Evaluation of inter- and intra-observer variations in prostate gland delineation using CT-alone versus CT/TPUS.

Background: This study aims to explore the role of four-dimensional (4D) transperineal ultrasound (TPUS) in the contouring of prostate gland with planning computed tomography (CT) images, in the absence of magnetic resonance imaging (MRI). Materials and methods: Five radiation oncologists (ROs) performed two rounds of prostate gland contouring (single-blinded) on CT-alone and CT/TPUS datasets obtained from 10 patients who underwent TPUS-guided external beam radiotherapy. Parameters include prostate volume, DICE similarity coefficient (DSC) and centroid position. Wilcoxon signed-rank test assessed the significance of inter-modality differences, and the intraclass correlation coefficient (ICC ) reflected inter- and intra-observer reliability of parameters. Results: Inter-modality analysis revealed high agreement (based on DSC and centroid position) of prostate gland contours between CT-alone and CT/TPUS. Statistical significant difference was observed in the superior-inferior direction of the prostate centroid position (p = 0.011). All modalities yielded excellent inter-observer reliability of delineated prostate volume with ICC > 0.9, mean DSC > 0.8 and centroid position: CT-alone (ICC = 1.000) and CT/TPUS (ICC = 0.999) left-right (L/R); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 0.998) anterior-posterior (A/P); CT-alone (ICC = 0.999) and CT/TPUS (ICC = 1.000) superior-inferior (S/I). Similarly, all modalities yielded excellent intra-observer reliability of delineated prostate volume, ICC > 0.9 and mean DSC > 0.8. Lastly, intra-observer reliability was excellent on both imaging modalities for the prostate centroid position, ICC > 0.9. Conclusion: TPUS does not add significantly to the amount of anatomical information provided by CT images. However, TPUS can supplement planning CT to achieve a higher positional accuracy in the S/I direction if access to CT/MRI fusion is limited.

Duration-dependent margins for prostate radiotherapy-a practical motion mitigation strategy.

BACKGROUND AND OBJECTIVE: The magnitude of intra-fractional prostate displacement (change from initial position over time) is associated with the duration of the patient lying on the radiotherapy treatment couch. This study reports a minute-by-minute association and calculates the impact of this displacement on duration-dependent margins using real-time intra-fractional position data monitored by four-dimensional transperineal ultrasound (4D TPUS). MATERIALS AND METHODS: A total of 55 patients were recruited prospectively. Intra-fractional position of the prostate was monitored in real-time using a 4D TPUS Clarity® system. A total of 1745 monitoring sessions were analysed. Van Herk's margin recipe (2.5∑ + 1.64((σ2 + σp2)1/2 - σp)) was used to estimate the duration-dependant margins for every minute, up to the 15th minute. Linear regression analysis was then performed on the overall margins against time and direction. RESULTS: The mean intra-fractional position was 0.76 mm Inferior (Inf), 0 mm Lateral (Lat) and 0.94 mm Posterior (Post) at the 15th minute. A minimum margin expansion of 2.42 mm (Superior/Inf), 1.02 mm (Left/Right) and 2.65 mm (Anterior/Post) was required for an 8­minute treatment compared to 4.29 mm (Sup/Inf), 1.84 mm (Lt/Rt) and 4.63 mm (Ant/Post) for a 15-minute treatment. The required margin expansion increased linearly (R2 = 0.99) in all directions (p < 0.01). However, while there was no statistically significant difference (p = 0.10) in the required margin expansion in the Sup/Inf and Ant/Post directions respective of the time duration, the margins were much bigger compared to those in the Lt/Rt direction (p < 0.01). CONCLUSION: We report our experience in deriving the minimum duration-dependant margin to generate the required planning target volume for prostate radiotherapy. The required margin increases linearly in all directions within the 15-min duration; thus, the margin will depend on the duration of the technique chosen (IMRT/VMAT/3DCRT/proton).

Deformable anthropomorphic pelvis phantom for dose accumulation verification.

