Proton Beam Treatment Research Articles

Evaluation of Delivered Doses in Proton Beam Therapy for Prostate Cancer Using Positron Emission Tomography/Computed Tomography Imaging

AimsProton beams deposit energy along their paths and stop abruptly without penetrating the opposite side, making it difficult to detect their actual paths. However, confirming the path may lead to evaluating the actual doses to organs at risk in proton therapy for prostate cancer. As proton beams produce positron emitters through nuclear fragmentation reactions, theoretically, proton beam paths can be measured by positron emission tomography/computed tomography (PET/CT). Therefore, this study investigated whether conducting PET/CT examinations immediately after proton beam therapy helps to assess the doses delivered to the rectal and urinary bladder walls, which are the major sites of radiation-related toxicity. Materials and methodsBetween June 2022 and June 2023, 51 consecutive patients with prostate cancer who underwent proton beam therapy were enrolled and imaged with PET/CT to measure these radioactive particles and validate the actual dose delivered to the rectal and urinary bladder walls. ResultsThe delivered doses assessed using PET/CT after proton beam therapy strongly correlated with the planned volume for proton beam treatment. ConclusionsPET/CT exhibited potential as a valuable tool for validating the irradiated dose to organs at risk.

May a post‐radiation ocular surface disorder compromise penetrating keratoplasty surgery? A case report

Aims/Purpose: Ocular surface disorder after ocular radiation therapy, even commonly reported, remains overlooked. Any delay in diagnosis may lead to vision threatening complications. The presented case highlights the clinical outcome of a severe post‐radiation ocular surface disorder, the importance of intense therapy and the limitations of further surgical interventions.Methods: Case report.Results: A 34‐year‐old woman was referred with complains of painful and reddish right eye since years. Her medical history revealed an iris melanoma excision at the age of 29 years. Due to recurrence, a proton beam treatment has been performed thereafter. Consequently, the patient developed post‐radiation retinopathy with macula edema, secondary glaucoma, cataract, as well as a severe ocular surface disorder with corneal decompensation and band keratopathy. Several surgical treatments have been attempted among which: phacoemulsification with IOL implantation, trabeculectomy with mitomycin C. Due to refractory glaucoma a Baerveldt glaucoma drainage was necessitated, thereafter. Despite these various therapeutic approaches, there was no improvement of the ocular surface problem. With increasing deterioration of the corneal situation, a penetrating keratoplasty, has been discussed.Conclusions: The continuous worsening of clinical symptomatology of the proton beam radiotherapy ocular surface disorder can be the result of a post‐radiation syndrome. An ischaemic retinopathy and anterior segment disorder lead to engorgement of posterior and anterior segment tissues. Gradual expansion of ischemia, vasculitis and inflammatory mediators compresses the retinal tissue leading to recurrent macular oedema; as well as to secondary glaucoma and corneal decompensation. Due to the worsening of the clinical presentation of ocular surface disorder a penetrated keratoplastic surgery has been discussed. It remains however still questionable whether such patients would make profit from penetrated keratoplastic surgery, as the resulting corneal stromal lymphangiogenesis and hemangiogenesis, in the presence of post‐radiation keratopathy, are essential conditions for allograft rejection.

Flash Therapy for Cancer: A Potentially New Radiotherapy Methodology.

In traditional treatment modalities and standard clinical practices, FLASH radiotherapy (FL-RT) administers radiation therapy at an exceptionally high dosage rate. When compared to standard dose rate radiation therapy, numerous preclinical investigations have demonstrated that FL-RT provides similar benefits in conserving normal tissue while maintaining equal antitumor efficacy, a phenomenon possible due to the 'FLASH effect' (FE) of FL-RT. The methodologies involve proton radiotherapy, intensity-modulated radiation treatment, and managing high-throughput damage by radiation to solid tissues. Recent results from animal studies indicate that FL-RT can reduce radiation-induced tissue damage, significantly enhancing anticancer potency. Focusing on the potential benefits of FL proton beam treatment in the years to come, this review details the FL-RT research that has been done so far and the existing theories illuminating the FL effects. This subject remains of interest, with many issues still needing to be answered. We offer a brief review to emphasize a few of the key efforts and difficulties in moving FL radiation research forward. The existing research state of FL-RT, its affecting variables, and its different specific impacts are presented in this current review. Key topics discussed include the biochemical mechanism during FL therapy, beam sources for FL therapy, the FL effect on immunity, clinical and preclinical studies on the protective effect of FL therapy, and parameters for effective FL therapy.

