Active Beam Scanning Research Articles

P18.11.A Active beam scanning proton therapy for large skull base benign meningiomas: long-term results

Abstract Purpose To report long-term results of active beam scanning proton therapy (PT) for large skull base benign meningiomas Material and Methods Eighty-two patients (pts) with large skull base meningiomas were treated with PT between April 2015 and December 2021. Median age was 62 years (range, 48-82) while KPS ranged between 60 and 100 (median 90); 60 were female (73%), and 22 were male (27%). Thirty-two pts (39%) had histologically proven World Health Organization (WHO) Grade I tumors. In remaining pts diagnosis was based on the typical imaging appearance of benign meningioma. All patients received PT for residual, progressive or non-operable lesions. Newly diagnosed tumors received total dose of 50 GyRBE (RBE: relative biologic effectiveness) while progressing meningiomas 54 GyRBE. All the treatments were delivered at 2 GyRBE per fraction. All pts were treated with active beam scanning PT using 3 fields with single field optimization technique. Treatment planning was based on morphological magnetic resonance imaging (MRI) with contrast enhancement medium administration. All pts received also 68-Ga-DOTATOC-PET. Gross tumor volume ranged from 21 to 64 cc. Toxicity was assessed according to Common Terminology Criteria for Adverse Events version 4.0. Median follow-up time was 40 months (range, 3-83). Results All pts completed the treatment without breaks. Registered acute side effects include grade 1 (19%) and grade 2 (8%) skin erythema, grade 1 (5%) and grade 2 (5%) alopecia, grade 1 (40%) fatigue, grade 1 (5%) and grade 2 (10%) conjunctivitis, grade 1 (10%) pain, grade 1 (5%) blurred vision, grade 1 (10%) headache, and grade 2 (5%) skin hyperpigmentation. One pts (1%) experienced grade 3 pain. There were no further grade 3 or higher acute toxicities. Registered late side effects include grade 1 (2%) and grade 2 (5%) alopecia, grade 1 (21%) fatigue, grade 1 (5%) and grade 2 (5%) headache, grade 1 (6%) dizziness, grade 1 (3%) blurred vision, grade 1 (3%) and grade 2 (6%) pain, grade 1 (2%) dry eye, and grade 1 (5%) skin hyperpigmentation. Two pts (2%) experienced grade 3 pain. Two further pts (2%) experienced grade 3 optic neuropathy. There were no further grade 3 or higher late toxicities. During follow-up one pts (1%) with cavernous sinus meningioma experienced complete obstruction of intracavernous carotid artery with mild transient symptoms that resolved in few days and brain tissue ischemia detected at MRI (grade 2). Before irradiation this pts already had a meningioma-related near-complete obstruction of the intracavernous carotid artery and received a vascular surgery evaluation. Currently, absolute tumor control is 99%. Moreover, relief of symptoms recorded before irradiation occurred in 40% of pts. Conclusion PT is safe and effective treatment for pts with large skull base benign meningiomas.

Neoadjuvant irradiation of extremity soft tissue sarcoma with ions (Extrem-ion): study protocol for a randomized phase II pilot trial

BackgroundThe standard of care treatment for soft tissue sarcoma of the extremities is a wide resection in combination with pre- or postoperative radiotherapy with high local control rates, sparing patients the necessity of amputation without compromising on overall survival rates.The currently preferred timing of radiotherapy is under debate. Albeit having higher rates of acute wound complications, late side effects like fibrosis, joint stiffness or edema are less frequent in preoperative compared to postoperative radiotherapy. This can be explained in smaller treatment volumes and a lower dose in the preoperative setting. Particles allow better sparing of surrounding tissues at risk, and carbon ions additionally offer biologic advantages and are preferred in less radiosensitive tumors. Hypofractionation allows for a significantly shorter treatment duration.MethodsExtrem-ion is a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the extremities will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5–6 fractions per week] in each arm). The primary objective is the proportion of therapies without wound healing disorder the first 120 days after surgery or discontinuation of treatment for any reason related to the treatment. The secondary endpoints of the study consist of local control, local progression-free survival, disease-free survival, overall survival, and quality of life.DiscussionThe aim of this study is to confirm that hypofractionated, preoperative radiotherapy is safe and feasible. The potential for reduced toxicity by the utilization of particle therapy is the rational of this trial. A subsequent randomized phase III trial will compare the hypofractionated proton and carbon ion irradiation in regards to local control.Trial registrationClinicalTrials.gov Identifier: NCT04946357; Retrospectively registered June 30, 2021.

