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Purpose: SABR may improve survival in patients with oligometastases, but for some lesions, safe delivery of SABR may require a reduction in delivered dose or target coverage. This study assessed the association between target coverage compromise and oncologic and survival outcomes. Methods and Materials: Patients with a controlled primary malignancy and 1 to 5 oligometastases were randomized (1:2) between standard of care (SOC) treatment and SOC plus SABR. In patients receiving SABR, the target dose coverage was reduced to meet organ at risk (OAR) constraints, if necessary. The D99 value (minimum dose received by the hottest 99% of the planning target volume [PTV]) was used as a measure of PTV coverage for each treatment plan, and the relationship between the coverage compromise index (CCI, defined as D99/prescription dose) and patient outcomes was assessed. Results: Sixty-two patients in the SABR arm had dosimetric information available and a total of 109 lesions were evaluated. The mean CCI per lesion was 0.96 (95% CI, 0.56-1.61). Of the 109 lesions evaluated, 29.4% (n = 32) required coverage compromise (CCI

Background and purpose Positional verification during single fraction lung SBRT could increase confidence and reduce the chance of geographic miss. As planar 2DkV imaging during VMAT irradiation is already available on current linear accelerators, markerless tracking based on these images could offer widely available and low-cost verification. We evaluated treatment delivery data and template matching and triangulation for 3D-positional verification during free-breathing, single fraction (34 Gy), 10 MV flattening-filter-free VMAT lung SBRT. Methods and materials Tumor tracking based on kV imaging at 7 frames/second was performed during irradiation in 6 consecutive patients (7 lesions). Tumor characteristics, tracking ability, comparison of tracking displacements with CBCT-based shifts, tumor position relative to the PTV margin, and treatment times are reported. Results For all 7 lesions combined, 3D tumor position could be determined for, on average, 71% (51–84%) of the total irradiation time. Visually estimated tracked and automated match +/− manually-corrected CBCT-derived displacements generally agreed within 1 mm. During the tracked period, the longitudinal, lateral and vertical position of the tumor was within a 5 mm/3 mm PTV margin 95.5/85.3% of the time. The PTV was derived from the ITV including all tumor motion. The total time from first set-up imaging to end of the last arc was 18.3–31.4 min (mean = 23.4, SD = 4.1). Conclusion 3D positional verification during irradiation of small lung targets with limited motion, was feasible. However, tumor position could not be determined for on average 29% of the time. Improvements are needed. Margin reduction may be feasible. Imaging and delivery of a single 34 Gy fraction was fast.

In the Netherlands, the model-based approach is used to identify patients with head and neck cancer who may benefit most from proton therapy in terms of prevention of late radiation-induced side effects in comparison with photon therapy. To this purpose, a National Indication Protocol Proton therapy for Head and Neck Cancer patients (NIPP-HNC) was developed, which has been approved by the health care authorities. When patients qualify according to the guidelines of the NIPP-HNC, proton therapy is fully reimbursed. This article describes the procedures that were followed to develop this NIPP-HNC and provides all necessary information to introduce model-based selection for patients with head and neck cancer into routine clinical practice.

Background and Purpose: Standard palliative radiotherapy workflows involve waiting times or multiple clinic visits. We developed and implemented a rapid palliative workflow using diagnostic imaging (dCT) for pre-planning, with subsequent on-couch target and plan adaptation based on a synthetic computed tomography (CT) obtained from cone-beam CT imaging (CBCT). Materials and methods: Patients with painful bone metastases and recent diagnostic imaging were eligible for inclusion in this prospective, ethics-approved study. The workflow consisted of 1) telephone consultation with a radiation oncologist (RO); 2) pre-planning on the dCT using planning templates and mostly intensity-modulated radiotherapy; 3) RO consultation on the day of treatment; 4) CBCT scan with on-couch adaptation of the target and treatment plan; 5) delivery of either scheduled or adapted treatment plan. Primary outcomes were dosimetric data and treatment times; secondary outcome was patient satisfaction. Results: 47 patients were enrolled between December 2021 and October 2022. In all treatments, adapted treatment plans were chosen due to significant improvements in target coverage (PTV/CTV V95%, p-value < 0.005) compared to the original treatment plan calculated on daily anatomy. Most patients were satisfied with the workflow. The average treatment time, including consultation and on-couch adaptive treatment, was 85 minutes. On-couch adaptation took on average 30 min. but was longer in cases where the automated deformable image registration failed to correctly propagate the targets. Conclusion: A fast treatment workflow for patients referred for painful bone metastases was implemented successfully using online adaptive radiotherapy, without a dedicated CT simulation. Patients were generally satisfied with the palliative radiotherapy workflow.

Technical improvements in head and neck cancer radiotherapy over the last decade have resulted in substantial reductions in dose to organs-at-risk. For a mix of tumors, we saw less xerostomia moving from 3D-conformal to more advanced techniques. For oropharynx-only there were additional improvements, including in global quality-of-life and sticky saliva.

Purpose Preclinical research into ultrahigh dose rate (eg, ≥40 Gy/s) “FLASH”-radiation therapy suggests a decrease in side effects compared with conventional irradiation while maintaining tumor control. When FLASH is delivered using a scanning proton beam, tissue becomes subject to a spatially dependent range of dose rates. This study systematically investigates dose rate distributions and delivery times for proton FLASH plans using stereotactic lung irradiation as the paradigm. Methods and Materials Stereotactic lung radiation therapy FLASH-plans, using 244 MeV scanning proton transmission beams, with the Bragg peak behind the body, were made for 7 patients. Evaluated parameters were dose rate distribution within a beam, overall irradiation time, number of times tissue is irradiated, and quality of the FLASH-plans compared with the clinical volumetric-modulated arc therapy (VMAT) plans. Results Sparing of lungs, thoracic wall, and heart in the FLASH-plans was equal to or better than that in the VMAT-plans. For a spot peak dose rate (SPDR, the dose rate in the middle of the spot) of 100 Gy/s, ∼40% of dose is delivered at FLASH dose rates, and for SPDR = 360 Gy/s this increased to ∼75%. One-hundred percent FLASH dose rate cannot be achieved owing to small contributions from distant spots with lower dose rates. The total irradiation time varied between 300 to 730 ms, and around 85% of the dose-receiving body volume was irradiated by either 1 or 2 beams. Conclusions Clinical implementation of FLASH using scanning proton beams requires multiple treatment planning considerations: dosimetric, temporal, and spatial parameters all seem important. The FLASH efficiency of a scanning proton beam increases with SPDR. The methodology proposed in this proof-of-principle study provides a framework for evaluating the FLASH characteristics of scanning proton beam plans and can be adapted as FLASH parameters are better defined. It currently seems logical to optimize plans for the shortest delivery time, maximum amount of high dose rate coverage, and maximum amount of single beam and continuous irradiation.

