Accelerated Hypofractionated Chemoradiation Followed by Stereotactic Ablative Radiotherapy Boost for Locally Advanced, Unresectable Non-Small Cell Lung Cancer: A Nonrandomized Controlled Trial.

Importance: Intrathoracic progression remains the predominant pattern of failure in patients treated with concurrent chemoradiation followed by a consolidation immune checkpoint inhibitor for locally advanced, unresectable non-small cell lung cancer (NSCLC). Objective: To determine the maximum tolerated dose (MTD) and use of hypofractionated concurrent chemoradiation with an adaptive stereotactic ablative radiotherapy (SABR) boost. Design, Setting, and Participants: This was an early-phase, single-institution, radiation dose-escalation nonrandomized controlled trial with concurrent chemotherapy among patients with clinical stage II (inoperable/patient refusal of surgery) or III NSCLC (American Joint Committee on Cancer Staging Manual, seventh edition). Patients were enrolled and treated from May 2011 to May 2018, with a median patient follow-up of 18.2 months. Patients advanced to a higher SABR boost dose if dose-limiting toxic effects (any grade 3 or higher pulmonary, gastrointestinal, or cardiac toxic effects, or any nonhematologic grade 4 or higher toxic effects) occurred in fewer than 33% of the boost cohort within 90 days of follow-up. The current analyses were conducted from January to September 2023. Intervention: All patients first received 4 Gy × 10 fractions followed by an adaptive SABR boost to residual metabolically active disease, consisting of an additional 25 Gy (low, 5 Gy × 5 fractions), 30 Gy (intermediate, 6 Gy × 5 fractions), or 35 Gy (high, 7 Gy × 5 fractions) with concurrent weekly carboplatin/paclitaxel. Main Outcome and Measure: The primary outcome was to determine the MTD. Results: Data from 28 patients (median [range] age, 70 [51-88] years; 16 [57%] male; 24 [86%] with stage III disease) enrolled across the low- (n = 10), intermediate- (n = 9), and high- (n = 9) dose cohorts were evaluated. The protocol-specified MTD was not exceeded. The incidences of nonhematologic acute and late (>90 days) grade 3 or higher toxic effects were 11% and 7%, respectively. No grade 3 toxic effects were observed in the intermediate-dose boost cohort. Two deaths occurred in the high-dose cohort. Two-year local control was 74.1%, 85.7%, and 100.0% for the low-, intermediate-, and high-dose cohorts, respectively. Two-year overall survival was 30.0%, 76.2%, and 55.6% for the low-, intermediate-, and high-dose cohorts, respectively. Conclusions and Relevance: This early-phase, dose-escalation nonrandomized controlled trial showed that concurrent chemoradiation with an adaptive SABR boost to 70 Gy in 15 fractions with concurrent chemotherapy is a safe and effective regimen for patients with locally advanced, unresectable NSCLC. Trial Registration: ClinicalTrials.gov Identifier: NCT01345851.

Seizure outcomes following single-fraction versus hypofractionated radiosurgery for brain metastases: a single-center experience.

OBJECTIVE: Although seizures are a relatively common phenomenon in the setting of brain metastases (BMs), there are no discrete recommendations regarding the use of antiepileptic drugs (AEDs) in this population, either in general or in the context of treatment. The authors' aim was to better understand the underlying pathological factors as well as the therapeutic techniques that may lead to seizures following the radiosurgical treatment of BMs with the goal of guiding appropriate AED prophylaxis. METHODS: Adult patients with BMs diagnosed from 2013 to 2020 at a single academic institution and treated with radiation therapy were included in this study. The authors evaluated factors associated with the incidence of seizures throughout the disease course, with a focus on seizures in the 90-day period following stereotactic radiosurgery (SRS). RESULTS: Four hundred forty-four patients with newly diagnosed BMs were identified, 10% of whom had seizures at the time of presentation and 28% of whom had a seizure at any point during the study period. Tumor histology was significantly associated with initial seizure risk. AED use was highly variable. In the 90-day post-SRS period, the summed total planning target volume (PTV) was independently predictive of post-SRS seizures, regardless of the fractionation scheme (single fraction vs hypofractionated) and other clinical factors. The number of supratentorial BMs was not predictive of post-SRS seizures. CONCLUSIONS: PTV is a superior predictor of post-SRS seizures relative to the number of supratentorial BMs, as it serves as a volumetric proxy for intracranial disease burden. A larger PTV, alongside tumor histology and prior seizure history, should be considered in the decision-making process for AED use following radiosurgery.