Phase II study of short course hypofractionated proton beam therapy incorporating 18F-DOPA-PET/MRI for elderly patients with newly diagnosed glioblastoma.

2002 Background: Elderly patients with glioblastoma have a poor prognosis with phase III trials reporting median overall survival (OS) and global time to deterioration of 6–9 and 1.2 months respectively. 18F-DOPA (3,4-dihydroxy-6-[18F]-fluoro-L-phenylalanine) positron emission tomography (PET) is sensitive and specific for identifying regions of high density and biologically aggressive glioblastoma. Proton beam therapy (PBT) can spare more healthy tissue that may improve quality of life for this patient population. With improved targeting of disease along with dosimetric advantages of PBT, this phase II trial tested whether hypofractionated PBT can offer both improved survival and quality of life. Methods: Patients with newly diagnosed glioblastoma aged ≥65 years without contraindications to 18F-DOPA were eligible. Target volumes were defined by PET (tumor/normal brain SUV ≥2.0) and MRI areas of contrast enhancement including surgical cavity. Patients received dose escalated hypofractionated PBT of 35-40 GyE to PET/MRI over 5-10 treatments with 10 mm margin. Patients received concurrent/adjuvant temozolomide. With an alpha of 0.1, 18 of 39 patients would be required to be alive at 12 months for the study to be considered a success. Kaplan-Meier/Cox regression analysis was performed for progression free survival (PFS) and OS. Toxicities were evaluated with CTCAE v4.0. Patients completed EORTC BN20, QLQ-C30, and MMSE questionnaires. Time to deterioration, defined as a 10-point decrease in the score of the function domain or 10-point increase in score of symptom domain, was evaluated. Results: Between 5/2019-6/2021, 43 patients were enrolled, with 4 patients withdrawing due to progression/insurance denial prior to beginning protocol therapy. The median age was 70.2 yrs. and median follow-up was 12.5 months. MGMT methylation was present in 13 (33%). Tumors were multifocal in 10 (26%) and unifocal in 29 (74%). The primary endpoint was met with median PFS/OS was 6.5/12.9 months for all patients and for MGMT methylated patients 11.9/29.8 months respectively. Grade 3 baseline adjusted treatment related adverse events included 1 (3%) confusion, 2 (5%) fatigue, and 1 (3%) seizure. There were no grade 4/5 events. Multivariate analysis revealed MGMT unmethylated, ECOG 2 and biopsy only patients had worse survival. PET volume was more predictive than MRI volume for OS with PET volume>26 cc having a hazard ratio of 3.7. The median time to global deterioration per QLC-C30 was 6.3 months. Conclusions: This phase II trial incorporating 18F-DOPA PET-guided dose escalated hypofractionated proton beam treatment for elderly patients with glioblastoma met its primary endpoint for improved OS and patient reported quality of life compared to historical controls. Further investigation is warranted. Clinical trial information: NCT03778294 .

Comparison of methodologies for creating spread-out Bragg peaks in proton therapy using TOPAS and MCNP codes

In proton beam treatments, the superposition of several weighted Bragg curves with different incident energies is required to homogeneously irradiate a large tumor volume, creating a spread-out Bragg peak (SOBP). This paper confirms on the suitability of two different methods to create SOBPs – Bortfeld/Jette's and MCMC (Monte Carlo calculations and Matrix Computations), using Monte Carlo simulations performed with TOPAS and MCNP6.1. To generate the SOBPs, algorithms were developed for implementation of the two methods, which enabled to find the weights for thirty variations of SOBPs, categorized according to their width and maximum depths. The MCMC method used weight optimization in designing SOBPs to avoid negative values. In contrast, the Bortfeld/Jette's method yielded the SOBPs according to the variation of a power-law parameter (p) introduced by the range-energy relationship. Optimal values of p, from MCNP and TOPAS, were selected in order to retrieve SOBPs with the best smoothness and then related to those obtained from the literature. In comparing both methods and codes, dose homogeneity parameters (HOM) were used to examine the SOBP flatness and gamma analyses were employed to assess the dose deposition along its full extension. The results showed that the SOBPs designed using the MCMC method had better HOM values and computational performance for both codes when compared to the Bortfeld/Jette's method. The gamma analyses highlighted significant differences between the entrance doses comparing the two different methods, for SOBPs with intermediate and high depths and small width. This evaluation was not possible with the HOM values alone, which stresses the relevance of a broad analysis to avoid unintended doses in healthy tissues.

