Is it beneficial to use apertures in proton radiosurgery with a scanning beam? A dosimetric comparison in neurinoma and meningioma patients.

PURPOSE: To assess the dosimetric advantages of apertures in intracranial single fraction proton radiosurgery. MATERIALS AND METHODS: Six neuroma and 10 meningioma patients were investigated. For each patient, six plans were computed, with two spot spacing and three aperture settings (no apertures, 5 and 8 mm margin between aperture and clinical target volume [CTV]). All plans were optimized on the CTV with the same beam arrangement and the same single-field robust optimization (2 mm setup errors, 3.5% range uncertainties). Robustness analysis was performed with 0.5 and 1.0 mm systematic setup errors and 3.5% range uncertainties. CTV coverage in the perturbed scenarios and healthy brain tissue sparing in the surrounding of the CTV were compared. RESULTS: Meningiomas were larger and at a shallow depth than neuromas. In neuromas, spot spacing did not affect OAR doses or the robustness of CTV coverage and the apertures reduced brain dose without any significant impact on CTV robustness. In meningiomas, smaller spot spacing produced a reduction in brain V5Gy and improved robustness of CTV coverage; in addition, an 8 mm margin aperture reduced low and medium brain tissue doses without affecting robustness in the 0.5 mm perturbed scenario. A 5 mm margin aperture caused a reduction of plan robustness. CONCLUSION: The optimal use of apertures is a trade-off between sparing of low and medium dose to the healthy brain and robustness of target coverage, also depending on size and depth of the lesion.

Magnetic Resonance Imaging during Proton Therapy Irradiation Allows for the Early Response Assessment of Pediatric Chordoma.

Chordoma in pediatric patients is very rare. Proton therapy has become a gold standard in the treatment of these neoplasms, as high dose escalation can be achieved regarding the target while maximizing the sparing of the healthy tissues near the tumor. The aim of the work was to assess the evolution of morphological sequences during treatment using T1/T2-weighted magnetic resonance imaging (MRI) for the early response assessment of a classic chordoma of the skull base in a pediatric patient who had undergone surgical excision. Our results demonstrated a significant quantitative reduction in the residual nodule component adhered to the medullary bulb junction, with an almost complete recovery of normal anatomy at the end of the irradiation treatment. This was mainly shown in the T2-weighted MRI. On the other hand, the classic component of the lesion was predominantly present and located around the tooth of the axis. The occipital condyles were morphologically and dimensionally stable for the entire irradiation period. In conclusion, the application of this type of monitoring methodology, which is unusual during the administration of a proton treatment for chordoma, highlighted the unexpected early response of the disease. At the same time, it allowed the continuous assessment of the reliability of the treatment plan.

Multicomponent T2 relaxometry reveals early myelin white matter changes induced by proton radiation treatment.

PURPOSE: To investigate MRI myelin water imaging (MWI) by multicomponent T2 relaxometry as a quantitative imaging biomarker for brain radiation-induced changes and to compare it with DTI. METHODS: Sixteen patients underwent fractionated proton therapy (PT) receiving dose to the healthy tissue because of direct or indirect (base skull tumors) irradiation. MWI was performed by a multi-echo sequence with 32 equally spaced echoes (10-320 ms). Decay data were processed to identify 3 T2 compartments: myelin water (Mw) below 40 ms, intra-extracellular water (IEw) between 40 and 250 ms, and free water (CSFw) above 250 ms. Both MWI and DTI scans were acquired pre (pre)-treatment and immediately at the end (end) of PT. After image registration, voxel-wise difference maps, obtained by subtracting MWI and DTI pre from those acquired at the end of PT, were compared with the corresponding biological equivalent dose (BED). RESULTS: Mw difference showed a positive correlation and IEw difference showed a negative correlation with BED considering end-pre changes (P < .01). The changes in CSFw were not significantly correlated with the delivered BED. The changes in DTI data, considering end-pre acquisitions, showed a positive correlation between fractional anisotropy and the delivered BED. CONCLUSION: MWI might detect early white matter radiation-induced alterations, providing additional information to DTI, which might improve the understanding of the pathogenesis of the radiation damage.