Prostate-Centric Versus Bony-Centric Registration in the Definitive Treatment of Node-Positive Prostate Cancer with Simultaneous Integrated Boost: A Dosimetric Comparison.

Purpose: To determine the effect of daily shifts based on rigid registration to intraprostatic markers on coverage of boost doses delivered to gross nodal disease for prostate cancer. Methods and Materials: Seventy-five cone beam computed tomographies (CBCTs) from 15 patients treated with definitive radiation for clinically node-positive prostate cancer underwent fiducial-based and pelvic bony-based registration to the initial planning scans. Gross tumor volumes of nodal boost targets were contoured directly on each CBCT registration. The nodal displacement (3-dimensional translation from the node centroid on planning CT to node centroid on registered CBCT) and dose coverage (minimum dose [Dmin], mean dose [Dmean], dose delivered to 95% of the gross tumor volumes [D95]) were calculated for each registration on all nodal targets. All doses for each node were normalized to its intended prescription dose (dose covering 95% of a 3 mm planning target volume [PTV] expansion). Results: Forty-one gross nodal targets were analyzed. Most boosted nodes (80.5%, 33/41) were treated with conventional fractionation using volumetric-arc radiation therapy, and 19.5% (8/41) underwent stereotactic body radiation therapy (SBRT). Dmin, Dmean, and D95 were all significantly lower with fiducial-based registration compared with bony-based registration (P < .0001). Nodal displacement was significantly higher for fiducial-based registrations (P < .0001). The 3-dimensional translation between the fiducial-based and bony-based registrations (bony-to-fiducial vector) was the most significant predictor of nodal displacement (P < .0001). On fiducial-based registrations, a 3 to 5 mm gross nodal PTV margin is sufficient in most directions; however, superior and posterior margins of 8 to 9 mm are required as a result of asymmetrical prostatic motion. Conclusions: Large and anisotropic PTV margins are likely needed to adequately dose gross nodal targets when patient setup is based on rigid registration to intraprostatic markers. Alternative approaches such as adaptive replanning may be required to overcome these limitations.

A Prospective Phase II Study of Automated Non-Coplanar VMAT for Recurrent Head and Neck Cancer: Initial Report of Feasibility, Safety, and Patient-Reported Outcomes.

This study reports the initial results for the first 15 patients on a prospective phase II clinical trial exploring the safety, feasibility, and efficacy of the HyperArc technique for recurrent head and neck cancer treatment. Eligible patients were simulated and planned with both conventional VMAT and HyperArc techniques and the plan with superior dosimetry was selected for treatment. Dosimetry, delivery feasibility and safety, treatment-related toxicity, and patient-reported quality of life (QOL) were all evaluated. HyperArc was chosen over conventional VMAT for all 15 patients and enabled statistically significant increases in dose conformity (R50% reduced by 1.2 ± 2.1, p < 0.05) and mean PTV and GTV doses (by 15.7 ± 4.9 Gy, p < 0.01 and 17.1 ± 6.0 Gy, p < 0.01, respectively). The average HyperArc delivery was 2.8 min longer than conventional VMAT (p < 0.01), and the mean intrafraction motion was ≤ 0.5 ± 0.4 mm and ≤0.3 ± 0.1°. With a median follow-up of 12 months, treatment-related toxicity was minimal (only one grade 3 acute toxicity above baseline) and patient-reported QOL metrics were favorable. HyperArc enabled superior dosimetry and significant target dose escalation compared to conventional VMAT planning, and treatment delivery was feasible, safe, and well-tolerated by patients.