Out-of-field doses in pediatric craniospinal irradiations with 3D-CRT, VMAT, and scanning proton radiotherapy: A phantom study.

Craniospinal irradiation (CSI) has greatly increased survival rates for patients with a diagnosis of medulloblastoma and other primitive neuroectodermal tumors. However, as it includes exposure of a large volume of healthy tissue to unwanted doses, there is a strong concern about the complications of the treatment, especially for the children. To estimate the risk of second cancers and other unwanted effects, out-of-field dose assessment is necessary. The purpose of this study is to evaluate and compare out-of-field doses in pediatric CSI treatment using conventional and advanced photon radiotherapy (RT) and advanced proton therapy. To our knowledge, it is the first such comparison based on in-phantom measurements. Additionally, for out-of-field doses during photon RT in this and other studies, comparisons were made using analytical modeling. In order to describe the out-of-field doses absorbed in a pediatric patient during actual clinical treatment, an anthropomorphic phantom, which mimics the 10-year-old child, was used. Photon 3D-conformal RT (3D-CRT) and two advanced, highly conformal techniques: photon volumetric-modulated arc therapy (VMAT) and active pencil beam scanning (PBS) proton RT were used for CSI treatment. Radiophotoluminescent and poly-allyl-diglycol-carbonate nuclear track detectors were used for photon and neutron dosimetry in the phantom, respectively. Out-of-field doses from neutrons were expressed in terms of dose equivalent. A two-Gaussian model was implemented for out-of-field doses during photon RT. The mean VMAT photon doses per target dose to all organs in this study were under 50% of the target dose (i.e.,<500mGy/Gy), while the mean 3D-CRT photon dose to oesophagus, gall bladder, and thyroid, exceeded that value. However, for 3D-CRT, better sparing was achieved for eyes and lungs. The mean PBS photon doses for all organs were up to three orders of magnitude lower compared to VMAT and 3D-CRT and exceeded 10mGy/Gy only for the oesophagus, intestine, and lungs. The mean neutron dose equivalent during PBS for eight organs of interest (thyroid, breasts, lungs, liver, stomach, gall bladder, bladder, prostate) ranged from 1.2mSv/Gy for bladder to 23.1 mSv/Gy for breasts. Comparison of out-of-field doses in this and other phantom studies found in the literature showed that a simple and fast two-Gaussian model for out-of-field doses as a function of distance from the field edge can be applied in a CSI using photon RT techniques. PBS is the most promising technique for out-of-field dose reduction in comparison to photon techniques. Among photon techniques, VMAT is a preferred choice for most of out-of-field organs and especially for the thyroid, while doses for eyes, breasts, and lungs are lower for 3D-CRT. For organs outside the field edge, a simple analytical model can be helpful for clinicians involved in treatment planning using photon RT but also for retrospective data analysis for cancer risk estimates and epidemiology in general.

Assessment of secondary neutrons in particle therapy by Monte Carlo simulations

Objective. The purpose of this study is to estimate the energy and angular distribution of secondary neutrons inside a phantom in hadron therapy, which will support decisions on detector choice and experimental setup design for in-phantom secondary neutron measurements. Approach. Dedicated Monte Carlo simulations were implemented, considering clinically relevant energies of protons, helium and carbon ions. Since scored quantities can vary from different radiation transport models, the codes FLUKA, TOPAS and MCNP were used. The geometry of an active scanning beam delivery system for heavy ion treatment was implemented, and simulations of pristine and spread-out Bragg peaks were carried out. Previous studies, focused on specific ion types or single energies, are qualitatively in agreement with the obtained results. Main results. The secondary neutrons energy distributions present a continuous spectrum with two peaks, one centred on the thermal/epithermal region, and one on the high-energy region, with the most probable energy ranging from 19 up to 240 MeV, depending on the ion type and its initial energy. The simulations show that the secondary neutron energies may exceed 400 MeV and, therefore, suitable neutron detectors for this energy range shall be needed. Additionally, the angular distribution of the low energy neutrons is quite isotropic, whereas the fast/relativistic neutrons are mainly scattered in the down-stream direction. Significance. It would be possible to minimize the influence of the heavy ions when measuring the neutron-generated recoil protons by selecting appropriate measurement positions within the phantom. Although there are discrepancies among the three Monte Carlo codes, the results agree qualitatively and in order of magnitude, being sufficient to support further investigations with the ultimate goal of mapping the secondary neutron doses both in- and out-of-field in hadrontherapy. The obtained secondary neutron spectra are available as supplementary material.