Methodologies to Increase the Level of Evidence of Real-life Proton Therapy in Head and Neck Tumors.

This review aims to present and assess available and new methodologies to increase the clinical evidence of proton therapy data for patients with head and neck cancer. Despite the increasing number of scientific reports showing the feasibility and effectiveness of proton therapy in head and neck cancer, clinical evidence on the potential benefits of its use remains low for several reasons. In this article, the pros and cons of consolidated and new methodologies in this setting such as randomized clinical trials, the model-based approach, and the use of prospective multicentric registries will be detailed.

Clinical validation of a GPU-based Monte Carlo dose engine of a commercial treatment planning system for pencil beam scanning proton therapy.

PURPOSE: To perform the validation of the GPU-based (Graphical Processing Unit based) proton Monte Carlo (MC) dose engine implemented in a commercial TPS (RayStation 10B) and to report final dose calculation times for clinical cases. MATERIALS AND METHODS: 440 patients treated at the Proton Therapy Center of Trento, Italy, between 2018 and 2019 were selected for this study. 636 approved plans with 3361 beams computed with the clinically implemented CPU-MC dose engine (version 4.2 and 4.5), were used for the validation of the new algorithm. For each beam, the dose was recalculated using the new GPU-MC dose engine with the initial CPU computation settings and compared to the original CPU-MC dose. Beam dose difference distributions were studied to ensure that the two dose distributions were equal within the expected fluctuations of the MC statistical uncertainty (s) of each computation. Plan dose distributions were compared with respect to the dosimetric indices D98, D50 and D1 of all ROIs defined as targets. A complete assessment of the computation time as a function of s and dose grid voxel size was done. RESULTS: The median over all mean beam dose differences between CPU- and GPU-MC was -0.01% and the median of the corresponding standard deviations was close to (√2s) both for simulations with an s of 0.5% and 1.0% per beam. This shows that the two dose distributions can be considered equal. All the DVH indices showed an average difference below 0.04%. About half of the plans were computed with 1.0% statistical uncertainty on a 2 mm dose calculation grid, for which the median computation time was 5.2 s. The median computational speed for all plans in the study was 8.4 million protons/second. CONCLUSION: A validation of a clinical MC algorithm running on GPU was performed on a large pool of patients treated with pencil beam scanning proton therapy. We demonstrated that the differences with the previous CPU-based MC were only due to the intrinsic statistical fluctuations of the MC method, which translated to insignificant differences on plan dose level. The significant increase in dose calculation speed is expected to facilitate new clinical workflows.

Rosette-Forming Glioneuronal Tumor of the Fourth Ventricle: A Case of Relapse Treated with Proton Beam Therapy.

Rosette-forming glioneuronal tumors (RGNTs) are rare, grade I, central nervous system (CNS) tumors typically localized to the fourth ventricle. We describe a 9-year-old girl with dizziness and occipital headache. A magnetic resonance imaging (MRI) revealed a large hypodense posterior fossa mass lesion in relation to the vermis, with cystic component. Surgical resection of the tumor was performed. A RGNT diagnosis was made at the histopathological examination. During follow-up, the patient experienced a first relapse, which was again surgically removed. Eight months after, MRI documented a second recurrence at the local level. She was a candidate for the proton beam therapy (PBT) program. Three years after the end of PBT, the patient had no evidence of disease recurrence. This report underlines that, although RGNTs are commonly associated with an indolent course, they may have the potential for aggressive behavior, suggesting the need for treatment in addition to surgery. Controversy exists in the literature regarding effective management of RGNTs. Chemotherapy and radiation are used as adjuvant therapy, but their efficacy management has not been adequately described in the literature. This is the first case report published in which PBT was proposed for adjuvant therapy in place of chemotherapy in RGNT relapse.

Quantitative Multicomponent T2 Relaxation Showed Greater Sensitivity Than Flair Imaging to Detect Subtle Alterations at the Periphery of Lower Grade Gliomas.