Practical Considerations for Single Isocenter LINAC Radiosurgery of Multiple Brain Metastases.

The purpose of this paper is to summarize treatment guidelines for the performance of single isocenter LINAC radiosurgery of multiple brain metastases developed and used by 3 experienced centers. This article is not meant to provide consensus guidelines. Rather, this is a practical, "how we do it" reference without substantial discussion. To serve as a treatment reference, the great majority of the information is presented in topic-specific tables.

Linear accelerator-based radiosurgery for trigeminal neuralgia: comparative outcomes of frame-based and mask-based techniques.

OBJECTIVE: Precise and accurate targeting is critical to optimize outcomes after stereotactic radiosurgery (SRS) for trigeminal neuralgia (TN). The aim of this study was to compare the outcomes after SRS for TN in which two different techniques were used: mask-based 4-mm cone versus frame-based 5-mm cone. METHODS: The authors performed a retrospective review of patients who underwent SRS for TN at their institution between 1996 and 2019. The Barrow Neurological Institute (BNI) pain score and facial hypesthesia scale were used to evaluate pain relief and facial numbness. RESULTS: A total of 234 patients were included in this study; the mean age was 67 years. In 97 patients (41.5%) radiation was collimated by a mask-based 4-mm cone, whereas a frame-based 5-mm cone was used in the remaining 137 patients (58.5%). The initial adequate pain control rate (BNI I-III) was 93.4% in the frame-based 5-mm group, compared to 87.6% in the mask-based 4-mm group. This difference between groups lasted, with an adequate pain control rate at ≥ 24 months of 89.9% and 77.8%, respectively. Pain relief was significantly different between groups from initial response until the last follow-up (≥ 24 months, p = 0.02). A new, permanent facial hypesthesia occurred in 30.3% of patients (33.6% in the frame-based 5-mm group vs 25.8% in the mask-based 4-mm group). However, no significant association between the BNI facial hypesthesia score and groups was found. Pain recurrence occurred earlier (median time to recurrence 12 months vs 29 months, p = 0.016) and more frequently (38.1% vs 20.4%, p = 0.003) in the mask-based 4-mm than in the frame-based 5-mm group. CONCLUSIONS: Frame-based 5-mm collimator SRS for TN resulted in a better long-term pain relief with similar toxicity profiles to that seen with mask-based 4-mm collimator SRS.

Intra-Fraction Motion Management for Radiosurgical Treatments of Trigeminal Neuralgia: Clinical Experience, Imaging Frequency, and Motion Analysis.

Purpose The aim of this study is to evaluate the patient positioning and intra-fraction motion management performance of an image-guidance protocol established for radiosurgical treatments of trigeminal neuralgia patients. Specifically, it also aims to analyze patient motion data for the evaluation of current motion tolerance levels and imaging frequency utilized for repositioning patients. Methods A linear accelerator equipped with ExacTrac is used for patient positioning with stereoscopic imaging and treatments. Treatments are delivered with 4-mm conical collimators using seven equally spaced arcs. Arcs are 20 degrees apart and span 100 arc degrees each. Following initial ExacTrac positioning, cone beam computed tomography (CBCT) is obtained for independent confirmation of patient position. Patients are then stereoscopically imaged prior to the delivery of each arc and repositioned when 0.5-mm translational tolerance in any direction is exceeded. After the patient has been repositioned, verification stereoscopic images are obtained. Data from 48 patients with 607 image pairs were analyzed for this study. Results Over the course of 48 patient treatments, the mean magnitude of mean 3D deviations was 0.64 mm ± 0.12 mm (range: 0.07-2.74 mm). With the current 0.50-mm tolerance level for repositioning, patients exceeded the tolerance 51.4% of the time considering only images following an arc segment. For those instances, patients were repositioned with a mean magnitude of 0.85 mm ± 0.15 mm (1 SD). For a 0.25-mm tolerance level, 86.1% of arc segments would have required repositioning following the delivery of an arc segment, with a mean magnitude of 0.68 mm ± 0.12 mm. Conversely, for 0.75-mm and 1.00-mm tolerance levels, the tolerance would have been exceeded only 21.5% and 6.6% of instances following the delivery of an arc segment, with a mean magnitude of 1.08 mm ± 0.21 mm and 1.34 mm ± 0.24 mm, respectively. Each repositioning adds approximately 2 minutes to treatment time, which accounts for parts of the variability in patient treatment times. Following the initial ExacTrac and CBCT, the mean treatment time from first arc to treatment end was 57 minutes (range: 33-63 minutes). Discussions The current 0.50-mm tolerance level results in a clinically manageable but significant number of patient repositions during trigeminal neuralgia treatments. Frequent patient repositioning can result from actual patient motion convolved with the accuracy and precision limitations of the image analysis. Increasing the repositioning tolerance could more selectively correct for actual patient motion and shorten the treatment time at the expense of more variations in patient position. A more lenient tolerance level of 0.75 mm would decrease the repositioning rate by approximately a factor of 2; however, the permissible magnitude of motion will increase, leading to possible dosimetric consequences. Once treatment begins, there was no trend as to when patients exceeded the tolerance. Conclusions Current imaging protocol for patient positioning and intra-fraction motion management fits the clinical workflow with clinically acceptable residual patient motion. The next important step would be to assess how the number of repositions and magnitude of residual movements affect treatment outcomes.

