Clinical efficacy and safety of surface imaging guided radiosurgery (SIG-RS) in the treatment of benign skull base tumors.

Frameless, surface imaging guided radiosurgery (SIG-RS) is a novel platform for stereotactic radiosurgery (SRS) wherein patient positioning is monitored in real-time through infra-red camera tracking of facial topography. Here we describe our initial clinical experience with SIG-RS for the treatment of benign neoplasms of the skull base. We identified 48 patients with benign skull base tumors consecutively treated with SIG-RS at a single institution between 2009 and 2011. Patients were diagnosed with meningioma (n = 22), vestibular schwannoma (n = 20), or nonfunctional pituitary adenoma (n = 6). Local control and treatment-related toxicity were retrospectively assessed. Median follow-up was 65 months (range 61-72 months). Prescription doses were 12-13 Gy in a single fraction (n = 18), 8 Gy × 3 fractions (n = 6), and 5 Gy × 5 fractions (n = 24). Actuarial tumor control rate at 5 years was 98%. No grade ≥3 treatment-related toxicity was observed. Grade ≤2 toxicity was associated with symptomatic lesions (p = 0.049) and single fraction treatment (p = 0.005). SIG-RS for benign skull base tumors produces clinical outcomes comparable to conventional frame-based SRS techniques while enhancing patient comfort.

Neurocognitive assessment following whole brain radiation therapy and radiosurgery for patients with cerebral metastases.

The treatment of metastatic brain lesions remains a central challenge in oncology. Because most chemotherapeutic agents do not effectively cross the blood-brain barrier, it is widely accepted that radiation remains the primary modality of treatment. The mode by which radiation should be delivered has, however, become a source of intense controversy in recent years. The controversy involves whether patients with a limited number of brain metastases should undergo whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) delivered only to the radiographically visible tumours. Survival is comparable for patients treated with either modality. Instead, the controversy involves the neurocognitive function (NCF) of radiating cerebrum that appeared radiographically normal relative to effects of the growth from micro-metastatic foci. A fundamental question in this debate involves quantifying the effect of WBRT in patients with cerebral metastasis. To disentangle the effects of WBRT on neurocognition from the effects inherent to the underlying disease, we analysed the results from randomised controlled studies of prophylactic cranial irradiation in oncology patients as well as studies where patients with limited cerebral metastasis were randomised to SRS versus SRS+WBRT. In aggregate, these results suggest deleterious effects of WBRT in select neurocognitive domains. However, there are insufficient data to resolve the controversy of upfront WBRT versus SRS in the management of patients with limited cerebral metastases.

Prospective study of functional bone marrow-sparing intensity modulated radiation therapy with concurrent chemotherapy for pelvic malignancies.

PURPOSE: To test the hypothesis that intensity modulated radiation therapy (IMRT) can reduce radiation dose to functional bone marrow (BM) in patients with pelvic malignancies (phase IA) and estimate the clinical feasibility and acute toxicity associated with this technique (phase IB). METHODS AND MATERIALS: We enrolled 31 subjects (19 with gynecologic cancer and 12 with anal cancer) in an institutional review board-approved prospective trial (6 in the pilot study, 10 in phase IA, and 15 in phase IB). The mean age was 52 years; 8 of 31 patients (26%) were men. Twenty-one subjects completed (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET)/computed tomography (CT) simulation and magnetic resonance imaging by use of quantitative IDEAL (IDEAL IQ; GE Healthcare, Waukesha, WI). The PET/CT and IDEAL IQ were registered, and BM subvolumes were segmented above the mean standardized uptake value and below the mean fat fraction within the pelvis and lumbar spine; their intersection was designated as functional BM for IMRT planning. Functional BM-sparing vs total BM-sparing IMRT plans were compared in 12 subjects; 10 were treated with functional BM-sparing pelvic IMRT per protocol. RESULTS: In gynecologic cancer patients, the mean functional BM V(10) (volume receiving ≥10 Gy) and V(20) (volume receiving ≥20 Gy) were 85% vs 94% (P<.0001) and 70% vs 82% (P<.0001), respectively, for functional BM-sparing IMRT vs total BM-sparing IMRT. In anal cancer patients, the corresponding values were 75% vs 77% (P=.06) and 62% vs 67% (P=.002), respectively. Of 10 subjects treated with functional BM-sparing pelvic IMRT, 3 (30%) had acute grade 3 hematologic toxicity or greater. CONCLUSIONS: IMRT can reduce dose to BM subregions identified by (18)F-fluorodeoxyglucose-PET/CT and IDEAL IQ. The efficacy of BM-sparing IMRT is being tested in a phase II trial.

