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PURPOSE: Present knowledge of patient setup and alignment errors in image guided radiation therapy (IGRT) relies on voluntary reporting, which is thought to underestimate error frequencies. A manual retrospective patient-setup misalignment error search is infeasible owing to the bulk of cases to be reviewed. We applied a deep learning-based misalignment error detection algorithm (EDA) to perform a fully automated retrospective error search of clinical IGRT databases and determine an absolute gross patient misalignment error rate. METHODS AND MATERIALS: The EDA was developed to analyze the registration between planning scans and pretreatment cone beam computed tomography scans, outputting a misalignment score ranging from 0 (most unlikely) to 1 (most likely). The algorithm was trained using simulated translational errors on a data set obtained from 680 patients treated at 2 radiation therapy clinics between 2017 and 2022. A receiver operating characteristic analysis was performed to obtain target thresholds. DICOM Query and Retrieval software was integrated with the EDA to interact with the clinical database and fully automate data retrieval and analysis during a retrospective error search from 2016 to 2017 and from 2021 to 2022 for the 2 institutions, respectively. Registrations were flagged for human review using both a hard-thresholding method and a prediction trending analysis over each individual patient's treatment course. Flagged registrations were manually reviewed and categorized as errors (>1 cm misalignment at the target) or nonerrors. RESULTS: A total of 17,612 registrations were analyzed by the EDA, resulting in 7.7% flagged events. Three previously reported errors were successfully flagged by the EDA, and 4 previously unreported vertebral body misalignment errors were discovered during case reviews. False positive cases often displayed substantial image artifacts, patient rotation, and soft tissue anatomy changes. CONCLUSIONS: Our results validated the clinical utility of the EDA for bulk image reviews and highlighted the reliability and safety of IGRT, with an absolute gross patient misalignment error rate of 0.04% ± 0.02% per delivered fraction.

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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.

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Background: Tumor surveillance of isocitrate dehydrogenase (IDH) mutant gliomas is accomplished via serial contrast MRI. When new contrast enhancement (CEnew) is detected during postsurgical surveillance, clinicians must assess whether CEnew indicates pseudoprogression (PsP) or tumor progression (TP). PsP has been better studied in IDH wild-type glioblastoma but has not been well characterized in IDH mutant gliomas. We conducted a retrospective study evaluating the incidence, predictors, natural history, and survival of PsP patients in a large cohort of IDH mutant glioma patients treated at a single institution. Methods: We identified 587 IDH mutant glioma patients treated at UCLA. We directly inspected MRI images and radiology reports to identify CEnew and categorized CEnew into TP or PsP using MRI or histopathology. Results: Fifty-six percent of patients developed CEnew (326/587); of these, 92/326 patients (28% of CEnew; 16% of all) developed PsP and 179/326 (55%) developed TP. All PsP patients had prior radiation, chemotherapy, or chemoradiotherapy. PsP was associated with longer overall survival (OS) versus TP patients and similar OS versus no CEnew. PsP differs from TP based on earlier time of onset (median 5.8 vs 17.4 months from treatment, P < .0001) and MRI features that include punctate enhancement and enhancement location. Conclusion: PsP patients represented 28% of CEnew patients and 16% of all patients; PsP patients demonstrated superior outcomes to TP patients, and equivalent survival to patients without CEnew. PsP persists for <1 year, occurs after treatment, and differs from TP based on time of onset and radiographic features. Poor outcomes after CEnew are driven by TP.

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Purpose: We sought to survey the attitudes and perceptions of US radiation oncologists toward the adoption of telemedicine during the COVID-19 pandemic and offer suggestions for its integration in the postpandemic era. Methods and Materials: A 25-question, anonymous online survey was distributed nationwide to radiation oncologists. Results: One hundred and twenty-one respondents completed the survey, with 92% from academia. Overall, 79% worked at institutions that had implemented a work-from-home policy, with which 74% were satisfied. Despite nearly all visit types being conducted in-person before COVID-19, 25%, 41%, and 5% of the respondents used telemedicine for more than half of their new consultations, follow-up, and on-treatment visits, respectively, during the COVID-19 pandemic. Most (83%) reported being comfortable integrating telemedicine. Although telemedicine was appreciated as being more convenient for patients (97%) and reducing transmission of infectious agents (83%), the most commonly perceived disadvantages were difficulty in performing physical examinations (90%), patients' inability to use technology adequately (74%), and technical malfunctions (72%). Compared with in-person visits, telemedicine was felt to be inferior in establishing a personal connection during consultation (90%) and assessing for toxicity while on-treatment (88%) and during follow-up (70%). For follow-up visits, genitourinary and thoracic were perceived as most appropriate for telemedicine while gynecologic and head and neck were considered the least appropriate. Overall, 70% were in favor of more telemedicine, even after pandemic is over. Conclusions: Telemedicine will likely remain part of the radiation oncology workflow in most clinics after the pandemic. It should be used in conjunction with in-person visits, and may be best used for conducting follow-up visits in certain disease sites such as genitourinary and thoracic malignancies.

