[18]F-fluoroethyl-l-tyrosine positron emission tomography for radiotherapy target delineation: Results from a Radiation Oncology credentialing program.

Background and purpose: The [18]F-fluoroethyl-l-tyrosine (FET) PET in Glioblastoma (FIG) study is an Australian prospective, multi-centre trial evaluating FET PET for newly diagnosed glioblastoma management. The Radiation Oncology credentialing program aimed to assess the feasibility in Radiation Oncologist (RO) derivation of standard-of-care target volumes (TVMR) and hybrid target volumes (TVMR+FET) incorporating pre-defined FET PET biological tumour volumes (BTVs). Materials and methods: Central review and analysis of TVMR and TVMR+FET was undertaken across three benchmarking cases. BTVs were pre-defined by a sole nuclear medicine expert. Intraclass correlation coefficient (ICC) confidence intervals (CIs) evaluated volume agreement. RO contour spatial and boundary agreement were evaluated (Dice similarity coefficient [DSC], Jaccard index [JAC], overlap volume [OV], Hausdorff distance [HD] and mean absolute surface distance [MASD]). Dose plan generation (one case per site) was assessed. Results: Data from 19 ROs across 10 trial sites (54 initial submissions, 8 resubmissions requested, 4 conditional passes) was assessed with an initial pass rate of 77.8 %; all resubmissions passed. TVMR+FET were significantly larger than TVMR (p < 0.001) for all cases. RO gross tumour volume (GTV) agreement was moderate-to-excellent for GTVMR (ICC = 0.910; 95 % CI, 0.708-0.997) and good-to-excellent for GTVMR+FET (ICC = 0.965; 95 % CI, 0.871-0.999). GTVMR+FET showed greater spatial overlap and boundary agreement compared to GTVMR. For the clinical target volume (CTV), CTVMR+FET showed lower average boundary agreement versus CTVMR (MASD: 1.73 mm vs. 1.61 mm, p = 0.042). All sites passed the planning exercise. Conclusions: The credentialing program demonstrated feasibility in successful credentialing of 19 ROs across 10 sites, increasing national expertise in TVMR+FET delineation.

Construction and validation of an infant chest phantom for paediatric computed tomography.

Paediatric imaging protocols should be carefully optimised to maintain the desired image quality while minimising the delivered patient dose. A paediatric chest phantom was designed, constructed and evaluated to optimise chest CT examinations for infants. The phantom was designed to enable dosimetry and image quality measurements within the anthropomorphic structure. It was constructed using tissue equivalent materials to mimic thoracic structures of infants, aged 0-6 months. The phantom materials were validated across a range of diagnostic tube voltages with resulting CT numbers found equivalent to paediatric tissues observed via a survey of clinical paediatric chest studies. The phantom has been successfully used to measure radiation dose and evaluate various image quality parameters for paediatric specific protocols.

The impact of fluorine-18-fluoroethyltyrosine positron emission tomography scan timing on radiotherapy planning in newly diagnosed patients with glioblastoma.

Background and purpose: Glioblastoma is one of the most common and aggressive primary brain tumours in adults. Though radiation therapy (RT) techniques have progressed significantly in recent decades, patient survival has seen little improvement. However, an area of promise is the use of fluorine-18-fluoroethyltyrosine positron-emission-tomography (18F-FET PET) imaging to assist in RT target delineation. This retrospective study aims to assess the impact of 18F-FET PET scan timing on the resultant RT target volumes and subsequent RT plans in post-operative glioblastoma patients. Materials and Methods: The imaging and RT treatment data of eight patients diagnosed with glioblastoma and treated at a single institution were analysed. Before starting RT, each patient had two 18F-FET-PET scans acquired within seven days of each other. The information from these 18F-FET-PET scans aided in the creation of two novel target volume sets. The new volumes and plans were compared with each other and the originals. Results: The median clinical target volume (CTV) 1 was statistically smaller than CTV 2. The median Dice score for the CTV1/CTV2 was 0.98 and, of the voxels that differ (median 6.5 cc), 99.7% were covered with a 5 mm expansion. Overall organs at risk (OAR) and target dosimetry were similar in the PTV1 and PTV2 plans. Conclusion: Provided the 18F-FET PET scan is acquired within two weeks of the RT planning and a comprehensive approach is taken to CTV delineation, the timing of scan acquisition has minimal impact on the resulting RT plan.

