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Fiducial markers are utilized for image guided radiotherapy (IGRT) alignment during the delivery of liver stereotactic body radiosurgery (SBRT). There are limited data demonstrating the impact of matching fiducials on the accuracy of liver SBRT. This study quantifies the benefit of fiducial-based alignment and improvements in inter-observer reliability. Nineteen patients with 24 liver lesions were treated with SBRT. Target localization was performed using fiducial markers on cone-beam computed tomography (CBCT). Each CBCT procedure was retrospectively realigned to match both the liver edge and fiducial markers. The shifts were recorded by seven independent observers. Inter-observer variability was analyzed by calculating the mean error and uncertainty for the set-up. The mean absolute Cartesian error observed from fiducial and liver edge-based alignment was 1.5 mm and 5.3 mm, respectively. The mean uncertainty from fiducial and liver edge-based alignment was 1.8 mm and 4.5 mm, respectively. An error of 5 mm or greater was observed 50% of the time when aligning to the liver surface versus 5% of the time when aligning to fiducial markers. Aligning to the liver edge significantly increased the error, resulting in increased shifts when compared to alignment to fiducials. Tumors of 3 cm or farther from the liver dome had higher mean errors when aligned without fiducials (4.8 cm vs. 4.4 cm, p = 0.003). Our data support the use of fiducial markers for safer and more accurate liver SBRT. [ABSTRACT FROM AUTHOR]

Purpose In the postoperative management of uterine carcinosarcoma (UCS), the roles of individual radiotherapy (RT) modalities, chiefly external-beam radiotherapy (EBRT) and brachytherapy (BT), remain undefined. We analyzed the survival impact of EBRT and BT using the National Cancer Database. Methods and materials We abstracted women diagnosed with UCS from 2004 to 2012 who received hysterectomy and had complete RT information. Cox multivariate analysis and propensity-score matched analyses were used to compare survival among radiotherapeutic approaches. Results We identified 1229 women receiving no radiotherapy, 472 receiving EBRT alone, 331 receiving BT alone, and 271 receiving EBRT+BT. On multivariate analysis of the entire analytic cohort, survival was significantly improved among patients receiving EBRT+BT combination (hazard ratio [HR] 0.72, 95% confidence interval [CI] = 0.58–0.89, p < 0.01), but not among those receiving EBRT alone (HR 0.93, 95% CI = 0.79–1.10, p = 0.41) or BT alone (HR 0.84, 95% CI = 0.68–1.03, p = 0.09). These results were confirmed on propensity-score matches for EBRT vs. no RT (HR 0.89, 95% CI = 0.73–1.07, p = 0.34), BT vs. no RT (HR 0.80, 95% CI = 0.63–1.03, p = 0.09), and EBRT+BT vs. no RT (HR 0.74, 95% CI = 0.58–0.96, p = 0.02). Conclusions EBRT+BT combination is associated with an overall survival advantage in UCS and warrants consideration in the adjuvant management of this disease. [ABSTRACT FROM AUTHOR]

Background: Sinonasal malignancies are a rare and heterogeneous group of tumors for which there is a paucity of robust data with which to guide management decisions. The authors used the National Cancer Data Base to better understand the presenting characteristics of these tumors and to compare outcomes by treatment modality.Methods: The National Cancer Data Base was queried for sinonasal malignancies diagnosed between 2004 and 2012. Overall survival was assessed using multivariate analyses and propensity score matching.Results: A total of 11,160 patients were identified for the initial analysis. The majority were male, aged 40 to 69 years, with tumors of the nasal cavity or maxillary sinus. Squamous cell histology was most common. The majority of patients presented with advanced tumor stage but without locoregional lymph node or distant metastases. Treatment modalities were compared for squamous cell carcinomas. In multivariate analysis, compared with surgery alone, patients who received adjuvant radiotherapy (hazard ratio [HR], 0.658 [P<.001]), adjuvant chemoradiotherapy (HR, 0.696 [P = .002]), or neoadjuvant therapy (HR, 0.656 [P = .007]) had improved overall survival. Patients who received radiotherapy alone (HR, 1.294 [P = .001]) or chemotherapy alone (HR, 1.834 [P<.001]) had worse outcomes. These findings were validated in propensity score matching. It is important to note that neoadjuvant chemoradiotherapy was associated with achieving a negative surgical margin (odds ratio, 2.641 [P = .045]).Conclusions: Surgery is the mainstay of therapy for patients with sinonasal malignancies, but multimodality therapy is associated with improved overall survival. Cancer 2017;123:3040-49. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background and purpose Ablative radiation therapy can be beneficial for pancreatic cancer, and motion mitigation helps to reduce dose to nearby organs-at-risk. Here, we compared two competing methods of motion mitigation—abdominal compression and respiratory gating. Materials and methods CBCT scans of 19 pancreatic cancer patients receiving stereotactic body radiation therapy were acquired with and without abdominal compression, and 3D target motion was reconstructed from CBCT projection images. Daily target motion without mitigation was compared against motion with compression and with simulated respiratory gating. Gating was free-breathing and based on an external surrogate. Target coverage was also evaluated for each scenario by simulating reduced target margins. Results Without mitigation, average daily target motion in LR/AP/SI directions was 5.3, 7.3, and 13.9 mm, respectively. With abdominal compression, these values were 5.2, 5.3, and 8.5 mm, and with respiratory gating they were 3.2, 3.9, and 5.5 mm, respectively. Reductions with compression were significant in AP/SI directions, while reductions with gating were significant in all directions. Respiratory gating also demonstrated better coverage in the reduced margins scenario. Conclusion Respiratory gating is the most effective strategy for reducing motion in pancreatic SBRT, and may allow for dose escalation through a reduction in target margin. [ABSTRACT FROM AUTHOR]

