Improved human observer performance in digital reconstructed radiograph verification in head and neck cancer radiotherapy.

Purpose: Digitally reconstructed radiographs (DRRs) are routinely used as an a priori reference for setup correction in radiotherapy. The spatial resolution of DRRs may be improved to reduce setup error in fractionated radiotherapy treatment protocols. The influence of finer CT slice thickness reconstruction (STR) and resultant increased resolution DRRs on physician setup accuracy was prospectively evaluated. Methods: Four head and neck patient CT-simulation images were acquired and used to create DRR cohorts by varying STRs at 0.5, 1, 2, 2.5, and 3 mm. DRRs were displaced relative to a fixed isocenter using 0–5 mm random shifts in the three cardinal axes. Physician observers reviewed DRRs of varying STRs and displacements and then aligned reference and test DRRs replicating daily KV imaging workflow. A total of 1,064 images were reviewed by four blinded physicians. Observer errors were analyzed using nonparametric statistics (Friedman’s test) to determine whether STR cohorts had detectably different displacement profiles. Post hoc bootstrap resampling was applied to evaluate potential generalizability. Results: The observer-based trial revealed a statistically significant difference between cohort means for observer displacement vector error (p = 0.02) and for Z-axis (p < 0.01). Bootstrap analysis suggests a 15% gain in isocenter translational setup error with reduction of STR from 3 mm to ≤2 mm, though interobserver variance was a larger feature than STR-associated measurement variance. Conclusions: Higher resolution DRRs generated using finer CT scan STR resulted in improved observer performance at shift detection and could decrease operator-dependent geometric error. Ideally, CT STRs ≤2 mm should be utilized for DRR generation in the head and break neck

Initial clinical experience of Stereotactic Body Radiation Therapy (SBRT) for liver metastases, primary liver malignancy, and pancreatic cancer with 4D-MRI based online adaptation and real-time MRI monitoring using a 1.5 Tesla MR-Linac.

Purpose/objectivesRecently a 1.5 Tesla MR Linac has been FDA approved and is commercially available. Clinical series describing treatment methods and outcomes for upper abdominal tumors using a 1.5 Tesla MR Linac are lacking. We present the first clinical series of upper abdominal tumors treated using a 1.5 Tesla MR Linac along with the acquisition of intra-treatment quantitative imaging.Materials/methods10 patients with abdominal tumors were treated at our institution. Each patient enrolled in an IRB approved advanced imaging protocol. Both daily real-time adaptive and non-adaptive methods were used, and selection criteria are described. Adaptive plans were based on pre-beam motion-averaged or mid-position images derived from respiratory-correlated 4D-MRI. Quantitative intravoxel incoherent motion diffusion-weighted imaging and T2 mapping were acquired during plan adaptation. Real-time motion monitoring using cine MRI was performed during beam-on.ResultsMedian patient age was 68.2, five patients were female. Tumor types included liver metastatic lesions from melanoma and sarcoma, primary liver hepatocellular carcinoma (HCC), and regional abdominal tumors included pancreatic metastatic lesions from renal cell carcinoma (RCC) along with two cases of recurrent pancreatic cancer. Doses included 30 Gy in 6 fractions, 33 Gy in 5 fractions, 50 Gy in 5 fractions, 45 Gy in 3 fractions, and 60 Gy in 3 fractions, depending on the location and clinical circumstances. Treatments were feasible and were successfully completed in all patients without significant acute toxicity, technical complications, or need for back up CT based treatment plans.ConclusionsWe present a first clinical series of patients treated for pancreatic tumors, primary liver tumors, and secondary liver tumors with a 1.5 Tesla MR Linear accelerator using adapt-to-position and adapt-to-shape strategies. Treatments were well tolerated by all patients. Acquisition of fully quantitative MR imaging was feasible during the course of the treatment delivery workflow without extending overall treatment times

Development and Validation of a Small Animal Immobilizer and Positioning System for the Study of Delivery of Intracranial and Extracranial Radiotherapy Using the Gamma Knife System

The purpose of this research is to establish a process of irradiating mice using the Gamma Knife as a versatile system for small animal irradiation and to validate accurate intracranial and extracranial dose delivery using this system. A stereotactic immobilization device was developed for small animals for the Gamma Knife head frame allowing for isocentric dose delivery. Intercranial positional reproducibility of a reference point from a primary reference animal was verified on an additional mouse. Extracranial positional reproducibility of the mouse aorta was verified using 3 mice. Accurate dose delivery was validated using film and thermoluminescent dosimeter measurements with a solid water phantom. Gamma Knife plans were developed to irradiate intracranial and extracranial targets. Mice were irradiated validating successful targeted radiation dose delivery. Intramouse positional variability of the right mandible reference point across 10 micro-computed tomography scans was 0.65 ± 0.48 mm. Intermouse positional reproducibility across 2 mice at the same reference point was 0.76 ± 0.46 mm. The accuracy of dose delivery was 0.67 ± 0.29 mm and 1.01 ± 0.43 mm in the coronal and sagittal planes, respectively. The planned dose delivered to a mouse phantom was 2 Gy at the 50% isodose with a measured thermoluminescent dosimeter dose of 2.9 ± 0.3 Gy. The phosphorylated form of member X of histone family H2A (γH2AX) staining of irradiated mouse brain and mouse aorta demonstrated adjacent tissue sparing. In conclusion, our system for preclinical studies of small animal irradiation using the Gamma Knife is able to accurately deliver intracranial and extracranial targeted focal radiation allowing for preclinical experiments studying focal radiation