Objective.The validation of deformable image registration (DIR) for contour propagation is often done using contour-based metrics. Meanwhile, dose accumulation requires evaluation of voxel mapping accuracy, which might not be accurately represented by contour-based metrics. By fabricating a deformable anthropomorphic pelvis phantom, we aim to (1) quantify the voxel mapping accuracy for various deformation scenarios, in high- and low-contrast regions, and (2) identify any correlation between dice similarity coefficient (DSC), a commonly used contour-based metric, and the voxel mapping accuracy for each organ.Approach. Four organs, i.e. pelvic bone, prostate, bladder and rectum (PBR), were 3D printed using PLA and a Polyjet digital material, and assembled. The latter three were implanted with glass bead and CT markers within or on their surfaces. Four deformation scenarios were simulated by varying the bladder and rectum volumes. For each scenario, nine DIRs with different parameters were performed on RayStation v10B. The voxel mapping accuracy was quantified by finding the discrepancy between true and mapped marker positions, termed the target registration error (TRE). Pearson correlation test was done between the DSC and mean TRE for each organ.Main results. For the first time, we fabricated a deformable phantom purely from 3D printing, which successfully reproduced realistic anatomical deformations. Overall, the voxel mapping accuracy dropped with increasing deformation magnitude, but improved when more organs were used to guide the DIR or limit the registration region. DSC was found to be a good indicator of voxel mapping accuracy for prostate and rectum, but a comparatively poorer one for bladder. DSC > 0.85/0.90 was established as the threshold of mean TRE ⩽ 0.3 cm for rectum/prostate. For bladder, extra metrics in addition to DSC should be considered.Significance. This work presented a 3D printed phantom, which enabled quantification of voxel mapping accuracy and evaluation of correlation between DSC and voxel mapping accuracy.

Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

"Seeing Is Believing": Additive Utility of 68Ga-PSMA-11 PET/CT in Prostate Cancer Diagnosis.

Widespread adoption of mpMRI has led to a decrease in the number of patients requiring prostate biopsies. 68Ga-PSMA-11 PET/CT has demonstrated added benefits in identifying csPCa. Integrating the use of these imaging techniques may hold promise for predicting the presence of csPCa without invasive biopsy. A retrospective analysis of 42 consecutive patients who underwent mpMRI, 68Ga-PSMA-11 PET/CT, prostatic biopsy, and radical prostatectomy (RP) was carried out. A lesion-based model (n = 122) using prostatectomy histopathology as reference standard was used to analyze the accuracy of 68Ga-PSMA-11 PET/CT, mpMRI alone, and both in combination to identify ISUP-grade group ≥ 2 lesions. 68Ga-PSMA-11 PET/CT demonstrated greater specificity and positive predictive value (PPV), with values of 73.3% (vs. 40.0%) and 90.1% (vs. 82.2%), while the mpMRI Prostate Imaging Reporting and Data System (PI-RADS) 4-5 had better sensitivity and negative predictive value (NPV): 90.2% (vs. 78.5%) and 57.1% (vs. 52.4%), respectively. When used in combination, the sensitivity, specificity, PPV, and NPV were 74.2%, 83.3%, 93.2%, and 51.0%, respectively. Subgroup analysis of PI-RADS 3, 4, and 5 lesions was carried out. For PI-RADS 3 lesions, 68Ga-PSMA-11 PET/CT demonstrated a NPV of 77.8%. For PI-RADS 4-5 lesions, 68Ga-PSMA-11 PET/CT achieved PPV values of 82.1% and 100%, respectively, with an NPV of 100% in PI-RADS 5 lesions. A combination of 68Ga-PSMA-11 PET/CT and mpMRI improved the radiological diagnosis of csPCa. This suggests that avoidance of prostate biopsy prior to RP may represent a valid option in a selected subgroup of high-risk patients with a high suspicion of csPCa on mpMRI and 68Ga-PSMA-11 PET/CT.

A Review of the Current Clinical Evidence for Loco-Regional Moderate Hyperthermia in the Adjunct Management of Cancers.

Regional hyperthermia therapy (RHT) is a treatment that applies moderate heat to tumours in an attempt to potentiate the effects of oncological treatments and improve responses. Although it has been used for many years, the mechanisms of action are not fully understood. Heterogenous practices, poor quality assurance, conflicting clinical evidence and lack of familiarity have hindered its use. Despite this, several centres recognise its potential and have adopted it in their standard treatment protocols. In recent times, significant technical improvements have been made and there is an increasing pool of evidence that could revolutionise its use. Our narrative review aims to summarise the recently published prospective trial evidence and present the clinical effects of RHT when added to standard cancer treatments. In total, 31 studies with higher-quality evidence across various subsites are discussed herein. Although not all of these studies are level 1 evidence, benefits of moderate RHT in improving local tumour control, survival outcomes and quality of life scores were observed across the different cancer subsites with minimal increase in toxicities. This paper may serve as a reference when considering this technique for specific indications.