Background: Although laryngectomy is the treatment of choice for patients with T4 larynx cancer, many patients are unable or unwilling to undergo laryngectomy and instead pursue larynx-preservation strategies combining radiotherapy (RT) and chemotherapy. Herein, the authors analyzed the National Cancer Data Base to evaluate overall survival (OS) between patients treated with surgical and organ-preserving modalities.Methods: The National Cancer Data Base was queried for patients diagnosed from 2004 through 2012 with T4M0 laryngeal cancer who underwent either laryngectomy (surgery) with adjuvant RT (SRT), chemotherapy starting concurrently within 7 days of RT (CCRT), or multiagent induction chemotherapy starting 43 to 98 days before RT (ICRT). Multivariate analysis and propensity score matching were used to explore the association between the intervention and OS. Recursive partitioning analysis was performed to identify groups benefiting from particular modalities.Results: A total of 1559 patients who underwent SRT, 1597 patients who underwent CCRT, and 386 patients who underwent ICRT were included. Adjusting for covariates, CCRT was found to be associated with inferior OS compared with SRT (hazard ratio [HR], 1.55; 95% confidence interval [95% CI], 1.41-1.70 [P<.01]) and with ICRT (HR, 1.25; 95% CI, 1.07-1.45 [P<.01]). OS among the patients treated with SRT did not appear to differ significantly from that of the ICRT cohort (HR, 0.87; 95% CI, 0.73-1.03 [P =  0.10]), a finding confirmed with propensity score matching. Recursive partitioning analysis identified no subset of patients that derived an OS benefit from either approach over the other.Conclusions: OS among patients undergoing SRT was found to be superior to that of patients treated with CCRT but did not significantly differ from that of those undergoing ICRT. Because these intriguing findings require validation, SRT should remain the standard of care for patients with this disease. However, organ preservation with ICRT may be a reasonable alternative in certain patients. Cancer 2017;123:600-608. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Given the rarity of anal cancer and the technical aspects involved in radiation (RT) planning, the authors conducted a population-based analysis evaluating the impact of radiation oncology facility volume on overall survival (OS) in patients with squamous cell carcinoma (SCC) of the anal canal.Methods: The National Cancer Data Base (NCDB) was queried for patients with SCC of the anal canal who underwent RT. All patients were coded as having received their entire course of RT at the NCDB reporting facility. Facility volume was categorized into tertiles (low, intermediate, and high) and was based on the number of times a facility's unique identification code appeared.Results: In total, 13,550 patients were identified. Patients who received treatment at higher volume radiation oncology facilities had longer OS based on multivariate analysis (MVA) (hazard ratio, 0.81; 95% confidence interval [CI], 0.73-0.90; P < .001) and propensity score matching analysis (hazard ratio, 0.79; 95% CI, 0.69-0.91; P < .001). For patients who received treatment at low-volume, intermediate-volume, and high-volume centers, the 5-year OS rate was 70%, 72.2%, and 75.4%, respectively (P < .001). Compared with low/intermediate-volume radiation oncology centers, high-volume centers were more likely to treat patients with concurrent chemotherapy (odds ratio, 1.27; 95% CI, 1.07-1.51; P = .006) and less likely to have treatment delays leading to an RT duration of >45 days (odds ratio, 0.74; 95% CI, 0.69-0.80; P < .001).Conclusions: Treatment at higher volume radiation oncology centers appears to be associated with improved OS in patients with SCC of the anal canal. These results likely reflect the relation between physician experience and delivery of high-quality RT, which perhaps is best evident in rare tumors such as anal SCC. Cancer 2017;123:228-236. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The overall survival (OS) benefit of concurrent chemoradiotherapy (CRT) for head and neck squamous cell carcinoma patients older than 70 years is debated. This study examines the outcomes of elderly patients receiving CRT versus radiotherapy (RT) alone.Methods: The National Cancer Data Base was queried for patients older than 70 years with nonmetastatic oropharyngeal, laryngeal, or hypopharyngeal cancer (T3-4 or N(+)). CRT was defined as chemotherapy started within 14 days of the initiation of RT. Univariate analysis, multivariate analysis (MVA), propensity score matching (PSM), and recursive partitioning analysis (RPA) were performed.Results: The study included 4042 patients: 2538 (63%) received CRT. The median follow-up was 19 months. The unadjusted median OS was longer with the addition of CRT (P < .001). OS was superior with CRT in the MVA (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.58-0.68; P < .001) and PSM analyses (HR, 0.73; 95% CI, 0.66-0.80; P < .001) in comparison with RT alone. According to RPA, CRT was associated with longer OS for patients 81 years or younger with low comorbidity scores and either T1-2/N2-3 disease or T3-4/N0-3 disease. The survival benefit with CRT disappeared for 2 subgroups in the 71- to 81-year age range: those with T1-2, N1, and Charlson-Deyo 0-1 (CD0-1) disease and those with T3-4, N1+, and CD1+ disease. Patients who were older than 81 years did not have increased survival with CRT. The receipt of CRT was associated with a longer duration of RT (odds ratio, 1.74; 95% CI, 1.50-2.01; P < .001).Conclusions: Patients older than 70 years should not be denied concurrent chemotherapy solely on the basis of age; additional factors, including the performance status and the tumor stage, should be taken into account. Cancer 2016;122:1533-43. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose The purpose was to evaluate survival outcomes between external beam radiotherapy (EBRT) plus brachytherapy and brachytherapy alone for intermediate-risk prostate cancer, using the National Cancer Data Base. Methods and Materials The National Cancer Data Base was queried for cN0M0 intermediate-risk patients treated from 2004 to 2006, with available data for Gleason score (GS), prostate-specific antigen (PSA), tumor stage, and receipt of radiation therapy (RT) and androgen deprivation therapy. RT comparison groups were the following: EBRT (40–50.4 Gy) plus brachytherapy and brachytherapy alone. Results A total of 10,571 patients were included: 3,148 received EBRT plus brachytherapy and 7,423 received brachytherapy alone. Median followup was 84 months (2–122 months); median age was 68 years (40–90 years). Unadjusted 5- and 7-year overall survival (OS) rates between EBRT plus brachytherapy vs. brachytherapy alone were 91.4% vs. 90.2% and 85.7% vs. 82.9%, respectively ( p < 0.001). EBRT plus brachytherapy was associated with longer OS compared with brachytherapy alone under multivariate (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.75–0.93; p = 0.001) and propensity score-matched analyses (HR, 0.85; 95% CI, 0.75–0.97; p = 0.006). Further subset analysis performed based on the Radiation Therapy Oncology Group 0232 inclusion criteria (GS 7 if PSA < 10 or GS < 7 if PSA 10–20) also demonstrated longer OS with EBRT plus brachytherapy (HR, 0.87; 95% CI, 0.77–0.98; p = 0.026). Conclusions EBRT plus brachytherapy is associated with a modest OS improvement compared with brachytherapy alone in this population-based analysis. Although this benefit appears statistically significant, the relatively small difference in OS raises the question of overall clinical benefit with combined modality RT for intermediate-risk prostate cancer, given the potential increased risk for toxicities. Future results from Radiation Therapy Oncology Group 0232 should provide further insight on this topic. [ABSTRACT FROM AUTHOR]