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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.

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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.

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PURPOSE/OBJECTIVE(S): To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins. MATERIALS/METHODS: Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0 mm, 1 mm and 2 mm margins were created, including plans with variable margins, where targets more than 6 cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements. RESULTS: The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from 0 to 1 mm and tripled when change from 0 to 2 mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6 cm away from the isocenter. With 0.5 mm re-positioning threshold, 57.4% of the time the patients are repositioned. Reducing the threshold to 0.25 mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. The 90th percentile of translational movements in all directions is 0.7 mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2 mm and 0.2 degrees, respectively. CONCLUSIONS: Based on the data presented, we have switched our modus operandi from 2 to 1 mm PTV margins, with an eventual goal of using 0.5 and 1.0 mm variable margins when an automated margin assignment method becomes available. The 0.5 mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.

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BACKGROUND: Up to 15% of previously irradiated metastatic spine tumors will progress. Re-irradiation of these tumors poses a significant risk of exceeding the radiation tolerance to the spinal cord. High-dose rate (HDR) brachytherapy is a treatment alternative. OBJECTIVE: To develop a novel HDR spine brachytherapy technique using an intraoperative computed tomography-guided navigation (iCT navigation). METHODS: Patients with progressive metastatic spine tumors were included in the study. HDR brachytherapy catheters were placed under iCT navigation. CT-based planning with magnetic resonance imaging fusion was performed to ensure conformal dose delivery to the target while sparing normal tissue, including the spinal cord. Patients received single fraction radiation treatment. RESULTS: Five patients with thoracolumbar tumors were treated with HDR brachytherapy. Four patients previously received radiotherapy to the same spinal level. Preimplant plans demonstrated median clinical target volume (CTV) D90 of 116.5% (110.8%-147.7%), V100 of 95.7% (95.5%-99.6%), and Dmax of 8.08 Gy (7.65-9.8 Gy) to the spinal cord/cauda equina. Postimplant plans provided median CTV D90 of 113.8% (93.6%-120.1%), V100 of 95.9% (87%-99%), and Dmax of 9.48 Gy (6.5-10.3 Gy) to cord/cauda equina. Patients who presented with back pain (n = 3) noted symptomatic improvement at a median follow-up of 22 d after treatment. Four patients demonstrated local tumor control of spinal metastatic tumor at a median follow-up of 92 d after treatment. One patient demonstrated radiographic evidence of local tumor progression 2.7 mo after treatment. CONCLUSION: HDR spine brachytherapy with iCT navigation is a promising treatment alternative to induce local tumor control and reduce pain symptoms associated with metastatic spine disease.

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PURPOSE: To examine the use of multiple fast-helical free breathing computed tomography (FHFBCT) scans for ventilation measurement. METHODS: Ten patients were scanned 25 times in alternating directions using a FHFBCT protocol. Simultaneously, an abdominal pneumatic bellows was used as a real-time breathing surrogate. Regions-of-interest (ROIs) were selected from the upper right lungs of each patient for analysis. The ROIs were first registered using a published registration technique (pTV). A subsequent follow-up registration employed an objective function with two terms, a ventilation-adjusted Hounsfield Unit difference and a conservation-of-mass term labeled ΔΓ that denoted the difference between the deformation Jacobian and the tissue density ratio. The ventilations were calculated voxel-by-voxel as the slope of a first-order fit of the Jacobian as a function of the breathing amplitude. RESULTS: The ventilations of the 10 patients showed different patterns and magnitudes. The average ventilation calculated from the deformation vector fields (DVFs) of the pTV and secondary registration was nearly identical, but the standard deviation of the voxel-to-voxel differences was approximately 0.1. The mean of the 90th percentile values of ΔΓ was reduced from 0.153 to 0.079 between the pTV and secondary registration, implying first that the secondary registration improved the conservation-of-mass criterion by almost 50% and that on average the correspondence between the Jacobian and density ratios as demonstrated by ΔΓ was less than 0.1. This improvement occurred in spite of the average of the 90th percentile changes in the DVF magnitudes being only 0.58 mm. CONCLUSIONS: This work introduces the use of multiple free-breathing CT scans for free-breathing ventilation measurements. The approach has some benefits over the traditional use of 4-dimensional CT (4DCT) or breath-hold scans. The benefit over 4DCT is that FHFBCT does not have sorting artifacts. The benefits over breath-hold scans include the relatively small motion induced by quiet respiration versus deep-inspiration breath hold and the potential for characterizing dynamic breathing processes that disappear during breath hold.