Purpose Accurate verification of tumor position during irradiation could reduce the probability of target miss. We investigated whether a commercial gantry-mounted 2-dimensional (2D) kilo-voltage (kV) imaging system could be used for real-time 3D tumor tracking during volumetric modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT). Markerless tumor tracking on kV fluoroscopic images was validated using a life-like moving thorax phantom and subsequently performed on kV images continuously acquired before and during free-breathing VMAT lung SBRT. Methods and Materials The 3D-printed/molded phantom containing 3 lung tumors was moved in 3D in TrueBeam developer mode, using simulated regular/irregular breathing patterns. Planar kV images were acquired at 7 frames/s during 11 Gy/fraction 10 MV flattening filter free VMAT. 2D reference templates were created for each gantry angle using the planning 4D computed tomography inspiration phase. kV images and templates were matched using normalized cross correlation to determine 2D tumor position, and triangulation of 2D matched projections determined the third dimension. 3D target tracking performed on cone beam computed tomography projection data from 18 patients (20 tumors) and real-time online tracking data from 2 of the 18 patients who underwent free-breathing VMAT lung SBRT are presented. Results For target 1 and 2 of the phantom (upper lung and middle/medial lung, mean density –130 Hounsfield units), 3D results within 2 mm of the known position were present in 92% and 96% of the kV projections, respectively. For target 3 (inferior lung, mean density –478 Hounsfield units) this dropped to 80%. Benchmarking against the respiratory signal, 13/20 (65%) tumors (10.5 ± 11.1 cm3) were considered successfully tracked on the cone beam computed tomography data. Tracking was less successful (≤50% of the time) in 7/20 (1.2 ± 1.5 cm3). Successful online tracking during lung SBRT was demonstrated. Conclusions 3D markerless tumor tracking on a standard linear accelerator using template matching and triangulation of free-breathing kV fluoroscopic images was possible in 65% of small lung tumors. The smallest tumors were most challenging.

Purpose To benchmark and improve, through means of a targeted intervention, the quality of intensity modulated radiation therapy treatment planning for locally advanced head and neck cancer (HNC) in the Netherlands. The short and long-term impact of this intervention was assessed. Methods and materials A delineated computed tomography-scan of an oropharynx HNC case was sent to all 15 Dutch radiation therapy centers treating HNC. Aims for planning target volume and organ-at-risk (OAR) dosimetry were established by consensus. Each center generated a treatment plan. In a targeted intervention, OAR sparing of all plans was discussed, and centers with the best OAR sparing shared their planning strategies. Impact of the intervention was assessed by (1) short-term (half a year after intervention) replanning of the original case and (2) long-term (1 and 3 years after intervention) planning of new cases. Results Benchmarking revealed substantial difference in OAR doses. Initial mean doses were 22 Gy (range, 15-31 Gy), 35 Gy (18-49 Gy), and 37 Gy (20-46 Gy) for the contralateral parotid gland, contralateral submandibular gland, and combined swallowing structures, respectively. Replanning after targeted intervention significantly reduced mean doses and variation, but clinically relevant differences still remained: 18 Gy (14-22 Gy), 28 Gy (17-45 Gy), and 29 Gy (18-39 Gy), respectively. One and 3 years later the variation remained stable. Conclusions Despite many years of HNC intensity modulated radiation therapy experience, initial treatment plans showed surprisingly large variations. The simple targeted intervention used in this analysis improved OAR sparing, and its impact was durable; however, fairly large dose differences still continue to exist. Additional work is needed to understand these variations and to minimize them. A national radiation oncology platform can be instrumental for developing and maintaining high-quality planning protocols.

Purpose: Organ-at-risk (OAR) delineation is a key step in treatment planning but can be time consuming, resource intensive, subject to variability, and dependent on anatomical knowledge. We studied deep learning (DL) for automated delineation of multiple OARs; in addition to geometric evaluation, the dosimetric impact of using DL contours for treatment planning was investigated. Methods and Materials: The following OARs were delineated with DL developed in-house: both submandibular and parotid glands, larynx, cricopharynx, pharyngeal constrictor muscle (PCM), upper esophageal sphincter, brain stem, oral cavity, and esophagus. DL contours were benchmarked against the manual delineation (MD) clinical contours using the Sørensen-Dice similarity coefficient. Automated knowledge-based treatment plans were used. The mean dose to the manually delineated OAR structures was reported for the MD and DL plans. Results: DL delineation of all OARs took 2 Gy higher and >2 Gy lower, respectively, in the DL plans. Conclusions: DL-based segmentation for head and neck OARs is fast; for most organs and most patients, it performs sufficiently well for treatment-planning purposes. It has the potential to increase efficiency and facilitate online adaptive radiation therapy.

INTRODUCTION: Radiotherapy treatment plan quality can influence clinical trial outcomes and general QA may not identify suboptimal organ-at-risk (OAR) sparing. We retrospectively performed patient-specific quality assurance (QA) of 100 head-and-neck cancer (HNC) plans from the EORTC-1219-DAHANCA-29 study.MATERIALS AND METHODS: A 177-patient RapidPlan (Varian Medical Systems) model comprising institutional HNC plans was used to QA trial plans (Ptrial). RapidPlan plans (Prapidplan) were created using RapidPlan and Eclipse scripting to achieve a high degree of automation. Comparison between Prapidplan mean predicted/achieved OAR doses, and Ptrial mean OAR doses was made for parotid/submandibular glands (PGs/SMGs) and swallowing muscles (SM).RESULTS: OAR predictions were made within 2 min per patient. Averaged PG/SMG/SM mean doses were 2.0/9.0/3.8 Gy lower in Prapidplan. Using predicted Prapidplan combined mean OAR dose as the benchmark, a total of 60/27/4 trial plans could be improved by 3/6/9 Gy respectively.DISCUSSION: Individualized QA indicated that OAR sparing could frequently be improved in EORTC-1219 study plans, even though they met the trial's generic plan criteria. Automated, patient-specific QA can be performed within a few minutes and should be considered to reduce the influence of planning variation on trial outcomes.

Transmission beam (TB) proton therapy (PT) uses single, high energy beams with Bragg-peak behind the target, sharp penumbras and simplified planning/delivery. TB facilitates ultra-high dose-rates (UHDRs, e.g., ≥40 Gy/s), which is a requirement for the FLASH-effect. We investigated (1) plan quality for conventionally-fractionated head-and-neck cancer treatment using spot-scanning proton TBs, intensity-modulated PT (IMPT) and photon volumetric-modulated arc therapy (VMAT), (2) UHDR-metrics. VMAT, 3-field IMPT and 10-field TB-plans, delivering 70/54.25 Gy in 35 fractions to boost/elective volumes, were compared (n = 10 patients). To increase spot peak dose-rates (SPDRs), TB-plans were split into three subplans, with varying spot monitor units and different gantry currents. Average TB-plan organs-at-risk (OAR) sparing was comparable to IMPT: mean oral cavity/body dose were 4.1/2.5 Gy higher (9.3/2.0 Gy lower than VMAT), most other OAR mean doses differed by &lt, 2 Gy. Average percentage of dose delivered at UHDRs was 46%/12% for split/non-split TB-plans and mean dose-averaged dose-rate 46/21 Gy/s. Average total beam-on irradiation time was 1.9/3.8 s for split/non-split plans and overall time including scanning 8.9/7.6 s. Conventionally-fractionated proton TB-plans achieved comparable OAR-sparing to IMPT and better than VMAT, with total beam-on irradiation times &lt, 10s. If a FLASH-effect can be demonstrated at conventional dose/fraction, this would further improve plan quality and TB-protons would be a suitable delivery system.

Purpose Contouring organs at risk remains a largely manual task, which is time consuming and prone to variation. Deep learning-based delineation (DLD) shows promise both in terms of quality and speed, but it does not yet perform perfectly. Because of that, manual checking of DLD is still recommended. There are currently no commercial tools to focus attention on the areas of greatest uncertainty within a DLD contour. Therefore, we explore the use of spatial probability maps (SPMs) to help efficiency and reproducibility of DLD checking and correction, using the salivary glands as the paradigm. Methods and Materials A 3-dimensional fully convolutional network was trained with 315/264 parotid/submandibular glands. Subsequently, SPMs were created using Monte Carlo dropout (MCD). The method was boosted by placing a Gaussian distribution (GD) over the model's parameters during sampling (MCD + GD). MCD and MCD + GD were quantitatively compared and the SPMs were visually inspected. Results The addition of the GD appears to increase the method's ability to detect uncertainty. In general, this technique demonstrated uncertainty in areas that (1) have lower contrast, (2) are less consistently contoured by clinicians, and (3) deviate from the anatomic norm. Conclusions We believe the integration of uncertainty information into contours made using DLD is an important step in highlighting where a contour may be less reliable. We have shown how SPMs are one way to achieve this and how they may be integrated into the online adaptive radiation therapy workflow.