Oncologic outcomes after MRI-assisted image-guided brachytherapy with hybrid interstitial and intra-cavitary applicators under moderate sedation for locally advanced cervix cancer.

Purpose: To report outcomes of using image-guided hybrid intra-cavitary/interstitial applicators under moderate sedation for locally advanced cervical cancer patients in our institution. Material and methods: A total of 69 fractions of brachytherapy with hybrid applicators were performed in 33 patients from January 2017 to April 2021. All patients underwent MRI pelvis 1 week pre-brachytherapy to determine suitability for interstitial brachytherapy and pre-plan needle placement. All insertion of applicators were performed under moderate sedation with midazolam and/or fentanyl. Fifty-eight (84.1%) fractions were planned with CT alone. Clinical outcomes, dose volume parameters, and toxicities were analyzed. Results: The median follow-up was 28 months. A total of 320 needles (median, 5 needles per fraction) were implanted, with a median insertion depth of 3 cm (range, 1.5-4 cm). The median high-risk clinical target volume (HR-CTV) during initial brachytherapy was 34.5 cc (range, 17.8-74.7 cc). The median total EQD2 D2cc of the rectum, bladder, sigmoid, and small intestine colon was 71.8 Gy, 81.5 Gy, 69 Gy, and 58.3 Gy, respectively. The 2-year local control and overall survival were 80.7% and 77.7%, respectively. Larger volume HR-CTV was significantly associated with worse local control (HR = 1.08, p = 0.005) and overall survival (HR = 1.04, p = 0.015). None of the patients required in-patient admission or blood transfusion post-procedure. Late grade 3 gastrointestinal and genitourinary toxicities were observed in 4 patients (12.2%). Conclusions: Hybrid applicators inserted under moderate sedation are feasible and safe. Image-guided interstitial brachytherapy with CT planning aided by MRI performed 1 week pre-brachytherapy is associated with favorable outcomes and modest toxicities.

Proton versus photon therapy for high-risk prostate cancer with dose escalation of dominant intraprostatic lesions: a preliminary planning study.

Background and purpose: This study aimed to investigate the feasibility of safe-dose escalation to dominant intraprostatic lesions (DILs) and assess the clinical impact using dose-volume (DV) and biological metrics in photon and proton therapy. Biological parameters defined as late grade ≥ 2 gastrointestinal (GI) and genitourinary (GU) derived from planned (D P) and accumulated dose (D A) were utilized. Materials and methods: In total, 10 patients with high-risk prostate cancer with multiparametric MRI-defined DILs were investigated. Each patient had two plans with a focal boost to the DILs using intensity-modulated proton therapy (IMPT) and volumetric-modulated arc therapy (VMAT). Plans were optimized to obtain DIL coverage while respecting the mandatory organ-at-risk constraints. For the planning evaluation, DV metrics, tumor control probability (TCP) for the DILs and whole prostate excluding the DILs (prostate-DILs), and normal tissue complication probability (NTCP) for the rectum and bladder were calculated. Wilcoxon signed-rank test was used for analyzing TCP and NTCP data. Results: IMPT achieved a higher Dmean for the DILs compared to VMAT (IMPT: 68.1 GyRBE vs. VMAT: 66.6 Gy, p < 0.05). Intermediate-high rectal and bladder doses were lower for IMPT (p < 0.05), while the high-dose region (V60 Gy) remained comparable. IMPT-TCP for prostate-DIL were higher compared to VMAT (IMPT: 86%; α/ß = 3, 94.3%; α/ß = 1.5 vs. VMAT: 84.7%; α/ß = 3, 93.9%; α/ß = 1.5, p < 0.05). Likewise, IMPT obtained a moderately higher DIL TCP (IMPT: 97%; α/ß = 3, 99.3%; α/ß = 1.5 vs. VMAT: 95.9%; α/ß = 3, 98.9%; α/ß = 1.5, p < 0.05). Rectal D A-NTCP displayed the highest GI toxicity risk at 5.6%, and IMPT has a lower GI toxicity risk compared to VMAT-predicted Quantec-NTCP (p < 0.05). Bladder D P-NTCP projected a higher GU toxicity than D A-NTCP, with VMAT having the highest risk (p < 0.05). Conclusion: Dose escalation using IMPT is able to achieve a high TCP for the DILs, with the lowest rectal and bladder DV doses at the intermediate-high-dose range. The reduction in physical dose was translated into a lower NTCP (p < 0.05) for the bladder, although rectal toxicity remained equivalent.