Additional file 1: Table S1. of Methodology for analysis and reporting patterns of failure in the Era of IMRT: head and neck cancer applications

IMRT target volume definitions and dose prescription. Table S2. Dosimetric patterns of failure. (DOCX 16 kb

Auto-segmentation of the brachial plexus assessed with TaCTICS – A software platform for rapid multiple-metric quantitative evaluation of contours

Auto-segmentation of the brachial plexus assessed with TaCTICS – A software platform for rapid multiple-metric quantitative evaluation of contour

A Nomogram to Predict Severe Late Toxicity after Definitive Reirradiation for Squamous Carcinoma of the Head and Neck

Purpose/Objective(s): Severe late toxicity is common after re-irradiation for recurrent or second primary (RSP) squamous carcinoma of the head and neck. Progressive disease after re-IMRT is also common, and the relationship between late effects and competing risks is critical to both patient and physician decision-making. From an updated multi-institution dataset, we developed a nomogram for patient-level prediction of radiation-related late toxicity while accounting for the competing risks of progression or death. Purpose/Objective(s): Patients with RSP squamous carcinoma originating in a field previously irradiated to at least 40 Gy and treated non-operatively with IMRT-based re-irradiation to at least 40 Gy were collected. Late toxicity developing beyond 3 months after the end of re-IMRT were collected using CTCAE v4.0 and specifically included osteoradionecrosis, aspiration pneumonia, esophageal strictures, carotid blowout syndrome, fistula and tissue necrosis. Feeding tube dependence beyond one year in the absence of progressive disease was also considered late toxicity. A multivariable competing-risk model was then fit to the actuarial risk of late toxicity with subsequent progression or death treated as competing risks. Variable selection for the model was performed based on reverse selection using the bootstrap optimized concordance statistic and predictive ability was plotted to generate a calibration curve. The final model was created into a nomogram for visual use. Results: From 9 institutions, 505 patients were included. The overall cumulative incidence of late toxicity was 16.1% at 2-years and the cumulative incidence of progression or death was 65.5%. The final model included the following factors, with the listed groups experiencing a higher rate of late toxicity: radiotherapy to the neck, BID fractionation, systemic therapy with re-irradiation, a shorter time between radiation courses, pre-treatment organ dysfunction, a lower rN-stage, better KPS, second primary tumor (rather than recurrence), pharynx/larynx tumors, higher first dose of radiation, non-IMRT RT during the first course and increased pack-years smoked. The model was well-calibrated between 0% and 40% risk of late toxicity and the concordance statistic of the final model was 0.764. Conclusion: Only 1 in 5 patients treated with definitive re-IMRT is alive at 2 years without progression, death, or late toxicity. The risk of severe late toxicity from re-IMRT is dependent on both treatment factors and factors that modulate the competing risk of progression or death. Modifiable treatment factors such as twice-daily fractionation and neck irradiation may affect this risk. Patients likely to survive without progression are also more likely to experience severe late toxicity. This model has significant implications for treatment selection and consent discussion for re-irradiation in the IMRT-era

A prospective in silico analysis of interdisciplinary and interobserver spatial variability in post-operative target delineation of high-risk oral cavity cancers: Does physician specialty matter?

Background: The aim of this study was to determine the interdisciplinary agreement in identifying the post-operative tumor bed. Methods: Three radiation oncologists (ROs), four surgeons, and three radiologists segmented post-operative tumor and nodal beds for three patients with oral cavity cancer. Specialty cohort composite contours were created by STAPLE algorithm implementation results for interspecialty comparison. Dice similarity coefficient and Hausdorff distance were utilized to compare spatial differentials between specialties. Results: There were significant differences between disciplines in target delineation. There was unacceptable variation in Dice similarity coefficient for each observer and discipline when compared to the STAPLE contours. Within surgery and radiology disciplines, there was good consistency in volumes. ROs and radiologists have similar Dice similarity coefficient scores compared to surgeons. Conclusion: There were significant interdisciplinary differences in perceptions of tissue-at-risk. Better communication and explicit description of at-risk areas between disciplines is required to ensure high-risk areas are adequately targeted. Keywords: Oral cavity cancer, Target delineation, Post-operative, Interdisciplinary, Interobserve