PURPOSE: To demonstrate that quantitative multicomponent T2 relaxation can be more sensitive than conventional FLAIR imaging for detecting cerebral tissue abnormalities. METHODS: Six patients affected by lower-grade non-enhancing gliomas underwent T2 relaxation and FLAIR imaging before a radiation treatment by proton therapy (PT) and were examined at follow-up. The T2 decay signal obtained by a thirty-two-echo sequence was decomposed into three main components, attributing to each component a different T2 range: water trapped in the lipid bilayer membrane of myelin, intra/extracellular water and cerebrospinal fluid. The T2 quantitative map of the intra/extracellular water was compared with FLAIR images. RESULTS: Before PT, in five patients a mismatch was observed between the intra/extracellular water T2 map and FLAIR images, with peri-tumoral areas of high T2 that typically extended outside the area of abnormal FLAIR hyper-intensity. Such mismatch regions evolved into two different types of patterns. The first type, observed in three patients, was a reduced extension of the abnormal regions on T2 map with respect to FLAIR images (T2 decrease pattern). The second type, observed in two patients, was the appearance of new areas of abnormal hyper-intensity on FLAIR images matching the anomalous T2 map extension (FLAIR increase pattern), that was considered as asymptomatic radiation induced damage. CONCLUSION: Our preliminarily results suggest that quantitative T2 mapping of the intra/extracellular water component was more sensitive than conventional FLAIR imaging to subtle cerebral tissue abnormalities, deserving to be further investigated in future clinical studies.

Proton therapy: A therapeutic opportunity for aggressive pediatric meningioma.

Meningiomas are an extremely rare histology among pediatric brain tumors, and there is a shortage of literature on their management. Proton therapy is currently used safely and effectively for many types of both pediatric and adult cancer, and its main advantage is the sparing of healthy tissues from radiation, which could translate in the reduction of late side effects. We review the literature on radiotherapy and proton therapy for pediatric meningiomas and report clinical outcomes for two aggressive pediatric meningiomas we treated with protons. Proton therapy might be a safe and effective therapeutic option for this rare subgroup of tumors.

Clinical implementation of pencil beam scanning proton therapy for liver cancer with forced deep expiration breath hold.

PURPOSE: To present our technique for liver cancer treatments with proton therapy in pencil beam scanning mode and to evaluate the impact of uncertainties on plan quality. MATERIALS AND METHODS: Seventeen patients affected by liver cancer were included in this study. Patients were imaged and treated in forced breath-hold using the Active Breathing Coordinator system and monitored with an optical tracking system. Three simulation CTs were acquired to estimate the anatomical variability between breath-holds and generate an internal target volume (ITV). The treatment plans were optimized with a Single Field Optimization technique aimed at minimizing the use of range shifter. Plan robustness was tested simulating systematic range and setup uncertainties, as well as the interplay effect between breath-holds. The appropriateness of margin was further verified based on the actual positioning data acquired during treatment. RESULTS: The dose distributions of the nominal plans achieved a satisfactory target coverage in 11 out of 17 patients, while in the remaining 6 D95 to the PTV was affected by the constraint on mean liver dose. The constraints for all other organs at risk were always within tolerances. The interplay effect had a limited impact on the dose distributions: the worst case scenario showed a D95 reduction in the ITV < 3.9 GyRBE and no OAR with D1 > 105% of the prescription dose. The robustness analysis showed that for 13 out of 17 patients the ITV coverage in terms of D95 was better than D95 of the PTV in the nominal plan. For the remaining 4 patients, the maximum difference between ITV D95 and PTV D95 was ≤0.7% even for the largest simulated setup error and it was deemed clinically acceptable. Hot spots in the OARs were always lower than 105% of the prescription dose. Positioning images confirmed that the breath hold technique and the PTV margin were adequate to compensate for inter- and intra-breath-hold variations in liver position. CONCLUSION: We designed and clinically applied a technique for the treatment of liver cancer with proton pencil beam scanning in forced deep expiration breath-hold. The initial data on plan robustness and patient positioning suggest that the choices in terms of planning technique and treatment margins are able to reach the desired balance between target coverage and organ at risk sparing.

Clinical results of active scanning proton therapy for primary liver tumors.