Development of a 3D printed phantom for commissioning and quality assurance of multiple brain targets stereotactic radiosurgery.

Single plan techniques for multiple brain targets (MBT) stereotactic radiosurgery (SRS) are now routine. Patient specific quality assurance (QA) for MBT poses challenges due to the limited capabilities of existing QA tools which necessitates several plan redeliveries. This study sought to develop an SRS QA phantom that enables flexible MBT patient specific QA in a single delivery, along with complex SRS commissioning. PLA marble and PLA StoneFil materials were selected based on the literature and previous research conducted in our department. The HU numbers were investigated to determine the appropriate percentage infill for skull and soft-tissue equivalence. A Prusa MK3S printer in conjunction with the above-mentioned filaments were used to print the SRS QA phantom. Quality control (QC) was performed on the printed skull, film inserts and plugs for point dose measurements. EBT3 film and point dose measurements were performed using a CC04 ionisation chamber. QC demonstrated that the SRS QA phantom transverse, coronal and sagittal film planes were orthogonal within 0.5°. HU numbers for the skull, film inserts and plugs were 858 ± 20 and 35 ± 12 respectively. Point and EBT3 film dose measurements were within 2.5% and 3%/2 mm 95% gamma pass rate, respectively except one Gross Tumour Volume (GTV) that had a slightly lower gamma pass rate. Dose distributions to five GTVs were measured with EBT3 film in a single plan delivery on CyberKnife. In conclusion, an SRS QA phantom was designed, and 3D printed and its use for performing complex MBT patient specific QA in a single delivery was demonstrated.

Development and optimisation of grid inserts for a preclinical radiotherapy system and corresponding Monte Carlo beam simulations.

Objective. To develop a physical grid collimator compatible with the X-RAD preclinical radiotherapy system and create a corresponding Monte Carlo (MC) model.Approach. This work presents a methodology for the fabrication of a grid collimator designed for utilisation on the X-RAD preclinical radiotherapy system. Additionally, a MC simulation of the grid is developed, which is compatible with the X-RAD treatment planning system. The grid was manufactured by casting a low melting point alloy, cerrobend, into a silicone mould. The silicone was moulded around a 3D-printed replica of the grid, enabling the production of diverging holes with precise radii and spacing. A MC simulation was conducted on an equivalent 3D grid model and validated using 11 layers of GAFChromic EBT-3 film interspersed in a 3D-printed water-equivalent phantom. A 3D dose distribution was constructed from the film layers, enabling a direct comparison with the MC Simulation.Main results. The film and the MC dose distribution demonstrated a gamma passing rate of 99% for a 1%, 0.5 mm criteria with a 10% threshold applied. The peak-to-valley dose ratio and output factor at the surface were determined to be 20.4 and 0.79, respectively.Significance. The pairing of the grid collimator with a MC simulation can significantly enhance the practicality of grid therapy on the X-RAD. This combination enables further exploration of the biological implications of grid therapy, supported by a knowledge of the complex dose distributions. Moreover, this methodology can be adapted for use in other systems and scenarios.

Towards optimal heterogeneous prostate radiotherapy dose prescriptions based on patient-specific or population-based biological features.