Independent predictors of vertebral compression fracture following radiation for metastatic spine disease.

The goal of this study was to determine independent risk factors for vertebral compression fracture (VCF) following radiation for metastatic spine disease, including low bone mineral density as estimated by Hounsfield units (HU). A retrospective chart review identified patients with a single vertebral column metastasis treated with radiation therapy, a pretreatment CT scan, and a follow-up CT scan at least 6 weeks after treatment. Patients with primary spine tumors, preradiation vertebroplasty, preradiation spine surgery, prior radiation to the treatment field, and proton beam treatment modality were excluded. The HU were measured in the vertebral bodies at the level superior to the metastasis, within the tumor and medullary bone of the metastatic level, and at the level inferior to the metastasis. Variables collected included basic demographics, Spine Instability Neoplastic Score (SINS), presenting symptoms, bone density treatment, primary tumor pathology, Weinstein-Boriani-Biagini (WBB) classification, Enneking stage, radiation treatment details, chemotherapy regimen, and prophylactic vertebroplasty. One hundred patients with an average age of 63 years and average follow-up of 18 months with radiation treatment dates ranging from 2017 to 2020 were included. Fifty-nine patients were treated with external-beam radiation therapy, with a median total dose of 20 Gy (range 8-40 Gy). Forty-one patients were treated with stereotactic body radiation therapy, with a median total dose of 24 Gy (range 18-39 Gy). The most common primary pathologies included lung (n = 22), prostate (n = 21), and breast (n = 14). Multivariable logistic regression analysis (area under the curve 0.89) demonstrated pretreatment HU (p < 0.01), SINS (p = 0.02), involvement of ≥ 3 WBB sectors (p < 0.01), primary pathology other than prostate (p = 0.04), and ongoing chemotherapy treatment (p = 0.04) to be independent predictors of postradiation VCF. Patients with pretreatment HU < 145 (n = 32), 145-220 (n = 31), and > 220 (n = 37) had a fracture rate of 59%, 39%, and 11%, respectively. An HU cutoff of 157 was found to maximize sensitivity (71%) and specificity (75%) in predicting postradiation VCF. Low preradiation HU, higher SINS, involvement of ≥ 3 WBB sectors, ongoing chemotherapy, and nonprostate primary pathology were independent predictors of postradiation VCF in patients with metastatic spine disease. Low bone mineral density, as estimated by HU, is a novel and potentially modifiable risk factor for VCF.

Proton and carbon ion beam treatment with active raster scanning method in 147 patients with skull base chordoma at the Heidelberg Ion Beam Therapy Center—a single-center experience

BackgroundThis study aimed to compare the results of irradiation with protons versus irradiation with carbon ions in a raster scan technique in patients with skull base chordomas and to identify risk factors that may compromise treatment results.MethodsA total of 147 patients (85 men, 62 women) were irradiated with carbon ions (111 patients) or protons (36 patients) with a median dose of 66 Gy (RBE (Relative biological effectiveness); carbon ions) in 4 weeks or 74 Gy (RBE; protons) in 7 weeks at the Heidelberg Ion Beam Therapy Center (HIT) in Heidelberg, Germany. The median follow-up time was 49.3 months. All patients had gross residual disease at the beginning of RT. Compression of the brainstem was present in 38%, contact without compression in 18%, and no contact but less than 3 mm distance in 16%. Local control and overall survival were evaluated using the Kaplan–Meier Method based on scheduled treatment (protons vs. carbon ions) and compared via the log rank test. Subgroup analyses were performed to identify possible prognostic factors.ResultsDuring the follow-up, 41 patients (27.9%) developed a local recurrence. The median follow-up time was 49.3 months (95% CI: 40.8–53.8; reverse Kaplan–Meier median follow-up time 56.3 months, 95% CI: 51.9–60.7). No significant differences between protons and carbon ions were observed regarding LC, OS, or overall toxicity. The 1‑year, 3‑year, and 5‑year LC rates were 97%, 80%, and 61% (protons) and 96%, 80%, and 65% (carbon ions), respectively. The corresponding OS rates were 100%, 92%, and 92% (protons) and 99%, 91%, and 83% (carbon ions). No significant prognostic factors for LC or OS could be determined regarding the whole cohort; however, a significantly improved LC could be observed if the tumor was > 3 mm distant from the brainstem in patients presenting in a primary situation.ConclusionOutcomes of proton and carbon ion treatment of skull base chordomas seem similar regarding tumor control, survival, and toxicity. Close proximity to the brainstem might be a negative prognostic factor, at least in patients presenting in a primary situation.