Purpose/objectives: The addition of whole pelvic (WP) compared with prostate-only (PO) radiation therapy (RT) for clinically node-negative prostate cancer remains controversial. The purpose of our study was to evaluate the survival benefit of adding WPRT versus PO-RT for high-risk, node-negative prostate cancer, using the National Cancer Data Base (NCDB).Methods and Materials: Patients with high-risk prostate cancer treated from 2004 to 2006, with available data for RT volume, coded as prostate and pelvis (WPRT) or prostate alone (PO-RT) were included. Multivariate analysis (MVA) and propensity-score matched analysis (PSM) were performed. Recursive partitioning analysis (RPA) based on overall survival (OS) using Gleason score (GS), T stage, and pretreatment prostate-specific antigen (PSA) was also conducted.Results: A total of 14,817 patients were included: 7606 (51.3%) received WPRT, and 7211 (48.7%) received PO-RT. The median follow-up time was 81 months (range, 2-122 months). Under MVA, the addition of WPRT for high-risk patients had no OS benefit compared with PO-RT (HR 1.05; P=.100). On subset analysis, patients receiving dose-escalated RT also did not benefit from WPRT (HR 1.01; P=.908). PSM confirmed no survival benefit with the addition of WPRT for high-risk patients (HR 1.05; P=.141). In addition, RPA was unable to demonstrate a survival benefit of WPRT for any subset. Other prognostic factors for inferior OS under MVA included older age (HR 1.25; P<.001), increasing comorbidity scores (HR 1.46; P<.001), higher T stage (HR 1.17; P<.001), PSA (HR 1.81; P<.001), and GS (HR 1.29; P<.001), and decreasing median county household income (HR 1.15; P=.011). Factors improving OS included the addition of androgen deprivation therapy (HR 0.92; P=.033), combination external beam RT plus brachytherapy boost (HR 0.71; P<.001), and treatment at an academic/research institution (HR 0.84; P=.002).Conclusion: In the largest reported analysis of WPRT for patients with high-risk prostate cancer treated in the dose-escalated era, the addition of WPRT demonstrated no survival advantage compared with PO-RT. [ABSTRACT FROM AUTHOR]