Automated Non-Coplanar VMAT for Dose Escalation in Recurrent Head and Neck Cancer Patients.

This study evaluates the potential for tumor dose escalation in recurrent head and neck cancer (rHNC) patients with automated non-coplanar volumetric modulated arc therapy (VMAT) stereotactic body radiation therapy (SBRT) planning (HyperArc). Twenty rHNC patients are planned with conventional VMAT SBRT to 40 Gy while minimizing organ-at-risk (OAR) doses. They are then re-planned with the HyperArc technique to match these minimal OAR doses while escalating the target dose as high as possible. Then, we compare the dosimetry, tumor control probability (TCP), and normal tissue complication probability (NTCP) for the two plan types. Our results show that the HyperArc technique significantly increases the mean planning target volume (PTV) and gross tumor volume (GTV) doses by 10.8 ± 4.4 Gy (25%) and 11.5 ± 5.1 Gy (26%) on average, respectively. There are no clinically significant differences in OAR doses, with maximum dose differences of <2 Gy on average. The average TCP is 23% (± 21%) higher for HyperArc than conventional plans, with no significant differences in NTCP for the brainstem, cord, mandible, or larynx. HyperArc can achieve significant tumor dose escalation while maintaining minimal OAR doses in the head and neck-potentially enabling improved local control for rHNC SBRT patients without increased risk of treatment-related toxicities.

Time-Driven Activity-Based Costing Comparison of Stereotactic Radiosurgery to Multiple Brain Lesions Using Single-Isocenter Versus Multiple-Isocenter Technique.

PURPOSE: Stereotactic radiosurgery (SRS) historically has been used to treat multiple brain lesions using a multiple-isocenter technique-frequently associated with significant complexity in treatment planning and long treatment times. Recently, given innovations in planning algorithms, patients with multiple brain lesions may now be treated with a single-isocenter technique using fewer total arcs and less time spent during image guidance (though with stricter image guided radiation therapy tolerances). This study used time-driven activity-based costing to determine the difference in cost to a provider for delivering SRS to multiple brain lesions using single-isocenter versus multiple-isocenter techniques. METHODS AND MATERIALS: Process maps, consisting of discrete steps, were created for each phase of the SRS care cycle and were based on interviews with department personnel. Actual treatment times (including image guidance) were extracted from treatment record and verify software. Additional sources of data to determine costs included salary/benefit data of personnel and average list price/maintenance costs for equipment. RESULTS: Data were collected for 22 patients who underwent single-isocenter SRS (mean lesions treated, 5.2; mean treatment time, 30.2 minutes) and 51 patients who underwent multiple-isocenter SRS (mean lesions treated, 4.4; mean treatment time, 75.2 minutes). Treatment time for multiple-isocenter SRS varied substantially with increasing number of lesions (11.8 minutes/lesion; P < .001), but to a much lesser degree in single-isocenter SRS (1.8 minutes/lesion; P = .029). The resulting cost savings from single-isocenter SRS based on number of lesions treated ranged from $296 to $3878 for 2 to 10 lesions treated. The 2-mm planning treatment volume margin used with single-isocenter SRS resulted in a mean 43% increase of total volume treated compared with a 1-mm planning treatment volume expansion. CONCLUSIONS: In a comparison of time-driven activity-based costing assessment of single-isocenter versus multiple-isocenter SRS for multiple brain lesions, single-isocenter SRS appears to save time and resources for as few as 2 lesions, with incremental benefits for additional lesions treated.