Predicting dice similarity coefficient of deformably registered contours using Siamese neural network.

Objective. Automatic deformable image registration (DIR) is a critical step in adaptive radiotherapy. Manually delineated organs-at-risk (OARs) contours on planning CT (pCT) scans are deformably registered onto daily cone-beam CT (CBCT) scans for delivered dose accumulation. However, evaluation of registered contours requires human assessment, which is time-consuming and subjects to high inter-observer variability. This work proposes a deep learning model that allows accurate prediction of Dice similarity coefficients (DSC) of registered contours in prostate radiotherapy.Approach. Our dataset comprises 20 prostate cancer patients with 37-39 daily CBCT scans each. The pCT scans and planning contours were deformably registered to each corresponding CBCT scan to generate virtual CT (vCT) scans and registered contours. The DSC score, which is a common contour-based validation metric for registration quality, between the registered and manual contours were computed. A Siamese neural network was trained on the vCT-CBCT image pairs to predict DSC. To assess the performance of the model, the root mean squared error (RMSE) between the actual and predicted DSC were computed.Main results. The model showed promising results for predicting DSC, giving RMSE of 0.070, 0.079 and 0.118 for rectum, prostate, and bladder respectively on the holdout test set. Clinically, a low RMSE implies that the predicted DSC can be reliably used to determine if further DIR assessment from physicians is required. Considering the event where a registered contour is classified as poor if its DSC is below 0.6 and good otherwise, the model achieves an accuracy of 92% for the rectum. A sensitivity of 0.97 suggests that the model can correctly identify 97% of poorly registered contours, allowing manual assessment of DIR to be triggered.Significance. We propose a neural network capable of accurately predicting DSC of deformably registered OAR contours, which can be used to evaluate eligibility for plan adaptation.

Application of an automated dose accumulation workflow in high-risk prostate cancer - validation and dose-volume analysis between planned and delivered dose.

Inter-fraction organ variations cause deviations between planned and delivered doses in patients receiving radiotherapy for prostate cancer. This study compared planned (DP) vs accumulated doses (DA) obtained from daily cone-beam computed tomography (CBCT) scans in high-risk- prostate cancer with pelvic lymph nodes irradiation. An intensity-based deformable image registration algorithm used to estimate contours for DA was validated using geometrical agreement between radiation oncologist's and deformable image registration algorithm propagated contours. Spearman rank correlations (rs) between geometric measures and changes in organ volumes were evaluated for 20 cases. Dose-volume (DV) differences between DA and DP were compared (Wilcoxon rank test, p < 0.05). A novel region-of-interest (ROI) method was developed and mean doses were analyzed. Geometrical measures for the prostate and organ-at-risk contours were within clinically acceptable criteria. Inter-group mean (± SD) CBCT volumes for the rectum were larger compared to planning CT (pCT) (51.1 ± 11.3 cm3vs 46.6 ± 16.1 cm3), and were moderately correlated with variations in pCT volumes, rs = 0.663, p < 0.01. Mean rectum DV for DA was higher at V30-40 Gy and lower at V70-75 Gy, p < 0.05. Mean bladder CBCT volumes were smaller compared to pCT (198.8 ± 55 cm3vs 211.5 ± 89.1 cm3), and was moderately correlated with pCT volumes, rs = 0.789, p < 0.01. Bladder DA was higher at V30-65 Gy and lower at V70-75 Gy (p < 0.05). For the ROI method, rectum and bladder DA were lower at 5 to 10 mm (p < 0.01) as compared to DP, whilst bladder DA was higher than DP at 20 to 50 mm (p < 0.01). Generated DA demonstrated significant differences in organ-at-risk doses as compared to DP. A well-constructed workflow incorporating a ROI DV-extraction method has been validated in terms of efficiency and accuracy designed for seamless integration in the clinic to guide future plan adaptation.

Predictive modelling for late rectal and urinary toxicities after prostate radiotherapy using planned and delivered dose.