BACKGROUND: Escalation of prescribed dose in prostate cancer (PCa) radiotherapy enables improvement in tumor control at the expense of increased toxicity. Opportunities for reduction of treatment toxicity may emerge if more efficient dose escalation can be achieved by redistributing the prescribed dose distribution according to the known heterogeneous, spatially-varying characteristics of the disease. PURPOSE: To examine the potential benefits, limitations and characteristics of heterogeneous boost dose redistribution in PCa radiotherapy based on patient-specific and population-based spatial maps of tumor biological features. METHOD: High-resolution prostate histology images, from a cohort of 63 patients, annotated with tumor location and grade, provided patient-specific "maps" and a population-based "atlas" of cell density and tumor probability. Dose prescriptions were derived for each patient based on a heterogeneous redistribution of the boost dose to the intraprostatic lesions, with the prescription maximizing patient tumor control probability (TCP). The impact on TCP was assessed under scenarios where the distribution of population-based biological data was ignored, partially included, or fully included in prescription generation. Heterogeneous dose prescriptions were generated for three combinations of maps and atlas, and for conventional fractionation (CF), extreme hypo-fractionation (EH), moderate hypo-fractionation (MH), and whole Pelvic RT + SBRT Boost (WPRT + SBRT). The predicted efficacy of the heterogeneous prescriptions was compared with equivalent homogeneous dose prescriptions. RESULTS: TCPs for heterogeneous dose prescriptions were generally higher than those for homogeneous dose prescriptions. TCP escalation by heterogeneous dose prescription was the largest for CF. When only using population-based atlas data, the generated heterogeneous dose prescriptions of 55 to 58 patients (out of 63) had a higher TCP than for the corresponding homogeneous dose prescriptions. The TCPs of the heterogeneous dose prescriptions generated with the population-based atlas and tumor probability maps did not differ significantly from those using patient-specific biological information. The generated heterogeneous dose prescriptions achieved significantly higher TCP than homogeneous dose prescriptions in the posterior section of the prostate. CONCLUSION: Heterogeneous dose prescriptions generated via biologically-optimized dose redistribution can produce higher TCP than the homogeneous dose prescriptions for the majority of the patients in the studied cohort. For scenarios where patient-specific biological information was unavailable or partially available, the generated heterogeneous dose prescriptions can still achieve TCP improvement relative to homogeneous dose prescriptions.

The prognostic value of F18 Fluorothymidine positron emission tomography for assessing the response of malignant pleural mesothelioma to chemotherapy - A prospective cohort study.

INTRODUCTION: Malignant pleural mesothelioma is difficult to prognosticate. F18-Fluorodeoxyglucose positron emission tomography (FDG PET) shows promise for response assessment but is confounded by talc pleurodesis. F18-Fluorothymidine (FLT) PET is an alternative tracer specific for proliferation. We compared the prognostic value of FDG and FLT PET and determined the influence of talc pleurodesis on these parameters. METHODS: Overall, 29 prospectively recruited patients had FLT PET, FDG PET and CT-scans performed prior to and post one chemotherapy cycle; 10 had prior talc pleurodesis. Patients were followed for overall survival. CT response was assessed using mRECIST. Radiomic features were extracted using the MiM software platform. Changes in maximum SUV (SUVmax), mean SUV (SUVmean), FDG total lesion glycolysis (TLG), FLT total lesion proliferation (TLP) and metabolic tumour volume (MTV) after one chemotherapy cycle. RESULTS: Cox univariate analysis demonstrated FDG PET radiomics were confounded by talc pleurodesis, and that percentage change in FLT MTV was predictive of overall survival. Cox multivariate analysis showed a 10% increase in FLT tumour volume corresponded with 9.5% worsened odds for overall survival (P = 0.028, HR = 1.095, 95% CI [1.010, 1.187]). No other variables were significant on multivariate analysis. CONCLUSION: This is the first prospective study showing the statistical significance of FLT PET tumour volumes for measuring mesothelioma treatment response. FLT may be better than FDG for monitoring mesothelioma treatment response, which could help optimise mesothelioma treatment regimes.

Quantitative [68Ga]Ga-PSMA-11 PET biomarkers for the analysis of lesion-level progression in biochemically recurrent prostate cancer: a multicentre study.

[68Ga]Ga-PSMA-11 PET has become the standard imaging modality for biochemically recurrent (BCR) prostate cancer (PCa). However, its prognostic value in assessing response at this stage remains uncertain. The study aimed to assess the prognostic significance of radiographic patient-level patterns of progression derived from lesion-level biomarker quantitation in metastatic disease sites. A total of 138 BCR PCa patients with both baseline and follow-up [68Ga]Ga-PSMA-11 PET scans were included in this analysis. Tumour response was quantified at the lesion level using commonly used quantitative parameters (SUVmean, SUVmax, SUVpeak, volume), and patients were classified as systemic, mixed, or no-progression based on these response classifications. A total of 328 matched lesions between baseline and follow-up scans were analysed. The results showed that systemic progressors had a significantly higher risk of death than patients with no progression with SUVmean demonstrating the highest prognostic value (HR = 5.70, 95% CI = 2.63-12.37, p < 0.001, C-Index = 0.69). Moreover, progressive disease as measured by SUVmean using the radiographic PSMA PET Progression Criteria (rPPP) was found to be significantly prognostic for patient overall survival (HR = 3.67, 95% CI = 1.82-7.39, p < 0.001, C-Index = 0.65). This work provides important evidence supporting the prognostic utility of PSMA response quantitation in the BCR setting.

