Evaluation of the clinical feasibility of cone-beam computed tomography guided online adaption for simulation-free palliative radiotherapy.

Background and purpose: Simulation-free radiotherapy, where diagnostic imaging is used for treatment planning, improves accessibility of radiotherapy for eligible palliative patients. Combining this pathway with online adaptive radiotherapy (oART) may improve accuracy of treatment, expanding the number of eligible patients. This study evaluated the adaptive process duration, plan dose volume histogram (DVH) metrics and geometric accuracy of a commercial cone-beam computed tomography (CBCT)-guided oART system for simulation-free, palliative radiotherapy. Materials and methods: Ten previously treated palliative cases were used to compare system-generated contours against clinician contours in a test environment with Dice Similarity Coefficient (DSC). Twenty simulation-free palliative patients were treated clinically using CBCT-guided oART. Analysis of oART clinical treatment data included; evaluation of the geometric accuracy of system-generated synthetic CT relative to session CBCT anatomy using a Likert scale, comparison of adaptive plan dose distributions to unadapted, using DVH metrics and recording the duration of key steps in the oART workflow. Results: Auto-generated contours achieved a DSC of higher than 0.85, excluding the stomach which was attributed to CBCT image quality issues. Synthetic CT was locally aligned to CBCT anatomy for approximately 80% of fractions, with the remaining suboptimal yet clinically acceptable. Adaptive plans achieved a median CTV V95% of 99.5%, compared to 95.6% for unadapted. The median overall oART process duration was found to be 13.2 mins, with contour editing being the most time-intensive adaptive step. Conclusions: The CBCT-guided oART system utilising a simulation-free planning approach was found to be sufficiently accurate for clinical implementation, this may further streamline and improve care for palliative patients.

First experimental evaluation of multi-target multileaf collimator tracking during volumetric modulated arc therapy for locally advanced prostate cancer.

PURPOSE: Locally advanced and oligometastatic cancer patients require radiotherapy treatment to multiple independently moving targets. There is no existing commercial solution that can simultaneously track and treat multiple targets. This study experimentally implemented and evaluated a real-time multi-target tracking system for locally advanced prostate cancer. METHODS: Real-time multi-target MLC tracking was integrated with 3D x-ray image guidance on a standard linac. Three locally advanced prostate cancer treatment plans were delivered to a static lymph node phantom and dynamic prostate phantom that reproduced three prostate trajectories. Treatments were delivered using multi-target MLC tracking, single-target MLC tracking, and no tracking. Doses were measured using Gafchromic film placed in the dynamic and static phantoms. Dosimetric error was quantified by the 2%/2 mm gamma failure rate. Geometric error was evaluated as the misalignment between target and aperture positions. The multi-target tracking system latency was measured. RESULTS: The mean (range) gamma failure rates for the prostate and lymph nodes, were 18.6% (5.2%, 28.5%) and 7.5% (1.1%, 13.7%) with multi-target tracking, 7.9% (0.7%, 15.4%) and 37.8% (18.0%, 57.9%) with single-target tracking, and 38.1% (0.6%, 75.3%) and 37.2% (29%, 45.3%) without tracking. Multi-target tracking had the lowest geometric error with means and standard deviations within 0.2 ± 1.5 for the prostate and 0.0 ± 0.3 mm for the lymph nodes. The latency was 730 ± 20 ms. CONCLUSION: This study presented the first experimental implementation of multi-target tracking to independently track prostate and lymph node displacement during VMAT. Multi-target tracking reduced dosimetric and geometric errors compared to single-target tracking and no tracking.

Introducing Computed Tomography Simulation-Free and Electronic Patient-Reported Outcomes-Monitored Palliative Radiation Therapy into Routine Care: Clinical Outcomes and Implementation Experience.

