Endobronchially Implanted Real-Time Electromagnetic Transponder Beacon-Guided, Respiratory-Gated SABR for Moving Lung Tumors: A Prospective Phase 1/2 Cohort Study.

Purpose: Endobronchial electromagnetic transponder beacons (EMT) provide real-time, precise positional data of moving lung tumors. We report results of a phase 1/2, prospective, single-arm cohort study evaluating the treatment planning effects of EMT-guided SABR for moving lung tumors. Methods and Materials: Eligible patients were adults, Eastern Cooperative Oncology Group 0 to 2, with T1-T2N0 non-small cell lung cancer or pulmonary metastasis ≤4 cm with motion amplitude ≥5 mm. Three EMTs were endobronchially implanted using navigational bronchoscopy. Four-dimensional free-breathing computed tomography simulation scans were obtained, and end-exhalation phases were used to define the gating window internal target volume. A 3-mm expansion of gating window internal target volume defined the planning target volume (PTV). EMT-guided, respiratory-gated (RG) SABR was delivered (54 Gy/3 fractions or 48 Gy/4 fractions) using volumetric modulated arc therapy. For each RG-SABR plan, a 10-phase image-guided SABR plan was generated for dosimetric comparison. PTV/organ-at-risk (OAR) metrics were tabulated and analyzed using the Wilcoxon signed-rank pair test. Treatment outcomes were evaluated using RECIST (Response Evaluation Criteria in Solid Tumours; version 1.1). Results: Of 41 patients screened, 17 were enrolled and 2 withdrew from the study. Median age was 73 years, with 7 women. Sixty percent had T1/T2 non-small cell lung cancer and 40% had M1 disease. Median tumor diameter was 1.9 cm with 73% of targets located peripherally. Mean respiratory tumor motion was 1.25 cm (range, 0.53-4.04 cm). Thirteen tumors were treated with EMT-guided SABR and 47% of patients received 48 Gy in 4 fractions while 53% received 54 Gy in 3 fractions. RG-SABR yielded an average PTV reduction of 46.9% (P < .005). Lung V5, V10, V20, and mean lung dose had mean relative reductions of 11.3%, 20.3%, 31.1%, and 20.3%, respectively (P < .005). Dose to OARs was significantly reduced (P < .05) except for spinal cord. At 6 months, mean radiographic tumor volume reduction was 53.5% (P < .005). Conclusions: EMT-guided RG-SABR significantly reduced PTVs of moving lung tumors compared with image-guided SABR. EMT-guided RG-SABR should be considered for tumors with large respiratory motion amplitudes or those located in close proximity to OARs.

Pan-Canadian consensus recommendations for proton beam therapy access in Canada.

PURPOSE: Proton Beam Therapy (PBT)is a treatment option for select cancer patients. It is currently not available in Canada. Assessment and referral processes for out-of-country treatment for eligible patients vary by jurisdiction, leading to variability in access to this treatment for Canadian cancer patients. The purpose of this initiative was to develop a framework document to inform consistent and equitable PBT access for appropriate patients through the creation of pan-Canadian PBT access consensus recommendations. MATERIALS AND METHODS: A modified Delphiprocess was used to develop pan-Canadian recommendations with input from 22 PBT clinical and administrative experts across all provinces, external peer-review by provincial cancer and system partners, and feedback from a targeted community consultation. This was conducted by electronic survey and live discussion. Consensus threshold was set at 70% agreement. RESULTS: Fourconsensus rounds resulted in a final set of 27 recommendations divided into three categories: patient eligibility (n = 9); program level (n = 10); and system level (n = 8). Patient eligibility included: anatomic site (n = 4), patient characteristics (n = 3), clinical efficacy (n = 2). Program level included: regulatory and staff requirements (n = 5), equipment and technologies (n = 4), quality assurance (n = 1). System level included: referral process (n = 5), costing, budget impact and quality adjusted life years (n = 2), eligible patient estimates (n = 1). Recommendations were released nationally in June 2021 and distributed to all 43 cancer programs in Canada. CONCLUSION: A pan-Canadian consensus-building approach was successful in creating an evidence-based, peer-reviewed suite of recommendations thatsupportapplication of consistent clinical criteria to inform treatment options, facility set-up and access to high quality proton therapy.

U-net architecture with embedded Inception-ResNet-v2 image encoding modules for automatic segmentation of organs-at-risk in head and neck cancer radiation therapy based on computed tomography scans.