Introduction Whole-brain radiation therapy (WBRT) is the standard approach for brain metastases (BM) arising in patients with small-cell lung cancer (SCLC), but the neurocognitive toxicities of WBRT are well documented. For this reason, stereotactic radiosurgery (SRS) alone is the preferred modality for limited BM in most histologies, but in SCLC there are few data exploring this approach. Methods We queried the National Cancer Database (NCDB) for patients with SCLC with BM at diagnosis and stratified by upfront SRS compared with upfront WBRT ± SRS. We utilized multivariate Cox regression and propensity score matching (PSM) to determine the impact on overall survival (OS) of each approach. Results 5952 eligible patients (WBRT: 5752; SRS: 200) were identified from 2010 to 2014 with a median follow-up of 40.0 months. Upfront SRS was associated with superior OS (median 10.8 vs 7.1 months, HR 0.65, 95% CI 0.55–0.75, p < 0.001), which persisted on multivariate analysis controlling for comorbidities, extracranial metastases, age, race/ethnicity, and gender (HR 0.70, 95% CI 0.60–0.81, p < 0.001). These results were confirmed in PSM analysis. A subset analysis comparing outcomes after SRS vs SRS + WBRT showed no differences in OS (p = .601). Conclusions To our knowledge, this is the largest dataset of patients treated with SRS alone for SCLC. The observation of favorable OS with SRS alone in this contemporary dataset suggests that SRS alone may be appropriate for some patients with SCLC. Prospective investigations of SRS in SCLC are warranted. [ABSTRACT FROM AUTHOR]

Background and purpose Recent studies suggest that 4DCT is unable to accurately measure respiratory-induced pancreatic tumor motion. In this work, we assessed the daily motion of pancreatic tumors treated with SBRT, and developed adaptive strategies to predict and account for this motion. Materials and methods The daily motion trajectory of pancreatic tumors during CBCT acquisition was calculated using a model which reconstructs the instantaneous 3D position in each 2D CBCT projection image. We developed a metric (termed “Spectral Coherence,” SC) based on the Fourier frequency spectrum of motion in the SI direction, and analyzed the ability of SC to predict motion-based errors and classify patients according to motion characteristics. Results The amplitude of daily motion exceeded the predictions of pre-treatment 4DCT imaging by an average of 3.0 mm, 2.3 mm, and 3.5 mm in the AP/LR/SI directions. SC was correlated with daily motion differences and tumor dose coverage. In a simulated adaptive protocol, target margins were adjusted based on SC, resulting in significant increases in mean target D95, D99, and minimum dose. Conclusion Our Fourier-based approach differentiates between consistent and inconsistent motion characteristics of respiration and correlates with daily motion deviations from pre-treatment 4DCT. The feasibility of an SC-based adaptive protocol was demonstrated, and this patient-specific respiratory information was used to improve target dosimetry by expanding coverage in inconsistent breathers while shrinking treatment volumes in consistent breathers. [ABSTRACT FROM AUTHOR]