Background and purpose: Normal tissue complication probability (NTCP) parameters derived from traditional 3D plans may not be ideal in defining toxicity outcomes for modern radiotherapy techniques. This study aimed to derive parameters of the Lyman-Kutcher-Burman (LKB) NTCP model using prospectively scored clinical data for late gastrointestinal (GI) and genitourinary (GU) toxicities for high-risk prostate cancer patients treated using volumetric-modulated-arc-therapy (VMAT). Dose-volume-histograms (DVH) extracted from planned (DP) and accumulated dose (DA) were used. Material and methods: DP and DA obtained from the DVH of 150 prostate cancer patients with pelvic-lymph-nodes irradiation treated using VMAT were used to generate LKB-NTCP parameters using maximum likelihood estimations. Defined GI and GU toxicities were recorded up to 3-years post RT follow-up. Model performance was measured using Hosmer-Lemeshow goodness of fit test and the mean area under the receiver operating characteristics curve (AUC). Bootstrapping method was used for internal validation. Results: For mild-severe (Grade ≥1) GI toxicity, the model generated similar parameters based on DA and DP DVH data (DA-D50:71.6 Gy vs DP-D50:73.4; DA-m:0.17 vs DP-m:0.19 and DA/P-n 0.04). The 95% CI for DA-D50 was narrower and achieved an AUC of >0.6. For moderate-severe (Grade ≥2) GI toxicity, DA-D50 parameter was higher and had a narrower 95% CI (DA-D50:77.9 Gy, 95% CI:76.4-79.6 Gy vs DP-D50:74.6, 95% CI:69.1-85.4 Gy) with good model performance (AUC>0.7). For Grade ≥1 late GU toxicity, D50 and n parameters for DA and DP were similar (DA-D50: 58.8 Gy vs DP-D50: 59.5 Gy; DA-n: 0.21 vs DP-n: 0.19) with a low AUC of<0.6. For Grade ≥2 late GU toxicity, similar NTCP parameters were attained from DA and DP DVH data (DA-D50:81.7 Gy vs DP-D50:81.9 Gy; DA-n:0.12 vs DP-n:0.14) with an acceptable AUCs of >0.6. Conclusions: The achieved NTCP parameters using modern RT techniques and accounting for organ motion differs from QUANTEC reported parameters. DA-D50 of 77.9 Gy for GI and DA/DP-D50 of 81.7-81.9 Gy for GU demonstrated good predictability in determining the risk of Grade ≥2 toxicities especially for GI derived D50 and are recommended to incorporate as part of the DV planning constraints to guide dose escalation strategies while minimising the risk of toxicity.

Cardiovascular toxicities of androgen deprivation therapy in Asian men with localized prostate cancer after curative radiotherapy: a registry-based observational study.

BACKGROUND: Androgen deprivation therapy (ADT) and radiotherapy (RT) are the mainstay treatment for localized prostate cancer and recurrence after surgery. Cardiovascular (CV) toxicity of ADT is increasingly recognized, and the risk relates to pre-existing risk factors and ADT modalities. Despite ethnic differences in the prevalence of CV risk factors and variations of CV mortality, data on ADT-related cardiotoxicities in the Asian population remain inconclusive. Our registry-based study investigated ADT-related major adverse cardiovascular events (MACE) after primary or salvage RT. METHODS: Our study combined two prospectively established registry databases from National Cancer Center Singapore and National Heart Center Singapore. The primary endpoint is time to first MACE after treatment. MACE is defined as myocardial infarction, stroke, unstable angina, or cardiovascular death. Two types of propensity score adjustments, including ADT propensity score as a covariate in the multivariable regression model and propensity score weighting, were applied to balance baseline features and CV risk factors between RT alone and RT + ADT groups. RESULTS: From 2000 to 2019, 1940 patients received either RT alone (n = 494) or RT + ADT (n = 1446) were included. After a median follow-up of 10 years (RT) and 7.2 years (RT+ ADT), the cumulative incidence of MACE at 1, 3 and 9 years was 1.2, 5 and 16.2% in RT group, and 1.1, 5.2 and 17.6% in RT + ADT group, respectively. There were no differences in the incidence of MACE between 2 groups (HR 1.01, 95% CI 0.78-1.30, p = 0.969). Pre-treatment CV risk factors were common (80%), and CV disease (15.9%) was the second leading cause of death after prostate cancer (21.1%). On univariate analysis, older age, Indians and Malays, pre-existing CV risk factors, and history of MACE were associated with higher MACE risk. After propensity score adjustments, there remained no significant differences in MACE risk between RT + ADT and RT group on multivariable analysis. CONCLUSIONS: In our registry-based study, ADT is not associated with increased risk of major cardiovascular events among Southeast Asian men with prostate cancer after curative radiotherapy.