Purpose.The purpose of this study was to utilize a deep learning model with an advanced inception module to automatically contour critical organs on the computed tomography (CT) scans of head and neck cancer patients who underwent radiation therapy treatment and interpret the clinical suitability of the model results through activation mapping.Materials and methods.This study included 25 critical organs that were delineated by expert radiation oncologists. Contoured medical images of 964 patients were sourced from a publicly available TCIA database. The proportion of training, validation, and testing samples for deep learning model development was 65%, 25%, and 10% respectively. The CT scans and segmentation masks were augmented with shift, scale, and rotate transformations. Additionally, medical images were pre-processed using contrast limited adaptive histogram equalization to enhance soft tissue contrast while contours were subjected to morphological operations to ensure their structural integrity. The segmentation model was based on the U-Net architecture with embedded Inception-ResNet-v2 blocks and was trained over 100 epochs with a batch size of 32 and an adaptive learning rate optimizer. The loss function combined the Jaccard Index and binary cross entropy. The model performance was evaluated with Dice Score, Jaccard Index, and Hausdorff Distances. The interpretability of the model was analyzed with guided gradient-weighted class activation mapping.Results.The Dice Score, Jaccard Index, and mean Hausdorff Distance averaged over all structures and patients were 0.82 ± 0.10, 0.71 ± 0.10, and 1.51 ± 1.17 mm respectively on the testing data sets. The Dice Scores for 86.4% of compared structures was within range or better than published interobserver variability derived from multi-institutional studies. The average model training time was 8 h per anatomical structure. The full segmentation of head and neck anatomy by the trained network required only 6.8 s per patient.Conclusions.High accuracy obtained on a large, multi-institutional data set, short segmentation time and clinically-realistic prediction reasoning make the model proposed in this work a feasible solution for head and neck CT scan segmentation in a clinical environment.

Adaptive radiation therapy strategies in the treatment of prostate cancer patients using hypofractionated VMAT.

PURPOSE: To perform a comprehensive evaluation of eight adaptive radiation therapy strategies in the treatment of prostate cancer patients who underwent hypofractionated volumetric modulated arc therapy (VMAT) treatment. MATERIAL AND METHODS: The retrospective study included 20 prostate cancer patients treated with 40 Gy total dose over five fractions (8 Gy/fraction) using VMAT. Daily cone beam computed tomography images were acquired before the delivery of every fraction and then, with the application of deformable image registration used for the estimation of daily dose, contouring and plan re-optimization. Dosimetric benefits of the various ART strategies were quantified by the comparison of dose and dose-volume metrics derived from treatment planning objectives for original treatment plan and adapted plans with the consideration of target volumes (PTV and CTV) as well as critical structures (bladder, rectum, left, and right femoral heads). RESULTS: Percentage difference (ΔD) between planning objectives and delivered dose in the D99%  > 4000cGy (CTV) metric was -3.9% for the non-ART plan and 2.1% to 4.1% for ART plans. For D99%  > 3800cGy and Dmax  < 4280cGy (PTV), ΔD was -11.2% and -6.5% for the non-ART plan as well as -3.9% to -1.6% and -0.2% to 1.8% for ART plans, respectively. For D15%  < 3200 cGy and D20%  < 2800 cGy (bladder), ΔD was -62.4% and -68.8% for the non-ART plan as well as -60.0% to -57.4% and -67.0% to -64.0% for ART plans. For D15%  < 3200 cGy and D20%  < 2800 cGy (rectum), ΔD was -11.4% and -8.15% for non-ART plan as well as -14.9% to -9.0% and -11.8% to -5.1% for ART plans. CONCLUSIONS: Daily on-line adaptation approaches were the most advantageous, although strategies adapting every other fraction were also impactful while reducing relative workload as well. Offline treatment adaptations were shown to be less beneficial due to increased dose delivered to bladder and rectum compared toother ART strategies.

Performance optimization of a tri-hybrid method for estimation of patient scatter into the EPID.