Radiomic Phenotypes for Improving Early Prediction of Survival in Stage III Non-Small Cell Lung Cancer Adenocarcinoma after Chemoradiation.

We evaluate radiomic phenotypes derived from CT scans as early predictors of overall survival (OS) after chemoradiation in stage III primary lung adenocarcinoma. We retrospectively analyzed 110 thoracic CT scans acquired between April 2012-October 2018. Patients received a median radiation dose of 66.6 Gy at 1.8 Gy/fraction delivered with proton (55.5%) and photon (44.5%) beam treatment, as well as concurrent chemotherapy (89%) with carboplatin-based (55.5%) and cisplatin-based (36.4%) doublets. A total of 56 death events were recorded. Using manual tumor segmentations, 107 radiomic features were extracted. Feature harmonization using ComBat was performed to mitigate image heterogeneity due to the presence or lack of intravenous contrast material and variability in CT scanner vendors. A binary radiomic phenotype to predict OS was derived through the unsupervised hierarchical clustering of the first principal components explaining 85% of the variance of the radiomic features. C-scores and likelihood ratio tests (LRT) were used to compare the performance of a baseline Cox model based on ECOG status and age, with a model integrating the radiomic phenotype with such clinical predictors. The model integrating the radiomic phenotype (C-score = 0.69, 95% CI = (0.62, 0.77)) significantly improved (p<0.005) upon the baseline model (C-score = 0.65, CI = (0.57, 0.73)). Our results suggest that harmonized radiomic phenotypes can significantly improve OS prediction in stage III NSCLC after chemoradiation.

Vitreoretinal Surgery in the Prevention and Treatment of Toxic Tumour Syndrome in Uveal Melanoma: A Systematic Review.

Toxic tumour syndrome (TTS) is a particularly aggressive form of secondary vasculopathy occurring after radiation therapy of uveal melanoma due to the persistence of the necrotic tumour mass inside the eye. The development of TTS confers a particularly unfavourable functional and anatomical ocular prognosis, ultimately requiring enucleation in most cases if untreated. Vitreoretinal (VR) surgery has been successfully applied for treatment and prevention of TTS using both resecting and non-resecting techniques. In this systematic review, we aim to define characteristics of uveal melanomas benefiting the most from secondary VR surgery and to outline the optimal type and timing of VR intervention in such cases. Analysis of the literature reveals that endoresection should be performed within 3 months after radiotherapy to tumours thicker than 7 mm and with a largest basal diameter between 8 mm and 15 mm with post-equatorial location, especially after proton beam treatment. Alternatively, endodrainage remains a valid therapeutic option in eyes with macula-off retinal detachment, tumour diameter larger than 15 mm or ciliary body involvement. VR surgery can be successful in the management of TTS following radiotherapy for uveal melanoma when timing and indication are appropriately evaluated.

Monte Carlo framework for commissioning a synchrotron-based discrete spot scanning proton beam system and treatment plan verification

This study aimed to develop a Monte Carlo (MC) framework for commissioning the narrow proton beams (spot size sigma, 5.2 mm 2 mm at isocenter for 69.4 MeV-221.3 MeV for the main beam option and 4.1 mm 1.3 mm for the minibeam option respectively) of a synchrotron-based proton therapy system and design an independent absolute dose calculation engine for intensity-modulated proton treatments. A proton therapy system (Hitachi PROBEAT-V) was simulated using divergent and convergent beam models at the nozzle entrance. The innovative source weighting scheme for the MC simulation with TOPAS (TOol for PArticle Simulations) was implemented using dose output data for the absolute dose calculations. The results of the MC simulation were compared to the experimental data, analyzed and used to commission the treatment planning system. Two MC models, divergent and convergent beams were implemented. The convergent beam model produced a high level of agreement when MC and measurements were analyzed. The beam ellipticity did not result in significant differences between MC simulated and treatment planning system calculated doses. A model of a synchrotron-based spot scanning proton therapy system has been developed and implemented in the TOPAS MC transport code framework. The dose computation engine is useful for treatment plan verification with primary and minibeam beam option.