BACKGROUND: Evidence for the efficacy of radiation therapy for primary liver cancer is growing. In this context, proton therapy (PT) can potentially improve the therapeutic ratio, as demonstrated by recent clinical studies. Here we report the first European clinical experience on the use of PT for primary liver cancer. METHODS: All patients treated for primary liver cancer in our center entered the analysis. Patients were simulated during deep expiration breath-hold. A 15-fraction treatment schedule was adopted using active scanning PT. Clinical outcome and toxicity were retrospectively analyzed. RESULTS: Between January 2018 and December 2019, 18 patients were treated. Fourteen patients had hepatocellular carcinoma (HCC), three patients had intrahepatic cholangiocarcinoma (ICC), and one patient had synchronous ICC-HCC. The Child-Pugh score was A5 in the majority of patients with HCC (71.4%). Median prescription dose was 58.05 Gy (range, 50.31-67.5). Median follow-up was 10 months (range, 1-19). The majority of deaths occurred from liver tumor progression. One-year overall survival (OS) was 63%. A significant correlation between worse OS and patient performance status, vascular invasion, and tumor stage was recorded. One-year local control was 90%. Toxicity was low, with a decrease in Child-Pugh score ⩾2 points detected in one patient. No cases of classic radiation-induced liver disease occurred. CONCLUSIONS: Our initial results of active scanning PT for primary liver cancer demonstrated the feasibility, safety, and effectiveness of this advanced technique in this setting. The potential of the combination of PT with other locoregional therapies is under evaluation.

Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization.

PURPOSE: Ventricular tachycardia (VT) is a life-threatening heart disorder. The aim of this preliminary study is to assess the feasibility of stereotactic body radiation therapy (SBRT) photon and proton therapy (PT) plans for the treatment of VT, adopting robust optimization technique for both irradiation techniques. METHODS: ECG gated CT images (in breath hold) were acquired for one patient. Conventional planning target volume (PTV) and robust optimized plans (25GyE in single fraction) were simulated for both photon (IMRT, 5 and 9 beams) and proton (SFO, 2 beams) plans. Robust optimized plans were obtained both for protons and photons considering in the optimization setup errors (5 mm in the three orthogonal directions), range (±3.5%) and the clinical target volume (CTV) motion due to heartbeat and breath-hold variability. RESULTS: The photon robust optimization method, compared to PTV-based plans, showed a reduction in the average dose to the heart by about 25%; robust optimization allowed also reducing the mean dose to the left lung from 3.4. to 2.8 Gy for 9-beams configuration and from 4.1 to 2.9 Gy for 5-beams configuration. Robust optimization with protons, allowed further reducing the OAR doses: average dose to the heart and to the left lung decreased from 7.3 Gy to 5.2 GyE and from 2.9 Gy to 2.2 GyE, respectively. CONCLUSIONS: Our study demonstrates the importance of the optimization technique adopted in the treatment planning system for VT treatment. It has been shown that robust optimization can significantly reduce the dose to healthy cardiac tissues and that PT further increases this gain.

Proton therapy re-irradiation preserves health-related quality of life in large recurrent glioblastoma.

PURPOSE: Proton therapy could minimize the risk of side effects and, therefore, reduce the possible detrimental effect on health-related quality of life (HRQOL) of re-irradiation. The aim of this study was to determine the effect of re-irradiation with active scanning proton therapy on recurrent glioblastoma (GBM) in terms of HRQOL scored by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ)-C30 and EORTC Quality of Life Questionnaire Brain Cancer Module (QLQ-BN20). METHODS: Thirty-three patients with recurrent GBM were re-irradiated with active scanning proton therapy. Subscales within the EORTC QLQ-C30 include five functional scales, six single-item scales, and global QoL. The BN20 assessed visual disorders, motor function, communication deficit, various disease symptoms, treatment, toxicity, and future uncertainty. The patients completed the questionnaires before starting proton therapy, the last day of proton therapy, and at every follow-up visit until progression of disease. RESULTS: The treatment was associated with improvement or stability in most of the preselected HRQOL domains. Global health improved over time with a maximum difference of six points between baseline and 3-months follow-up. Social functioning and motor dysfunction improved over time with a maximum difference of eight and two points, respectively. We showed a non-significant decrease in cognitive and emotional functioning. Fatigue remained stable during the analysis such as the other preselected domains. CONCLUSIONS: Re-irradiation with proton therapy is a safe and effective treatment in patients with recurrent glioblastoma. Proton therapy does not negatively effect on HRQOL, but rather it seems to preserve HRQOL until the time of disease progression.