Technical Note: Robust individual thermoluminescence dosimeter tracking using optical fingerprinting.

PURPOSE: The thermoluminescence dosimeter (TLD) has desirable features including low cost, reusability, small size, and relatively low energy dependence. However, the commonly available poly-crystal TLDs (e.g., TLD-100) exhibit high interdetector variability that requires individual calibration for high detection accuracy. To improve individual TLD tracking robustness, we developed an optical fingerprinting method to identify the TLD-100 chips. METHODS: Seven hundred and fifty-two images were initially captured using a digital microscope camera to build a feature library for both facets of 376 TLD-100 chips. A median intensity thresholding method was used to segment images into foreground and background. The affine transformation was used to register the segmented images to the same position. The fingerprint of each image was calculated from its registered image. All fingerprints were then recorded in an Elasticsearch® search database. The TLD fingerprint match was tested three times when the library was established and repeated once 20 months later. All chips were irradiated at 0, 1, 4, and 8 Gy on a calibrated clinical MV linac to establish the individual calibration curve. RESULTS: The true positive rate of identifying TLDs based on their optical fingerprints was 100% at initialization of the inventory. After 20 months and multiple deployments for characterization, calibration, and dose measurement, the true positive match rate dropped to 99% with zero false-positive matches. The TLDs exhibited high self-consistency in the dose-response test with R2 between 0.988 and 1 with linear regression. CONCLUSIONS: The TLD-100 chips surface textures are unique and sufficient to support accurate identification based on the optical fingerprinting. This method provides inexpensive and robust management of the TLDs for individual calibration and dosimetry.

Comparison of Clinical Outcomes Stratified by Target Delineation for Patients Undergoing Stereotactic Body Radiotherapy for Spinal Metastases.

OBJECTIVE: Stereotactic body radiotherapy (SBRT) is an effective treatment of spinal metastases in the vertebral body. However, variation has existed between practitioners regarding the appropriate target delineation. As such, we compared the tumor control, rates of compression fractures, and pain control for patients who had undergone SBRT for spinal metastases to either the lesion only (LO) or the full vertebral body (FVB). METHODS: A total of 126 spinal metastases in 84 patients had received single-fraction SBRT from January 2009 to February 2015. Of the 126 lesions, 36 (29%) were in the FVB group and 90 were in the LO group. The SBRT plans were reviewed to determine the treatment volume. Odds ratios were used to compare the rates of compression fracture and local failure. Regression analysis was performed to identify the predictors of outcome. RESULTS: A total of 5 failures had occurred in the FVB group and 14 in the LO group; however, the difference was not statistically significant (P = 0.5). No difference was found in pain reduction between the 2 groups (P = 0.9). Seven post-treatment compression fractures occurred in the LO group and four in the FVB group; however, the difference was not statistically significant (P = 0.6). The minimum dose to the planning target volume, patient age, and planning target volume size were the only significant factors predicting for local failure, vertebral body fracture, and pain control, respectively. CONCLUSIONS: Given that we found no difference in tumor control, pain reduction, or fracture rate between patients treated to the FVB versus the. LO, it might be reasonable to consider SBRT to the LO for select patients.