A Comparison of the Transcriptomes of Cowpeas in Response to Two Different Ionizing Radiations.

In this study, gene expression changes in cowpea plants irradiated by two different types of radiation: proton-beams and gamma-rays were investigated. Seeds of the Okdang cultivar were exposed to 100, 200, and 300 Gy of gamma-rays and proton-beams. In transcriptome analysis, the 32, 75, and 69 differentially expressed genes (DEGs) at each dose of gamma-ray irradiation compared with that of the control were identified. A total of eight genes were commonly up-regulated for all gamma-ray doses. However, there were no down-regulated genes. In contrast, 168, 434, and 387 DEGs were identified for each dose of proton-beam irradiation compared with that of the control. A total of 61 DEGs were commonly up-regulated for all proton-beam doses. As a result of GO and KEGG analysis, the ranks of functional categories according to the number of DEGs were not the same in both treatments and were more diverse in terms of pathways in the proton-beam treatments than gamma-ray treatments. The number of genes related to defense, photosynthesis, reactive oxygen species (ROS), plant hormones, and transcription factors (TF) that were up-/down-regulated was higher in the proton beam treatment than that in gamma ray treatment. Proton-beam treatment had a distinct mutation spectrum and gene expression pattern compared to that of gamma-ray treatment. These results provide important information on the mechanism for gene regulation in response to two ionizing radiations in cowpeas.

How can scanned proton beam treatment planning for low-grade glioma cope with increased distal RBE and locally increased radiosensitivity for late MR-detected brain lesions?

A novel risk model has recently been proposed for the occurrence of late contrast-enhancing brain lesions (CEBLs) after proton irradiation of low-grade glioma (LGG) patients. It predicts a strong dependence on dose-weighted linear-energy transfer (LETd effect) and an increased radiosensitivity of the ventricular proximity, a 4-mm fringe surrounding the ventricular system (VP4mm effect). On this basis, we investigated (A) how these two risk factors and patient-specific anatomical and treatment plan (TP) features contribute to normal tissue complication probability (NTCP) and (B) if conventional LETd -reduction techniques like multiple-field TP are able to reduce NTCP. (A) The LGG model cohort (N=110) was stratified with respect to prescribed dose, tumor grade, and treatment field configuration. NTCP predictions and CEBL occurrence rates per strata were analyzed. (B) The effect of multiple-field TP was investigated in two patient groups: (i) nine high-risk subjects with extended lateral target volumes who had developed CEBLs after single-beam treatments were retrospectively replanned with a clinical standard two-field setting using almost orthogonal fields and strictly opposing fields, (ii) single-field treatments were simulated for seven low-risk patients with small central target volumes clinically treated with two strictly opposing fields. (A) In the model cohort, we identified the exposure of the radiosensitive VP4mm fringe with proton field components of increased biological effectiveness as dominant NTCP driving factor. We observed that larger target volumes and location lateral to the main ventricles, both being characteristic for WHO°II tumors, presented with the highest complication risks. Among subjects of an equal dose prescription of 54Gy(RBE), the highest median NTCP was obtained for the WHO°II group treated with two fields using sharp angles. (B) Regarding the effect of multiple-field plans, we found that an NTCP reduction was only achievable in the low-risk group where the LETd effect dominates and the VP4mm effect is small. NTCP of the single-field plans was 23% higher compared to the clinical opposing field plan. In the high-risk group, where the VP4mm effect dominates the risk, both two-field scenarios yielded 44% higher NTCP predictions compared to the clinical single-field plans. The interplay of an increased radiosensitivity in the VP4mm fringe with proton field components of increased biological effectiveness creates a geometric complexity that can hardly be managed by current clinical TP. Our results underline that advanced biologically guided TP approaches become crucial for an effective risk minimization in proton therapy of LGG.