Focal Boost in Prostate Cancer Radiotherapy: A Review of Planning Studies and Clinical Trials.

BACKGROUND: Focal boost radiotherapy was developed to deliver elevated doses to functional sub-volumes within a target. Such a technique was hypothesized to improve treatment outcomes without increasing toxicity in prostate cancer treatment. PURPOSE: To summarize and evaluate the efficacy and variability of focal boost radiotherapy by reviewing focal boost planning studies and clinical trials that have been published in the last ten years. METHODS: Published reports of focal boost radiotherapy, that specifically incorporate dose escalation to intra-prostatic lesions (IPLs), were reviewed and summarized. Correlations between acute/late ≥G2 genitourinary (GU) or gastrointestinal (GI) toxicity and clinical factors were determined by a meta-analysis. RESULTS: By reviewing and summarizing 34 planning studies and 35 trials, a significant dose escalation to the GTV and thus higher tumor control of focal boost radiotherapy were reported consistently by all reviewed studies. Reviewed trials reported a not significant difference in toxicity between focal boost and conventional radiotherapy. Acute ≥G2 GU and late ≥G2 GI toxicities were reported the most and least prevalent, respectively, and a negative correlation was found between the rate of toxicity and proportion of low-risk or intermediate-risk patients in the cohort. CONCLUSION: Focal boost prostate cancer radiotherapy has the potential to be a new standard of care.

Prospective inter- and intra-tracer repeatability analysis of radiomics features in [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET scans in metastatic prostate cancer.

OBJECTIVE: This study aimed to quantify both the intra- and intertracer repeatability of lesion-level radiomics features in [68Ga]Ga-prostate-specific membrane antigen (PSMA)-11 and [18F]F-PSMA-1007 positron emission tomography (PET) scans. METHODS: Eighteen patients with metastatic prostate cancer (mPCa) were prospectively recruited for the study and randomised to one of three test-retest groups: (i) intratracer [68Ga]Ga-PSMA-11 PET, (ii) intratracer [18F]F-PSMA-1007 PET or (iii) intertracer between [68Ga]Ga-PSMA-11 and [18F]F-PSMA-1007 PET. Four conventional PET metrics (standardised uptake value (SUV)max, SUVmean, SUVtotal and volume) and 107 radiomics features were extracted from 75 lesions and assessed using the repeatability coefficient (RC) and the ICC. Radiomic feature repeatability was also quantified after the application of 16 filters to the PET image. RESULTS: Test-retest scans were taken a median of 5 days apart (range: 2-7 days). SUVmean demonstrated the lowest RC limits of the conventional features, with RCs of 7.9%, 14.2% and 24.7% for the [68Ga]Ga-PSMA-11 PET, [18F]F-PSMA-1007 PET, and intertracer groups, respectively. 69%, 66% and 9% of all radiomics features had good or excellent ICC values (ICC ≥ 0.75) for the same groups. Feature repeatability therefore diminished considerably for the intertracer group relative to intratracer groups. CONCLUSION: In this study, robust biomarkers for each tracer group that can be used in subsequent clinical studies were identified. Overall, the repeatability of conventional and radiomic features were found to be substantially lower for the intertracer group relative to both intratracer groups, suggesting that assessing patient response quantitatively should be done using the same radiotracer where possible. ADVANCES IN KNOWLEDGE: Intertracer biomarker repeatability limits are significantly larger than intratracer limits.

Delineation and agreement of FET PET biological volumes in glioblastoma: results of the nuclear medicine credentialing program from the prospective, multi-centre trial evaluating FET PET In Glioblastoma (FIG) study-TROG 18.06.