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Radiation oncology practices use a suite of dedicated software and hardware that are not common to other medical subspecialties, making radiation treatment history inaccessible to colleagues. A radiation dose distribution map is generated for each patient internally that allows for visualization of the dose given to each anatomic structure volumetrically; however, this crucial information is not shared systematically to multidisciplinary medical, surgery, and radiology colleagues. A framework was developed in which dose distribution volumes are uploaded onto the medical center's picture archiving and communication system (PACS) to rapidly retrieve and review exactly where, when, and to what dose a lesion or structure was treated. The ability to easily visualize radiation therapy information allows radiology clinics to incorporate radiation dose into image interpretation without direct access to radiation oncology planning software and data. Tumor board discussions are simplified by incorporating radiation therapy information collectively in real time, and daily onboard imaging can also be uploaded while a patient is still undergoing radiation therapy. Placing dose distribution information into PACS facilitates central access into the electronic medical record and provides a succinct visual summary of a patient's radiation history for all medical providers. More broadly, the radiation dose map provides greater visibility and facilitates incorporation of a patient's radiation history to improve oncologic decision making and patient outcomes. Keywords: Brain/Brain Stem, CNS, MRI, Neuro-Oncology, Radiation Effects, Radiation Therapy, Radiation Therapy/Oncology, Radiosurgery, Skull Base, Spine, Technology Assessment Supplemental material is available for this article. © RSNA, 2021 See also commentary by Khandelwal and Scarboro in this issue.

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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.

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The development and integration of electronic patient-reported outcomes (ePROs) into the radiation oncology clinic workflow provide novel opportunities, accompanied by unique design considerations and implementation challenges. The processes required for implementation of ePROs are entirely distinct from standard paper-based surveys, with the majority of time devoted to conception and design before initiating questionnaire build, detailed workflow process mapping including development of new workflows, comprehensive communication of the vision between providers and the information technology team, and quality assurance. Based on our experience with implementation of ePROs in our radiation oncology department, we developed a stepwise framework for approaching ePRO conceptual design, build, workflow integration, and the electronic health record interface. Here, we provide a guide for the numerous considerations, decision points, and solutions associated with the implementation of ePROs in the radiation oncology department setting. Although various ePRO tools and electronic health record capabilities impose different requirements, opportunities, and limitations, the conceptual processes and many of the electronic build considerations are broadly applicable.

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PURPOSE: "Near miss" events are valuable low-cost learning opportunities in radiation oncology as they do not result in patient harm and are more pervasive than adverse events that do. Near misses vary depending on the presence of a latent error of behavior or process, and the presence of an enabling condition predisposing the patient to harm. These nuanced distinctions across near miss types can elicit different cognitive biases affecting the recognition of near misses as learning opportunities. We define near miss types in radiation oncology and explore the differential perceptions among radiation oncology staff. METHODS AND MATERIALS: Six event types were defined based on attributes of latent error and enabling conditions: "hit," "potential hit," "almost happened," "fortuitous catch," "could have happened," and "process-based catch." These events were illustrated with an example of a patient receiving pacemaker cardiac clearance before radiation treatment. A survey assessing (1) success versus failure of an event and (2) willingness to report the event was administered to a radiation oncology department using the pacemaker example. Mean scores for each near miss type were compared. RESULTS: Ninety-five staff members (74%) completed the survey. Perceived success scores and willing-to-report scores significantly differed by near miss type (P = .042 for success ratings; P < .0001 for willingness to report). "Could have happened" events were viewed as less successful and were more likely to be reported than "almost happened" events (P < .0001). CONCLUSIONS: Cognitive biases appear to influence whether and how near miss types are recognized as report-worthy. Education of near miss types and engaging staff for quality improvement may improve recognition.