Increased cochlear radiation dose predicts delayed hearing loss following both stereotactic radiosurgery and fractionated stereotactic radiotherapy for vestibular schwannoma.

PURPOSE: Stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) are noninvasive therapies for vestibular schwannomas providing excellent tumor control. However, delayed hearing loss after radiation therapy remains an issue. One potential target to for improving hearing rates is limiting radiation exposure to the cochlea. METHODS: We retrospectively reviewed 100 patients undergoing either SRS with 12 Gy (n = 43) or fSRT with 50 Gy over 28 fractions (n = 57) for vestibular schwannoma. Univariate and multivariate analysis were carried out to identify predictors of hearing loss as measured by the Gardner Robertson scale after radiation therapy. RESULTS: Deterioration of hearing occurred in 30% of patients with SRS and 26% with fSRT. The overall long term (> 2 year) progression rates were 20% for SRS and 16% for fSRT. Patients with a decrease in their Gardner Robertson hearing score and those that loss serviceable hearing had significantly higher average minimal doses to the cochlea in both SRS and fSRT cohorts. ROC analysis showed that a cut off of 5 Gy and 35 Gy, for SRS and fSRT respectively, predicted hearing loss with high sensitivity/specificity. CONCLUSION: Our data suggests the minimal dose of radiation that the cochlear volume is exposed to is a predictor of delayed hearing loss after either SRS or fSRT. A threshold of 5 Gy/35 Gy may lead to improved hearing preservation after radiotherapy. Further prospective multi center studies can further elucidate this mechanism.

Timing of adjuvant radiation therapy and survival outcomes after surgical resection of intracranial non-small cell lung cancer metastases.

OBJECTIVE: To investigate if delay of adjuvant radiotherapy (ART) beyond 6 post-operative weeks affects survival outcomes in patients undergoing craniotomy or craniectomy for resection of non-small cell lung cancer (NSCLC) intracranial metastases. PATIENTS AND METHODS: We performed a retrospective analysis of 28 patients undergoing resection of intracranial metastases and ART at our institution from 2001 to 2016. We assessed survival outcomes for patients who received delayed versus non-delayed ART, as well as associated risk factors. RESULTS: Among 28 patients, 8 (29%) had delayed ART beyond 6 post-operative weeks. Fifteen received stereotactic radiotherapy (SRT), 8 (29%) received whole brain radiotherapy (WBRT), and 5 (18%) received combination WBRT + SRT. There were no significant differences in ART modality or dosing, age, sex, number of intracranial metastases, primary metastasis volume, rates of chemotherapy, extracranial metastases, or post-operative functional scores between groups. Expected post-operative survival was shorter with delayed ART (7 months versus 28 months, P = 0.01). The most common reason for delayed ART was complicated post-operative course (n = 3.38%). Significant risk factors for delayed ART included non-routine discharge (P = 0.01) and additional invasive procedures between surgery and ART start date (P = 0.02). CONCLUSIONS: Our results suggest delayed ART in patients undergoing surgical resection of intracranial NSCLC metastases is associated with shorter overall survival. However, risk factors for delayed ART, including non-routine discharge and the need for additional invasive procedures, may have in themselves reflected poorer clinical courses that may have also contributed to the observed survival differences.

Hearing Preservation for Vestibular Schwannomas Treated with Stereotactic Radiosurgery or Fractionated Stereotactic Radiotherapy.