Introduction: Manual quality assurance (QA) of radiotherapy contours for clinical trials is time and labor intensive and subject to inter-observer variability. Therefore, we investigated whether deep-learning (DL) can provide an automated solution to salivary gland contour QA. Material and methods: DL-models were trained to generate contours for parotid (PG) and submandibular glands (SMG). Sørensen–Dice coefficient (SDC) and Hausdorff distance (HD) were used to assess agreement between DL and clinical contours and thresholds were defined to highlight cases as potentially sub-optimal. 3 types of deliberate errors (expansion, contraction and displacement) were gradually applied to a test set, to confirm that SDC and HD were suitable QA metrics. DL-based QA was performed on 62 patients from the EORTC-1219-DAHANCA-29 trial. All highlighted contours were visually inspected. Results: Increasing the magnitude of all 3 types of errors resulted in progressively severe deterioration/increase in average SDC/HD. 19/124 clinical PG contours were highlighted as potentially sub-optimal, of which 5 (26%) were actually deemed clinically sub-optimal. 2/19 non-highlighted contours were false negatives (11%). 15/69 clinical SMG contours were highlighted, with 7 (47%) deemed clinically sub-optimal and 2/15 non-highlighted contours were false negatives (13%). For most incorrectly highlighted contours causes for low agreement could be identified. Conclusion: Automated DL-based contour QA is feasible but some visual inspection remains essential. The substantial number of false positives were caused by sub-optimal performance of the DL-model. Improvements to the model will increase the extent of automation and reliability, facilitating the adoption of DL-based contour QA in clinical trials and routine practice.

Background Deep learning-based delineation of organs-at-risk for radiotherapy purposes has been investigated to reduce the time-intensiveness and inter-/intra-observer variability associated with manual delineation. We systematically evaluated ways to improve the performance and reliability of deep learning for organ-at-risk segmentation, with the salivary glands as the paradigm. Improving deep learning performance is clinically relevant with applications ranging from the initial contouring process, to on-line adaptive radiotherapy. Methods Various experiments were designed: increasing the amount of training data (1) with original images, (2) with traditional data augmentation and (3) with domain-specific data augmentation; (4) the influence of data quality was tested by comparing training/testing on clinical versus curated contours, (5) the effect of using several custom cost functions was explored, and (6) patient-specific Hounsfield unit windowing was applied during inference; lastly, (7) the effect of model ensembles was analyzed. Model performance was measured with geometric parameters and model reliability with those parameters’ variance. Results A positive effect was observed from increasing the (1) training set size, (2/3) data augmentation, (6) patient-specific Hounsfield unit windowing and (7) model ensembles. The effects of the strategies on performance diminished when the base model performance was already ‘high’. The effect of combining all beneficial strategies was an increase in average Sørensen–Dice coefficient of about 4% and 3% and a decrease in standard deviation of about 1% and 1% for the submandibular and parotid gland, respectively. Conclusions A subset of the strategies that were investigated provided a positive effect on model performance and reliability. The clinical impact of such strategies would be an expected reduction in post-segmentation editing, which facilitates the adoption of deep learning for autonomous automated salivary gland segmentation.

Purpose: To present the radiation therapy quality assurance results from a prospective multicenter phase 2 randomized trial of short versus protracted urethra-sparing stereotactic body radiation therapy (SBRT) for localized prostate cancer. Methods and Materials: Between 2012 and 2015, 165 patients with prostate cancer from 9 centers were randomized and treated with SBRT delivered either every other day (arm A, n = 82) or once a week (arm B, n = 83); 36.25 Gy in 5 fractions were prescribed to the prostate with (n = 92) or without (n = 73) inclusion of the seminal vesicles (SV), and the urethra planning-risk volume received 32.5 Gy. Patients were treated either with volumetric modulated arc therapy (VMAT; n = 112) or with intensity modulated radiation therapy (IMRT; n = 53). Deviations from protocol dose constraints, planning target volume (PTV) homogeneity index, PTV Dice similarity coefficient, and number of monitor units for each treatment plan were retrospectively analyzed. Dosimetric results of VMAT versus IMRT and treatment plans with versus without inclusion of SV were compared. Results: At least 1 major protocol deviation occurred in 51 patients (31%), whereas none was observed in 41. Protocol violations were more frequent in the IMRT group (P 98% (31.1 vs 30.8 Gy, P 2% (37.9 vs 38.7 Gy, P 50% (24.5% vs 33.5%, P =.0001). To achieve its goals volumetric modulated arc therapy required fewer monitor units than IMRT (2275 vs 3378, P 90% (9.1% vs 10.4%, P =.0003) and V80% (13.2% vs 15.7%, P =.0003). Conclusions: Protocol deviations with potential impact on tumor control or toxicity occurred in 31% of patients in this prospective clinical trial. Protocol deviations were more frequent with IMRT. Prospective radiation therapy quality assurance protocols should be strongly recommended for SBRT trials to minimize potential protocol deviations.

A substantial barrier to the single-and multi-institutional aggregation of data to supporting clinical trials, practice quality improvement efforts, and development of big data analytics resource systems is the lack of standardized nomenclatures for expressing dosimetric data. To address this issue, the American Association of Physicists in Medicine (AAPM) Task Group 263 was charged with providing nomenclature guidelines and values in radiation oncology for use in clinical trials, data-pooling initiatives, population-based studies, and routine clinical care by standardizing: (1) structure names across image processing and treatment planning system platforms; (2) nomenclature for dosimetric data (eg, doseevolume histogram [DVH]-based metrics); (3) templates for clinical trial groups and users of an initial subset of software platforms to facilitate adoption of the standards; (4) formalism for nomenclature schema, which can accommodate the addition of other structures defined in the future. A multisociety, multidisciplinary, multinational group of 57 members representing stake holders ranging from large academic centers to community clinics and vendors was assembled, including physicists, physicians, dosimetrists, and vendors. The stakeholder groups represented in the membership included the AAPM, American Society for Radiation Oncology (ASTRO), NRG Oncology, European Society for Radiation Oncology (ESTRO), Radiation Therapy Oncology Group (RTOG), Children's Oncology Group (COG), Integrating Healthcare Enterprise in Radiation Oncology (IHE-RO), and Digital Imaging and Communications in Medicine working group (DICOM WG); A nomenclature system for target and organ at risk volumes and DVH nomenclature was developed and piloted to demonstrate viability across a range of clinics and within the framework of clinical trials. The final report was approved by AAPM in October 2017. The approval process included review by 8 AAPM committees, with additional review by ASTRO, European Society for Radiation Oncology (ESTRO), and American Association of Medical Dosimetrists (AAMD). This Executive Summary of the report highlights the key recommendations for clinical practice, research, and trials. (C) 2017 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Purpose Imaging phantoms are widely used for testing and optimization of imaging devices without the need to expose humans to irradiation. However, commercially available phantoms are commonly manufactured in simple, generic forms and sizes and therefore do not resemble the clinical situation for many patients. Methods Using 3D printing techniques, we created a life-size phantom based on a clinical CT scan of the thorax from a patient with lung cancer. It was assembled from bony structures printed in gypsum, lung structures consisting of airways, blood vessels >1 mm, and outer lung surface, three lung tumors printed in nylon, and soft tissues represented by silicone (poured into a 3D printed mold). Results Kilovoltage X-ray and CT images of the phantom closely resemble those of the real patient in terms of size, shapes, and structures. Surface comparison using 3D models obtained from the phantom and the 3D models used for printing showed mean differences