On-treatment EPID images are contaminated with patient-generated scattered photons. If this component can be accurately estimated, its effect can be removed, and therefore a corresponding in vivo patient dose estimate will be more accurate. Our group previously developed a "tri-hybrid" (TH) algorithm to provide fast but accurate estimates of patient-generated photon scatter. The algorithm uses an analytical method to solve for singly-scattered photon fluence, a modified Monte Carlo hybrid method to solve for multiply-scattered photon fluence, and a pencil beam scatter kernel method to solve for electron interaction generated scattered photon fluence. However, for efficient clinical implementation, spatial and energy sampling must be optimized for speed while maintaining overall accuracy. In this work, the most significant sampling issues were examined, including spatial sampling settings for the patient voxel size, the number of Monte Carlo histories used in the modified hybrid MC method, scatter order sampling for the hybrid method, and also a range of energy spectrum sampling (i.e., energy bin sizes). The total predicted patient-scattered photon fluence entering the EPID was compared with full MC simulation (EGSnrc) for validation. Three phantoms were tested with 6 and 18 MV beam energies, field sizes of 4 × 4, 10 × 10, and 20 × 20 cm2 , and source-to-imager distance of 140 cm to develop a set of optimal sampling settings. With the recommended sampling, accuracy and precision of the total-scattered energy fluence of the TH patient scatter prediction method are within 0.9% and 1.2%, respectively, for all test cases compared with full MC simulation results. For the mean energy spectrum across the imaging plane, comparison of TH with full MC simulation showed 95% overlap. This study has optimized sampling settings so that they have minimal impact on patient scatter prediction accuracy while maintaining maximum execution speed, a critical step for future clinical implementation.

Machine learning for dose-volume histogram based clinical decision-making support system in radiation therapy plans for brain tumors.

PURPOSE: To create and investigate a novel, clinical decision-support system using machine learning (ML). METHODS AND MATERIALS: The ML model was developed based on 79 radiotherapy plans of brain tumor patients that were prescribed a total dose of 60 Gy delivered with volumetric-modulated arc therapy (VMAT). Structures considered for analysis included planning target volume (PTV), brainstem, cochleae, and optic chiasm. The model aimed to classify the target variable that included class-0 corresponding to plans for which the PTV treatment planning objective was met and class-1 that was associated with plans for which the PTV objective was not met due to the priority trade-off to meet one or more organs-at-risk constraints. Several models were evaluated using double-nested cross-validation and an area-under-the-curve (AUC) metric, with the highest performing one selected for further investigation. The model predictions were explained with Shapely additive explanation (SHAP) interaction values. RESULTS: The highest-performing model was Logistic Regression achieving an accuracy of 93.8 ± 4.1% and AUC of 0.98 ± 0.02 on the testing data. The SHAP analysis indicated that the ΔD99% metric for PTV had the greatest influence on the model predictions. The least important feature was ΔDMAX for the left and right cochleae. CONCLUSIONS: The trained model achieved satisfactory accuracy and can be used by medical physicists in a data-driven quality assurance program as well as by radiation oncologists to support their decision-making process in terms of treatment plan approval and potential plan modifications. Model explanation analysis showed that the model relies on clinically valid logic when making predictions.

Verification of the delivered patient radiation dose for non-coplanar beam therapy.

PURPOSE: There is an increased interest in using non-coplanar beams for radiotherapy, including SBRT and SRS. This approach can significantly reduce doses to organs-at-risk, however, it requires stringent quality assurance, especially when a dynamic treatment couch is used. In this work, new functionality that allows using non-coplanar beam arrangements in addition to conventional coplanar beams was added and validated to the previously developed in vivo dose verification system. METHODS: The existing program code was modified to manage the additional treatment couch parameters: angle and positions. Ten non-coplanar test plans that use a static couch were created in the treatment planning system. Also, two plans that use a dynamic treatment couch were created and delivered using Varian Developer mode, since the treatment planning system does not support a dynamic couch. All non-coplanar test trajectories were delivered on a simple geometric phantom, using an Edge linear accelerator (Varian Medical Systems) with the megavoltage imager deployed and acquiring megavoltage transmission images that were used to calculate the delivered 3D dose distributions in the phantom with the updated dose calculation algorithm. The reconstructed dose distributions were compared using the 3D chi-comparison test with 2%/2mm tolerances to the corresponding reference dose distributions obtained from the treatment planning system. RESULTS: The chi-comparison test resulted in at least a 97.0% pass rate over the entire 3D volume for all tested trajectories. For static gantry, static couch non-coplanar fields, and non-coplanar arcs using dynamic couch the pass rates observed were at least 98%, while for the static couch, non-transverse coplanar arc fields, pass rates were at least 97%. CONCLUSIONS: A model-based 3D dose calculation algorithm has been extended and validated for a variety of non-coplanar beam trajectories of different complexities. This system can potentially be applied for quality assurance of treatment delivery systems that use complex, non-coplanar beam arrangements.