Clinical practice patterns of lung stereotactic body radiation therapy in the United States: a secondary analysis.

OBJECTIVES: Stereotactic body radiation therapy (SBRT) is a technique used to deliver high, ablative doses of radiation in a limited number of fractions to ≥1 extracranial target(s). Although recent studies have shown that SBRT provides effective local tumor control in medically inoperable early-stage lung cancer patients, its implementation in clinical practice is unknown. METHODS: A random sample of 1600 American radiation oncologists was surveyed regarding lung SBRT usage, including year adopted, most common prescription, respiratory motion management, and target localization. A biological equivalent dose (BED) was calculated using the linear quadratic model with α/ß=10. Spearman rank correlation coefficients (r(s)) were calculated to identify factors associated with BED. RESULTS: Of 1373 contactable physicians, 551 responses (40%) were received. Of 510 evaluable responses, 275 physicians (54%) reported using lung SBRT, over half of whom adopted it in 2008 or later. The most commonly reported prescriptions were 20 Gy×3 (22%), 18 Gy×3 (21%), and 12 Gy×4 (17%). Three fraction regimens were most common (48%), with nearly all (89%) prescribing ≥18 Gy/fraction. The median BED was 132 Gy, with 95% of reported prescriptions having BED≥100 Gy. Factors associated with increased BED included use of fiducial markers (r(s)=0.26, P<0.001), use of planar imaging (r(s)=0.18, P<0.01), and years of experience with lung SBRT (r(s)=0.13, P=0.04). CONCLUSIONS: Lung SBRT has rapidly become a widely adopted treatment approach in the United States with a range of varying implementations. Further research and additional prospective trials are necessary to optimize this novel approach.

Frameless, real-time, surface imaging-guided radiosurgery: clinical outcomes for brain metastases.

BACKGROUND: Frameless stereotactic radiosurgery is commonly used to treat intracranial metastases, but mask-based immobilization can be uncomfortable for patients. OBJECTIVE: To describe the clinical outcomes using a novel real-time, frameless, surface imaging--guided radiosurgery (SIG-RS) technique to treat brain metastases. METHODS: Data were prospectively gathered for 44 consecutive patients totaling 115 intracranial metastases treated with SIG-RS in a median of 1 fraction (range, 1-5) to a median dose of 20 Gy (range, 15-30 Gy). Local control, regional control, and overall survival were estimated by the Kaplan-Meier method. RESULTS: Median follow-up for all patients was 6.0 months (range, 0.3-21.6 months), with 31 of 44 (70%) deceased at the time of analysis. The 35 patients (80%) with follow-up imaging totaled 88 lesions evaluable for local control. Actuarial 6- and 12-month local control was 90% (95% confidence interval, 82-98) and 76% (95% confidence interval, 60-91), respectively. Regional failure was observed in 16 patients (46%). The median actuarial overall survival was 7.7 months (95% confidence interval, 5.7-9.7). Analysis of the subset of 22 patients (55 lesions) who received SIG-RS alone (no prior treatment) in a single fraction yielded comparable clinical outcomes. Grade 3 or greater toxicity occurred in 4 patients (9%). The median treatment time from beam on to beam off was 15 minutes (range, 3-36 minutes). CONCLUSION: SIG-RS for treating intracranial metastases can produce clinical outcomes comparable to those with conventional frame-based and frameless stereotactic radiosurgery techniques while providing greater patient comfort with an open-faced mask and fast treatment times.

Patterns of imaging failures in glioblastoma patients treated with chemoradiation: a retrospective study.