Ultra-High Dose-Rate Particle Therapy: On the Delivery of Active Beam Scanning at a Synchrotron-Based Facility With p, 4He, 12C and 16O

<h3>Purpose/Objective(s)</h3> Despite being a principal research interest, feasibility of raster-scanned ultra-high dose-rate particle beams remains largely unknown. Moreover, with the increasing evidence of potential normal tissue sparing with uHDR delivery, there is an urgent need for comprehensive assessments of facility-specific delivery capacity and characteristics to ultimately drive forward radiobiological investigations of the FLASH effect and subsequent modeling. This work aims to establish and assess the range and limits of uHDR delivery for raster-scanned particle therapy at a synchrotron-based facility for "light" (p, He) and "heavy" (C, O) ion beams. <h3>Materials/Methods</h3> For p, He, C and O ions, different settings of the synchrotron are tested to assess the linearity window for clinically ideal spill characteristics at FLASH dose levels and dose-rates. For instance, different parameters require modification and/or monitoring for each delivery scenario, e.g., monitor chamber current, delivery time, field size, the number of scanned spot positions, the number of particles and thus the achievable dose level. The dose can be assessed in two particular positions, either the entrance channel of a pristine peak or within a spread-out Bragg peak using a range modulator. Limitations in dose level and dose-rate were investigated within the entrance channel where, conceptually, normal tissues reside within the irradiation field. In addition, the influences of the field size and number of scanned-spots on spatially dependent dose-time structure and delivery time are investigated. <h3>Results</h3> For the entrance channel, parameters which primarily impact dose delivery characteristics were both the number of particles to be delivered within a single spill by the synchrotron and the requested beam intensities. Parameter settings influence delivery characteristics differently for "light" and "heavy" particles: for "light ions" maximizing a number of particles per spill to FLASH dose levels can be limited while for "heavy" ions, extraction intensity is the main obstacle in achieving FLASH dose-rates. Characterized for the four ions, the dose-time evolution is spatially dependent and varies with the number of spots and scanning patterns. <h3>Conclusion</h3> In parallel with mean delivery time and mean dose-rate measured live via monitoring systems, temporal delivery aspects of in-field dose distributions can be assessed and verified (experimentally or in-silico) for active beam delivery that could complement further bio-modelling. The results of this work make evident the importance of a proper assessment of dosimetry and delivery characteristics prior to biological experimentation, as demonstrated at our synchrotron-based facility where delivery parameters may fluctuate between treatment sessions.

Next Evolutions in Particle Therapy: Helium Ion Treatment Planning, Delivery and Clinical Implications of Biological Modeling

This work aims to investigate the implication of relevant biological parameters in clinical treatment planning for the first helium ion beam therapy with active beam delivery.Patient plan optimization was performed using the first clinical TPS commissioned for Helium ion therapy with active beam delivery. Biological calculations are coupled to the modified microdosimetric kinetic model (mMKM) for considering bio-effect specific to each tumor and mixed radiation field spectra. Several plans for patients previously treated with proton beams were re-optimized with helium ions. Comparisons of the resulting biological dose distributions between the ions for the same fractionation scheme were conducted. Sensitivity studies were performed with these plans with respect to the chosen (α/β)x for changes in β (high or low in its clinical range) or on the fractionation scheme. Physical and biological quantities such as physical dose, LET and BED were also compared after computation with the secondary dose engine FRoG.During treatment plan optimization, all clinical constraints were reached with the helium ions. Overall, results indicate better CTV conformity and sparing of surrounding healthy tissue. Robustness analysis on 2mm/3% do not show any disadvantages in setup/SPR inaccuracies of helium ions compared to protons. Investigation on the sensitivity studies suggest clinically relevant levels of RBE-related uncertainties with selected (α/β)x, thus calling for compromise between fractionation scheme and RBE sensitivity in treatment design. All plans were dosimetrically verified in water and found to be within clinical tolerances.Prior to the first patient treatment using helium ions with active beam scanning delivery, assessment of clinical parameters and feasibility of patient planning using the mMKM was successfully performed.