4D in vivo dose verification for real-time tumor tracking treatments using EPID dosimetry.

The use of sophisticated techniques such as gating and tracking treatments requires additional quality assurance to mitigate increased patient risks. To address this need, we have developed and validated an in vivo method of dose delivery verification for real-time aperture tracking techniques, using an electronic portal imaging device (EPID)-based, on-treatment patient dose reconstruction and a dynamic anthropomorphic phantom. Using 4DCT scan of the phantom, ten individual treatment plans were created, 1 for each of the 10 separate phases of the respiratory cycle. The 10 MLC apertures were combined into a single dynamic intensity-modulated radiation therapy (IMRT) plan that tracked the tumor motion. The tumor motion and linac delivery were synchronized using an RPM system (Varian Medical Systems) in gating mode with a custom breathing trace. On-treatment EPID frames were captured using a data-acquisition computer with a dedicated frame-grabber. Our in-house EPID-based in vivo dose reconstruction model was modified to reconstruct the 4D accumulated dose distribution for a dynamic MLC (DMLC) tracking plan using the 10-phase 4DCT dataset. Dose estimation accuracy was assessed for the DMLC tracking plan and a single-phase (50% phase) static tumor plan, represented a static field test to verify baseline accuracy. The 3%/3 mm chi-comparison between the EPID-based dose reconstruction for the static tumor delivery and the TPS dose calculation for the static plan resulted in 100% pass rate for planning target volume (PTV) voxels while the mean percentage dose difference was 0.6%. Comparing the EPID-based dose reconstruction for the DMLC tracking to the TPS calculation for the static plan gave a 3%/3 mm chi pass rate of 99.3% for PTV voxels and a mean percentage dose difference of 1.1%. While further work is required to assess the accuracy of this approach in more clinically relevant situations, we have established clinical feasibility and baseline accuracy of using the transmission EPID-based, in vivo patient dose verification for MLC-tracking treatments.

Modeling the temporal-spatial nature of the readout of an electronic portal imaging device (EPID).

PURPOSE: In real-time electronic portal imaging device (EPID) dosimetry applications where on-treatment measured transmission images are compared to an ideal predicted image, ideally a tight tolerance should be set on the quantitative image comparison in order to detect a wide variety of possible delivery errors. However, this is currently not possible due to the appearance of banding artifacts in individual frames of the measured EPID image sequences. The purpose of this work was to investigate simulating banding artifacts in our cine-EPID predicted image sequences to improve matching of individual image frames to the acquired image sequence. Increased sensitivity of this method to potential treatment delivery errors would represent an improvement in patient safety and treatment accuracy. METHODS: A circuit board was designed and built to capture the target current (TARG-I) and forward power signals produced by the linac to help model the discrete beam-formation process of the linac. To simulate the temporal-spatial nature of the EPID readout, a moving read out mask was applied with the timing of the application of the readout mask synchronized to the TARG-I pulses. Since identifying the timing of the first TARG-I pulse affected the location of the banding artifacts throughout the image sequence, and furthermore the first several TARG-I pulses at the beginning of "beam on" are not at full height yet (i.e., dose rate is ramping up), the forward-power signal was also used to assist in reliable detection of the first radiation pulse of the beam delivery. The predicted EPID cine-image sequence obtained using a comprehensive physics-based model was modified to incorporate the discrete nature of the EPID frame readout. This modified banding predicted EPID (MBP-EPID) image sequence was then compared to its corresponding measured EPID cine-image sequence on a frame-by-frame basis. The EPID was mounted on a Clinac 2100ix linac (Varian Medical Systems, Palo Alto, CA). The field size was set to 21.4  ×  28.6 cm2 with no MLC modulation, beam energy of 6 MV, dose rate of 600 MU/min, and 700 MU were delivered for each clockwise (CW) and counter-clockwise (CCW) arc. No phantoms were placed in the beam. RESULTS: The dose rate ramp up effect was observed at the beginning irradiations, and the identification and timing of the radiation pulses, even during the dose rate ramp up, were able to be quantified using the TARG-I and forward power signals. The approach of capturing individual dose pulses and synchronizing with the mask image applied to the original predicted EPID image sequence was demonstrated to model the actual EPID readout. The MBP-EPID image sequences closely reproduced the location and magnitude of the banding features observed in the acquired (i.e., measured) image sequence, for all test irradiations examined here. CONCLUSIONS: The banding artifacts observed in the measured EPID cine-frame sequences were reproduced in the predicted EPID cine-frames by simulating the discrete temporal-spatial nature of the EPID read out. The MBP-EPID images showed good agreement qualitatively to the corresponding measured EPID frame sequence of a simple square test field, without any phantom in the beam. This approach will lead to improved image comparison tolerances for real-time patient dosimetry applications.