Purpose: Cone-beam CT (CBCT) projection images provide anatomical data in real-time over several respiratory cycles, forming a comprehensive picture of tumor movement. The authors developed and validated a method which uses these projections to determine the trajectory of and dose to highly mobile tumors during each fraction of treatment. Methods: CBCT images of a respiration phantom were acquired, the trajectory of which mimicked a lung tumor with high amplitude (up to 2.5 cm) and hysteresis. A template-matching algorithm was used to identify the location of a steel BB in each CBCT projection, and a Gaussian probability density function for the absolute BB position was calculated which best fit the observed trajectory of the BB in the imager geometry. Two modifications of the trajectory reconstruction were investigated: first, using respiratory phase information to refine the trajectory estimation (Phase), and second, using the Monte Carlo (MC) method to sample the estimated Gaussian tumor position distribution. The accuracies of the proposed methods were evaluated by comparing the known and calculated BB trajectories in phantom-simulated clinical scenarios using abdominal tumor volumes. Results: With all methods, the mean position of the BB was determined with accuracy better than 0.1 mm, and root-mean-square trajectory errors averaged 3.8% ± 1.1% of the marker amplitude. Dosimetric calculations using Phase methods were more accurate, with mean absolute error less than 0.5%, and with error less than 1% in the highest-noise trajectory. MC-based trajectories prevent the overestimation of dose, but when viewed in an absolute sense, add a small amount of dosimetric error (<0.1%). Conclusions: Marker trajectory and target dose-of-the-day were accurately calculated using CBCT projections. This technique provides a method to evaluate highly mobile tumors using ordinary CBCT data, and could facilitate better strategies to mitigate or compensate for motion during stereotactic body radiotherapy. [ABSTRACT FROM AUTHOR]

Purpose: To develop an accurate and comprehensive Monte Carlo (MC) model of an experimental benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) setup and apply this MC model to optimize incident x-ray spectrum for improving production/detection of x-ray fluorescence photons from gold nanoparticles (GNPs). Methods: A detailed MC model, based on an experimental XFCT system, was created using the Monte Carlo N-Particle (MCNP) transport code. The model was validated by comparing MC results including x-ray fluorescence (XRF) and scatter photon spectra with measured data obtained under identical conditions using 105 kVp cone-beam x-rays filtered by either 1 mm of lead (Pb) or 0.9 mm of tin (Sn). After validation, the model was used to investigate the effects of additional filtration of the incident beam with Pb and Sn. Supplementary incident x-ray spectra, representing heavier filtration (Pb: 2 and 3 mm; Sn: 1, 2, and 3 mm) were computationally generated and used with the model to obtain XRF/scatter spectra. Quasimonochromatic incident x-ray spectra (81, 85, 90, 95, and 100 keV with 10 keV full width at half maximum) were also investigated to determine the ideal energy for distinguishing gold XRF signal from the scatter background. Fluorescence signal-to-dose ratio (FSDR) and fluorescence-normalized scan time (FNST) were used as metrics to assess results. Results: Calculated XRF/scatter spectra for 1-mm Pb and 0.9-mm Sn filters matched (r = 0.996) experimental measurements. Calculated spectra representing additional filtration for both filter materials showed that the spectral hardening improved the FSDR at the expense of requiring a much longer FNST. In general, using Sn instead of Pb, at a given filter thickness, allowed an increase of up to 20% in FSDR, more prominent gold XRF peaks, and up to an order of magnitude decrease in FNST. Simulations using quasimonochromatic spectra suggested that increasing source x-ray energy, in the investigated range of 81-100 keV, increased the FSDR up to a factor of 20, compared to 1 mm Pb, and further facilitated separation of gold XRF peaks from the scatter background. Conclusions: A detailed MC model of an experimental benchtop XFCT system has been developed and validated. In exemplary calculations to illustrate the usefulness of this model, it was shown that potential use of quasimonochromatic spectra or judicious choice of filter material/thickness to tailor the spectrum of a polychromatic x-ray source can significantly improve the performance of benchtop XFCT, while considering trade-offs between FSDR and FNST. As demonstrated, the current MC model is a reliable and powerful computational tool that can greatly expedite the further development of a benchtop XFCT system for routine preclinical molecular imaging with GNPs and other metal probes. [ABSTRACT FROM AUTHOR]