Neoadjuvant irradiation of retroperitoneal soft tissue sarcoma with ions (Retro-Ion): study protocol for a randomized phase II pilot trial

BackgroundFollowing surgery for soft tissue sarcoma of the retroperitoneum, the predominant pattern of failure is local recurrence, which remains the main cause of death. Radiotherapy is utilized to reduce recurrence rates but the efficacy of this strategy has not been definitely established. As treatment tolerability is more favorable with preoperative radiotherapy, normofractionated neoadjuvant treatment is the current approach. The final results of the prospective, randomized STRASS (EORTC 62092) trial, which compared the efficacy of this combined treatment to that of surgery alone, are still awaited; preliminary results presented at the 2019 ASCO Annual Meeting indicated that combined treatment is associated with better local control in patients with liposarcoma (74.5% of the cohort, 11% benefit in abdominal progression free survival after 3 years, p = 0.049). Particles allow better sparing of surrounding tissues at risk, e.g., bowel epithelium, and carbon ions additionally offer biologic advantages and are preferred in slow growing tumors. Furthermore, hypofractionation allows for a significantly shorter treatment interval with a lower risk of progression during radiotherapy.Methods and designWe present a prospective, randomized, monocentric phase II trial. Patients with resectable or marginally resectable, histologically confirmed soft tissue sarcoma of the retroperitoneum will be randomized between neoadjuvant proton or neoadjuvant carbon ion radiotherapy in active scanning beam application technique (39 Gy [relative biological effectiveness, RBE] in 13 fractions [5–6 fractions per week] in each arm). The primary objective is the safety and feasibility based on the proportion of grade 3–5 toxicity (CTCAE, version 5.0) in the first 12 months after surgery or discontinuation of treatment for any reason related to the treatment. Local control, local progression-free survival, disease-free survival, overall survival, and quality of life are the secondary endpoints of the study.DiscussionThe aim of this study is to confirm that hypofractionated, accelerated preoperative radiotherapy is safe and feasible. The rationale for the use of particle therapy is the potential for reduced toxicity. The data will lay the groundwork for a randomized phase III trial comparing hypofractionated proton and carbon ion irradiation with regard to local control.Trial registrationClinicalTrials.gov NCT04219202. Retrospectively registered on January 6, 2020

Upgrading an Integrating Carbon-Ion Transmission Imaging System With Active Scanning Beam Delivery Toward Low Dose Ion Imaging

The dosimetric advantages of ion therapy come at the cost of an increased sensitivity to range inaccuracies in the treatment planning and delivery stages. This prompts the development of imaging techniques capable of an accurate assessment of the relative stopping power (RSP). We investigate carbon-ion imaging based on a prototype integration-mode detector working as a range telescope. Experiments were conducted at the Heidelberg Ion-Beam Therapy Center with active pencil beam scanning. The aim of this article is to experimentally operate the imaging system in low-dose regimes. Therefore, an adjustment of the synchronization mechanism between beam delivery and data acquisition was required. Different from the previous studies, this article investigates unexplored dosimetric scenarios and faced the related technological challenges. Radiographic and tomographic images of two tissue-equivalent phantoms were acquired and the image quality was evaluated. Relying on dedicated signal processing to solve the range mixing problem, the tomographic images showed an RSP accuracy of better than 0.6%. This article evaluates the imaging performance with low-dose exposure, focusing on the technological requirements and pointing out the current limitations. Hence, this article supports the development of upgraded integration-mode ion imaging systems for reducing range uncertainties in particle therapy.

Monte Carlo study of out-of-field exposure in carbon-ion radiotherapy: Organ doses in pediatric brain tumor treatment.

To estimate out-of-field doses during carbon-ion radiotherapy (CIRT) for pediatric cerebellar ependymoma. Given that the out-of-field dose of CIRT depends on beam parameters, we set them for treatment of typical pediatric cerebellar ependymoma based on a previous study. The out-of-field dose during CIRT for pediatric cerebellar ependymoma was then estimated using the Particle and Heavy-Ion Transport code System with Monte Carlo simulations and a computational phantom developed at the University of Florida. From the simulation results, out-of-field doses at dose equivalents of passive beam and active scanning beam CIRT were calculated and compared to the secondary neutron-equivalent dose of passive beam CIRT and proton therapy. The out-of-field dose equivalent decreases from 1.45mSv/Gy (relative biological effectiveness - RBE) at the thyroid to 0.06mSv/Gy (RBE) at the bladder, verifying decay as the distance from the treatment target increases. The out-of-field neutron-equivalent dose in organs per prescribed dose for passive beam CIRT is lower than that for passive beam proton therapy. Moreover, the out-of-field organ dose equivalent per prescribed dose for the active scanning beam CIRT is lower than that for the passive beam CIRT. Active scanning beam CIRT is promising for pediatric cerebellar ependymoma regarding out-of-field exposure, outperforming the comparison radiotherapy modalities.