Glioblastoma multiforme (GBM) is the most common primary brain tumor of adults and carries a poor prognosis. This study sought to investigate recurrence patterns of GBM treated with temozolomide-based chemoradiation. Records for 31 patients treated for newly diagnosed GBM between 2007 and 2009 were retrospectively analyzed. Ten patients received maximal surgical resection followed by conventionally fractionated radiation (CFR) to a median dose of 60 Gy with concurrent and planned adjuvant temozolomide. Twelve patients were treated with maximal surgical debulking, intracavitary brachytherapy (ICB), and external beam radiation therapy with concurrent and planned adjuvant temozolomide. The remaining 9 patients had unresectable disease and underwent biopsy followed by a hypofractionated course of radiation to a median dose of 60 Gy over 10 fractions. Tumor failure was classified as local, marginal, or distant according to whether the recurrence was completely inside, crossed, or completely outside the 100% isodose line. With a median follow-up of 12.6 months, 5 patients were lost to follow-up, while the remaining 26 patients (100%) developed recurrent disease. The first failures totaled 29 discrete lesions, of which 15 (52%), 6 (21%), and 8 (28%) were local, marginal, and distant failures at median times of 6.8, 10.1, and 7.9 months, respectively. Marginal or distant failure was more likely in ICB patients as compared to CFR patients. While local failure predominated, distant failures were not uncommon, particularly at later time points. As local control of GBM improves, further study is needed to identify and appropriately treat patients susceptible to distant failure.

Initial clinical experience with a frameless and maskless stereotactic radiosurgery treatment.

PURPOSE: To evaluate the initial clinical experience with a frameless and maskless technique for stereotactic radiosurgery using minimal patient immobilization and real-time patient motion monitoring during treatment. We focus on the evaluation of the patient treatment process. METHODS AND MATERIALS: The study considered the first 23 patients treated with this technique. Head positioning was achieved with a patient-specific head mold made out of expandable foam that conforms to the patient's head. The face of the patient is left open for maximal comfort and so that motion of a region of interest consisting of the forehead, nose, eyes, and temporal bones can be monitored during treatment using a video surface imaging system (VisionRT Inc, London, UK). Initial setup of the patient was performed with the surface imaging system using the surface of the patient obtained from the treatment planning computed tomographic (CT) scan. The initial setup was confirmed and finalized with cone-beam CT (CBCT) prior to treatment. The shifts for final setup based on the CBCT and the duration of all the steps in the treatment process were recorded. Patients were monitored during treatment with surface imaging, and a beam hold-off was initiated when the patient's motion exceeded a prespecified tolerance. RESULTS: The average total setup time including surface imaging and CBCT was 26 minutes, while the portion corresponding to surface imaging was 14 minutes. The average treatment time from when the patient was placed on the treatment table until the last treatment beam was 40 minutes. Eight (35%) patients needed repositioning during the treatment. The average shifts identified from CBCT after initial setup with surface imaging were 1.85 mm in the anterior-posterior direction, and less than 1.0 mm in the lateral and superior-inferior directions. The longest treatment times (including beam hold-offs) happened for patients who fell asleep on the treatment table and were moving involuntarily. CONCLUSIONS: The frameless and maskless treatment using minimal immobilization and surface imaging has proven to be reasonably fast for routine clinical use. We observed that patient compliance is important. An additional degree of semi-rigid immobilization would be helpful for patients who fall asleep and involuntarily move during the procedure.

DNA damage response and repair: insights into strategies for radiation sensitization of gliomas.

The incorporation of radiotherapy into multimodality treatment plans has led to significant improvements in glioma patient survival. However, local recurrence from glioma resistance to ionizing radiation remains a therapeutic challenge. The tumoricidal effect of radiation therapy is largely attributed to the induction of dsDNA breaks (DSBs). In the past decade, there have been tremendous strides in understanding the molecular mechanisms underlying DSB repair. The identification of gene products required for DSB repair has provided novel therapeutic targets. Recent studies revealed that many US FDA-approved cancer agents inhibit DSB repair by interacting with repair proteins. This article will aim to provide discussion of DSB repair mechanisms to provide molecular targets for radiation sensitization of gliomas and a discussion of FDA-approved cancer therapies that modulate DSB repair to highlight opportunities for combination therapy with radiotherapy for glioma therapy.

Frameless image-guided stereotactic body radiation therapy for lung tumors with 4-dimensional computed tomography or 4-dimensional positron emission tomography/ computed tomography.