PURPOSE: Our purpose was to report outcomes of a novel palliative radiation therapy protocol that omits computed tomography simulation and prospectively collects electronic patient-reported outcomes (ePROs). METHODS AND MATERIALS: Patients receiving extracranial, nonstereotactic, linear accelerator-based palliative radiation therapy who met inclusion criteria (no mask-based immobilization and a diagnostic computed tomography within 4 weeks) were eligible. Global pain was scored with the 11-point numerical pain rating scale (NPRS). Patients were coded as having osseous or soft tissue metastases and no/mild versus severe baseline pain (NPRS ≥ 5). Pain response at 4 weeks was measured according to the international consensus (no analgesia adjustment). Transition to ePRO questionnaires was completed in 3 phases. Initially, pain assessments were collected on paper for 11 months, then pilot ePROs for 1 month and then, after adjustments, revised ePROs from 1 year onwards. ePRO feasibility criteria were established with reference to the paper-based process and published evidence. RESULTS: Between May 2018 and November 2019, 542 consecutive patients were screened, of whom 163 were eligible (30%), and 160 patients were successfully treated. The proportion of patients eligible for the study improved from approximately 20% to 50% by study end. Routine care pain monitoring via ePROs was feasible. One hundred twenty-seven patients had a baseline NPRS recording. Ninety-five patients had osseous (61% severe pain) and 32 had soft tissue (25% severe pain) metastases. Eighty-four patients (66%) were assessable for pain response at 4 weeks. In the 41 patients with severe osseous pain, overall and complete pain response was 78% and 22%, respectively. CONCLUSIONS: By study completion, 50% of patients receiving palliative extracranial radiation therapy avoided simulation, streamlining the treatment process and maximizing patient convenience. Pain response for patients with severe pain from osseous lesions was equivalent to published evidence.

Utility of adjuvant whole abdominal radiation therapy in ovarian clear cell cancer (OCCC): a pragmatic cohort study of women with classic immuno-phenotypic signature.

BACKGROUND: To evaluate the initial experience and clinical utility of first-line adjuvant intensity-modulated whole abdominal radiation therapy (WART) in women with ovarian clear cell cancer (OCCC) referred to an academic center. METHODS: Progression-free and overall survival was analyzed in a pragmatic observational cohort study of histologically pure OCCC patients over-expressing HNF-1ß treated between 2013 and end-December 2018. An in-house intensity-modulated WART program was developed from a published pre-clinical model. Radiation dose-volume data was curated to American Association of Physics in Medicine (AAPM) Task Group 263 recommendations. A dedicated database prospectively recorded presenting characteristics and outcomes in a standardized fashion. RESULTS: Five women with FIGO (2018) stage IA to IIIA2 OCCC were treated with first-line WART. Median age was 58 years (range 47-68 years). At diagnosis CA-125 was elevated in 4 cases (median 56 kU/L: range 18.4-370 kU/L) before primary de-bulking surgery. Severe premorbid endometriosis was documented in 3 patients. At a median follow-up of 77 months (range 16-83 mo.), all patients remain alive and progression-free on clinical, biochemical (CA-125), and 18Fluoro-deoxyglucose (FDG) PET/CT re-evaluation. Late radiation toxicity was significant (G3) in 1 case who required a limited bowel resection and chronic nutritional support at 9 months post-WART; 2 further patients had asymptomatic (G2) osteoporotic fragility fractures of axial skeleton at 12 months post-radiation treated with anti-resorptive agents (denosumab). CONCLUSIONS: The clinical utility of intensity-modulated WART in OCCC over-expressing HNF-1ß was suggested in this small observational cohort study. The hypothesis that HNF-1ß is a portent of platinum-resistance and an important predictive biomarker in OCCC needs further confirmation. Curating multi-institutional cohort studies utilizing WART by means of "Big Data" may improve OCCC care standards in the future.

Adapting to the motion of multiple independent targets using multileaf collimator tracking for locally advanced prostate cancer: Proof of principle simulation study.

PURPOSE: For patients with locally advanced cancer, multiple targets are treated simultaneously with radiotherapy. Differential motion between targets can compromise the treatment accuracy, yet there are currently no methods able to adapt to independent target motion. This study developed a multileaf collimator (MLC) tracking algorithm for differential motion adaptation and evaluated it in simulated treatments of locally advanced prostate cancer. METHODS: A multi-target MLC tracking algorithm was developed that consisted of three steps: (a) dividing the MLC aperture into two possibly overlapping sections assigned to the prostate and lymph nodes, (b) calculating the ideally shaped MLC aperture as a union of the individually translated sections, and (c) fitting the MLC positions to the ideal aperture shape within the physical constraints of the MLC leaves. The multi-target tracking method was evaluated and compared with two existing motion management methods: single-target tracking and no tracking. Treatment simulations of six locally advanced prostate cancer patients with three prostate motion traces were performed for all three motion adaptation methods. The geometric error for each motion adaptation method was calculated using the area of overexposure and underexposure of each field. The dosimetric error was estimated by calculating the dose delivered to the prostate, lymph nodes, bladder, rectum, and small bowel using a motion-encoded dose reconstruction method. RESULTS: Multi-target MLC tracking showed an average improvement in geometric error of 84% compared to single-target tracking, and 83% compared to no tracking. Multi-target tracking maintained dose coverage to the prostate clinical target volume (CTV) D98% and planning target volume (PTV) D95% to within 4.8% and 3.9% of the planned values, compared to 1.4% and 0.7% with single-target tracking, and 20.4% and 31.8% with no tracking. With multi-target tracking, the node CTV D95%, PTV D90%, and gross tumor volume (GTV) D95% were within 0.3%, 0.6%, and 0.3% of the planned values, compared to 9.1%, 11.2%, and 21.1% for single-target tracking, and 0.8%, 2.0%, and 3.2% with no tracking. The small bowel V57% was maintained within 0.2% to the plan using multi-target tracking, compared to 8% and 3.5% for single-target tracking and no tracking, respectively. Meanwhile, the bladder and rectum V50% increased by up to 13.6% and 5.2%, respectively, using multi-target tracking, compared to 2.7% and 1.9% for single-target tracking, and 11.2% and 11.5% for no tracking. CONCLUSIONS: A multi-target tracking algorithm was developed and tracked the prostate and lymph nodes independently during simulated treatments. As the algorithm optimizes for target coverage, tracking both targets simultaneously may increase the dose delivered to the organs at risk.