Modelling the risk of radiation induced alopecia in brain tumor patients treated with scanned proton beams.

PURPOSE: To develop normal tissue complication probability (NTCP) models for radiation-induced alopecia (RIA) in brain tumor patients treated with proton therapy (PT). METHODS AND MATERIALS: We analyzed 116 brain tumor adult patients undergoing scanning beam PT (median dose 54 GyRBE; range 36-72) for CTCAE v.4 grade 2 (G2) acute (≤90 days), late (>90 days) and permanent (>12 months) RIA. The relative dose-surface histogram (DSH) of the scalp was extracted and used for Lyman-Kutcher-Burman (LKB) modelling. Moreover, DSH metrics (Sx: the surface receiving ≥ X Gy, D2%: near maximum dose, Dmean: mean dose) and non-dosimetric variables were included in a multivariable logistic regression NTCP model. Model performances were evaluated by the cross-validated area under the receiver operator curve (ROC-AUC). RESULTS: Acute, late and permanent G2-RIA was observed in 52%, 35% and 19% of the patients, respectively. The LKB models showed a weak dose-surface effect (0.09 ≤ n ≤ 0.19) with relative steepness 0.29 ≤ m ≤ 0.56, and increasing tolerance dose values when moving from acute and late (22 and 24 GyRBE) to permanent RIA (44 GyRBE). Multivariable modelling selected S21Gy for acute and S25Gy, for late G2-RIA as the most predictive DSH factors. Younger age was selected as risk factor for acute G2-RIA while surgery as risk factor for late G2-RIA. D2% was the only variable selected for permanent G2-RIA. Both LKB and logistic models exhibited high predictive performances (ROC-AUCs range 0.86-0.90). CONCLUSION: We derived NTCP models to predict G2-RIA after PT, providing a comprehensive modelling framework for acute, late and permanent occurrences that, once externally validated, could be exploited for individualized scalp sparing treatment planning strategies in brain tumor patients.

Clinical implementation in proton therapy of multi-field optimization by a hybrid method combining conventional PTV with robust optimization.

To implement a robust multi-field optimization (MFO) technique compatible with the application of a Monte Carlo (MC) algorithm and to evaluate its robustness. Nine patients (three brain, five head-and-neck, one spine) underwent proton treatment generated by a novel robust MFO technique. A hybrid (hMFO) approach was implemented, planning dose coverage on isotropic PTV compensating for setup errors, whereas range calibration uncertainties are incorporated into PTV robust optimization process. hMFO was compared with single-field optimization (SFO) and full robust multi-field optimization (fMFO), both on the nominal plan and the worst-case scenarios assessed by robustness analysis. The SFO and the fMFO plans were normalized to hMFO on CTV to obtain iso-D95 coverage, and then the organs at risk (OARs) doses were compared. On the same OARs, in the normalized nominal plans the potential impact of variable relative biological effectiveness (RBE) was investigated. hMFO reduces the number of scenarios computed for robust optimization (from twenty-one in fMFO to three), making it practicable with the application of a MC algorithm. After normalizing on D95 CTV coverage, nominal hMFO plans were superior compared to SFO in terms of OARs sparing (p  < 0.01), without significant differences compared to fMFO. The improvement in OAR sparing with hMFO with respect to SFO was preserved in worst-case scenarios (p  < 0.01), confirming that hMFO is as robust as SFO to physical uncertainties, with no significant differences when compared to the worst case scenarios obtained by fMFO. The dose increase on OARs due to variable RBE was comparable to the increase due to physical uncertainties (i.e. 4-5 Gy(RBE)), but without significant differences between these techniques. hMFO allows improving plan quality with respect to SFO, with no significant differences with fMFO and without affecting robustness to setup, range and RBE uncertainties, making clinically feasible the application of MC-based robust optimization.