Introduction Treatment patterns in stage III NSCLC can vary considerably between countries. The PACIFIC trial reported improvements in progression-free and overall survival with adjuvant durvalumab after concurrent chemoradiotherapy (CCRT). We studied treatment decision-making by three Dutch regional thoracic multidisciplinary tumor boards between 2015 and 2019, to identify changes in practice when adjuvant durvalumab became available. Methods Details of patients presenting with stage III NSCLC were retrospectively collected. Both CCRT and multimodality schemes incorporating planned surgery were defined as being radical-intent treatment (RIT). Results Of 855 eligible patients, most (95%) were discussed at a thoracic multidisciplinary tumor board, which recommended a RIT in 63% (n = 510). Only 52% (n = 424) of the patients finally received a RIT. Predictors for not recommending RIT were age greater than or equal to 70 years, WHO performance score greater than or equal to 2, Charlson comorbidity index greater than or equal to 2 (excluding age), forced expiratory volume in 1 second less than 80% of predicted value, N3 disease, and period of diagnosis. Between 2015 to 2017 and 2018 to 2019, the proportion of patients undergoing CCRT increased from 34% to 42% (p = 0.02) and use of sequential chemoradiotherapy declined (21%–16%, p = 0.05). Rates of early toxicity and 1-year mortality were comparable for both periods. After 2018, 57% of the patients who underwent CCRT (90 of 159) received adjuvant durvalumab. Conclusions After publication of the PACIFIC trial, a significant increase was observed in the use of CCRT for patients with stage III NSCLC with rates of early toxicity and mortality being unchanged. Since 2018, 57% of the patients undergoing CCRT went on to receive adjuvant durvalumab. Nevertheless, approximately half of the patients were still considered unfit for a RIT.

Background and purpose Patient selection for proton therapy by comparing proton/photon treatment plans is time-consuming and prone to bias. RapidPlan™, a knowledge-based-planning solution, uses plan-libraries to model and predict organ-at-risk (OAR) dose-volume-histograms (DVHs). We investigated whether RapidPlan, utilizing an algorithm based only on photon beam characteristics, could generate proton DVH-predictions and whether these could correctly identify patients for proton therapy. Material and methods ModelPROT and ModelPHOT comprised 30 head-and-neck cancer proton and photon plans, respectively. Proton and photon knowledge-based-plans (KBPs) were made for ten evaluation-patients. DVH-prediction accuracy was analyzed by comparing predicted-vs-achieved mean OAR doses. KBPs and manual plans were compared using salivary gland and swallowing muscle mean doses. For illustration, patients were selected for protons if predicted ModelPHOT mean dose minus predicted ModelPROT mean dose (ΔPrediction) for combined OARs was ≥6 Gy, and benchmarked using achieved KBP doses. Results Achieved and predicted ModelPROT/ModelPHOT mean dose R2 was 0.95/0.98. Generally, achieved mean dose for ModelPHOT/ModelPROT KBPs was respectively lower/higher than predicted. Comparing ModelPROT/ModelPHOT KBPs with manual plans, salivary and swallowing mean doses increased/decreased by

Background and purpose: The TRENDY trial is an international multi-center phase-II study, randomizing hepatocellular carcinoma (HCC) patients between transarterial chemoembolization (TACE) and stereotactic body radiation therapy (SBRT) with a target dose of 48-54 Gy in six fractions. The radiotherapy quality assurance (QA) program, including prospective plan feedback based on automated treatment planning, is described and results are reported.Materials and methods: Scans of a single patient were used as a benchmark case. Contours submitted by nine participating centers were compared with reference contours. The subsequent planning round was based on a single set of contours. A total of 20 plans from participating centers, including 12 from the benchmark case, 5 from a clinical pilot and 3 from the first study patients, were compared to automatically generated VMAT plans.Results: For the submitted liver contours, Dice Similarity Coefficients (DSC) with the reference delineation ranged from 0.925 to 0.954. For the GTV, the DSC varied between 0.721 and 0.876. For the 12 plans on the benchmark case, healthy liver normal-tissue complication probabilities (NTCPs) ranged from 0.2% to 22.2% with little correlation between NCTP and PTV-D95% (R-2 Conclusions: Delineation variation resulted in feedback to participating centers. Automated treatment planning can play an important role in clinical trials for prospective plan QA as suboptimal plans were detected. (c) 2017 Elsevier B.V. All rights reserved.

Purpose Stereotactic ablative body radiation therapy (SABR) for lung tumors ≥5 cm can be associated with more toxicity than that for smaller tumors. We investigated the relationship between dosimetry and toxicity and used a knowledge-based planning solution to retrospectively perform individualized treatment plan quality assurance (QA) with the aim of identifying where planning could have been improved. Methods and Materials Previous retrospective analysis of 53 patients with primary or recurrent non-small cell lung cancer ≥5 cm, treated with 5- or 8-fraction volumetric modulated arc therapy SABR between 2008 and 2014, showed 30% with grade ≥3 toxicity. During this period, several improvements were made to departmental planning protocols. RapidPlan was used to compare dosimetry of patients with or without grade ≥3 toxicity. A model comprising plans from patients without toxicity and compliant with the current planning protocol was used to provide QA for the plans from patients who had toxicity. Results Sixteen of 53 patients had grade ≥3 toxicity, including 10 with radiation pneumonitis (RP), 3 with lung hemorrhage (1 of these also had RP), and 1 with airway stenosis/atelectasis. RP was again shown to be significantly correlated with contralateral and total-lung V5 and mean lung dose. The 4 highest contralateral-lung doses belonged to patients with RP. Five of 10 clinical plans in patients with RP had a contralateral-lung mean dose up to 2.5 times higher than that of the knowledge-based plan. For 2 of 3 patients with lung hemorrhage and 1 with airway stenosis/atelectasis, the clinical plans had the highest proximal bronchial tree doses, which was also higher than in plans from the model. In 8 patients with grade ≥3 toxicity, clinical plans had dosimetry similar to that in the predictions from the model. Conclusions A “no-toxicity” RapidPlan model identified the potential for dosimetric improvement in nearly 50% of historical treatment plans from patients with grade ≥3 toxicity after SABR for lung tumors ≥5 cm. Model-based QA may be useful for benchmarking treatment planning protocols in routine practice and in clinical studies.

Purpose To investigate changes in head-and-neck cancer (HNC) plan quality following the introduction of new technologies and planning techniques in the last decade. Methods and materials Thirty plans were selected from each of four successive periods (P). P1: 7-field static intensity-modulated radiotherapy (IMRT) with parotid gland sparing; P2: dual-arc volumetric-modulated arc therapy (VMAT, similar to P3-P4), including submandibular gland sparing; P3: inclusion of individual swallowing muscles and attempts to further reduce parotid and oral cavity doses through manual interactive optimization; P4: containing the same organs-at-risk (OARs) as P3, but automatically interactively optimized. Plan benchmarking included mean salivary gland/swallowing muscle/oral cavity (D sal /D swal /D oc ) doses. Differences in mean doses between the periods were analyzed by an ANCOVA, taking geometric differences across periods into account. Results Compared to P1, P2 plans improved D sal by 3.4Gy on average. P3 improved D sal /D swal /D oc by 6.9/11.5/7.2Gy over P2, showing that D swal and D sal could be improved simultaneously. In P4, D oc /D swal slightly improved over P3 by 1.7/3.8Gy. Improved OAR sparing in P3/P4 did not come at the cost of increased dose deposition elsewhere and planning target volume (PTV) dose homogeneity was similar. Conclusions New technologies and planning techniques were successfully implemented into routine clinical care and resulting in improved HNC plan quality.