PURPOSE: The O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET in Glioblastoma (FIG) trial is an Australian prospective, multi-centre study evaluating FET PET for glioblastoma patient management. FET PET imaging timepoints are pre-chemoradiotherapy (FET1), 1-month post-chemoradiotherapy (FET2), and at suspected progression (FET3). Before participant recruitment, site nuclear medicine physicians (NMPs) underwent credentialing of FET PET delineation and image interpretation. METHODS: Sites were required to complete contouring and dynamic analysis by ≥ 2 NMPs on benchmarking cases (n = 6) assessing biological tumour volume (BTV) delineation (3 × FET1) and image interpretation (3 × FET3). Data was reviewed by experts and violations noted. BTV definition includes tumour-to-background ratio (TBR) threshold of 1.6 with crescent-shaped background contour in the contralateral normal brain. Recurrence/pseudoprogression interpretation (FET3) required assessment of maximum TBR (TBRmax), dynamic analysis (time activity curve [TAC] type, time to peak), and qualitative assessment. Intraclass correlation coefficient (ICC) assessed volume agreement, coefficient of variation (CoV) compared maximum/mean TBR (TBRmax/TBRmean) across cases, and pairwise analysis assessed spatial (Dice similarity coefficient [DSC]) and boundary agreement (Hausdorff distance [HD], mean absolute surface distance [MASD]). RESULTS: Data was accrued from 21 NMPs (10 centres, n ≥ 2 each) and 20 underwent review. The initial pass rate was 93/119 (78.2%) and 27/30 requested resubmissions were completed. Violations were found in 25/72 (34.7%; 13/12 minor/major) of FET1 and 22/74 (29.7%; 14/8 minor/major) of FET3 reports. The primary reasons for resubmission were as follows: BTV over-contour (15/30, 50.0%), background placement (8/30, 26.7%), TAC classification (9/30, 30.0%), and image interpretation (7/30, 23.3%). CoV median and range for BTV, TBRmax, and TBRmean were 21.53% (12.00-30.10%), 5.89% (5.01-6.68%), and 5.01% (3.37-6.34%), respectively. BTV agreement was moderate to excellent (ICC = 0.82; 95% CI, 0.63-0.97) with good spatial (DSC = 0.84 ± 0.09) and boundary (HD = 15.78 ± 8.30 mm; MASD = 1.47 ± 1.36 mm) agreement. CONCLUSION: The FIG study credentialing program has increased expertise across study sites. TBRmax and TBRmean were robust, with considerable variability in BTV delineation and image interpretation observed.

Comparison of the accuracy of Monte Carlo and Ray Tracing dose calculation algorithms for multiple target brain treatments on CyberKnife.

Single plan multiple brain targets (MBT) stereotactic radiosurgery dose difference between Monte Carlo (MC) and Ray Tracing (RT) algorithms has not been studied. A retrospective study and dose measurements were performed to access factors influencing dose differences. Fifty-three RT treatment plans with a total of 209 brain metastases were extracted from Precision Treatment Planning System (TPS). These plans were generated using fixed cones and were delivered using the CyberKnife M6 system. The same treatment plans were recalculated using MC algorithm and keeping the beam parameters unchanged. MC calculated plan parameters were extracted and dose differences were normalised to MC calculated dose. Correlations were investigated. RT and MC calculated off-centre-ratio (OCR) and tissue-phantom-ratio (TPRs) were exported from the TPS and compared with measured. Plans with 5 gross tumour volumes (GTVs) were created on a phantom and dose measured using a CC04 ionisation chamber and microdiamond detector for comparison with calculated doses. Calculated and measured TPR agreed within ± 1% beyond depth of maximum dose. The OCR showed differences up to 4.3% in the penumbra and out-of-field (OOF) regions. Largest RT and MC calculated GTV mean dose difference was - 5.7%. An increase in the number of GTVs and reduction in the geometric separation of metastases were associated with increased differences between RT and MC calculated doses. In conclusion, calculated dose disagreement in MBT depends on the number of GTVs per plan, number of GTVs within a certain separation distance and plan complexity. MC dose calculation is recommended for complex CyberKnife SRS of MBT.

Prognostic utility of RECIP 1.0 with manual and AI-based segmentations in biochemically recurrent prostate cancer from [68Ga]Ga-PSMA-11 PET images.