BACKGROUND/PURPOSE: To augment the accuracy of stereotactic body radiation therapy (SBRT), a variety of image guidance systems are used for patient positioning and target localization. Clinical outcomes evaluating these systems, especially frameless image-guided systems, are still limited. This article aims to describe and evaluate our frameless image-guided SBRT technique for lung tumors. METHODS: Between 2007 and 2009, 85 pulmonary tumors (50 primaries and 35 metastases) were treated with SBRT using daily image guidance for patient positioning and target localization in lieu of a body frame. Four-dimensional computed tomography (4DCT) or an in-house protocol for integrated 4D positron emission computed tomography (4DPET/CT) was used for planning simulation. RESULTS: Median follow-up was 17 months (range, 4-42). Median overall survival (OS) was 31 months (95% CI, 26-34), and median local failure-free survival was 30 months (95% CI, 18-32). At last follow-up, 9 of 83 evaluable lesions failed locally. Actuarial local control at 24 months was 87% (95% CI, 75-98) and was significantly worse for metastatic lesions (95% vs. 74%; P = .045; log-rank test). No acute or late toxicities (grade ≥ 4) were observed. CONCLUSIONS: Frameless image-guided SBRT is a feasible, safe, and effective treatment for lung tumors.

A survey of stereotactic body radiotherapy use in the United States.

BACKGROUND: Stereotactic body radiotherapy (SBRT) is a technique used to deliver high, ablative doses of radiation in a limited number of fractions to ≥ 1 extracranial target(s). To the authors' knowledge, the prevalence of SBRT use among radiation oncologists in the United States is unknown. METHODS: A random sample of 1600 American radiation oncologists was surveyed via e-mail and facsimile (fax) regarding SBRT usage, including year of adoption, motivations, disease sites treated, and common prescriptions used. RESULTS: Of 1373 contactable physicians, 551 responses (40.1%) were received. The percentage of physicians using SBRT was 63.9% (95% confidence interval, 60%-68%), of whom nearly half adopted it in 2008 or later. The most commonly cited reasons for adopting SBRT were to allow the delivery of higher than conventional radiation doses (90.3%) and to allow retreatment (73.9%) in select patients. Academic physicians were more likely to report research as a motivation for SBRT adoption, whereas physicians in private practice were more likely to list competitive reasons. Among SBRT users, the most common disease sites treated were lung (89.3%), spine (67.5%), and liver (54.5%) tumors. Overall, 76.0% of current SBRT users planned to increase their use, whereas 66.5% of nonusers planned to adopt the technology in the future. CONCLUSIONS: SBRT has rapidly become a widely adopted treatment approach among American radiation oncologists. Further research and prospective trials are necessary to assess the benefits and risks of this novel technology.

Locoregional and distant failure following image-guided stereotactic body radiation for early-stage primary lung cancer.

PURPOSE: To report our institutional experience using image-guided stereotactic body radiation therapy (SBRT) for early stage lung cancer, including an analysis into factors associated with nodal and distant failures (NF, DF). METHODS: Forty-eight patients with early-stage primary lung cancer were treated with image-guided SBRT between 2007 and 2009. Median prescription dose was 48 Gy in 4 fractions. Toxicity was graded according to the NCI CTCAE v3.0 scale. RESULTS: Local failure was detected in two lesions and actuarial 24-month local control was 95%. At 24 months, the cumulative incidence of NF was 6%, and DF was 29%. Larger lesions (>3 cm) and younger age (<70 years) were the only factors found to be significantly correlated with increased DF (p=0.005 and p=0.015, respectively). A single grade ≥ 3 toxicity was observed. After adjusting for age and lesion size, distant failure was significantly associated with a poorer OS (Cox regression, p=0.0059). CONCLUSION: Image-guided SBRT can produce excellent LC rates with minimal toxicity. Distant failure was a major determinant of OS and the most common pattern of failure, indicating a potential role for systemic therapy in younger patients with large lesions.

Novel use of the Contura for high dose rate cranial brachytherapy.

A popular choice for treatment of recurrent gliomas was cranial brachytherapy using the GliaSite Radiation Therapy System. However, this device was taken off the market in late 2008, thus leaving a treatment void. This case study presents our experience treating a cranial lesion for the first time using a Contura multilumen, high-dose-rate (HDR) brachytherapy balloon applicator. The patient was a 47-year-old male who was diagnosed with a recurrent right frontal anaplastic oligodendroglioma. Previous radiosurgery made him a good candidate for brachytherapy. An intracavitary HDR balloon brachytherapy device (Contura) was placed in the resection cavity and treated with a single fraction of 20 Gy. The implant, treatment, and removal of the device were all completed without incident. Dosimetry of the device was excellent because the dose conformed very well to the target. V90, V100, V150, and V200 were 98.9%, 95.7%, 27.2, and 8.8 cc, respectively. This patient was treated successfully using the Contura multilumen balloon. Contura was originally designed for deployment in a postlumpectomy breast for treatment by accelerated partial breast irradiation. Being an intracavitary balloon device, its similarity to the GliaSite system makes it a viable replacement candidate. Multiple lumens in the device also make it possible to shape the dose delivered to the target, something not possible before with the GliaSite applicator.