Harmonization of proton treatment planning for head and neck cancer using pencil beam scanning: first report of the IPACS collaboration group.

Background and purpose: A collaborative network between proton therapy (PT) centres in Trento in Italy, Poland, Austria, Czech Republic and Sweden (IPACS) was founded to implement trials and harmonize PT. This is the first report of IPACS with the aim to show the level of harmonization that can be achieved for proton therapy planning of head and neck (sino-nasal) cancer.Methods: CT-data sets of five patients were included. During several face-to-face and online meetings, a common treatment planning protocol was developed. Each centre used its own treatment planning system (TPS) and planning approach with some restrictions specified in the treatment planning protocol. In addition, volumetric modulated arc therapy (VMAT) photon plans were created.Results: For CTV1, the average Dmedian was 59.3 ± 2.4 Gy(RBE) for protons and 58.8 ± 2.0 Gy(RBE) for VMAT (aim was 56 Gy(RBE)). For CTV2, the average Dmedian was 71.2 ± 1.0 Gy(RBE) for protons and 70.6 ± 0.4 Gy(RBE) for VMAT (aim was 70 Gy(RBE)). The average D2% for the spinal cord was 25.1 ± 8.5 Gy(RBE) for protons and 47.6 ± 1.4 Gy(RBE) for VMAT. The average D2% for chiasm was 46.5 ± 4.4 Gy(RBE) for protons and 50.8 ± 1.4 Gy(RBE) for VMAT, respectively. Robust evaluation was performed and showed the least robust plans for plans with a low number of beams.Discussion: In conclusion, several influences on harmonization were identified: adherence/interpretation to/of the protocol, available technology, experience in treatment planning and use of different beam arrangements. In future, all OARs that should be included in the optimization need to be specified in order to further harmonize treatment planning.

Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement.

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI. Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses. Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p < .05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values. Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.

Implementation of proton therapy treatments with pencil beam scanning of targets with limited intrafraction motion.

PURPOSE: To report on the implementation, validation and results of the first two proton therapy PBS treatments of limited amplitudes moving targets performed at our center. METHODS AND MATERIALS: A real time optical tracking system was used to monitor the patient surface during the CT scan and treatment. This system is also able to trigger the beam during the treatment. A 4DCT (10 phases) and a Free-Breathing CT (FBCT) were used for the planning. The physician used the 4DCT for ITV delineation, while planning was performed on the FBCT. The approved plan was evaluated in two ways:The largest breathing amplitude recorded during 4DCT scan was used as gating safety threshold during treatment delivery. This planning and treatment workflow was then applied for two patients affected by thoracic thymoma. RESULTS: The dosimetric evaluation of the plan showed no interplay effect. The second patient showed an overdosage to the coronary and Left Anterior Descending area in the worst case scenario but it was below the constraints. Duty Cycle together with number of beam interruptions gave information about the patient compliance to the treatment: the first patient breath is stable and within thresholds, whilst the second patient had more variations, causing multiple beam interruptions. CONCLUSION: We defined and used for two patients a protocol for the treatment of small amplitude moving targets. The planning and delivery of the treatments gave very good results in terms of coverage, OARs sparing, 4D dose evaluation of the plan and interplay effect assessment.

Carbon-fiber-reinforced PEEK fixation system in the treatment of spine tumors: a preliminary report.