Phantom design and dosimetric characterization for multiple simultaneous cell irradiations with active pencil beam scanning

A new phantom was designed for in vitro studies on cell lines in horizontal particle beams. The phantom enables simultaneous irradiation at multiple positions along the beam path. The main purpose of this study was the detailed dosimetric characterization of the phantom which consists of various heterogeneous structures. The dosimetric measurements described here were performed under non-reference conditions. The experiment involved a CT scan of the phantom, dose calculations performed with the treatment planning system (TPS) RayStation employing both the Pencil Beam (PB) and Monte Carlo (MC) algorithms, and proton beam delivery. Two treatment plans reflecting the typical target location for head and neck cancer and prostate cancer treatment were created. Absorbed dose to water and dose homogeneity were experimentally assessed within the phantom along the Bragg curve with ionization chambers (ICs) and EBT3 films. LETd distributions were obtained from the TPS. Measured depth dose distributions were in good agreement with the Monte Carlo-based TPS data. Absorbed dose calculated with the PB algorithm was 4% higher than the absorbed dose measured with ICs at the deepest measurement point along the spread-out Bragg peak. Results of experiments using melanoma (SKMel) cell line are also presented. The study suggested a pronounced correlation between the relative biological effectiveness (RBE) and LETd, where higher LETd leads to elevated cell death and cell inactivation. Obtained RBE values ranged from 1.4 to 1.8 at the survival level of 10% (RBE10). It is concluded that dosimetric characterization of a phantom before its use for RBE experiments is essential, since a high dosimetric accuracy contributes to reliable RBE data and allows for a clearer differentiation between physical and biological uncertainties.

P14.75 Active beam scanning proton therapy radiosurgery: early outcomes

Abstract BACKGROUND Stereotactic radiosurgery (SRS) is an important treatment option for intracranial lesions and several photon-SRS techniques have been developed. Proton therapy (PT) has special characteristics that allow normal tissues to be spared better as well as greater homogeneity than with the use of photons, but limited data are available for proton-SRS. Nowadays, PT-SRS is delivered only with passive scattering technique while active pencil beam scanning (PBS) that is considered the most advanced proton technique has not been reported for SRS treatments yet. Here we report early clinical outcomes of PBS PT SRS. MATERIAL AND METHODS Between June 2017 and January 2019, 14 patients (pts) with 20 lesions underwent PBS PT SRS at our institution. Median age was 62 years (range, 28–87). Median Karnofsky performance status was 90 (range, 70–100). Six were male. Tumors included 16 meningiomas (MG) and 4 vestibular schwannomas (VS). Median GTV was 1.05 cc (range, 0.2–2.71). Dose prescription was 12 Gy radiobiologic equivalent (RBE) in one fraction for VS and 15 GyRBE in one fraction for MG. Pts were immobilized using a frameless system: Type-S proton overlay and Type-S proton mask (CIVCO medical solutions, Kalona, IA, USA) together with Moldcare headrest (Q-Fix systems, Avondale, PA, USA). All pts were treated with PBS PT using 2–3 fields with single field optimization technique, and using min-max robust robust optimization (2 mm setup errors, 3.5% range uncertainties), with a Monte Carlo algorithm and 1 mm grid size. Toxicity was assessed using Common Terminology Criteria for Adverse Events version 4.0. RESULTS Median follow-up (FU) was 9 months (range, 3–22). All pts completed the treatment with excellent compliance and no side effects were registered during the procedure. Registered acute side effects include grade 1 (14%) fatigue, grade 2 (7%) headache, and grade 2 (28%) alopecia. There were no grade 3 or higher acute toxicities. Registered late side effects include grade 1 (7%) headache, and grade 1 (14%) alopecia. There were no grade 3 or higher late toxicities. Currently, absolute tumor control is 100% regardless the type of tumor. Despite the short FU radiological reduction was registered in 9 lesions (45%). CONCLUSION PBS PT SRS is a feasible and safe treatment in pts with MG or VS. A high radiological response rate was observed. Longer FU is necessary to assess definitive safety and efficacy.