Dose perturbation caused by metallic port in breast tissue expander in proton beam therapy

Proton beam treatment is being looked favourably now in breast treatment. Tissue expanders are often placed after mastectomy that contains metallic port for saline injection which produces dose perturbations in proton beam therapy with uncertain dosimetry. Dose perturbation for a stainless-steel injection port from a breast implant is investigated in this study. Measurements, Monte-Carlo simulation, and calculated dose distribution of plans based on kVCT and MVCT images are compared. Treatment plans are performed on kVCT and MVCT images to observe the effect of metal artifact from the breast implant. The kVCT based plan underestimates the beam range due to the overestimated water equivalent thickness of the metal ports as a result of image degradation. Compared to the measurement with metal port in the proton beam, the MVCT-based treatment planning provides more accurate dose calculation than the kVCT-based results. The dose perturbation factor calculated from MVCT planning is within 10% of the measurement results while HU corrected kVCT plan still shows dose difference as large as 100% due to the incorrect range pull back calculation caused by the misrepresentation of the volume between the plastic cap and the stainless-steel base. The dose enhancement observed at the metal and solid water interface is as large as 15%, which needs to be accounted for in the planning process if there is a clinical concern. Dose reduction as large as 16% is observed with depth from 1 cm to 4 cm underneath the thickest part of the metallic port whereas lateral dose perturbation is also seen up to 7 mm. The measurement data are supported by the Monte-Carlo simulated results with a maximum dose difference of 6%. It is concluded that if proton beam is used with metallic port, MVCT imaging data is recommended. In lieu of MVCT, DECT, CT scanner with metal artifact reduction software or in the very least, extended HU range should be used to reduce the streaking artifact as well as to produce a more accurate image of the metallic port.

Key Clinical Concepts from Multi-Institutional Experience with Dedicated Fixed Low-Energy Proton Ocular Beamlines

Proton beam treatment for ocular tumors has been well established with dedicated eye beamlines internationally. Given the emergence of universal, high-energy, non-fixed beamline options, we share key practices for uveal melanoma (UM) treatment planning and delivery. We focus particularly on practical clinical and physics concepts to minimize important ocular side effects. Practices were studied from two well-established international dedicated proton ocular institutions with very longstanding facilities, both using fixed, low-energy, ocular beamlines to treat eye tumors only. Since the 1970s and 1980s until now, the respective cyclotrons produce 67.5 and 60.0 MeV proton beams (range up to 3 cm). In total 5927 ocular patients, 93% with UM, have been treated. Standard UM dose is 56 Gray Equivalent (GyE) and 57.2 GyE, respectively, delivered in 4 fractions. Planning and delivery procedures were analyzed as a bi-institutional effort to communicate key concepts to newer developing proton centers. Normal eye tissue sparing is related to critical beam characteristics provided in the setting of low-energy dedicated eye beamlines. Both centers offer a very sharp dose fall off (distal ∼1 mm and lateral ∼1.1-1.6 mm), high dose homogeneity, excellent range precision and short treatment time (∼0.5-2 minutes). Planned doses to critical ocular structures are independent predictors of ocular complications such as vision loss and neovascular glaucoma, including the following parameters: 28 GyE to macula [P<.0001], optic nerve [P<0.0004], lens [P<.0001], and ciliary body [P<.0001]. A systematic tumor/critical structure dose evaluation is used to optimize treatment parameters, i.e. lateral margin, distal range, gaze angle, and aperture shape. New high-energy non-dedicated beam designs, which degrade energy to deliver ocular treatment, may require significant beam adjustment and treatment planning procedures to achieve adequate characteristics. Regarding UM dose, a common regimen is 60 GyE in 4 fractions globally. Unrandomized early retrospective data shows lower local tumor control with 48 GyE (P = 0.02). Critical structures including the retina, lacrimal gland, cornea, tear ducts, lids, bony orbit, and limbal stem cells are methodically evaluated to minimize side effects. Eyelid toxicity is reduced by institutional retraction techniques or treatment through closed lids. Experienced international specialty proton ocular centers with dedicated, low-energy, fixed eyelines, provide important practical concepts for consideration by developing centers to optimize high-energy universal beamline designs for eye treatments. As new centers with different beam designs emerge globally, key clinical and treatment planning/delivery practices will need to be applied, particularly to reduce potential normal tissue toxicity for ocular patients.