BACKGROUND: Protocols including combination of surgery and radiotherapy are more and more frequent in the treatment of bone tumors of the spine. In metastatic disease, combination of surgery and radiotherapy is since long time accepted, as based on clinical evidence. In primary tumors, combination of surgery and radiotherapy can be considered in all the cases in which a satisfactory oncological margin cannot be achieved: high-grade malignancies, recurrent tumors, huge tumors expanding in an extracompartimental area, and when tumor-free margin requires unacceptable functional sacrifices. However, metal implants are an obstacle in the collaboration between surgeons and radiation oncologists. Carbon-fiber-reinforced polyethil-ether-ether-ketone (CFR-PEEK) composite implants could make easier and more effective the treatment as radiolucent and not interfering with ionizing radiation and accelerated particles. The purpose of this article is to report the preliminary results from a cohort of patients treated with CFR-PEEK and to evaluate the safety and the non-inferiority of the device respect the commonly used titanium implants. MATERIALS AND METHODS: This study concerns an ambispective cohort series of 34 tumor patients (14 metastases and 20 primaries, most of them recurrent) submitted to thoracic and lumbar spine fixation with a CFR-PEEK composite implants. Oncologic surgery was palliative decompression and fixation in 9 cases, tumor excision in 21, and enbloc resection in 4. Data collected for this preliminary report were all intraoperative remarks, incidence of complications, changes in neurological status, local control, and survival. All the cases were followed 6-36 months (mean 13 months). RESULTS: Only one intraoperative screw breakage occurred out of 232 implanted screws. Pain control and neurological improvement were the early clinical results. Two sacral screws loosening were found at 9 and 12 months in multilevel constructs performed on multirecurrent tumors. Six local recurrences were early found thanks to the implant radiolucency. Radiation oncologists' opinion was favourable as concerning better treatment planning on CT and lacking of scattering effect during the treatment. CONCLUSIONS: No artifacts on imaging studies mean early local recurrence detection. For radiation oncologists, no artifacts on imaging studies mean easier planning and no scattering effect means more effective and safe radiotherapy, particularly when particles are used. Moreover, it seems that the clinical use of CFR-PEEK composite implants may be safe and at least comparable with the commonly used titanium implants in terms of intraoperative complications, stability at weight bearing and at functional recovery. Larger patient series and longer follow-up are required to confirm these data.

Profile of European proton and carbon ion therapy centers assessed by the EORTC facility questionnaire.

BACKGROUND: We performed a survey using the modified EORTC Facility questionnaire (pFQ) to evaluate the human, technical and organizational resources of particle centers in Europe. MATERIAL AND METHODS: The modified pFQ consisted of 235 questions distributed in 11 sections accessible on line on an EORTC server. Fifteen centers from 8 countries completed the pFQ between May 2015 and December 2015. RESULTS: The average number of patients treated per year and per particle center was 221 (range, 40-557). The majority (66.7%) of centers had pencil beam or raster scanning capability. Four (27%) centers were dedicated to eye treatment only. An increase in the patients-health professional FTE ratio was observed for eye tumor only centers when compared to other centers. All centers treated routinely chordomas/chondrosarcomas, brain tumors and sarcomas but rarely breast cancer. The majority of centers treated pediatric cases with particles. Only a minority of the queried institutions treated non-static targets. CONCLUSIONS: As the number of particle centers coming online will increase, the experience with this treatment modality will rise in Europe. Children can currently be treated in these facilities in a majority of cases. The majority of these centers provide state of the art particle beam therapy.

Supine craniospinal irradiation in pediatric patients by proton pencil beam scanning.

BACKGROUND AND PURPOSE: Proton therapy is the emerging treatment modality for craniospinal irradiation (CSI) in pediatric patients. Herein, special methods adopted for CSI at proton Therapy Center of Trento by pencil beam scanning (PBS) are comprehensively described. MATERIALS AND METHODS: Twelve pediatric patients were treated by proton PBS using two/three isocenters. Special methods refer to: (i) patient positioning in supine position on immobilization devices crossed by the beams; (ii) planning field-junctions via the ancillary-beam technique; (iii) achieving lens-sparing by three-beams whole-brain-irradiation; (iv) applying a movable-snout and beam-splitting technique to reduce the lateral penumbra. Patient-specific quality assurance (QA) program was performed using two-dimensional ion chamber array and γ-analysis. Daily kilovoltage alignment was performed. RESULTS: PBS allowed to obtain optimal target coverage (mean D98%>98%) with reduced dose to organs-at-risk. Lens sparing was obtained (mean D1∼730cGyE). Reducing lateral penumbra decreased the dose to the kidneys (mean Dmean<600cGyE). After kilovoltage alignment, potential dose deviations in the upper and lower junctions were small (average 0.8% and 1.2% respectively). Due to imperfect modeling of range shifter, QA showed better agreements between measurements and calculations at depths >4cm (mean γ>95%) than at depths<4cm. CONCLUSIONS: The reported methods allowed to effectively perform proton PBS CSI.