An inflatable endorectal balloon (ERB) is often used during stereotactic body radiation therapy (SBRT) for treatment of prostate cancer in order to reduce both intrafraction motion of the target and risk of rectal toxicity. However, the ERB can exert significant force on the prostate, and this work assessed the impact of ERB position errors on deformation of the prostate and treatment dose metrics. Seventy-one cone-beam computed tomography (CBCT) image datasets of nine patients with clinical stage T1cN0M0 prostate cancer were studied. An ERB (Flexi-Cuff, EZ-EM, Westbury, NY) inflated with 60 cm3 of air was used during simulation and treatment, and daily kilovoltage (kV) CBCT imaging was performed to localize the prostate. The shape of the ERB in each CBCT was analyzed to determine errors in position, size, and shape. A deformable registration algorithm was used to track the dose received by (and deformation of) the prostate, and dosimetric values such as D95, PTV coverage, and Dice coefficient for the prostate were calculated. The average balloon position error was 0.5 cm in the inferior direction, with errors ranging from 2 cm inferiorly to 1 cm superiorly. The prostate was deformed primarily in the AP direction, and tilted primarily in the anterior–posterior/superior–inferior plane. A significant correlation was seen between errors in depth of ERB insertion (DOI) and mean voxel-wise deformation, prostate tilt, Dice coefficient, and planning-to-treatment prostate inter-surface distance (p < 0.001). Dosimetrically, DOI is negatively correlated with prostate D95 and PTV coverage (p < 0.001). For the model of ERB studied, error in ERB position can cause deformations in the prostate that negatively affect treatment, and this additional aspect of setup error should be considered when ERBs are used for prostate SBRT. Before treatment, the ERB position should be verified, and the ERB should be adjusted if the error is observed to exceed tolerable values. [ABSTRACT FROM AUTHOR]

This report presents the first experimental demonstration, to our knowledge, of benchtop polychromatic cone-beam x-ray fluorescence computed tomography (XFCT) for a simultaneous determination of the spatial distribution and amount of gold nanoparticles (GNPs) within small-animal-sized objects. The current benchtop experimental setup successfully produced XFCT images accurately showing the regions containing small amount of GNPs (on the order of 0.1 mg) within a 3 cm diameter plastic phantom. In particular, the performance of the current XFCT setup was improved remarkably (e.g., at least a factor of 3 reduction in XFCT scan time) using a tin-filtered polychromatic beam in comparison with a lead-filtered beam. The results of this study strongly suggest that the current benchtop XFCT configuration can be made practical with a few modifications such as the deployment of array detectors, while meeting realistic constraints on x-ray dose, scan time and image resolution for routine pre-clinical in vivo imaging with GNPs. [ABSTRACT FROM AUTHOR]

Purpose: During stereotactic body radiation therapy (SBRT) for the treatment of prostate cancer, an inflatable endorectal balloon (ERB) may be used to reduce motion of the target and reduce the dose to the posterior rectal wall. This work assessed the dosimetric impact of manual interventions on ERB position in patients receiving prostate SBRT and investigated the impact of ERB interventions on prostate shape. Methods: The data of seven consecutive patients receiving SBRT for the treatment of clinical stage T1cN0M0 prostate cancer enrolled in a multi-institutional, IRB-approved trial were analyzed. The SBRT dose was 50 Gy in five fractions to a planning target volume (PTV) that included the prostate (implanted with three fiducial markers) with a 3-5 mm margin. All plans were based on simulation images that included an ERB inflated with 60 cm3 of air. Daily kilovoltage cone-beam computed tomography (CBCT) imaging was performed to localize the PTV, and an automated fusion with the planning images yielded displacements required for PTV relocalization. When the ERB volume and/or position were judged to yield inaccurate repositioning, manual adjustment (ERB reinflation and/or repositioning) was performed. Based on all 59 CBCT image sets acquired, a deformable registration algorithm was used to determine the dose received by, displacement of, and deformation of the prostate, bladder (BLA), and anterior rectal wall (ARW). This dose tracking methodology was applied to images taken before and after manual adjustment of the ERB (intervention), and the delivered dose was compared to that which would have been delivered in the absence of intervention. Results: Interventions occurred in 24 out of 35 (69%) of the treated fractions. The direct effect of these interventions was an increase in the prostate radiation dose that included 95% of the PTV (D95) from 9.6 ± 1.0 to 10.0 ± 0.2 Gy (p = 0.06) and an increase in prostate coverage from 94.0% ± 8.5% to 97.8% ± 1.9% (p = 0.03). Additionally, ERB interventions reduced prostate deformation in the anterior-posterior (AP) direction, reduced errors in the sagittal rotation of the prostate, and increased the similarity in shape of the prostate to the radiotherapy plan (increased Dice coefficient from 0.76 ± 0.06 to 0.80 ± 0.04, p = 0.01). Postintervention decreases in prostate volume receiving less than the prescribed dose and decreases in the voxel-wise displacement of the prostate, bladder, and anterior rectal wall were observed, which resulted in improved dose-volume histogram (DVH) characteristics. Conclusions: Image-guided interventions in ERB volume and/or position during prostate SBRT were necessary to ensure the delivery of the dose distribution as planned. ERB interventions resulted in reductions in prostate deformations that would have prevented accurate localization of patient anatomy. [ABSTRACT FROM AUTHOR]