Возможности протонной терапии при повторном облучении рецидивных глиом

Purpose: To define efficiency and safety of use of the active scanning proton beam in reirradiation of recurrent malignant gliomas. Material and methods: Researched group included 26 patients who were treated on a complex of proton therapy Prometeus. 57.7 % of tumors were glioblastoma, 26.9 % – gliomas of GII and 15.4 % GIII gliomas. Proton therapy was carried out with use of the active scanning beam, image-guiding system and use of the individual fixing devices. To all patients PET/CT with 11C-methionine and MRI were carried out, target volume delineation was carried out by results of coregistration of both images. Results: Terms of observation were from 1 to 32 months. The assessment of direct efficiency is carried out at 19 patients in 3 months after completion of treatment. From the group 52.7 % of patients (n = 10) had disease stabilization. At 11.5 % (n = 3) – partial response. Tumor regression volume varied from 50 to 90 %. Progressing of a disease developed in 31.5 % of the considered cases (n = 6). Other 7 patients expect control inspection. 15.4 % (n = 4) patients developed grade 2 radiodermatitis in the field of radiation fields, the remaining 84.6 % (n = 22) had grade 1 radiodermatitis. Of the entire group of patients, only one case of the development of a late radiation complication in the form of radionecrosis is observed at an observation period of 13 months. Conclusion: Preliminary results of a research showed that performing proton therapy by the active scanning beam is the effective method of treatment of patients with the diagnosed recurrent gliomas, allowing to increase life expectancy of patients with maintaining satisfactory general condition.

P05.58 Active beam scanning proton therapy for large skull base benign meningiomas: early outcomes

P05.58 Active beam scanning proton therapy for large skull base benign meningiomas: early outcomes

Proton therapy technology evolution in the clinic: impact on radiation protection

The use of proton therapy as a treatment modality is becoming more widespread in conventional radiation therapy practice. Commercialisation and introduction of compact systems has led to embedding of proton therapy facilities in existing hospital environments. In addition, technologically, proton therapy is currently undergoing an important evolution, moving from passive scattering delivery techniques to active pencil beam scanning, adopting image guidance techniques from conventional radiotherapy and introducing various range verification techniques in the clinic. An overview is given of today's technological evolution of proton therapy in clinical environments, and its impact on aspects of radiation protection.

Improving the modelling of irradiation-induced brain activation for in vivo PET verification of proton therapy

Background and purposesA reliable Monte Carlo prediction of proton-induced brain tissue activation used for comparison to particle therapy positron-emission-tomography (PT-PET) measurements is crucial for in vivo treatment verification. Major limitations of current approaches to overcome include the CT-based patient model and the description of activity washout due to tissue perfusion. Material and methodsTwo approaches were studied to improve the activity prediction for brain irradiation: (i) a refined patient model using tissue classification based on MR information and (ii) a PT-PET data-driven refinement of washout model parameters. Improvements of the activity predictions compared to post-treatment PT-PET measurements were assessed in terms of activity profile similarity for six patients treated with a single or two almost parallel fields delivered by active proton beam scanning. ResultsThe refined patient model yields a generally higher similarity for most of the patients, except in highly pathological areas leading to tissue misclassification. Using washout model parameters deduced from clinical patient data could considerably improve the activity profile similarity for all patients. ConclusionsCurrent methods used to predict proton-induced brain tissue activation can be improved with MR-based tissue classification and data-driven washout parameters, thus providing a more reliable basis for PT-PET verification.

EP-1729: Dosimetric characterization of a novel phantom for cell irradiation in active proton beam scanning

EP-1729: Dosimetric characterization of a novel phantom for cell irradiation in active proton beam scanning

EP-1210: Active beam scanning proton therapy for vestibular schwannomas: early outcomes

EP-1210: Active beam scanning proton therapy for vestibular schwannomas: early outcomes