BACKGROUND: Vestibular schwannomas (VS) are benign intracranial neoplasms arising from the eighth cranial nerve for which targeted radiation therapy (RT) has proved increasingly successful. However, long-term hearing and related cranial nerve outcomes have been disputed for the 3 current RT modalities. OBJECTIVE: To determine differences in hearing preservation for patients treated with stereotactic radiosurgery (SRS), fractionated stereotactic radiotherapy (FSRT), or hypofractionated stereotactic radiotherapy (hypoFSRT) for VS. METHODS: A retrospective electronic chart review was conducted for all patients with unilateral VS treated with primary RT at a single academic medical center between 2000 and 2017. The primary outcome measure was preservation of serviceable hearing status in the affected ear at last follow-up. Secondary outcomes included tinnitus, vertigo, and imbalance. RESULTS: A total of 33 FSRT cases, 21 SRS cases, and 6 hypoFSRT cases were identified. Postoperative deterioration in serviceable hearing and tinnitus showed significant differences across cohorts. The SRS cohort had a higher baseline incidence of nonserviceable hearing and disequilibrium compared with other cohorts before RT (P = 0.001 and 0.022, respectively); no differences in baseline morbidity were observed for vertigo and tinnitus. The 5-year tumor control rate was 95.2%, 93.9%, and 100% with SRS, FSRT, and hypoFSRT, respectively. CONCLUSIONS: Our series indicated an excellent tumor control rate in all the modalities. Our SRS cohort showed increased incidence and shorter time to hearing deterioration compared with the FSRT and hypoFSRT cohorts. The FSRT and hypoFSRT cohorts have shown comparable overall outcomes. Onset of post-RT tinnitus was observed only with FSRT.

Safety-oriented design of in-house software for new techniques: A case study using a model-based 4DCT protocol.

PURPOSE: In-house software is commonly employed to implement new imaging and therapy techniques before commercial solutions are available. Risk analysis methods, as detailed in the TG-100 report of the American Association of Physicists in Medicine, provide a framework for quality management of processes but offer little guidance on software design. In this work, we examine a novel model-based four-dimensional computed tomography (4DCT) protocol using the TG-100 approach and describe two additional methods for promoting safety of the associated in-house software. METHODS: To implement a previously published model-based 4DCT protocol, in-house software was necessary for tasks such as synchronizing a respiratory signal to computed tomography images, deformable image registration (DIR), model parameter fitting, and interfacing with a treatment planning system. A process map was generated detailing the workflow. Failure modes and effects analysis (FMEA) was performed to identify critical steps and guide quality interventions. Software system safety was addressed through writing "use cases," narratives that characterize the behavior of the software, for all major operations to elicit safety requirements. Safety requirements were codified using the easy approach to requirements syntax (EARS) to ensure testability and eliminate ambiguity. RESULTS: Sixty-one failure modes were identified and assigned risk priority numbers using FMEA. Resultant quality management interventions include integration of a comprehensive reporting and logging system into the software, mandating daily and monthly equipment quality assurance procedures, and a checklist to be completed at image acquisition. Use cases and resulting safety requirements informed the design of needed in-house software as well as a suite of tests performed during the image generation process. CONCLUSIONS: TG-100 methods were used to construct a process-level quality management program for a 4DCT imaging protocol. Two supplemental tools from the field of requirements engineering facilitated elicitation and codification of safety requirements that informed the design and testing of in-house software necessary to implement the protocol. These general tools can be applied to promote safety when in-house software is needed to bring new techniques to the clinic.

Impact of Cochlear Dose on Hearing Preservation following Stereotactic Radiosurgery and Fractionated Stereotactic Radiotherapy for the Treatment of Vestibular Schwannoma.

Objective The objective of this study was to examine the effect of cochlear dose on hearing preservation in stereotactic radiosurgery (SRS) and fractionated stereotactic radiotherapy (fSRT) for vestibular schwannoma (VS). Design This is a retrospective case-control study. Setting This study was completed at the Ronald Reagan UCLA Medical Center, a university-affiliated tertiary care center. Participants Patients who underwent SRS (marginal dose of 12 Gy) or fSRT (marginal dose of 50.4 Gy) procedures for VS were included in the study. Main Outcome Measures The main outcome measure was hearing preservation. Audiometric data, when available, were used to determine the level of hearing according to the Gardner Robertson scale. Results A total of 38 patients (14 SRS and 24 fSRT) were analyzed. SRS patients with decreased hearing received a significantly higher minimum cochlear dose (7.41 vs. 4.24 Gy, p = 0.02) as compared with those with stable hearing. In fSRT patients, there were no significant differences in cochlear dose for patients with decreased hearing as compared with those with stable hearing. For SRS patients, who received a minimum cochlear dose above 6 Gy, there was a significant risk of decreased hearing preservation (odds ratio: 32, p = 0.02). Conclusion Higher minimum cochlear dose was predictive of decreased hearing preservation following SRS. Though the study is low powered, the radiation dose to the cochlea should be a parameter that is considered when planning SRS or fSRT therapies for patients with VS.