PURPOSE: This study aimed to (i) validate the Response Evaluation Criteria in PSMA (RECIP 1.0) criteria in a cohort of biochemically recurrent (BCR) prostate cancer (PCa) patients and (ii) determine if this classification could be performed fully automatically using a trained artificial intelligence (AI) model. METHODS: One hundred ninety-nine patients were imaged with [68Ga]Ga-PSMA-11 PET/CT once at the time of biochemical recurrence and then a second time a median of 6.0 months later to assess disease progression. Standard-of-care treatments were administered to patients in the interim. Whole-body tumour volume was quantified semi-automatically (TTVman) in all patients and using a novel AI method (TTVAI) in a subset (n = 74, the remainder were used in the training process of the model). Patients were classified as having progressive disease (RECIP-PD), or non-progressive disease (non RECIP-PD). Association of RECIP classifications with patient overall survival (OS) was assessed using the Kaplan-Meier method with the log rank test and univariate Cox regression analysis with derivation of hazard ratios (HRs). Concordance of manual and AI response classifications was evaluated using the Cohen's kappa statistic. RESULTS: Twenty-six patients (26/199 = 13.1%) presented with RECIP-PD according to semi-automated delineations, which was associated with a significantly lower survival probability (log rank p < 0.005) and higher risk of death (HR = 3.78 (1.96-7.28), p < 0.005). Twelve patients (12/74 = 16.2%) presented with RECIP-PD according to AI-based segmentations, which was also associated with a significantly lower survival (log rank p = 0.013) and higher risk of death (HR = 3.75 (1.23-11.47), p = 0.02). Overall, semi-automated and AI-based RECIP classifications were in fair agreement (Cohen's k = 0.31). CONCLUSION: RECIP 1.0 was demonstrated to be prognostic in a BCR PCa population and is robust to two different segmentation methods, including a novel AI-based method. RECIP 1.0 can be used to assess disease progression in PCa patients with less advanced disease. This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12615000608561) on 11 June 2015.

Clinical target volume delineation quality assurance for MRI-guided prostate radiotherapy using deep learning with uncertainty estimation.

BACKGROUND AND PURPOSE: Previous studies on automatic delineation quality assurance (QA) have mostly focused on CT-based planning. As MRI-guided radiotherapy is increasingly utilized in prostate cancer treatment, there is a need for more research on MRI-specific automatic QA. This work proposes a clinical target volume (CTV) delineation QA framework based on deep learning (DL) for MRI-guided prostate radiotherapy. MATERIALS AND METHODS: The proposed workflow utilized a 3D dropblock ResUnet++ (DB-ResUnet++) to generate multiple segmentation predictions via Monte Carlo dropout which were used to compute an average delineation and area of uncertainty. A logistic regression (LR) classifier was employed to classify the manual delineation as pass or discrepancy based on the spatial association between the manual delineation and the network's outputs. This approach was evaluated on a multicentre MRI-only prostate radiotherapy dataset and compared with our previously published QA framework based on AN-AG Unet. RESULTS: The proposed framework achieved an area under the receiver operating curve (AUROC) of 0.92, a true positive rate (TPR) of 0.92 and a false positive rate of 0.09 with an average processing time per delineation of 1.3 min. Compared with our previous work using AN-AG Unet, this method generated fewer false positive detections at the same TPR with a much faster processing speed. CONCLUSION: To the best of our knowledge, this is the first study to propose an automatic delineation QA tool using DL with uncertainty estimation for MRI-guided prostate radiotherapy, which can potentially be used for reviewing prostate CTV delineation in multicentre clinical trials.

Risk of cardiac implantable device malfunction in cancer patients receiving proton therapy: an overview.

Age is a risk factor for both cardiovascular disease and cancer, and as such radiation oncologists frequently see a number of patients with cardiac implantable electronic devices (CIEDs) receiving proton therapy (PT). CIED malfunctions induced by PT are nonnegligible and can occur in both passive scattering and pencil beam scanning modes. In the absence of an evidence-based protocol, the authors emphasise that this patient cohort should be managed differently to electron- and photon- external beam radiation therapy (EBRT) patients due to distinct properties of proton beams. Given the lack of a PT-specific guideline for managing this cohort and limited studies on this important topic; the process was initiated by evaluating all PT-related CIED malfunctions to provide a baseline for future reporting and research. In this review, different modes of PT and their interactions with a variety of CIEDs and pacing leads are discussed. Effects of PT on CIEDs were classified into a variety of hardware and software malfunctions. Apart from secondary neutrons, cumulative radiation dose, dose rate, CIED model/manufacturer, distance from CIED to proton field, and materials used in CIEDs/pacing leads were all evaluated to determine the probability of malfunctions. The importance of proton beam arrangements is highlighted in this study. Manufacturers should specify recommended dose limits for patients undergoing PT. The establishment of an international multidisciplinary team dedicated to CIED-bearing patients receiving PT may be beneficial.