Observed magnetic resonance imaging changes in pediatric patients treated with stereotactic radiosurgery for intracranial tumors.

PURPOSE: This study seeks to characterize magnetic resonance imaging (MRI) changes following stereotactic radiosurgery (SRS) of pediatric brain malignancies. METHODS: Serial MRI evaluations were performed on 21 lesions treated with SRS for either medulloblastoma (n=12), juvenile pilocytic astrocytoma (n=4), ependymoma (n=2), atypical rhabdoid teratoid tumor (n=2), or pineocytoma (n=1). Prescription doses ranged from 14 to 30 Gy in one to five fractions. Tumor response was qualified as complete (CR), partial (PR), stable disease (SD), or progressive disease (PD) according to the RECIST v1.1. Median radiographic follow-up after SRS was 17 months. RESULTS: A total of 80 follow-up MRI scans were reviewed with a median of eight per patient. During serial MRI evaluation, eight lesions met criteria for PD at a median of 6 months. However, of these, three (37%) represented transient tumor edema with two lesions later developing a CR at a median of 15 months and one persisting as SD at 12 months. The remaining five lesions were true local failures. Of the 13 lesions that did not show evidence of PD, a CR was obtained in 11 lesions at a median of 3 months (range, 2-6), and SD was seen in the remaining two tumors at last follow-up. CONCLUSION: Lesion enlargement following SRS for pediatric intracranial tumors is common, and a proportion of patients meeting requirements for PD at early radiographic follow-up may later develop complete resolution of their lesions. Physicians should be aware of these radiographic changes to avoid unwarranted medical and surgical interventions.

Longitudinal MRI evidence for decreased survival among periventricular glioblastoma.

While the prognosis of patients with glioblastoma (GBM) remains poor despite recent therapeutic advances, variable survival times suggest wide variation in tumor biology and an opportunity for stratified intervention. We used volumetric analysis and morphometrics to measure the spatial relationship between subventricular zone (SVZ) proximity and survival in a cohort of 39 newly diagnosed GBM patients. We collected T2-weighted and gadolinium-enhanced T1-weighted magnetic resonance images (MRI) at pre-operative, post-operative, pre-radiation therapy, and post-radiation therapy time points, measured tumor volumes and distances to the SVZ, and collected clinical data. Univariate and multivariate Cox regression showed that tumors involving the SVZ and tumor growth rate during radiation therapy were independent predictors of shorter progression-free and overall survival. These results suggest that GBMs in close proximity to the ependymal surface of the ventricles convey a worse prognosis-an observation that may be useful for stratifying treatment.

A survey of image-guided radiation therapy use in the United States.

BACKGROUND: Image-guided radiation therapy (IGRT) is a novel array of in-room imaging modalities that are used for tumor localization and patient setup in radiation oncology. The prevalence of IGRT use among US radiation oncologists is unknown. METHODS: A random sample of 1600 radiation oncologists was surveyed by Internet, e-mail and fax regarding the frequency of IGRT use, clinical applications, and future plans for use. The definition of IGRT included imaging technologies that are used for setup verification or tumor localization during treatment. RESULTS: Of 1089 evaluable respondents, 393 responses (36.1%) were received. The proportion of radiation oncologists using IGRT was 93.5%. When the use of megavoltage (MV) portal imaging was excluded from the definition of IGRT, the proportion using IGRT was 82.3%. The majority used IGRT rarely (in <25% of their patients; 28.9%) or infrequently (in 25%-50% of their patients; 33.1%). The percentages using ultrasound, video, MV-planar, kilovoltage (kV)-planar, and volumetric technologies were 22.3%, 3.2%, 62.7%, 57.7%, and 58.8%, respectively. Among IGRT users, the most common disease sites treated were genitourinary (91.1%), head and neck (74.2%), central nervous system (71.9%), and lung (66.9%). Overall, 59.1% of IGRT users planned to increase use, and 71.4% of nonusers planned to adopt IGRT in the future. CONCLUSIONS: IGRT is widely used among radiation oncologists. On the basis of prospective plans of responders, its use is expected to increase. Further research will be required to determine the safety, cost efficacy, and optimal applications of these technologies.