Purpose: An approach known as gold nanoparticle-aided radiation therapy (GNRT) is a recent development in radiation therapy which seeks to make a tumor more susceptible to radiation damage by modifying its photon interaction properties with an infusion of gold nanoparticles (GNPs). The purpose of this study was to quantify the energy deposition due to secondary electrons from GNPs on a nanometer scale and to calculate the corresponding microscopic dose enhancement factor around GNPs. Methods: The Monte Carlo code EGSnrc was modified to obtain the spectra of secondary electrons from atoms of gold approximating GNPs and molecules of water under photon irradiation of a tumor loaded with GNPs. Six different photon sources were used: 125I, 103Pd, 169Yb, 192Ir, 50 kVp, and 6 MV x rays. Treating the scored electron spectra as point sources within an infinite medium of water, the event-by-event Monte Carlo code NOREC was used to quantify the radial dose distribution, giving rise to gold/water electron dose point kernels and corresponding microscopic dose enhancement factors. These kernels were applied to a test case based on a scanning electron microscope image of a GNP distribution in tissue, enabling the determination of the microscopic dose enhancement at each dose point. Results: For the lower energy sources 125I, 103Pd, 169Yb, and 50 kVp, the secondary electron fluence within a GNP-loaded tumor was increased by as much as two orders of magnitude, leading to two orders of magnitude increase in electron energy deposition over radial distances up to 10 μm. For the test case considered, the dose was enhanced by factors ranging from 2 to 20 within 5 μm of GNPs, and by 5% as far away as 30 μm. Conclusions: This study demonstrates a remarkable microscopic dose enhancement due to GNPs and low energy photon sources. By quantifying the microscopic dose enhancement factor for a given photon source as a function of distance from GNPs, it also enables the selection of either a passive or an active tumor targeting strategy using GNPs which will maximize the radiobiological benefit from GNRT. [ABSTRACT FROM AUTHOR]

Background: The comparative efficacy of cisplatin (CDDP), carboplatin, and cetuximab (CTX) delivered concurrently with radiation for locally advanced oropharyngeal squamous cell carcinoma continues to be evaluated.Methods: The linked Surveillance, Epidemiology, and End Results-Medicare database was used to identify and compare patient and disease profiles, mortality, toxicity, and overall cost for patients with oropharynx cancer undergoing definitive concurrent chemoradiation with CDDP, carboplatin, or CTX between 2006 and 2011. The human papillomavirus status was unknown. The primary outcome was 2-year overall survival (OS).Results: Four hundred nine patients receiving concurrent CDDP (n = 167), carboplatin (n = 69), or CTX (n = 173) were included. Those who were older, those who were nonwhite, and those with a Charlson Comorbidity Index ≥ 2 were less likely to receive CDDP. Two-year OS was inferior with CTX (hazard ratio [HR], 1.68; 95% confidence interval [CI], 1.08-2.60; P = .020) and no different with carboplatin (HR, 1.31; 95% CI, 0.73-2.35; P = .362) in a Cox proportional hazards model (reference CDDP). There was no statistically significant difference between carboplatin and CTX (HR, 1.28; 95% CI, 0.77-2.14; P = .891). Rates of antiemetic use and hospital visits for nausea/emesis/diarrhea or dehydration were statistically higher with CDDP. Pneumonia rates were higher with carboplatin. In the multivariate model, the corrected mean per-patient spending was significantly higher for CTX and carboplatin than CDDP ($61,133 and $65,721 vs $48,709).Conclusions: Patients who received CDDP had improved OS. CDDP was also associated with slightly lower overall costs and higher antiemetic usage and hospital visit rates, although a strong selection bias was observed because those receiving CTX and carboplatin were older and had higher comorbidity scores. [ABSTRACT FROM AUTHOR]