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BACKGROUND: Psychological safety, a shared belief that interpersonal risk taking is safe, is an important determinant of incident reporting. However, how psychological safety affects near-miss reporting is unclear, as near misses contain contrasting cues that highlight both resilience ("we avoided failure") and vulnerability ("we nearly failed"). Near misses offer learning opportunities for addressing underlying causes of potential incidents, and it is crucial to understand what facilitates near-miss reporting. METHODS: A survey of radiation oncology department staff in an academic hospital assessed psychological safety and presented five scenarios with varying proximity to patient harm: "standard care" involving no harm, three near misses with varying proximity to harm ("could have happened," "fortuitous catch," "almost happened"), and one "hit" involving harm. Respondents evaluated each event as success or failure and reported willingness to report on a seven-point Likert scale. The analysis employed ordered logistic regression models. RESULTS: A total of 78 staff (61.4%) completed the survey. The odds of reporting "hit" (odds ratio [OR]: 1.96, 95% confidence interval [CI]: 1.19-3.23), "almost happened" (OR: 1.60, 95% CI: 1.07-2.37), and "fortuitous catch" (OR: 1.60, 95% CI: 1.10-2.33) improved with an increase in psychological safety. The relationship of psychological safety to reporting "standard care" and "could have happened" was not statistically significant. The odds of reporting were higher when a near miss was discerned as failure (vs. success). CONCLUSION: Near misses are not processed and reported equally. The effect of psychological safety on reporting near misses becomes stronger with their increasing proximity to a negative outcome. Educating health care workers to properly identify near misses and fostering psychological safety may increase near-miss reporting and improve patient safety.

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PURPOSE: The ambulatory patient experience is heavily influenced by wait times for provider care. Delayed patient visit start times may negatively affect overall satisfaction, and increased wait times affect the perception of the information, instructions, and treatment given by health care providers. Improving institutional practices overall requires the determination of the essential quality metrics that will make such an achievement possible. A protracted time leading up to the initiation of radiation therapy may promote poor satisfaction and perceived quality of care for both patients and referring providers alike, which may then create a barrier to patients being treated with radiation therapy. This institution piloted and sucessfully completed a study into improving the timeliness of initiation of patient radiation therapy for our patients. METHODS AND MATERIALS: This work sought to identify inefficiencies in radiation therapy treatment planning to shorten the time each patient waited for treatment. We examined the time between simulation to the start of the first fraction of treatment. This period includes simulation, contouring, treatment planning, and quality assurance of the plan. RESULTS: Before the study, the planning process would typically take 2 weeks. Target and organs-at-risk contouring were found to be the main inefficiency delaying treatment start dates. This delineating process includes drawing contours on radiologic images, typically computed tomography and magnetic resonance imaging. We focused on the time needed for the contouring process to be completed and took steps to increase efficiency. The length of time from simulation to contour approval was decreased by more than 60%, a reduction from an average of more than 4 days to less than 1.5 days. Overall planning time dropped from 2 weeks to less than 5 days. CONCLUSIONS: Process improvements and implementation of task-specific tools improved the timeliness of patient treatments, reducing the overall planning time from simulation to treatments to less than 5 days. Continuous monitoring and modification of these processes revealed that the successes achieved toward better quality of care have been sustained.

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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.