Proton Therapy Reirradiation in Difficult-to-Treat Recurrent Glioblastoma

To report preliminary results of re-irradiation with proton therapy (PT) with or without chemotherapy (CHT) in difficult-to-treat recurrent glioblastoma (rGBM): patients (pts) were selected for PT due to the large tumor size or proximity to dose-limiting organs at risk that previously had received near-maximum dose tolerance during the first radiation course. Between January 2015 and January 2017 twenty pts with rGBM were re-irradiated with PT. All pts had been previously treated with Stupp regimen. Fifteen (75%) were re-irradiated at first relapse/progression, five at the second/third one. Six patients (30%) were re-irradiated after partial tumor resection. Median age and Karnofsky performance status at re-irradiation were 56 years and 90%, respectively. Median time between prior radiotherapy and PT was 13 months. Target definition was based on CT, MR, and 18F-DOPA PET imaging. Gross Tumor Volume (GTV) included any area of contrast enhancement after contrast medium administration plus any pathological PET uptake regions. Clinical Target Volume (CTV) was generated by adding to GTV a 3-mm uniform margin manually corrected in proximity of anatomical barriers. Median CTV volume was 47 cc (range, 13-153 cc). All pts received 36 GyRBE in 18 fractions. PT was delivered with or without chemotherapy as follows: four (20%) pts (Group 1) also received concomitant TMZ (75 mg/m2/die, 7 days/week); 3 (15%) pts (Group 2) also received concomitant (as above) and adjuvant TMZ (150-200 mg/m2/die, 5 days/month); 5 (25%) pts (Group 3) received PT only; 8 (40%) pts (Group 4) received PT followed by CHT (different regimens/drugs). All pts were treated with active pencil beam scanning PT. Registered side effects were graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Treatment response was assessed according to Response Assessment in Neuro-Oncology (RANO) criteria. Survival and progression-free survival after re-irradiation were calculated from initiation of PT until tumor progression or death (by any cause), using the Kaplan Meier method. All pts completed the treatment without breaks. There were no grade 3 or higher acute toxicities. One pts developed TMZ-related grade 1 neutropenia. There were no grade 3 or higher late toxicities. During follow-up three pts (15%) developed radionecrosis (diagnosed at imaging) with mild symptoms controlled with steroids. The median progression-free survival (PFS) was 6.3 months, while 6-month PFS rate was 60%. The median PFS was 6.8, 4.3, 5.4, and 5.5 for Group 1-2-3-4, respectively. Median overall survival (OS) after PT was 10.7 months. PT re-irradiation of difficult-to-treat rGBM showed to be feasible and safe even with concomitant and adjuvant chemotherapy administration. Despite the small number of patients of this series and the retrospective nature of the study PFS and OS rates are promising and deserve further evaluation in a larger pts sample to assess the most effective strategy.

Lateral variations of radiobiological properties of therapeutic fields of 1H, 4He, 12C and 16O ions studied with Geant4 and microdosimetric kinetic model

As known, in cancer therapy with ion beams the relative biological effectiveness (RBE) of ions changes in the course of their propagation in tissues. Such changes are caused not only by increasing the linear energy transfer (LET) of beam particles with the penetration depth towards the Bragg peak, but also by nuclear reactions induced by beam nuclei leading to the production of various secondary particles. Although the changes of RBE along the beam axis have been studied quite well, much less attention has been paid to the evolution of RBE in the transverse direction, perpendicular to the beam axis. In order to fill this gap, we simulated radiation fields of 1H, 4He, 12C and 16O nuclei of 20 mm in diameter by means of a Geant4-based Monte Carlo model for heavy-ion therapy connected with the modified microdosimetric kinetic model to describe the response of normal ( Gy) and early-responding ( Gy) tissues. Depth and radial distributions of saturation-corrected dose-mean lineal energy, RBE and RBE-weighted dose are investigated for passive beam shaping and active beam scanning. The field of 4He has a small lateral spread as compared with 1H field, and it is characterised by a modest lateral variation of RBE suggesting the use of fixed RBE values across the field transverse cross section at each depth. Reduced uncertainties of RBE on the boundary of a 4He treatment field can be advantageous in a specific case of an organ at risk located in lateral proximity to the target volume. It is found that the lateral distributions of RBE calculated for 12C and 16O fields demonstrate fast variations in the radial direction due to changes of dose and composition of secondary fragments in the field penumbra. Nevertheless, the radiation fields of all four projectiles at radii larger than 20 mm can be characterized by a common RBE value defined by tissue radiosensitivity. These findings can help, in particular, in accessing the transverse homogeneity of radiation fields of ions used in studies in vitro.

P12.01 Active beam scanning proton therapy for intracranial meningiomas: early treatment outcomes from Trento proton therapy center

P12.01 Active beam scanning proton therapy for intracranial meningiomas: early treatment outcomes from Trento proton therapy center