Development of an automated radiotherapy dose accumulation workflow for locally advanced high-risk prostate cancer - A technical report.

An automated dose accumulation and contour propagation workflow using daily cone beam computed tomography (CBCTs) images for prostate cases that require pelvic lymph nodes irradiation (PLNs) was developed. This workflow was constructed using MIM® software with the intention to provide accurate dose transformations for plans with two different isocentres, whereby two sequential treatment phases were prescribed. The pre-processing steps for data extractions from treatment plans, CBCTs, determination of couch shift information and management of missing CBCTs are described. To ensure that the imported translational couch shifts were in the correct orientation and readable in MIM, phantom commissioning was performed. For dose transformation, rigid registration with corrected setup shifts and scaled fractional dose was performed for pCT to daily CBCTs, which were then deformed onto CBCT1 . Fractional dose summation resulted in the final accumulated dose for the patient allowing differences in dosimetry between the planned and accumulated dose to be analysed. Contour propagations of the prostate, bladder and rectum were performed within the same workflow. Transformed contours were then deformed onto daily CBCTs to generate trending reports for analysis, including Dice Similarity Coefficient (DSC) and Mean Distance to Agreement (MDA). Results obtained from phantom commissioning (DSC = 0.96, MDA = 0.89 mm) and geometrical analysis of the propagated contours for twenty patients; prostate (DSC: 0.9 ± 0.0, MDA: 1.0 ± 0.3 mm), rectum (DSC: 0.8 ± 0.1, mm, MDA: 1.7 ± 0.6 mm) and bladder (DSC: 0.8 ± 0.1, MDA: 2.8 ± 1.0 mm) were within clinically accepted tolerances for both DSC (>0.8) and MDA (< 0.3 mm). The developed workflow is being performed on a larger patient cohort for predictive model building, with the goal of correlating observed toxicity with the actual accumulated dose received by the patient.

Technical considerations for positioning and placement of a transperineal ultrasound probe during prostate radiotherapy.

This technical evaluation aims to provide practice 'how to' guidelines for radiation therapists (RTs) when positioning a transperineal ultrasound (TPUS) probe during prostate radiotherapy. Recommendations and practical tips will be provided for the best practice in TPUS-guided workflow to obtain optimal ultrasound images for accurate interpretation and registration of the prostate gland. This will assist the RTs in making consistent and accurate clinical decision in an ultrasound-guided radiotherapy workflow for prostate treatment. The implementation process and the associated successes and challenges will also be described to assist institutions who may be investigating the potential of implementing this system.

A Deep Learning-Based Automated CT Segmentation of Prostate Cancer Anatomy for Radiation Therapy Planning-A Retrospective Multicenter Study.

A commercial deep learning (DL)-based automated segmentation tool (AST) for computed tomography (CT) is evaluated for accuracy and efficiency gain within prostate cancer patients. Thirty patients from six clinics were reviewed with manual- (MC), automated- (AC) and automated and edited (AEC) contouring methods. In the AEC group, created contours (prostate, seminal vesicles, bladder, rectum, femoral heads and penile bulb) were edited, whereas the MC group included empty datasets for MC. In one clinic, lymph node CTV delineations were evaluated for interobserver variability. Compared to MC, the mean time saved using the AST was 12 min for the whole data set (46%) and 12 min for the lymph node CTV (60%), respectively. The delineation consistency between MC and AEC groups according to the Dice similarity coefficient (DSC) improved from 0.78 to 0.94 for the whole data set and from 0.76 to 0.91 for the lymph nodes. The mean DSCs between MC and AC for all six clinics were 0.82 for prostate, 0.72 for seminal vesicles, 0.93 for bladder, 0.84 for rectum, 0.69 for femoral heads and 0.51 for penile bulb. This study proves that using a general DL-based AST for CT images saves time and improves consistency.

Analysis of intra-fraction prostate motion and derivation of duration-dependent margins for radiotherapy using real-time 4D ultrasound.