A tri-hybrid method to estimate the patient-generated scattered photon fluence components to the EPID image plane.

In vivo dosimetry methods can verify the prescription dose is delivered to the patient during treatment. Unfortunately, in exit dosimetry, the megavoltage image is contaminated with patient-generated scattered photons. However, estimation and removal of the effect of this fluence improves accuracy of in vivo dosimetry methods. This work develops a 'tri-hybrid' algorithm combining analytical, Monte Carlo (MC) and pencil-beam scatter kernel methods to provide accurate estimates of the total patient-generated scattered photon fluence entering the MV imager. For the multiply-scattered photon fluence, a modified MC simulation method was applied, using only a few histories. From each second- and higher-order interaction site in the simulation, energy fluence entering all pixels of the imager was calculated using analytical methods. For photon fluence generated by electron interactions in the patient (i.e. bremsstrahlung and positron annihilation), a convolution/superposition approach was employed using pencil-beam scatter fluence kernels as a function of patient thickness and air gap distance, superposed on the incident fluence distribution. The total patient-scattered photon fluence entering the imager was compared with a corresponding full MC simulation (EGSnrc) for several test cases. These included three geometric phantoms (water, half-water/half-lung, computed tomography thorax) using monoenergetic (1.5, 5.5 and 12.5 MeV) and polyenergetic (6 and 18 MV) photon beams, 10 × 10 cm2 field, source-to-surface distance 100 cm, source-to-imager distance 150 cm and 40 × 40 cm2 imager. The proposed tri-hybrid method is demonstrated to agree well with full MC simulation, with the average fluence differences and standard deviations found to be within 0.5% and 1%, respectively, for test cases examined here. The method, as implemented here with a single CPU (non-parallelized), takes ∼80 s, which is considerably shorter compared to full MC simulation (∼30 h). This is a promising method for fast yet accurate calculation of patient-scattered fluence at the imaging plane for in vivo dosimetry applications.

Feasibility study for marker-based VMAT plan optimization toward tumor tracking.

This work investigates the incorporation of fiducial marker-based visibility parameters into the optimization of volumetric modulated arc therapy (VMAT) plans. We propose that via this incorporation, one may produce treatment plans that aid real-time tumor tracking approaches employing exit imaging of the therapeutic beam (e.g., via EPID), in addition to satisfying purely dosimetric requirements. We investigated the feasibility of this approach for a thorax and prostate site using optimization software (MonArc). For a thorax phantom and a lung patient, three fiducial markers were inserted around the tumor and VMAT plans were created with two partial arcs and prescription dose of 48 Gy (4 fractions). For a prostate patient with three markers in the prostate organ, a VMAT plan was created with two partial arcs and prescription dose 72.8 Gy (28 fractions). We modified MonArc to include marker-based visibility constraints ("hard"and "soft"). A hard constraint (HC) imposes full visibility for all markers, while a soft constraint (SC) penalizes visibility for specific markers in the beams-eye-view. Dose distributions from constrained plans (HC and SC) were compared to the reference nonconstrained (NC) plan using metrics including conformity index (CI), homogeneity index (HI), gradient measure (GM), and dose to 95% of planning target volume (PTV) and organs at risk (OARs). The NC plan produced the best target conformity and the least doses to the OARs for the entire dataset, followed by the SC and HC plans. Using SC plans provided acceptable dosimetric tolerances for both the target and OARs. However, OAR doses may be increased or decreased based on the constrained marker location and number of trackable markers. In conclusion, we demonstrate that visibility constraints can be incorporated into the optimization together with dosimetric objectives to produce treatment plans satisfying both objectives. This approach should ensure greater clinical success when applying real-time tracking algorithms, using VMAT delivery.