Study on Treatment Planning for the Prostate in Proton Therapy with Oxygen Enhancement Ratio Effect

The purpose of this study was to investigate the oxygen enhancement ratio (OER) effects on treatment planning for a hypoxic prostate tumor with proton scanning beams. Two different OER-based dose calculation models (the average model and the voxel model) were investigated by using hypoxic tumor models in this simulation study. For the hypoxic tumor model, an oxygen distribution with a range of 2.4–9.4 mmHg was used according to the clinical data. The results given by the average model and the voxel model were compared for 50% and 90% tumor control probabilities with variations in the hypoxic tumor volume and fractionation. Comparison between the treatment plans with OER-based higher predicted dose and with the conventional prescription dose was conducted to investigate the organ-at-risk (OAR) doses for the prostate case. The average model showed a higher calculated dose than the voxel model. The voxel model with a 50% control probability showed good agreement with the current prescription dose. The OER values of the average model ranged from 1.05 to 1.25, which were applied to the whole tumor volume in treatment planning. The voxel-model-based OERs were higher (1.50–1.75) than those of average model, and these OERs should be applied only for the hypoxic boost region. Regarding treatment plans, the doses of the rectum and the bladder were reduced to the tolerable range V80Gy (volume receiving equal to or greater than 80Gy) < 15% and V75Gy (volume receiving equal to or greater than 75Gy) < 15% respectively after an optimization, but the maximum dose to femoral heads was higher than 50 Gy. In conclusion, we investigated the possible ranges of the OER (1.3–1.8) for proton-beam treatment of prostate cases. A dose escalation of up to about 1.8 times can be applied for the small hypoxic region. This result, which was obtained using a model study, should be verified through clinical experiment.

Catheter-free ablation of infarct scar through proton beam therapy: Tissue effects in a porcine model

Scar-related ventricular arrhythmias are common after myocardial infarction. Catheter ablation can improve prognosis, but the procedure is invasive and results are not always satisfactory. Noninvasive, catheter-free ablation using ionizing radiation has recently gained interest among electrophysiologists, but the tissue effects and physiological outcome have not been fully characterized. The purpose of this study was to investigate the structural effects of cardiac scanned pencil beam proton therapy on infarct scar, the time course of imaging biomarkers, arrhythmias, and cardiac function in a porcine model. Fourteen infarcted swine underwent proton beam treatment of the scar (40 or 30 Gy) and were followed for up to 30 weeks. Magnetic resonance imaging was performed every 4 weeks. Treated scar areas showed a significantly lower fraction of surviving myocytes at 30 weeks compared to untreated scar (30.1% ± 18.5% and 59.9% ± 10.1% in treated and untreated infarct, respectively), indicating scar homogenization. Four animals died suddenly during follow-up, all from documented monomorphic ventricular tachycardia. Cardiac function remained stable over the course of the study. Distinct imaging morphologies corresponded to certain tissue dose ranges and time points. Radioablation of cardiac infarct scar leads to significant homogenization of the scar, replicating the histologic effects of radiofrequency ablation. These changes correspond to distinct imaging morphologies on delayed contrast-enhanced cardiac magnetic resonance imaging, enabling noninvasive confirmation of tissue ablation effects The present study is the first to thoroughly investigate the structural effects of cardiac proton beam therapy in infarcted myocardium.

Delayed response to proton beam treatment of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has become one of the leading causes of cancer death worldwide. There has been anecdotal report regarding the effectiveness of proton beam treatment for HCC. In this pre-clinical investigation, the woodchuck model of viral hepatitis infection-induced HCC was used for proton beam treatment experiment. The radiopaque fiducial markers that are biodegradable were injected around the tumor under ultrasound guidance to facilitate positioning in sequential treatments. An α cradle mode was used to ensure reproducibility of animal positioning on the treatment couch. A CT scan was performed first for contouring by a radiation oncologist. The CT data set with contours was then exported for dose planning. Three fractionations, each 750 CcGyE, were applied every other day with a Mevion S250 passive scattering proton therapy system. Multiphase contrast-enhanced CT scans were performed after the treatment and at later times for follow-ups. 3 weeks post-treatment, shrinking of the HCC nodule was detected and constituted to a partial response (30% reduction along the long axis). By week nine after treatment, the nodule disappeared during the arterial phase of multiphase contrast-enhanced CT scan. Pathological evaluation corroborated with this imaging response. A delayed, but complete imaging response to proton beam treatment applied to HCC was achieved with this unique and clinically relevant animal model of HCC.

Clinical implementation and commissioning of the MedAustron Particle Therapy Accelerator for non-isocentric scanned proton beam treatments.