Diagnostic Computed Tomography Enabled Planning for Palliative Radiation Therapy: Removing the Need for a Planning Computed Tomography Scan.

PURPOSE: This study aimed to investigate the feasibility of using diagnostic computed tomography (dCT) for palliative radiation planning, removing the need for a planning computed tomography (pCT) scan. METHODS AND MATERIALS: A sequential 2-stage study was performed. Stage 1 was a retrospective analysis of 150 patients' dCTs and pCTs to review potential barriers to radiation planning, as well as assess the field of view (FOV), patient positioning, couch curvature, and Hounsfield unit (HU) variation, and its dosimetric impact. Stage 2 was a clinical implementation of dCT planning into the clinical care path. Eligible patients were simulated per the standard department protocol in the dCT position. Treatment was planned on the dCT and replicated on the pCT as a backup and comparator. The dCT plan was delivered with cone beam computed tomography (CT) image guidance. After treatment, the delivered plan was recalculated on the modified dCT to compare planned with delivered planning target volume (PTV) dose. RESULTS: Positron emission tomography-CT imaging was the most suited for diagnostic treatment planning. Metastases in the pelvis, abdomen, thoracic, and lumbar spines were the most reproducible. A curved, full-body vac-bag was designed to enable better replication of the posterior body curvature of dCT for treatment. There was minimal variation in mean HU from dCT to pCT scans. Dose difference due to HU variation in the thorax region due to the low-density tissue had the greatest variation. All patients in stage 2 (n = 30) were successfully treated using the dCT plan. Dosimetric evaluations were conducted comparing dCT and modified dCT plans, with the 95% dose coverage change in PTV between -2% to +2.5%. CONCLUSIONS: For palliative patients with bony and soft-tissue metastases, clinically acceptable plans can be produced using dCT. Diagnostic position can be replicated at treatment, eliminating the need for pCT with implications for streamlining and improving care for patients who require palliative radiation therapy.

Quality improvement process to assess tattoo alignment, set-up accuracy and isocentre reproducibility in pelvic radiotherapy patients.

INTRODUCTION: This quality improvement study tested three methods of tattoo alignment and isocentre definition to investigate if aligning lateral tattoos to minimise pitch, roll and yaw decreased set-up error, and if defining the isocentre using the lateral tattoos for cranio-caudal (CC) position improved isocentre reproducibility. The study population was patients receiving curative external beam radiotherapy (EBRT) for prostate cancer. The results are applicable to all supine pelvic EBRT patients. METHODS: The three sequential cohorts recruited 11, 11 and 10 patients respectively. A data set of 20 orthogonal pairs of electronic portal images (EPI) was acquired for each patient. EPIs were matched offline to digitally reconstructed radiographs. In cohort 1, lateral tattoos were adjusted to minimise roll. The anterior tattoo was used to define the isocentre. In cohort 2, lateral tattoos were aligned to minimise roll and yaw. Isocentre was defined as per cohort 1. In cohort 3, lateral tattoos were aligned as per cohort 2 and the anterior tattoo was adjusted to minimise pitch. Isocentre was defined by the lateral tattoos for CC position and the anterior tattoo for the left-right position. RESULTS: Cohort 3 results were superior as CC systematic and random set-up errors reduced from -1.3 mm to -0.5 mm, and 3.1 mm to 1.4 mm respectively, from cohort 1 to cohort 3. Isocentre reproducibility also improved from 86.7% to 92.1% of treatment isocentres within 5 mm of the planned isocentre. CONCLUSION: The methods of tattoo alignment and isocentre definition in cohort 3 reduced set-up errors and improved isocentre reproducibility.