Accelerating prostate stereotactic ablative body radiotherapy: Efficacy and toxicity of a randomized phase II study of 11 versus 29 days overall treatment time (PATRIOT).

BACKGROUND: Prostate stereotactic ablative radiotherapy (SABR) regimens differ in time, dose, and fractionation. We report an update of a multicentre, Canadian randomized phase II study to investigate the impact of overall treatment time on quality of life (QOL), efficacy, and toxicity. METHODS: Men with intermediate risk prostate cancer were randomized to 40 Gy in 5 fractions delivered every other day (EOD) versus once per week (QW). Primary outcome was proportion of patients experiencing a minimally clinically important change (MCIC) in acute bowel QOL using EPIC. Secondary outcomes were toxicity, biochemical failure (BF), other QOL domains, and the rate of salvage therapy. FINDINGS: 152 men from 3 centers were randomized; the median follow-up was 62 months. Results are described for EOD versus QW. Acute bowel and urinary QOL was reported previously. Late changes in QOL were not significantly different between the two arms. There were 1 (1.3%) vs 3 (2.7%) late grade 3 + GI toxicities (p = 0.36) and 5 (6.7%) vs 2 (2.7%) late grade 3 GU toxicities (p = 0.44). Two and 5 patients had BF (5-year failure rate 3.0 vs 7.2%, p = 0.22); 0 and 4 patients received salvage therapy (p = 0.04). 5-Year OS and CSS was 95.8% and 98.6% with no difference between arms (p = 0.49, p = 0.15). 3 patients in the QW arm developed metastases. INTERPRETATION: Although we previously reported that weekly prostate SABR had better bowel and urinary QOL compared to EOD, the updated results show no difference in late toxicity, QOL, BF, or PSA kinetics. Patients should be counseled that QW SABR reduces short-term toxicity compared to QW SABR.

Technical note: development and validation of a Monte Carlo tool for analysis of patient-generated photon scatter.

Scattered radiation unavoidably generated in the patient will negatively impact both kilovoltage (KV) and megavoltage (MV) imaging applications. Recently, 'hybrid' methods (i.e. combining analytical and Monte Carlo (MC) techniques) are being investigated as a solution to accurately yet quickly calculate the scattered contribution for both KV and MV images. We have developed a customized MC simulation user code for investigating the individual components of patient-scattered photon fluence, which serves as a valuable tool in this area of research. The MC tool is based on the EGSnrc/DOSXYZnrc user code. The IAUSFL flag options associated with subroutine AUSGAB, combined with LATCH tracking, are used to classify the various interactions of particles with the media. Photons are grouped into six different categories: primary, 1st Compton scatter, 1st Rayleigh scatter, multiple scatter, bremsstrahlung, and positron annihilation. We take advantage of the geometric boundary check in DOSXYZnrc, to write exiting photon particle information to a phase-space file. The tool is validated using homogeneous and heterogeneous phantom configurations with monoenergetic and polyenergetic beams under parallel and divergent beam geometry, comparing MC-simulated exit primary fluence and singly-scattered fluence to corresponding analytical calculations. This MC tool has been validated to separately score the primary and scatter fluence components of the KV and MV imaging applications in the field of radiation therapy. The results are acceptable for the various configurations and beam energies tested here. Overall, the mean percentage differences are less than 0.2% and standard deviations less than 1.6%. This will be a critical test instrument for research in photon scatter applications and particularly for the development of hybrid methods, and is freely available from the authors for research purposes.5.

Constrained optimization towards marker-based tumor tracking in VMAT.