BACKGROUND AND PURPOSE: During radiotherapy, prostate motion changes over time. Quantifying and accounting for this motion is essential. This study aimed to assess intra-fraction prostate motion and derive duration-dependent planning margins for two treatment techniques. MATERIAL AND METHODS: A four-dimension (4D) transperineal ultrasound Clarity® system was used to track prostate motion. We analysed 1913 fractions from 60 patients undergoing volumetric-modulated arc therapy (VMAT) to the prostate. The mean VMAT treatment duration was 3.4 min. Extended monitoring was conducted weekly to simulate motion during intensity-modulated radiation therapy (IMRT) treatment (an additional seven minutes). A motion-time trend analysis was conducted and the mean intra-fraction motion between VMAT and IMRT treatments compared. Duration-dependent margins were calculated and anisotropic margins for VMAT and IMRT treatments were derived. RESULTS: There were statistically significant differences in the mean intra-fraction motion between VMAT and the simulated IMRT duration in the inferior (0.1 mm versus 0.3 mm) and posterior (-0.2 versus -0.4 mm) directions respectively (p ≪ 0.01). An intra-fraction motion trend inferiorly and posteriorly was observed. The recommended minimum anisotropic margins are 1.7 mm/2.7 mm (superior/inferior); 0.8 mm (left/right), 1.7 mm/2.9 mm (anterior/posterior) for VMAT treatments and 2.9 mm/4.3 mm (superior/inferior), 1.5 mm (left/right), 2.8 mm/4.8 mm (anterior/posterior) for IMRT treatments. Smaller anisotropic margins were required for VMAT compared to IMRT (differences ranging from 1.2 to 1.6 mm superiorly/inferiorly, 0.7 mm laterally and 1.1-1.9 mm anteriorly/posteriorly). CONCLUSIONS: VMAT treatment is preferred over IMRT as prostate motion increases with time. Larger margins should be employed in the inferior and posterior directions for both treatment durations. Duration-dependent margins should be applied in the presence of prolonged imaging and verification time.

Reduction of intra-fraction prostate motion - Determining optimal bladder volume and filling for prostate radiotherapy using daily 4D TPUS and CBCT.

BACKGROUND AND PURPOSE: Inconsistent bladder and rectal volumes have been associated with motion uncertainties during prostate radiotherapy. This study investigates the impact of these volumes to determine the optimal bladder volume. MATERIALS AND METHODS: 60 patients from two Asian hospitals were recruited prospectively. 1887 daily cone-beam computed tomography (CBCT) images were analysed. Intra-fraction motion of the prostate was monitored real-time using a four-dimension transperineal ultrasound (4D TPUS) Clarity® system. The impact of planned bladder volume, adequacy of daily bladder filling, and rectum volume on mean intra-fraction motion of the prostate was analysed. Patients' ability to comply with the full bladder hydration protocol and level of frustration was assessed using a questionaire. Acute side effects were assessed using the Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 and quality of life (QoL) assessed using the International Prostate Symptom Score (IPSS). RESULTS: The mean (SD) bladder and rectum volumes achieved during daily treatment were 139.7 cm3 (82.4 cm3) and 53.3 cm3 (18 cm3) respectively. Mean (SD) percentage change from planned CT volumes in bladder volume was reduced by 8.2% (48.7%) and rectum volume was increased by 12.4% (42.2%). Linear Mixed effect model analysis revealed a reduction in intra-fraction motion in both the Sup/Inf (p = 0.008) and Ant/Post (p = 0.0001) directions when the daily bladder was filled between 82 and 113% (3rd Quartiles) of the planned CT volumes. A reduction in intra-fraction motion of the prostate in the Ant/Post direction (z-plane) (p = 0.03) was observed when the planned bladder volume was greater than 200 ml. Patients complied well with the hydration protocol with minimal frustration (mean (SD) scores of 2.1 (1.4) and 1.8 (1.2) respectively). There was a moderate positive correlation (0.496) between mean bladder volume and IPSS reported post-treatment urinary straining (p = 0.001). CONCLUSIONS: A planned bladder volume >200 cm3 and daily filling between 82 and 113%, reduced intra-fraction motion of the prostate. The hydration protocol was well tolerated.

A comparison of interfraction setup error, patient comfort, and therapist acceptance for 2 different prostate radiation therapy immobilization devices.