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BACKGROUND: The role of elective whole-pelvis radiotherapy (WPRT) remains controversial. Few studies have investigated it in Gleason grade group (GG) 5 prostate cancer (PCa), known to have a high risk of nodal metastases. OBJECTIVE: To assess the impact of WPRT on patients with GG 5 PCa treated with external-beam radiotherapy (EBRT) or EBRT with a brachytherapy boost (EBRT+BT). DESIGN, SETTING, AND PARTICIPANTS: We identified 1170 patients with biopsy-proven GG 5 PCa from 11 centers in the United States and one in Norway treated between 2000 and 2013 (734 with EBRT and 436 with EBRT+BT). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Biochemical recurrence-free survival (bRFS), distant metastasis-free survival (DMFS), and prostate cancer-specific survival (PCSS) were compared using Cox proportional hazards models with propensity score adjustment. RESULTS AND LIMITATIONS: A total of 299 EBRT patients (41%) and 320 EBRT+BT patients (73%) received WPRT. The adjusted 5-yr bRFS rates with WPRT in the EBRT and EBRT+BT groups were 66% and 88%, respectively. Without WPRT, these rates for the EBRT and EBRT+BT groups were 58% and 78%, respectively. The median follow-up was 5.6yr. WPRT was associated with improved bRFS among patients treated with EBRT+BT (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.2-0.9, p=0.02), but no evidence for improvement was found in those treated with EBRT (HR 0.8, 95% CI 0.6-1.2, p=0.4). WPRT was not significantly associated with improved DMFS or PCSS in the EBRT group (HR 1.1, 95% CI 0.7-1.7, p=0.8 for DMFS and HR 0.7, 95% CI 0.4-1.1, p=0.1 for PCSS), or in the EBRT+BT group (HR 0.6, 95% CI 0.3-1.4, p=0.2 for DMFS and HR 0.5 95% CI 0.2-1.2, p=0.1 for PCSS). CONCLUSIONS: WPRT was not associated with improved PCSS or DMFS in patients with GG 5 PCa who received either EBRT or EBRT+BT. However, WPRT was associated with a significant improvement in bRFS among patients receiving EBRT+BT. Strategies to optimize WPRT, potentially with the use of advanced imaging techniques to identify occult nodal disease, are warranted. PATIENT SUMMARY: When men with a high Gleason grade prostate cancer receive radiation with external radiation and brachytherapy, the addition of radiation to the pelvis results in a longer duration of prostate-specific antigen control. However, we did not find a difference in their survival from prostate cancer or in their survival without metastatic disease. We also did not find a benefit for radiation to the pelvis in men who received radiation without brachytherapy.

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BACKGROUND: We evaluated priorities, expectations, and regret among patients treated on a phase II trial of de-escalated chemoradiation for human papillomavirus (HPV)-positive oropharyngeal cancer. METHODS: Eligibility included stage III/IV squamous cell carcinoma of the oropharynx, p16-positivity, age ≥18 years, and Zubrod score 0-1. Participants were surveyed with validated measures evaluating their treatment experience. RESULTS: Twenty-four of 27 (89%) patients participated with a median follow-up of 24 months. Twenty-three subjects (96%) selected "being cured" or "living as long as possible" as top priority. No patient reported any regret about the decision to enroll on a de-escalation protocol. Sixteen participants (67%) found retrospectively reported long-term swallowing function to be either better than or as originally expected. CONCLUSIONS: These data offer a baseline landscape of perspectives and priorities for patients treated with de-escalation for HPV-positive oropharyngeal carcinoma and provide support to the fundamental premise underlying ongoing efforts to establish a new standard of care.

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PURPOSE: Gleason score (GS) 10 disease is the most aggressive form of clinically localized prostate adenocarcinoma (PCa). The long-term clinical outcomes and overall prognosis of patients presenting with GS 10 PCa are largely unknown because of its rarity. METHODS AND MATERIALS: The study included 112 patients with biopsy-determined GS 10 PCa who received treatment with radical prostatectomy (RP, n = 26), external beam radiation therapy (EBRT, n = 48), or EBRT with a brachytherapy boost (EBRT-BT, n = 38) between 2000 and 2013. Propensity scores were included as covariates for comparative analysis. Overall survival, prostate cancer-specific survival, and distant metastasis-free survival (DMFS) were estimated by the Kaplan-Meier method with inverse probability of treatment weighting to control for confounding. RESULTS: The median follow-up period was 4.9 years overall (3.9 years for RP, 4.8 years for EBRT, and 5.7 years for EBRT-BT). Significantly more EBRT patients than EBRT-BT patients received upfront androgen deprivation therapy (98% vs 79%, P < .01 by χ2 test), though the durations were similar (median, 24 months vs 22.5 months). Of the RP patients, 34% received postoperative EBRT, and 35% received neoadjuvant systemic therapy. The propensity score-adjusted 5-year overall survival rate was 80% for the RP group, 73% for the EBRT group, and 83% for the EBRT-BT group. The corresponding adjusted 5-year prostate cancer-specific survival rates were 87%, 75%, and 94%, respectively. The EBRT-BT group trended toward superior DMFS when compared with the RP group (hazard ratio, 0.3; 95% confidence interval 0.1-1.06; P = .06) and had superior DMFS when compared with the EBRT group (hazard ratio, 0.4; 95% confidence interval 0.1-0.99; P = .048). CONCLUSIONS: To our knowledge, this is the largest series ever reported on the clinical outcomes of patients with biopsy-determined GS 10 PCa. These data provide useful prognostic benchmark information for physicians and patients. Aggressive therapy with curative intent is warranted, as >50% of patients remain free of systemic disease 5 years after treatment.

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