Correction factors for commissioning and patient specific quality assurance of stereotactic fields in a Monte Carlo based treatment planning system : TPS correction factors.

Validation of small field dosimetry is crucial for stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT). Accurate and considered measurement of linear accelerator dose must be compared to precise and accurate calculation by the treatment planning system (TPS). Monte Carlo calculated distributions contain statistical noise, reducing the reliance that should be given to single voxel doses. The average dose to a small volume of interest (VOI) can minimise the influence of noise, but for small fields introduces significant volume averaging. Similar challenges present during measurement of composite dose from clinical plans when a small volume ionisation chamber is used. This study derived correction factors for VOI averaged TPS doses calculated for small fields, allowing correction to an isocentre dose following account for statistical noise. These factors were used to determine an optimal VOI to represent small volume ionisation chambers during patient specific quality assurance (PSQA). A retrospective comparison of 82 SRS and 28 SBRT PSQA measurements to TPS calculated doses from varying VOI was completed to evaluate the determined volumes. Small field commissioning correction factors of under 5% were obtained for field sizes of 8 mm and larger. Optimal spherical VOI with radius between 1.5 and 1.8 mm and 2.5 to 2.9 mm were determined for IBA CC01 and CC04 ionisation chambers respectively. Review of PSQA confirmed an optimal agreement between CC01 measured doses and a volume of 1.5 to 1.8 mm while CC04 measured doses showed no variation with VOI.

Validation of prediction models for radiation-induced late rectal bleeding: Evidence from a large pooled population of prostate cancer patients.

PURPOSE: To validate published models for the risk estimate of grade ≥ 1 (G1+), grade ≥ 2 (G2+) and grade = 3 (G3) late rectal bleeding (LRB) after radical radiotherapy for prostate cancer in a large pooled population from three prospective trials. MATERIALS AND METHODS: The external validation population included patients from Europe, and Oceanian centres enrolled between 2003 and 2014. Patients received 3DCRT or IMRT at doses between 66-80 Gy. IMRT was administered with conventional or hypofractionated schemes (2.35-2.65 Gy/fr). LRB was prospectively scored using patient-reported questionnaires (LENT/SOMA scale) with a 3-year follow-up. All Normal Tissue Complication Probability (NTCP) models published until 2021 based on the Equivalent Uniform Dose (EUD) from the rectal Dose Volume Histogram (DVH) were considered for validation. Model performance in validation was evaluated through calibration and discrimination. RESULTS: Sixteen NTCP models were tested on data from 1633 patients. G1+ LRB was scored in 465 patients (28.5%), G2+ in 255 patients (15.6%) and G3 in 112 patients (6.8%). The best performances for G2+ and G3 LRB highlighted the importance of the medium-high doses to the rectum (volume parameters n = 0.24 and n = 0.18, respectively). Good performance was seen for models of severe LRB. Moreover, a multivariate model with two clinical factors found the best calibration slope. CONCLUSION: Five published NTCP models developed on non-contemporary cohorts were able to predict a relative increase in the toxicity response in a more recent validation population. Compared to QUANTEC findings, dosimetric results pointed toward mid-high doses of rectal DVH. The external validation cohort confirmed abdominal surgery and cardiovascular diseases as risk factors.

Intrafraction motion during CyberKnife® prostate SBRT: impact of imaging frequency and patient factors.

PURPOSE:  To determine the relationship between imaging frequencies and prostate motion during CyberKnife stereotactic body radiotherapy (SBRT) for prostate cancer. METHODS:  Intrafraction displacement data for 331 patients who received treatment with CyberKnife for prostate cancer were retrospectively analysed. Prostate positions were tracked with a large variation in imaging frequencies. The percent of treatment time that patients remained inside various motion thresholds for both real and simulated imaging frequencies was calculated. Results: 84,920 image acquisitions over 1635 fractions were analysed. Fiducial distance travelled between consecutive images were less than 2, 3, 5, and 10 mm for 92.4%, 94.4%, 96.2%, and 97.7% of all consecutive imaging pairs respectively. The percent of treatment time that patients received adequate geometric coverage increased with more frequent imaging intervals. No significant correlations between age, weight, height, BMI, rectal, bladder or prostate volumes and intrafraction prostate motion were observed. CONCLUSIONS: There are several combinations of imaging intervals and movement thresholds that may be suitable for consideration during treatment planning with respect to imaging and calculation of the margin between the clinical target volume and planning target volume (CTV-to-PTV), resulting in adequate geometric coverage for approximately 95% of treatment time. Rectal toxicities and treatment duration need to be considered when implementing combinations clinically.