This study proposes that incorporating marker-based visibility constraints into the optimization of volumetric modulated arc therapy (VMAT) will generate treatment plans which not only ensure a higher chance of successfully applying real-time tumor tracking techniques, but also simultaneously satisfy dosimetric objectives. This was applied clinically and investigated for multiple disease sites (10 prostate, 5 liver, and 5 lung) using a radiotherapy optimization software (MonArc), where these new constraints were added to conventional dosimetric constraints. For all the investigated sites, three fiducial markers were located inside or around the planning target volume (PTV), and VMAT plans were created for each patient. We modifiedMonArcto analyze the multi-leaf collimator (MLC) beam's-eye-view at all control points in the gantry arc, while including marker-based visibility constraints of type 'hard' (i.e. requiring 100% visibility of all markers, HC) and 'soft' (i.e. penalizes visibility for one marker [SCI] or two markers [SCII] only) in the optimization process. Dose distributions resulting from the constrained plans (HC, SCI, and SCII) were compared to the non-constrained plan (NC-plans optimized without visibility constraints) using several quantitative dose metrics including the conformity index, homogeneity index, doses to PTV and to organs-at-risk (OAR). Generally, the NC plan produced the best PTV dose conformity and the least OAR doses for the entire patient datasets, followed by the SC and then HC plans, with all the optimization approaches typically achieving acceptable dose metrics. Across the three disease sites, visibility of all three markers in MLC apertures increased from 32% to 100% of available control points as visibility constraints strengthened. Although dose metrics showed some deterioration for constrained plans (-6% for SCIup to -15% for HC using the PTV average index), the required dosimetric objectives were still satisfied in at least 90% of patients. In conclusion, we demonstrated that marker and tumour visibility constraints can be incorporated with dosimetric objectives to produce treatment plans satisfying both objectives, which should ensure greater success when applying real-time tracking for VMAT delivery.

In vivo dosimetry in external beam photon radiotherapy: Requirements and future directions for research, development, and clinical practice.

External beam radiotherapy with photon beams is a highly accurate treatment modality, but requires extensive quality assurance programs to confirm that radiation therapy will be or was administered appropriately. In vivo dosimetry (IVD) is an essential element of modern radiation therapy because it provides the ability to catch treatment delivery errors, assist in treatment adaptation, and record the actual dose delivered to the patient. However, for various reasons, its clinical implementation has been slow and limited. The purpose of this report is to stimulate the wider use of IVD for external beam radiotherapy, and in particular of systems using electronic portal imaging devices (EPIDs). After documenting the current IVD methods, this report provides detailed software, hardware and system requirements for in vivo EPID dosimetry systems in order to help in bridging the current vendor-user gap. The report also outlines directions for further development and research. In vivo EPID dosimetry vendors, in collaboration with users across multiple institutions, are requested to improve the understanding and reduce the uncertainties of the system and to help in the determination of optimal action limits for error detection. Finally, the report recommends that automation of all aspects of IVD is needed to help facilitate clinical adoption, including automation of image acquisition, analysis, result interpretation, and reporting/documentation. With the guidance of this report, it is hoped that widespread clinical use of IVD will be significantly accelerated.

Dosimetric predictors of toxicity and quality of life following prostate stereotactic ablative radiotherapy.

PURPOSE: SABR offers an effective treatment option for clinically localized prostate cancer. Here we report the dosimetric predictors of late toxicity and quality of life (QOL) in a pooled cohort of patients from four phase II trials. METHODS: The combined cohort included all three prostate cancer risk groups. The prescription dose was 35-40 Gy in 5 fractions. Toxicity (CTCAE) and QOL (EPIC) were collected. Multiple dosimetric parameters for the bladder, rectum and penile bulb were collected. Univariate (UVA) followed by multivariate (MVA) logistic regression analysis was conducted to search for significant dosimetric predictors of late GI/GU toxicity, or minimal clinically important change in the relevant QOL domain. RESULTS: 258 patients were included with median follow up of 6.1 years. For QOL, bladder Dmax, V38, D1cc, D2cc, D5cc and rectal V35 were predictors of urinary and bowel MCIC on UVA. On MVA, only bladder V38 remained significant. For late toxicity, various parameters were significant on UVA but only rectal Dmax, V38 and bladder D2cc were significant predictors on MVA. CONCLUSIONS: This report confirms that the high-dose regions in the bladder and rectum are more significant predictors of late toxicity and QOL after prostate SABR compared to low-dose regions. Caution must be taken to avoid high doses and hotspots in those organs.

A modern mold room: Meshing 3D surface scanning, digital design, and 3D printing with bolus fabrication.