Purpose: Interactive optimization during treatment planning requires intermittent adjustment of organ-at-risk (OAR) objectives relative to the dose–volume histogram line. This is a labor-intensive process and the resulting plans are prone to variations in quality. The authors’ in-house developed approach to automated interactive optimization (AIO) automatically moves the mouse cursor to adjust the position of on-screen optimization objectives. This allows for the use of more objectives per OAR and results in a more frequent and consistent adjustment of these objectives during optimization. The authors report a detailed evaluation of AIO performance in support of its implementation for routine head and neck cancer (HNC) planning and an evaluation for locally advanced lungcancer (LC) planning which requires a different optimization strategy. Methods: Volumetric modulated arc therapy AIO plans (APs) were created for 70 HNC patients with a simultaneously integrated boost and 20 LC patients and benchmarked against their respective manually interactively optimized plans (MPs). The same set of optimization objectives and priorities was used for all APs, although planning target volume (PTV) optimization priorities could be increased manually in a subsequent “continue previous optimization” calculation. HNC plans were benchmarked using mean dose to individual and composite OARs and elective/boost PTV (PTVE/PTVB) volumes receiving 95% and 107% of the prescription dose (V95% and V107%, respectively). A clinician performed blinded comparison of 20 APs and respective MPs. LC plans were compared using PTV V95%/V107%, contralateral lung (CL) volume receiving 5 Gy (V5Gy), total lung (TL)-PTV V5Gy/V20Gy, and esophagus and heart V40Gy/V60Gy/mean doses. Results: For HNC, statistically significant improvements in sparing of all OARs, except for the ipsilateral submandibular gland and trachea, were obtained in the APs compared to MPs. Average mean dose to oral cavity, composite salivary, and swallowing structures were 25.4/23.8, 24.2/23.2, and 29.5/25.5 Gy, respectively, for the MPs/APs. PTV heterogeneity was similar: in the APs, PTVB V95% was 0.2% higher while PTV B/PTV E V107% was 0.4%/1.0% lower. In 19 out of 20 HNC patients, the clinician preferred the AP, mainly because of better OAR sparing and PTV dose homogeneity. For LC, APs had a significantly lower CL V5Gy (6.1%), heart mean dose/V60Gy (0.9 Gy/1.2%) and esophagus mean dose/V60Gy (0.9 Gy/2.8%), a nonsignificantly higher TL V20Gy (1.4%), and a slight, but significantly higher dose deposition to the body. PTV dose coverage and homogeneity were similar in the APs and MPs. AIO was considered sufficiently robust for clinical use in LC. Conclusions: HNC and LC APs were at least as good as, and often of improved quality over MPs. To date, AIO has been clinically implemented for HNC planning.

To the Editor,Concurrent chemo-radiotherapy (CRT) is a guideline recommended treatment for fit patients presenting with locally advanced non-small cell lung cancer (NSCLC) [1]. However, for many pa...

Background Automated treatment planning and/or optimization systems (ATPS) are in the process of broad clinical implementation aiming at reducing inter-planner variability, reducing the planning time allocated for the optimization process and improving plan quality. Five different ATPS used clinically were evaluated for advanced head and neck cancer (HNC). Methods Three radiation oncology departments compared 5 different ATPS: 1) Automatic Interactive Optimizer (AIO) in combination with RapidArc (in-house developed and Varian Medical Systems); 2) Auto-Planning (AP) (Philips Radiation Oncology Systems); 3) RapidPlan version 13.6 (RP1) with HNC model from University Hospital A (Varian Medical Systems, Palo Alto, USA); 4) RapidPlan version 13.7 (RP2) combined with scripting for automated setup of fields with HNC model from University Hospital B; 5) Raystation multicriteria optimization algorithm version 5 (RS) (Laboratories AB, Stockholm, Sweden). Eight randomly selected HNC cases from institution A and 8 from institution B were used. PTV coverage, mean and maximum dose to the organs at risk and effective planning time were compared. Ranking was done based on 3 Gy increments for the parallel organs. Results All planning systems achieved the hard dose constraints for the PTVs and serial organs for all patients. Overall, AP achieved the best ranking for the parallel organs followed by RS, AIO, RP2 and RP1. The oral cavity mean dose was the lowest for RS (31.3 ± 17.6 Gy), followed by AP (33.8 ± 17.8 Gy), RP1 (34.1 ± 16.7 Gy), AIO (36.1 ± 16.8 Gy) and RP2 (36.3 ± 16.2 Gy). The submandibular glands mean dose was 33.6 ± 10.8 Gy (AP), 35.2 ± 8.4 Gy (AIO), 35.5 ± 9.3 Gy (RP2), 36.9 ± 7.6 Gy (RS) and 38.2 ± 7.0 Gy (RP1). The average effective planning working time was substantially different between the five ATPS (in minutes)

PURPOSE: To correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model.METHODS AND MATERIALS: Patients with a central lung tumor from 2 centers, who underwent stereotactic or hypofractionated radiotherapy (≤12 fractions), were analyzed. Doses were recalculated to an equivalent dose of 2 Gy with an α/β ratio of 10 (EQD210). The esophagus was manually delineated and DVH-parameters (Dmax,EQD2, D1cc,EQD2, D2cc,EQD2, D5cc,EQD2) were analyzed and used for NTCP modeling based on logistic regression analysis.RESULTS: Two-hundred-and-thirty-one patients with 252 tumors were eligible. No acute or late grade 3-5 esophageal toxicity was reported. Acute grade 1-2 esophagus toxicity was recorded in 38 patients (17%). All DVH-parameters were significantly higher in patients with toxicity. NTCP models showed a 50% probability of acute grade 1-2 toxicity at a Dmax of 67 Gy EQD210 and D1cc of 42 Gy EQD210. No difference in overall survival was observed between patients with and without toxicity (p = 0.428).CONCLUSION: As no grade 3-5 esophageal toxicity was observed in our cohort, a Dmax of 56 Gy EQD210 and a D5cc of 35.5 Gy EQD210 could be delivered without high risks of severe toxicity. The NTCP models of this study might be used as practical guidelines for the treatment of central lung tumors with stereotactic radiotherapy.

Purpose The purpose was to report our initial experience with online markerless 3-dimensional (3D) spine position monitoring. We used template matching plus triangulation of fluoroscopic kilovoltage images acquired with the gantry-mounted imager during flattening filter-free volumetric modulated arc spine stereotactic body radiation therapy delivery on a conventional linear accelerator. Methods and Materials Kilovoltage images were acquired at 7 frames per second and streamed to a stand-alone computer. Two-dimensional templates (1/°) containing the clinical target volume were generated from planning computed tomography (CT) data before the first fraction and matched to the (prefiltered) kilovoltage images during treatment. Each 2-dimensional registration was triangulated with multiple previous registrations, resulting in the 3D spine position offset from the planned position in real time during treatment. If the offset was more than a certain threshold, the treatment was manually stopped and a cone beam CT scan was acquired to reposition the patient. Results During irradiation of 10 fractions in 3 patients, images were analyzed at an average rate of 1.0 to 1.3 frames per second; all other frames were excluded from the analysis because of limitations in processing speed. As a result of the start-up period of triangulation and poorer image quality at the start of treatment (lateral imaging angles), the first 3D position was determined after an average of 4.9 seconds. On the basis of the position results, we interrupted the treatment beam 2 times for different patients. In all cases the spine position results corresponded well with the CT–cone beam CT match values used for subsequent repositioning. Conclusions For the first time, we have determined the spine position during stereotactic body radiation therapy delivery on a standard linear accelerator using the gantry-mounted kilovoltage imager. This has the potential to increase confidence in the treatment, and the need for 2 treatment interruptions demonstrates the benefit of monitoring during irradiation. However, software improvements are needed to increase processing speed.

