Novel HPV Associated Oropharyngeal Squamous Cell Carcinoma Surveillance DNA Assay Cost Analysis.

OBJECTIVES: We aim to propose a modified surveillance strategy using a novel blood assay that detects plasma circulating tumor-specific HPV DNA with reported 100% NPV and 94% PPV as the main method of detection to understand the cost implications of potentially avoiding routine imaging and surveillance visits at our institution. METHODS: We performed a retrospective chart review focusing on recurrences in p16+ patients with OPSCC and defined two surveillance strategies: "Strategy A", follow-up visits with flexible laryngoscopy (FL) plus regular imaging studies; "Strategy B", follow-up visits with FL plus regular NavDx assays and imaging used at the discretion of the physician(s) in cases of high clinical suspicion. RESULTS: Of the p16+ OPSCC patients (n = 214), 23 had confirmed recurrence (11%). Standard work-flow model determined 72 imaging studies and 2198 physical examinations with FL were needed to detect one recurrence. Potential individual patient cost reduction during surveillance was 42%. CONCLUSION: Implementing NavDx for HPV + OPSCC surveillance would benefit patients by reducing costs and unnecessary diagnostic testing. LEVEL OF EVIDENCE: Step/Level 3 Laryngoscope, 133:3006-3012, 2023.

Safety and feasibility of STAT RAD: Improvement of a novel rapid tomotherapy-based radiation therapy workflow by failure mode and effects analysis.

PURPOSE: The clinical challenge of radiation therapy (RT) for painful bone metastases requires clinicians to consider both treatment efficacy and patient prognosis when selecting a radiation therapy regimen. The traditional RT workflow requires several weeks for common palliative RT schedules of 30 Gy in 10 fractions or 20 Gy in 5 fractions. At our institution, we have created a new RT workflow termed "STAT RAD" that allows clinicians to perform computed tomographic (CT) simulation, planning, and highly conformal single fraction treatment delivery within 2 hours. In this study, we evaluate the safety and feasibility of the STAT RAD workflow. METHODS AND MATERIALS: A failure mode and effects analysis (FMEA) was performed on the STAT RAD workflow, including development of a process map, identification of potential failure modes, description of the cause and effect, temporal occurrence, and team member involvement in each failure mode, and examination of existing safety controls. A risk probability number (RPN) was calculated for each failure mode. As necessary, workflow adjustments were then made to safeguard failure modes of significant RPN values. After workflow alterations, RPN numbers were again recomputed. RESULTS: A total of 72 potential failure modes were identified in the pre-FMEA STAT RAD workflow, of which 22 met the RPN threshold for clinical significance. Workflow adjustments included the addition of a team member checklist, changing simulation from megavoltage CT to kilovoltage CT, alteration of patient-specific quality assurance testing, and allocating increased time for critical workflow steps. After these modifications, only 1 failure mode maintained RPN significance; patient motion after alignment or during treatment. CONCLUSIONS: Performing the FMEA for the STAT RAD workflow before clinical implementation has significantly strengthened the safety and feasibility of STAT RAD. The FMEA proved a valuable evaluation tool, identifying potential problem areas so that we could create a safer workflow.

Phantomless patient-specific TomoTherapy QA via delivery performance monitoring and a secondary Monte Carlo dose calculation.

PURPOSE: To describe the validation and implementation of a novel quality assurance (QA) system for TomoTherapy using a Monte Carlo (MC)-based secondary dose calculation and CT detector-based multileaf collimator (MLC) leaf opening time measurement QA verification. This system is capable of detecting plan transfer and delivery errors and evaluating the dosimetric impact of those errors. METHODS: The authors' QA process, MCLogQA, utilizes an independent pretreatment MC secondary dose calculation and postdelivery TomoTherapy exit detector-based MLC sinogram comparison and log file examination to confirm accurate dose calculation, accurate dose delivery, and to verify machine performance. MC radiation transport simulations are performed to estimate patient dose utilizing prestored treatment machine-specific phase-space information, the patient's planning CT, and MLC sinogram data. Sinogram data are generated from both the treatment planning system (MC_TPS) and from beam delivery log files (MC_Log). TomoTherapy treatment planning dose (DTPS) is compared with DMC_TPS and DMC_Log via dose-volume metrics and mean region of interest dose statistics. For validation, in-phantom ionization chamber dose measurements (DIC) for ten sample patient plans are compared with the computed values. RESULTS: Dose comparisons to in-phantom ion chamber measurements validate the capability of the MCLogQA method to detect delivery errors. DMC_Log agreed with DIC within 1%, while DTPS values varied by 2%-5% compared to DIC. The authors demonstrated that TomoTherapy treatments can be vulnerable to MLC deviations and interfraction output variations during treatment delivery. Interfractional Linac output variations for each patient were approximately 2% and average output was 1%-1.5% below the gold standard. While average MLC leaf opening time error from patient to patient varied from -0.6% to 1.6%, the MLC leaf errors varied little between fractions for the same patient plan, excluding one patient. CONCLUSIONS: MCLogQA is a new TomoTherapy QA process that validates the planned dose before delivery and analyzes the delivered dose using the treatment exit detector and log file data. The MCLogQA procedure is an effective and efficient alternative to traditional phantom-based TomoTherapy plan-specific QA because it allows for comprehensive 3D dose verification, accounts for tissue heterogeneity, uses patient CT density tables, reduces total QA time, and provides for a comprehensive QA methodology for each treatment fraction.