PURPOSE: Our purpose was to investigate interfraction setup error of the immobilization device required to implement transperineal ultrasound compared with the current, standard immobilization device. Patient comfort and radiation therapist (RT) satisfaction were also assessed. METHODS AND MATERIALS: Cone beam computed tomography images were acquired before 4069 fractions from 111 patients (control group, n = 56; intervention group, n = 55) were analyzed. The intervention group was immobilized using the Clarity Immobilization System (CIS), comprising a knee rest with autoscan probe kit and transperineal ultrasound probe (n = 55), and control group using a leg immobilizer (LI) (n = 56). Interfraction setup errors were compared for both groups. Weekly questionnaires using a 10-point visual analog scale were administered to both patient groups to measure and compare patient comfort. RT acceptance for both devices was also compared using a survey. RESULTS: There was no significant difference in the magnitude of interfraction cone beam computed tomography-derived setup shifts in the lateral and anteroposterior direction between the LI and CIS (P = .878 and .690, respectively). However, a significant difference (P = .003) was observed in the superoinferior direction between the 2 groups of patients. Patient-reported level of comfort and stability demonstrated no significant difference between groups (P = .994 and .132). RT user acceptance measures for the LI and CIS were ease of handling (100% vs 53.7%), storage (100% vs 61.1%), and cleaning of the devices (100% vs 64.8%), respectively. CONCLUSIONS: The CIS demonstrated stability and reproducibility in prostate treatment setup comparable to LI. The CIS device had no impact on patient comfort; however, RTs indicated a preference for LI over the CIS mainly because of its weight and bulkiness.

Late toxicities after conventional radiation therapy alone for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: We sought to evaluate the nature and frequency of late toxicities in a cohort of nasopharyngeal cancer (NPC) patients treated with conventional radiotherapy alone. METHODS AND MATERIALS: Seven-hundred and ninety-six consecutive NPC patients treated using conventional radiotherapy at a single center from 1992 to 1995 were retrospectively analyzed. Patients with histology proven, completely staged, Stage I-IVB World Health Organization Type I-III NPC and completed radical radiotherapy were included. Patients with incomplete staging investigations, distant metastases at diagnosis, previous treatment, and incomplete radiotherapy were excluded. Radiotherapy-related complications were categorized using the RTOG Late Radiation Morbidity Scoring Criteria. RESULTS: Median follow-up was 7.2 years. The 5-year overall survival and disease free survival were 69% and 56%, respectively, and the corresponding 10-year rates were 52% and 44%. Among 771 patients with at least 3 months of follow-up post treatment, 565 (73%) developed RT-related complications. Diagnosed neurological complications were cranial nerve palsies (n=70; 9%), temporal lobe necrosis (n=37; 5%), Lhermitte's syndrome (n=7; 1%), and brachial plexopathy (n=2; 0.3%). Non-neurological complications included xerostomia (n=353; 46%), neck fibrosis (n=169; 22%), hypo-pituitarism (n=48; 6%), hearing loss (n=120; 16%), dysphagia (n=116; 15%), otorrhea (n=101; 13%), tinnitus (n=94; 12%), permanent tube feeding (n=61; 8%), trismus (n=45; 6%), second malignancies within treatment field (n=17; 2%), and osteo-radionecrosis (n=13; 2%). CONCLUSIONS: While radiotherapy is curative in NPC, many patients suffer significant late treatment morbidities with conventional radiotherapy techniques.

Retropharyngeal nodal metastasis related to higher rate of distant metastasis in patients with N0 and N1 nasopharyngeal cancer.

BACKGROUND: Retropharyngeal lymph node (RLN) staging in nasopharyngeal carcinoma (NPC) can be controversial. METHODS: We retrospectively reviewed all patients with T(2-4), N(0-1) NPC treated between 1992 and 1994 to examine if RLN metastasis resulted in an increased incidence of distant metastases. RESULTS: Of the 667 patients with NPC, 395 had T(2-4), N(0-1) disease, 140 had N(0), and 255 had N(1). All had staging CT scans and were treated with radiotherapy. Median follow-up was 8.3 years. Seventy-four percent showed undifferentiated histology. In this cohort, 187 (47%) had RLN metastases. Multivariate analysis showed that RLN conferred a higher hazard for distant metastasis (p = .04). Using the Kaplan-Meier method, patients with N(0) disease and RLN had a similar hazard for distant metastases as patients with N(1) disease when compared with patients with N(0) disease and without RLN. CONCLUSION: Patients with N(0) disease and RLN appear to share a similar prognosis to patients with N(1) disease.