Purpose: Four-dimensional (4D) cone-beam computed tomography (CBCT) of the lung is an effective tool for motion management in radiotherapy but presents a challenge because of slow gantry rotation times. Sorting the individual projections by breathing phase and using an established technique such as Feldkamp–Davis–Kress (FDK) to generate corresponding phase-correlated (PC) three-dimensional (3D) images results in reconstructions (FDK-PC) that often contain severe streaking artifacts due to the sparse angular sampling distributions. These can be reduced by further slowing down the gantry at the expense of incurring unwanted increases in scan times and dose. A computationally efficient alternative is the McKinnon-Bates (MKB) reconstruction algorithm that has shown promise in reducing view aliasing-induced streaking but can produce ghosting artifacts that reduce contrast and impede the determination of motion trajectories. The purpose of this work was to identify and correct shortcomings in the MKB algorithm. Methods: In the general MKB approach, a time-averaged 3D prior image is first reconstructed. The prior is then forward-projected at the same angles as the original projection data creating time-averaged reprojections. These reprojections are subsequently subtracted from the original (unblurred) projections to create motion-encoded difference projections. The difference projections are reconstructed into PC difference images that are added to the well-sampled 3D prior to create the higher quality 4D image. The cause of the ghosting in the traditional 4D MKB images was studied and traced to motion-induced streaking in the prior that, when reprojected, has the undesirable effect of re-encoding for motion in what should be a purely time-averaged reprojection. A new method, designated as the modified McKinnon-Bates (mMKB) algorithm, was developed based on destreaking the prior. This was coupled with a postprocessing 4D bilateral filter for noise suppression and edge preservation (mMKBbf). The algorithms were tested with the 4D XCAT phantom using four simulated scan times (57, 60, 120, 180 s) and with two in vivo thorax studies (acquisition time of 60 and 90 s). Contrast-to-noise ratios (CNRs) of the target lesions and overall visual quality of the images were assessed. Results: Prior destreaking (mMKB algorithm) reduced ghosting artifacts and increased CNRs for all cases, with the biggest impacts seen in the end inhale (EI) and end exhale (EE) phases of the respiratory cycle. For the XCAT phantom, mMKB lesion CNR was 44% higher than the MKB lesion CNR and was 81% higher than the FDK-PC lesion CNR (EI and EE phases). The bilateral filter provided a further average CNR improvement of 87% with the highest increases associated with longer scan times. Across all phases and scan times, the maximum mMKBbf-to-FDK-PC CNR improvement was over 300%. In vivo results agreed with XCAT results. Significantly less ghosting was observed throughout the mMKB images including near the lesions-of-interest and the diaphragm allowing for, in one case, visualization of a small tumor with nearly 30 mm of motion. The maximum FDK-PC-to-MKBbf CNR improvement for Patient 1's lesion was 261% and for Patient 2's lesion was 318%. Conclusions: The 4D mMKB algorithm yields good quality coronal and sagittal images in the thorax that may provide sufficient information for patient verification.

Background: Radiotherapy treatment planning as an increasingly automated and knowledge-based planning has been shown to match and sometimes improve upon manual clinical plans, with increased consistency and efficiency. In this study, we benchmarked a novel prototype knowledge-based intensity-modulated proton therapy (IMPT) planning solution, against three international proton centers. Methods: A model library was constructed, comprising 50 head and neck cancer (HNC) manual IMPT plans from a single center. Three external-centers each provided seven manual benchmark IMPT plans. A knowledge-based plan (KBP) using a standard beam arrangement for each patient was compared with the benchmark plan on the basis of planning target volume (PTV) coverage and homogeneity and mean organ-at-risk (OAR) dose. Results: PTV coverage and homogeneity of KBPs and benchmark plans were comparable. KBP mean OAR dose was lower in 32/54, 45/48 and 38/53 OARs from center-A, -B and -C, with 23/32, 38/45 and 23/38 being &gt, 2 Gy improvements, respectively. In isolated cases the standard beam arrangement or an OAR not being included in the model or being contoured differently, led to higher individual KBP OAR doses. Generating a KBP typically required &lt, 10 min. Conclusions: A knowledge-based IMPT planning solution using a single-center model could efficiently generate plans of comparable quality to manual HNC IMPT plans from centers with differing planning aims. Occasional higher KBP OAR doses highlight need for beam angle optimization and manual review of KBPs. The solution furthermore demonstrated the potential for robust optimization.

Background This is a dosimetric comparative study intended to establish appropriate low-to-intermediate dose-constraints for the rectal wall (Rwall) in the context of a randomized phase-II trial on urethra-sparing stereotactic body radiotherapy (SBRT) for prostate cancer. The effect of plan optimization on low-to-intermediate Rwall dose and the potential benefit of an endorectal balloon (ERB) are investigated. Methods Ten prostate cancer patients, simulated with and without an ERB, were planned to receive 36.25Gy (7.25Gyx5) to the planning treatment volume (PTV) and 32.5Gy to the urethral planning risk volume (uPRV). Reference plans with and without the ERB, optimized with respect to PTV and uPRV coverage objectives and the organs at risk dose constraints, were further optimized using a standardized stepwise approach to push down dose constraints to the Rwall in the low to intermediate range in five sequential steps to obtain paired plans with and without ERB (Vm1 to Vm5). Homogeneity index for the PTV and the uPRV, and the Dice similarity coefficient (DSC) for the PTV were analyzed. Dosimetric parameters for Rwall including the median dose and the dose received by 10 to 60% of the Rwall, bladder wall (Bwall) and femoral heads (FHeads) were compared. The monitor units (MU) per plan were recorded. Results Vm4 reduced by half D30%, D40%, D50%, and Dmed for Rwall and decreased by a third D60% while HIPTV, HIuPRV and DSC remained stable with and without ERB compared to Vmref. HIPTV worsened at Vm5 both with and without ERB. No statistical differences were observed between paired plans on Rwall, Bwall except a higher D2% for Fheads with and without an ERB. Conclusions Further optimization to the Rwall in the context of urethra sparing prostate SBRT is feasible without compromising the dose homogeneity to the target. Independent of the use or not of an ERB, low-to-intermediate doses to the Rwall can be significantly reduced using a four-step sequential optimization approach.

