-off were submillimetric for both particle types in the whole investigated energy range. For modulated SOBPs, a submillimetric deviation was found when comparing both experimental MLIC QUBE data against the reference values and MC calculations. The relative dose deviations for the experimental MLIC QUBE acquisitions, with respect to Peakfinder data, ranged from ~1% to ~3.5%. Maximum value of 14.1 µSv/h was measured in contact with QUBE entrance window soon after a long irradiation with carbon ions. CONCLUSION: MLIC QUBE appears to be a promising detector for accurately measuring pristine ICs and SOBPs. A simple procedure to improve the intrinsic spatial resolution of the detector is proposed. Being the detector very accurate, precise, fast responding, and easy to handle, it is therefore well suited for daily checks in PT.

MRI evaluation of sacral chordoma treated with carbon ion radiotherapy alone.

BACKGROUND AND PURPOSE: To compare RECIST 1.1 with volume modifications in patients with sacral chordoma not suitable for surgery treated with carbon ions radiotherapy (CIRT) alone. To evaluate patients pain before and after CIRT. To detect if baseline Apparent Diffusion Coefficient values (ADC) from Diffusion Weighted sequences could predict response to treatment. MATERIAL AND METHODS: Patients included had one cycle of CIRT and underwent MRI before and after treatment. For each MRI, lesion maximum diameter and volume were obtained, and ADC values were analyzed within the whole lesion volume. Patients pain was evaluated with Numerical Rating Scale (NRS), considering the upper tumor level at baseline MRIs. RESULTS: 39 patients were studied (mean follow-up 18 months). Considering RECIST 1.1 there was not a significant reduction in tumor diameters (p = 0.19), instead there was a significant reduction in tumor volume (p < 0.001), with a significant reduction in pain (p = 0.021) if the tumors were above vertebrae S2-S3 at baseline MRIs. The assessment of baseline ADC maps demonstrated higher median values and more negative skewness values in progressive disease (PD) patients versus both partial response (PR) and stable disease (SD). CONCLUSIONS: Lesion volume measurement is more accurate than maximum diameter to better stratify the response of sacral chordoma treated with CIRT. Preliminary results suggest that baseline ADC values could be predictive of response to CIRT.