A Prospective Phase 2 Study Evaluating Safety and Efficacy of Combining Stereotactic Body Radiation Therapy With Heat-based Ablation for Centrally Located Lung Tumors.

PURPOSE: Stereotactic body radiation therapy (SBRT) and heat-based ablation (HBA) are both potentially safe and effective treatments for primary and metastatic lung tumors. Both are suboptimal for centrally located tumors, with SBRT having a higher risk of significant toxicity and HBA having lower efficacy. This study evaluates the safety and efficacy of combination SBRT-HBA to determine whether combined treatment can result in superior outcomes to each treatment alone. METHODS AND MATERIALS: Patients with 1 or 2 primary or metastatic lung tumors ≤ 5 cm in size were enrolled in a prospective phase 2 trial and treated with SBRT in 3 fractions followed by HBA. Tumors < 1 cm from the central bronchial tree received a total of 36 Gy, and tumors 1 to 2 cm away received 42 Gy. HBA was delivered within 10 days after SBRT. The primary endpoints were local control, toxicity, and degree of decline in lung function. The secondary endpoints were progression-free survival and overall survival. RESULTS: We treated 16 patients with 17 tumors. The median follow-up time was 26 months. Fifteen tumors were evaluable for local control. The 1- and 2-year actuarial local control rates were 93% and 81%, respectively. Three patients had grade ≥ 3 toxicity: bronchial stenosis, pain, and pulmonary hemorrhage. The percent predicted forced expiratory volume in 1 second and functional vital capacity decreased by 8% and 8.5%, respectively, at 3 months after treatment (P < .001 for both). CONCLUSIONS: Combining SBRT and HBA for centrally located lung tumors offers reasonable local control and toxicity despite the anatomic challenges of this location. HBA may be a reasonable supplement to SBRT when trachea and bronchus, large vessel, or esophageal constraints cannot be met with full-dose SBRT and a biologically effective dose < 100 Gy is delivered because of an ultra-central location or large tumor size.

Planned Subtotal Resection of Vestibular Schwannoma Differs from the Ideal Radiosurgical Target Defined by Adaptive Hybrid Surgery.

OBJECTIVE: To retrospectively compare ideal radiosurgical target volumes defined by a manual method (surgeon) to those determined by Adaptive Hybrid Surgery (AHS) operative planning software in 7 patients with vestibular schwannoma (VS). METHODS: Four attending surgeons (3 neurosurgeons and 1 ear, nose, and throat surgeon) manually contoured planned residual tumors volumes for 7 consecutive patients with VS. Next, the AHS software determined the ideal radiosurgical target volumes based on a specified radiotherapy plan. Our primary measure was the difference between the average planned residual tumor volumes and the ideal radiosurgical target volumes defined by AHS (dRVAHS-planned). RESULTS: We included 7 consecutive patients with VS in this study. The planned residual tumor volumes were smaller than the ideal radiosurgical target volumes defined by AHS (1.6 vs. 4.5 cm3, P = 0.004). On average, the actual post-operative residual tumor volumes were smaller than the ideal radiosurgical target volumes defined by AHS (2.2 cm3 vs. 4.5 cm3; P = 0.02). The average difference between the ideal radiosurgical target volume defined by AHS and the planned residual tumor volume (dRVAHS-planned) was 2.9 ± 1.7 cm3, and we observed a trend toward larger dRVAHS-planned in patients who lost serviceable facial nerve function compared with patients who maintained serviceable facial nerve function (4.7 cm3 vs. 1.9 cm3; P = 0.06). CONCLUSIONS: Planned subtotal resection of VS diverges from the ideal radiosurgical target defined by AHS, but whether that influences clinical outcomes is unclear.