Background and purpose Central lung stereotactic body radiotherapy (SBRT) can cause proximal bronchial tree (PBT) toxicity. Information on PBT position relative to the high-dose could aid risk management. We investigated template matching + triangulation for high-frequency markerless 3D PBT position monitoring. Materials and methods Kilovoltage projections of a moving phantom (full-fan cone-beam CT [CBCT, 15 frames/second] without MV irradiation: 889 images/dataset + CBCT and 7 frames/second fluoroscopy with MV irradiation) and ten patients undergoing free-breathing stereotactic/hypofractionated lung irradiation (full-fan CBCT without MV irradiation, 470–500 images/dataset) were retrospectively analyzed. 2D PBT reference templates (1 filtered digitally reconstructed radiograph/°) were created from planning CT data. Using normalized cross-correlation, templates were matched to projection images for 2D position. Multiple registrations were triangulated for 3D position. Results For the phantom, 2D right/left PBT position could be determined in 86.6/75.1% of the CBCT dataset without MV irradiation, and 3D position (excluding first 20° due to the minimum triangulation angle) in 84.7/72.7%. With MV irradiation, this was up to 2% less. For right/left PBT, root-mean-square errors of measured versus “known” position were 0.5/0.8, 0.4–0.5/0.7, and 0.4/0.5–0.6 mm for left–right, superior–inferior, and anterior–posterior directions, respectively. 2D PBT position was determined in, on average, 89.8% of each patient dataset (range: 79.4–99.2%), and 3D position (excluding first 20°) in 85.1% (range: 67.9–99.6%). Motion was mainly superior–inferior (range: 4.5–13.6 mm, average: 8.5 mm). Conclusions High-frequency 3D PBT position verification during free-breathing is technically feasible using markerless template matching + triangulation of kilovoltage projection images acquired during gantry rotation. Applications include organ-at-risk position monitoring during central lung SBRT.

Background and purpose: Current standards for organ-at-risk (OAR) contouring encourage anatomical accuracy which can be resource intensive. Certain OARs may be suitable for alternative delineation strategies. We investigated whether simplified salivary and swallowing structure contouring can still lead to good OAR sparing in automated head and neck cancer (HNC) plans. Materials and methods: For 15 HNC patients, knowledge-based plans (KBPs) using RapidPlan™ were created using: (1) standard clinical contours for all OARs (benchmark-plans), (2) automated knowledge-based contours for the salivary glands, with standard contours for the remaining OARs (SS-plans) and (3) simplified contours (SC-plans) consisting of quick-to-draw tubular structures to account for the oral cavity, salivary glands and swallowing muscles. Individual clinical OAR contours in a RapidPlan™ model were combined to create composite salivary/swallowing structures. These were matched to tube-contours to create SC-plans. All plans were compared based on dose to anatomically accurate clinical OAR contours. Results: Salivary gland delineation in SS-plans required on average 2 min, compared with 7 min for manual delineation of all tubular-contours. Automated atlas-based contours overlapped with, on average, 71% of clinical salivary gland contours while tube-contours overlapped with 95%/75%/93% of salivary gland/oral cavity/swallowing structure contours. On average, SC-plans were comparable to benchmark-plans and SS-plans, with average differences in composite salivary and swallowing structure dose ≤2 Gy and

Not all clinics have breath‐hold radiotherapy available for left‐breast irradiation. However intensity‐modulated radiotherapy (IMRT) has also been advocated as a means of lowering heart doses. There is currently no large‐scale, long‐term follow‐up data after breast IMRT and, since dose distributions may differ from classic tangent‐based radiotherapy, caution is needed to avoid unexpected worsening of the late toxicity profile. We compared four IMRT techniques for free‐breathing left‐breast irradiation. Consistent with the aforementioned concerns, our goal in planning was to prioritize organ at risk (OAR) sparing in a way that mimicked tangent‐based radiotherapy. Ten simultaneous integrated boost treatment plans (PTVelective=15×2.67 Gy;PTVboost=15×3.35 Gy) were created using 1) hybrid‐IMRT (H‐IMRT), 2) full IMRT (F‐IMRT), and 3) volumetric‐modulated arc therapy with two partial arcs (2ARC) and 4) six partial arcs (6ARC). Reduction in OAR mean and low dose was prioritized. End‐points included OAR sparing (e.g., heart, left anterior descending artery [LAD+3 mm], lungs, and contralateral breast) and PTV coverage/dose homogeneity. Under these conditions we found the following: 1) H‐IMRT provided the best mean and low dose OAR sparing, PTVelective coverage (mean V95%=98%),PTVboost coverage (V95%=98%), and PTV homogeneity. However, it delivered most intermediate–high dose to the heart, LAD+3 mm and ipsilateral lung; 2) 6ARC had the best intermediate–high dose sparing, followed by F‐IMRT, but this was at the expense of more dose in the contralateral lung and breast and worse PTV coverage (PTVelective mean V95%=96%/97% and PTVboost mean V95%=91%/96% for 6ARC/F‐IMRT). When trying to spare mean and low dose to OARs, the preferred IMRT technique for left‐breast irradiation without breath‐hold was H‐IMRT. This is currently the standard solution in our institution for left‐breast radiotherapy under free‐breathing and breath‐hold conditions. PACS numbers: 87.53kn, 87.53Jw, 87.55.D‐, 87.55.de, 87.55.dk

Purpose: (1) To validate retrospective markerless tracking software for small lung tumors by comparing tracked motion in 4-dimensional planning computed tomography (4DCT) derived kV projection images and known tumor motion in the same 4DCT. (2) To evaluate variability of tumor motion using kV projection images from cone-beam computed tomography (CBCT) scans acquired on different days. Methods: Nonclinical tumor tracking software (TTS) used a normalized cross correlation algorithm to track the tumor on enhanced kV projection images (e.g., from a CBCT scan). The reference dataset consisted of digitally reconstructed radiographs (DRRs) from one phase of a planning 4DCT. TTS matches two in-plane coordinates and obtains the out-of-plane coordinate by triangulating with match results from other projections. (1) To validate TTS, tracking results were compared with known 4DCT tumor motion for two patients (A and B). Projection images (1 image/1°) were digitally reconstructed for each 4DCT phase. From these, kV projection series were composed simulating full breathing cycles every 20° of gantry rotation [breathing period = 20°/(6°/s) = 3.33 s]. Reference templates were 360 “tumor enhanced” DRRs from the 4DCT expiration phase. TTS-derived tumor motion was compared to known tumor motion on 4DCT. (2) For five patients, TTS-assessed motion during clinical CBCT acquisition was compared with motion on the planning 4DCT, and the motion component in the Y (cranio–caudal)-direction was compared with the motion of an external marker box (RPM, real-time position management). Results: (1) Validation results: TTS for case A (tumor 6.2 cm3, 32 mm axial diameter) over 360° showed mean motion X (medial–lateral) = 3.4, Y = 11.5, and Z (ventral–dorsal) = 4.9 mm (1 SD < 1.0 mm). Corresponding 4DCT motion was X = 3.1, Y = 11.3, and Z = 5.1 mm. Correlation coefficients between TTS tumor motion and displacement of the tumor’s center of mass (CoM) on 4DCT were 0.64, 0.96, and 0.82 (X, Y, and Z, respectively). For case B (4.1 cm3, 20 mm diameter), due to temporarily decreased tumor visibility preventing TTS from resolving the tumor, robust tracking data were only available between angles 300°–40° and 120°–220°. Mean motion according to TTS was X = 2.0, Y = 7.7, and Z = 8.2 mm (1 SD 2.0 mm (1 SD) in four of five patients. In addition, clinical tumor motion amplitude differed from that seen on planning 4DCT. Internal and external structures that create abrupt density change (e.g., table-top edge, interface between lung/mediastinum and lung/heart) were observed to prevent 360° tracking of the tumor. Correlation coefficients between TTS motion in the Y-direction and the RPM signal (22 observations) ranged from 0.78 to 0.96. In 2D, 241 TTS matches at end-inspiration and end-expiration were visually validated: mean difference was 0.8 mm (SD = 0.7) for both. Conclusions: TTS can track small lung tumors if these are visible in kV projections. A 4DCT dataset can be used to validate kV tracking of moving targets. TTS and 4DCT displacement agreed to within 2 mm. TTS and RPM motion were closely associated but tumor motion during CBCT can vary from the planning 4DCT.