Dosimetric evaluation of an intraoperative radiotherapy system: a measurement-based and Monte-Carlo modelling investigation.

Intraoperative radiotherapy (IORT) is a specialised subset of radiotherapy, where a high radiation dose is delivered to a surgically exposed tumour bed in order to eradicate any remaining cancer cells. The aim of this study was to examine the dose characteristics of the Zeiss Intrabeam IORT device which provides near-isotropic emission of up to 50 kV X-rays. The EGSnrc Monte Carlo (MC) code system was used to simulate the device and percentage depth dose (PDD) data measured with a soft X-ray parallel-plate ionisation chamber were used for model verification. The model provided energy spectra, isodose curves and mean photon energies. In addition, EBT3 Gafchromic film was used to verify the MC model by examining PDDs and 2D dose distributions for various applicators. The differences between MC model and ionisation chamber measurements were within 3% for most points, with a maximum deviation of ~ 9%. Most of the simulated PDD points were within 5% of the film-measured data, with a maximum deviation of ~ 10%. The mean energy of the bare probe was found to be 21.19 keV. The mean photon energy from applicators ranged from 29.00 to 30.85 keV. Results of this study may be useful for future work on creating a system for treatment planning.

Patient-specific voxel-level dose prescription for prostate cancer radiotherapy considering tumor cell density and grade distribution.

BACKGROUND: In prostate radiation therapy, recent studies have indicated a benefit in increasing the dose to intraprostatic lesions (IPL) compared with standard whole gland radiation therapy. Such approaches typically aim to deliver a target dose to the IPL(s) with no deliberate effort to modulate the dose within the IPL. Prostate cancers demonstrate intra-tumor heterogeneity and hence it is hypothesized that further gains in the optimal delivery of radiation therapy can be achieved through modulation of the dose distribution within the tumor. To account for tumor heterogeneity, biologically targeted radiation therapy (BiRT) aims to utilize a voxel-wise approach to IPL dose prescription by incorporating knowledge of the spatial distribution of tumor characteristics. PURPOSE: The aim of this study was to develop a workflow for generating voxel-wise optimal dose prescriptions that maximize patient tumor control probability (TCP), and evaluate the feasibility and benefits of applying this workflow on a cohort of 62 prostate cancer patients. METHOD: The source data for this proof-of-concept study included high resolution histology images annotated with tumor location and grade. Image processing techniques were used to compute voxel-level cell density distribution maps. An absolute tumor cell distribution was calculated via linearly scaling according to published estimated tumor cell numbers. For the IPLs of each patient, optimal dose prescriptions were obtained via three alternative methods for redistribution of IPL boost doses according to maximization of TCP. The radiosensitivity uncertainties were considered using a truncated log-normally distributed linear radiosensitivity parameter ( α k ${\alpha }_k$ ) and compared with Gleason pattern (GP) dependent radiosensitivity parameters that were derived based on previously published methods. An ensemble machine learning method was implemented to identify patient-specific features that predict the TCP improvement resulting from dose redistribution relative to a uniform dose distribution. RESULTS: The Gleason pattern-dependent radiosensitivity parameters were calculated for 20 published prostate cancer α / ß ${{\alpha}}/{{\beta}}$ ratios. Optimal voxel-level dose prescriptions were generated for all 62 PCa patients. For all dose redistribution scenarios, the optimal dose distribution always shows a higher (or equivalent) TCP level than the uniform dose distribution. The applied random forest regressor could predict patient-specific TCP improvement with low root mean square error (≤1.5%) by using total tumor number, volume of IPLs and the standard deviation of tumor cell number among all voxels. CONCLUSION: Biologically-optimized redistribution of a boost dose can yield TCP improvement relative to a uniform-boost dose distribution. Patient-specific tumor characteristics can be used to predict the likelihood of benefit from a redistribution approach for the individual patient.