This paper describes the clinical implementation and medical commissioning of the MedAustron Particle Therapy Accelerator (MAPTA) for non-isocentric scanned proton beam treatments. Medical physics involvement during technical commissioning work is presented. Acceptance testing procedures, including advanced measurement methods of intra-spill beam variations, are defined. Beam monitor calibration using two independent methods based on a dose-area product formalism is described. Emphasis is given to the medical commissioning work and the specificities related to non-isocentric irradiation, since a key feature of MedAustron is the routine delivery of non-isocentric scanned proton beam treatments. Key commissioning results and beam stability trend lines for more than 2yr of clinical operation have been provided. Intra-spill beam range, size, and position variations were within specifications of 0.3mm, 15%, and 0.5mm, respectively. The agreement between two independent beam monitor calibration methods was better than 1.0%. Non-isocentric treatment delivery allowed lateral penumbra reduction of up to about 30%. Daily QA measurements of the beam range, size, position, and dose were always within 1mm, 10%, 1mm, and 2% from the baseline data, respectively. Non-isocentric treatments have been successfully implemented at MedAustron for routine scanned proton beam therapy using horizontal and vertical fixed beamlines. Up to now every patient was treated in non-isocentric conditions. The presented methodology to implement a new Scanned Ion Beam Delivery (SIBD) system into clinical routine for proton therapy may serve as a guidance for other centers.

A new concept for verifying the isocentric alignment of the proton-rotational gantry for radiation control.

The purpose of this study was to introduce the modified Winston-Lutz (mWL) test and to evaluate its feasibility. This is a new method to completely absorb the proton beam around the isocenter inside a phantom for radiation control. The mWL test was performed using a 14-cm-diameter acrylic Lucy 3D QA Phantom for a passive-scattering proton beam gantry. The energy of the unmodulated proton beam was adjusted such that the residual range was < 130mm, and the energy of the proton beam was completely lost around the isocenter. The radiation field was formed with a multi-leaf collimator at 8.6 × 8.6mm2 in the isocenter plane. The phantom was loaded with a 4-mm-diameter tungsten ball, and the EBT3 was set up at the isocenter. The proton beam was irradiated at gantry angles with 45° steps, and the isocenter deviation of the proton beam was measured and subsequently analyzed. Although the radiation field penumbra was blurred under the influence of scattered radiation due to placement in the phantom compared to the traditional WL test placed in the air, evaluation of the beam axis accuracy was possible. The results confirmed that the maximum total displacement was less than 0.9mm, and the specifications of the device were met. The mWL test is feasible and effective to reduce the building activation in proton beam treatment facilities. Thus, it can be considered a useful method that sufficiently satisfies the shielding calculation conditions.

Assessment of Changes of the Distance from Liver Surface to Isocenter during Proton Beam Treatment for Liver Cancer

In proton beam therapy, although it is possible to obtain a high therapeutic effect while suppressing the influence on liver function by conducting concentrated irradiation on liver tumor, hepatic parenchyma and liver tumors irradiated by proton beam show atrophic changes after therapy. If atrophic changes occur in period of proton beam therapy, it may change dose distribution for liver tumor. We tried to evaluate the changes of size and shape of liver during proton beam treatment by the use of CT images. 18 consecutive cases (16 males and 2 females, from 56 to 84 years (median 69.5 years)) treated with proton beam therapy for liver cancer were included. 15 cases had hepatocellular carcinoma, 2 cases had metastatic liver cancer, a case had intrahepatic bile duct cancer, and 4 cases were treated with 66GyE in 10 fractions for two weeks, 8 cases with 76GyE in 20 fractions and 6 cases were treated with others (70-83.6GyE in 22-38 fractions.) The distances from the liver surface to the isocenter along the proton beam were measured on the CT images for radiation planning and compared with those measured on the CT images obtained on the day of the last irradiation. Total 42 beam directions of 18 cases were studied. In 13 beams, the distances increased by 0.4 to 4 mm, whereas, those were shortened by 0.4 to 9.5 mm in 24 beams. 5 beams had no changes of distances. 1 of 4 cases treated with 10 fractions, 2 of 8 cases with 20 fractions, and 1 of 6 cases with over 20 fractions showed the changes more than 5mm. The change of the distance from liver surface to isocenters occurred in period of proton beam therapy. Although a large part of changes were acceptable, some case showed the changes more than 5mm and these change may occur change dose distribution for liver tumor. It was suggested that it would be useful to evaluate the deformation of the liver during proton therapy and correct plans as necessary.