Markerless lung tumor tracking and trajectory reconstruction using rotational cone-beam projections: a feasibility study.

Algorithms for direct tumor tracking in rotational cone-beam projections and for reconstruction of phase-binned 3D tumor trajectories were developed. The feasibility of the algorithm was demonstrated on a digital phantom, a physical phantom and two patients. Tracking results were obtained by comparing reference templates generated from 4DCT to rotational cone-beam projections. The 95th percentile absolute errors (e(95)) in phantom tracking results did not exceed 1.7 mm in either imager dimension, while e(95) in the patients was 3.3 mm or less. Accurate phase-binned trajectories were reconstructed in each case, with 3D maximum errors of no more than 1.0 mm in the phantoms and 2.0 mm in the patients. This work shows the feasibility of a direct tumor tracking technique for rotational images, and demonstrates that an accurate 3D tumor trajectory can be reconstructed from relatively less accurate tracking results. The ability to reconstruct the tumor's average trajectory from a 3D cone-beam CT scan on the day of treatment could allow for better patient setup and quality assurance, while direct tumor tracking in rotational projections could be clinically useful for rotational therapy such as volumetric modulated arc therapy (VMAT).

Frame-less and mask-less cranial stereotactic radiosurgery: a feasibility study.

Currently, high-precision delivery in stereotactic radiosurgery (SRS) is achieved via high-precision target localization and rigid patient immobilization. Rigid patient immobilization can result in, however, patient discomfort, which is exacerbated by the long duration of SRS treatments and may induce patient movement. To address this issue, we developed a new SRS technique that is aimed to minimize patient discomfort while maintaining high-precision treatment, based on a less-rigid patient immobilization combined with continuous patient motion monitoring. In this paper, we examine the feasibility of this new technique. An anthropomorphic head phantom is used to check the accuracy of a 3D surface imaging system that provides the monitoring. Volunteers are used to study patient motion inside a new type of head mold that is used for minimal immobilization. Results show that for different couch angles, the difference between the phantom positions recorded by the surface imaging system and by an infrared optical tracking system was within 1 mm in displacements and 1 degrees in rotation. The motion detected by both systems during couch shifts is within 1 mm agreement. The average maximum volunteer head motion in the head mold during the 20 min interval in any direction was 0.7 mm (range: 0.4-1.1 mm). Patient motion due to couch motion was always less than 0.2 mm. We conclude that motion inside the minimally immobilizing head mold is small and can be accurately detected by real-time surface imaging.

Evaluation of automatic atlas-based lymph node segmentation for head-and-neck cancer.

PURPOSE: To evaluate if automatic atlas-based lymph node segmentation (LNS) improves efficiency and decreases inter-observer variability while maintaining accuracy. METHODS AND MATERIALS: Five physicians with head-and-neck IMRT experience used computed tomography (CT) data from 5 patients to create bilateral neck clinical target volumes covering specified nodal levels. A second contour set was automatically generated using a commercially available atlas. Physicians modified the automatic contours to make them acceptable for treatment planning. To assess contour variability, the Simultaneous Truth and Performance Level Estimation (STAPLE) algorithm was used to take collections of contours and calculate a probabilistic estimate of the "true" segmentation. Differences between the manual, automatic, and automatic-modified (AM) contours were analyzed using multiple metrics. RESULTS: Compared with the "true" segmentation created from manual contours, the automatic contours had a high degree of accuracy, with sensitivity, Dice similarity coefficient, and mean/max surface disagreement values comparable to the average manual contour (86%, 76%, 3.3/17.4 mm automatic vs. 73%, 79%, 2.8/17 mm manual). The AM group was more consistent than the manual group for multiple metrics, most notably reducing the range of contour volume (106-430 mL manual vs. 176-347 mL AM) and percent false positivity (1-37% manual vs. 1-7% AM). Average contouring time savings with the automatic segmentation was 11.5 min per patient, a 35% reduction. CONCLUSIONS: Using the STAPLE algorithm to generate "true" contours from multiple physician contours, we demonstrated that, in comparison with manual segmentation, atlas-based automatic LNS for head-and-neck cancer is accurate, efficient, and reduces interobserver variability.