Computed tomography-based anatomic assessment overestimates local tumor recurrence in patients with mass-like consolidation after stereotactic body radiotherapy for early-stage non-small cell lung cancer.

PURPOSE: To investigate pulmonary radiologic changes after lung stereotactic body radiotherapy (SBRT), to distinguish between mass-like fibrosis and tumor recurrence. METHODS AND MATERIALS: Eighty consecutive patients treated with 3- to 5-fraction SBRT for early-stage peripheral non-small cell lung cancer with a minimum follow-up of 12 months were reviewed. The mean biologic equivalent dose received was 150 Gy (range, 78-180 Gy). Patients were followed with serial CT imaging every 3 months. The CT appearance of consolidation was defined as diffuse or mass-like. Progressive disease on CT was defined according to Response Evaluation Criteria in Solid Tumors 1.1. Positron emission tomography (PET) CT was used as an adjunct test. Tumor recurrence was defined as a standardized uptake value equal to or greater than the pretreatment value. Biopsy was used to further assess consolidation in select patients. RESULTS: Median follow-up was 24 months (range, 12.0-36.0 months). Abnormal mass-like consolidation was identified in 44 patients (55%), whereas diffuse consolidation was identified in 12 patients (15%), at a median time from end of treatment of 10.3 months and 11.5 months, respectively. Tumor recurrence was found in 35 of 44 patients with mass-like consolidation using CT alone. Combined with PET, 10 of the 44 patients had tumor recurrence. Tumor size (hazard ratio 1.12, P=.05) and time to consolidation (hazard ratio 0.622, P=.03) were predictors for tumor recurrence. Three consecutive increases in volume and increasing volume at 12 months after treatment in mass-like consolidation were highly specific for tumor recurrence (100% and 80%, respectively). Patients with diffuse consolidation were more likely to develop grade ≥ 2 pneumonitis (odds ratio 26.5, P=.02) than those with mass-like consolidation (odds ratio 0.42, P=.07). CONCLUSION: Incorporating the kinetics of mass-like consolidation and PET to the current criteria for evaluating posttreatment response will increase the likelihood of correctly identifying patients with progressive disease after lung SBRT.

Dynamic MRI of grid-tagged hyperpolarized helium-3 for the assessment of lung motion during breathing.

PURPOSE: To develop a dynamic magnetic resonance imaging (MRI) tagging technique using hyperpolarized helium-3 (HP He-3) to track lung motion. METHODS AND MATERIALS: An accelerated non-Cartesian k-space trajectory was used to gain acquisition speed, at the cost of introducing image artifacts, providing a viable strategy for obtaining whole-lung coverage with adequate temporal resolution. Multiple-slice two-dimensional dynamic images of the lung were obtained in three healthy subjects after inhaling He-3 gas polarized to 35%-40%. Displacement, strain, and ventilation maps were computed from the observed motion of the grid peaks. RESULTS: Both temporal and spatial variations of pulmonary mechanics were observed in normal subjects, including shear motion between different lobes of the same lung. CONCLUSION: These initial results suggest that dynamic imaging of grid-tagged hyperpolarized magnetization may potentially be a powerful tool for observing and quantifying pulmonary biomechanics on a regional basis and for assessing, validating, and improving lung deformable image registration algorithms.

A rabbit irradiation platform for outcome assessment of lung stereotactic radiosurgery.

PURPOSE: To evaluate a helical tomotherapy-based rodent radiosurgery platform that reproduces human image-guided radiosurgery treatment to study radiobiologic effects of stereotactic radiosurgery on lung tissues using functional magnetic resonance imaging (MRI). METHODS AND MATERIALS: Hypofractionated radisourgery (20 Gy x 3) was delivered to the right lung of three New Zealand rabbits using Helical TomoTherapy with MVCT image guidance. Contrast-enhanced MR perfusion, hyperpolarized helium-3 MR ventilation, and CT were obtained before radiation and monthly for 4 months after radiation. All MRI was performed on a 1.5-T whole-body scanner with broad-band capabilities. RESULTS: Precise dose delivery to 1.6 cc of the lower right lung was achieved without additional immobilization. No deficits were detected at baseline with respect to perfusion and ventilation. Lung perfusion deficits in the irradiated lung regions began at 2 months after radiation and worsened with time. No ventilation deficits were observed after radiation. Decrease in lung CT density in irradiated regions was observed after radiation, but the changes were less significant than those in perfusion MRI. CONCLUSIONS: We demonstrated that highly conformal radiation can be reproducibly delivered to a small volume of rodent lung on a widely available clinical unit. The radiation-induced lung injury can be detected as early as 2 months after radiation with perfusion MRI. The primary pattern of injury agrees with previously reported endothelial damage to radiosurgical radiation doses. This experimental design provides a cost-effective methodology for producing radiosurgical injuries in rodents that reproduces current human treatments for studying radiation injury and agents that might affect it.