BACKGROUND AND PURPOSE: Proof of tumor position during stereotactic body radiotherapy (SBRT) delivery is desirable. We investigated if cone-beam CT (CBCT) scans reconstructed from (collimated) fluoroscopic kV images acquired during irradiation could show the dominant tumor position.MATERIALS AND METHODS: Full-arc CBCT scans were reconstructed using FDK filtered back projection from 38kV fluoroscopy datasets (16 patients) continuously acquired during volumetric modulated spine SBRT. CBCT-CT match values were compared to the average spine offset values found using template matching+triangulation of the individual kV images. Multiple limited-arc CBCTs were reconstructed from fluoroscopic images acquired during lung SBRT of an anthropomorphic thorax phantom using 20-180° arc lengths and for 3 breath-hold lung SBRT patients.RESULTS: Differences between 3D CBCT-CT match results and average spine offsets found using template matching+triangulation were 0.1±0.1mm for all directions (range: 0.0-0.5mm). For limited-arc CBCTs of the thorax phantom, the automatic 3D CBCT-CT match results for arc lengths of 80-180° were ≤1mm. 20° CBCT reconstruction still allowed for positional verification in 2D.CONCLUSIONS: (Limited-arc) CBCT reconstructions of kV images acquired during irradiation can identify the dominant position of the tumor during treatment delivery.

Introduction Stereotactic ablative radiotherapy (SABR) is currently not the guideline-recommended treatment for lung tumors measuring more than 5 cm. However, improvements in radiotherapy techniques have led to increasing use of SABR for larger tumors. Methods We analyzed the clinical outcomes in patients with a primary or recurrent NSCLC measuring more than 5 cm and treated with five or eight fractions of SABR at our center. Patients who had prior thoracic radiotherapy were excluded. Results A total of 63 consecutive patients with a median tumor diameter of 5.8 cm (range 5.1–10.4) were identified; 81% had T2N0 disease and 18% had T3N0 disease. The median Charlson comorbidity index was 2 (range 0–6). After a median follow-up of 54.7 months, median survival was 28.3 months. Disease-free survival at 2 years was 82.1%, and the local, regional, and distant control rates at 2 years were 95.8%, 93.7%, and 83.6%, respectively. An out-of-field distant recurrence at one or more sites was the most common pattern of failure (10%). Grade 3 or higher toxicity was recorded in 30% of patients, with radiation pneumonitis being the most common toxicity (19%). A likely (n = 4) or possible (n = 8) treatment-related death was scored in 19% of patients. There was preexisting interstitial lung disease in eight patients (13%), with fatal toxicity developing in five of them (63%). Conclusions Lung SABR in tumors larger than 5 cm resulted in high local control rates and acceptable survival outcomes in a patient population with appreciable comorbidity. Patients with interstitial lung disease should be considered a very high-risk population for SABR.

PURPOSE: To evaluate clinical pulmonary and radiographic bronchial toxicity after stereotactic ablative radiation therapy and hypofractionated radiation therapy for central lung tumors, and perform normal tissue complication probability modeling and multivariable analyses to identify predictors for toxicity.METHODS AND MATERIALS: A pooled analysis was performed of patients with a central lung tumor treated using ≤12 fractions at 2 centers between 2006 and 2015. Airways were manually contoured on planning computed tomography scans, and doses were recalculated to an equivalent dose of 2 Gy per fraction with an α/β ratio of 3. Grade ≥3 (≥G3) clinical pulmonary toxicity was evaluated by 2 or more physicians. Radiographic toxicity was defined as a stenosis or an occlusion with or without atelectasis using follow-up computed tomography scans. Logistic regression analyses were used for statistical analyses.RESULTS: A total of 585 bronchial structures were studied in 195 patients who were mainly treated using 5 or 8 fractions (60%). Median patient survival was 27.9 months (95% confidence interval 22.3-33.6 months). Clinical ≥G3 toxicity was observed in 24 patients (12%) and radiographic bronchial toxicity in 55 patients (28%), both mainly manifesting ≤12 months after treatment. All analyzed dosimetric parameters correlated with clinical and lobar bronchial radiographic toxicity, with V130Gy,EQD having the highest odds ratio. Normal tissue complication probability modeling showed a volume dependency for the development of both clinical and radiographic toxicity. On multivariate analyses, significant predictors for ≥G3 toxicity were a planning target volume overlapping the trachea or main stem bronchus (P = .005), chronic obstructive pulmonary disease (P = .034), and the total V130Gy,EQD (P = .012). Radiographic bronchial toxicity did not significantly correlate with clinical toxicity (P = .663).CONCLUSIONS: We identified patient and dosimetric factors associated with clinical and radiographic toxicity after high-dose radiation therapy for central lung tumors. Additional data from prospective studies are needed to validate these findings.

Over the past three decades several randomized trials have enabled evidence-based practice for patients presenting with limited brain metastases. These trials have focused on the role of surgery or stereotactic radiosurgery (SRS) with or without whole brain radiation therapy (WBRT). As a result, it is clear that local control should be optimized with surgery or SRS in patients with optimal prognostic factors presenting with up to 4 brain metastases. The routine use of adjuvant WBRT remains debatable, as although greater distant brain control rates are observed, there is no impact on survival, and modern outcomes suggest adverse effects from WBRT on patient cognition and quality of life. With dramatic technologic advances in radiation oncology facilitating the adoption of SRS into mainstream practice, the optimal management of patients with multiple brain metastases is now being put forward. Practice is evolving to SRS alone in these patients despite a lack of level 1 evidence to support a clinical departure from WBRT. The purpose of this review is to summarize the current state of the evidence for patients presenting with limited and multiple metastases, and to present an in-depth analysis of the technology and dosimetric issues specific to the treatment of multiple metastases.

Background: Volumetric-modulated arc therapy (VMAT) delivery for stereotactic ablative radiotherapy (SABR) of multiple lung tumors allows for faster treatments. We report on clinical outcomes and describe a general approach for treatment planning. Material and methods: Patients undergoing multi iso-center VMAT-based SABR for ≥2 lung lesions between 2009 and 2014 were identified from the VU University Medical Center and London Health Sciences Centre. Patients were eligible if the start date of the SABR treatment for the different lesions was within a time range of 30 days. SABR was delivered using separate iso-centers for lesions at a substantial distance from each other. Tumors were either treated with a single fraction of 34 Gy, or using three risk-adapted dose-fractionation schemes, namely three fractions of 18 Gy, five fractions of 11 Gy, or eight fractions of 7.5 Gy, depending on the tumor size and the location. Multivariable analysis was performed to assess factors predictive of clinical outcomes. Results: Of 84 patients (188 lesions) identified, 46% were treated for multiple metastases and 54% for multiple primary NSCLC. About 97% were treated for two or three lesions, and 56% had bilateral disease. After a median follow-up of 28 months, median overall survival (OS) for primary tumors was 27.6 months, and not reached for metastatic lesions (p = .028). Grade ≥3 toxicity was observed in 2% of patients. Multivariable analysis showed that grade 2 or higher radiation pneumonitis (n = 9) was best predicted by a total lung V35Gy of ≥6.5% (in 2Gy/fraction equivalent) (p = .007). Conclusion: Severe toxicity was uncommon following SABR using VMAT for up to three lung tumors. Further investigations of planning parameters are needed in patients presenting with more lesions.

Knowledge-based planning for stereotactic radiotherapy of peripheral early-stage lung cancer