PURPOSE: This case series represents an initial experience with implementing 3-dimensional (3D) surface scanning, digital design, and 3D printing for bolus fabrication for patients with complex surface anatomy where traditional approaches are challenging. METHODS AND MATERIALS: For 10 patients requiring bolus in regions with complex contours, bolus was designed digitally from 3D surface scanning data or computed tomography (CT) images using either a treatment planning system or mesh editing software. Boluses were printed using a fused deposition modeling printer with polylactic acid. Quality assurance tests were performed for each printed bolus to verify density and shape. RESULTS: For 9 of 10 patients, digitally designed boluses were used for treatment with no issues. In 1 case, the bolus was not used because dosimetric requirements were met without the bolus. QA tests revealed that the bulk density was within 3% of the reference value for 9 of 12 prints, and with more judicious selection of print settings this could be increased. For these 9 prints, density uniformity was as good as or better than our traditional sheet bolus material. The average shape error of the pieces was less than 0.5 mm, and no issues with fit or comfort were encountered during use. CONCLUSIONS: This study demonstrates that new technologies such as 3D surface scanning, digital design and 3D printing can be safely and effectively used to modernize bolus fabrication.

Two versus five stereotactic ablative radiotherapy treatments for localized prostate cancer: A quality of life analysis of two prospective clinical trials.

PURPOSE: Stereotactic ablative radiotherapy (SABR) is appealing for prostate cancer (PCa) due to low α/ß, and increasing the dose per fraction could improve the therapeutic index and lead to a better quality of life (QOL). Here we report the outcomes of a QOL comparison between two phase II clinical trials: two vs. five fraction prostate SABR. METHODS: Patients had low or intermediate risk PCa. The doses prescribed were 26 Gy/2 and 40 Gy/5. Expanded prostate cancer index composite was collected. Urinary, bowel and sexual domains were analyzed. Minimal clinically important change (MCIC) was defined as >0.5 standard deviation. RESULTS: 30 and 152 patients were treated with 2-fraction and 5-fraction SABR. Median follow-up was 55 and 62 months. Five-year biochemical failure rate was 3.3% and 4.6%. The 2-fraction cohort had a significantly better mean QOL over time in the bowel domain (p = 0.0004), without a significant difference in the urinary or sexual domains. The 2-fraction cohort had a significantly lower rate of bowel MCIC (17.8% vs 42.3%, p = 0.01), but there was no difference in urinary (24.1% vs 35.7%) or sexual (15.3% vs 29.2%) MCIC. For MCIC x2 (moderate QOL change), the 2-fraction trial had significantly lower MCIC rates in both the bowel (7.1% vs 24%, p = 0.04) and sexual (0 vs 17.6%, p = 0.01) domains. CONCLUSIONS: 2-Fraction SABR is feasible to deliver and well tolerated, with significant signals of improved bowel and sexual QOL. A randomized trial of two vs. five fractions for prostate SABR is needed to confirm the promising findings of this study.

Low-cost optical scanner and 3-dimensional printing technology to create lead shielding for radiation therapy of facial skin cancer: First clinical case series.

PURPOSE: Three-dimensional printing has been implemented at our institution to create customized treatment accessories, including lead shields used during radiation therapy for facial skin cancer. To effectively use 3-dimensional printing, the topography of the patient must first be acquired. We evaluated a low-cost, structured-light, 3-dimensional, optical scanner to assess the clinical viability of this technology. METHODS AND MATERIALS: For ease of use, the scanner was mounted to a simple gantry that guided its motion and maintained an optimum distance between the scanner and the object. To characterize the spatial accuracy of the scanner, we used a geometric phantom and an anthropomorphic head phantom. The geometric phantom was machined from plastic and included hemispherical and tetrahedral protrusions that were roughly the dimensions of an average forehead and nose, respectively. Polygon meshes acquired by the optical scanner were compared with meshes generated from high-resolution computed tomography images. Most optical scans contained minor artifacts. Using an algorithm that calculated the distances between the 2 meshes, we found that most of the optical scanner measurements agreed with those from the computed tomography scanner within approximately 1 mm for the geometric phantom and approximately 2 mm for the head phantom. We used this optical scanner along with 3-dimensional printer technology to create custom lead shields for 10 patients receiving orthovoltage treatments of nonmelanoma skin cancers of the face. Patient, tumor, and treatment data were documented. RESULTS: Lead shields created using this approach were accurate, fitting the contours of each patient's face. This process added to patient convenience and addressed potential claustrophobia and medical inability to lie supine. CONCLUSIONS: The scanner was found to be clinically acceptable, and we suggest that the use of an optical scanner and 3-dimensional printer technology become the new standard of care to generate lead shielding for orthovoltage radiation therapy of nonmelanoma facial skin cancer.