Introduction: Extracapsular extension (ECE) in regional lymph nodes and positive surgical margins (PSM) are considered high-risk adverse pathologic features in patients with oropharyngeal squamous cell carcinoma (OPSCC) that each constitute an indication for postoperative adjuvant chemoradiation. We identify pre-operative clinical factors that can predict post-operative ECE and/or PSM and create a nomogram to help clinical decision making.Methods: Adult patients with non-metastatic OPSCC with initial surgical treatment and confirmed HPV status diagnosed between 2010 and 2014 were selected from the National Cancer Database. Clinical staging was modified to American Joint Committee on Cancer 8th edition parameters. Logistic regression was used for multivariate analysis to identify predictors of pathologic ECE and/or PSM.Results: 5065 patients were included. 47.5% of the 3336 HPV-positive (HPV+) patients had ECE/PSM. 40.4% of the 1729 HPV-negative (HPV-) patients with had ECE/PSM. A model was built that included age, clinical ECE, tumor grade, and clinical T and N staging for HPV+ patients. Increasing N-classification was highly predictive of pathologic ECE and/or PSM (N1 OR = 3.6, N2 OR = 7.0, N3 OR = 11.2, p < 0.01). Clinical ECE (OR = 4.1, p < 0.01), tumor grade (ORs 2.2-4.4 with p < 0.05), and increasing clinical T-classification (ORs 1.2-1.8, p < 0.05) were also associated with ECE and/or PSM. A similar model was built for HPV- with similar predictive capability. Two internally validated nomograms were designed that demonstrated good discrimination (HPV+ AUC = 0.66, 95% CI: 0.64-0.68, and HPV- AUC = 0.70, 95% CI: 0.67-0.72) and good calibration (goodness-of-fit statistic of HPV+ 6.32, p = 0.61 and HPV- 11.66, p = 0.17).Conclusions: These are the first nomograms designed to help predict ECE or PSM for both HPV+ and HPV- OPSCC. The nomograms can facilitate shared decision-making between clinicians and patients as they consider upfront treatment selection for OPSCC. [ABSTRACT FROM AUTHOR]

Background Patients with melanoma brain metastases (MBM) have been excluded from trials evaluating immunotherapy in melanoma. As such, immunotherapy's role in MBM is poorly understood, particularly in combination with radiotherapy. Methods The National Cancer Database was queried for patients with MBM receiving brain radiotherapy. They were classified according to immunotherapy receipt. Multivariate Cox regression was performed to identify factors associated with survival. Results Among 1287 patients, 185 received immunotherapy. Factors associated with improved survival included younger age, academic facility, lower extracranial disease burden, stereotactic radiotherapy, chemotherapy, and immunotherapy. Conclusions Adding immunotherapy to radiotherapy for MBM is associated with improved survival. [ABSTRACT FROM AUTHOR]

Objectives: Among patients with T2N0M0 glottic larynx cancer undergoing definitive radiotherapy, recent retrospective and prospective data have suggested improved outcomes with altered fractionation over conventional fractionation (CFxn). We sought to characterize national fractionation patterns and to compare outcomes among them.Materials and Methods: We queried the National Cancer Database for T2N0M0 squamous cell carcinomas of the glottis diagnosed from 2004-2014 and managed with definitive radiotherapy. Dose-per-fraction and duration of radiotherapy were used to define cohorts undergoing CFxn, hypofractionation (HypoFxn), and hyperfractionation (HyperFxn). Logistic regression was performed to identify predictors of receiving altered fractionation. Cox regression and propensity-score matching (PSM) analyses were used to compare survival between schedules.Results: We abstracted 2 006 CFxn patients, 1 166 HypoFxn patients, and 161 HyperFxn patients. Fractionation patterns changed significantly from 2004 to 2014, with use of HyperFxn decreasing from 6.3% to 1.8% and use of HypoFxn increasing from 23.9% to 54.1% (p<0.001). Receipt of altered fractionation was independently associated with later year of diagnosis and higher facility volume. On Cox regression, both HypoFxn (hazard ratio [HR] for mortality 0.84, 95% confidence interval [95%CI] 0.73-0.97) and HyperFxn (HR 0.74, 95%CI 0.56-0.99) were associated with improved survival over CFxn. The survival advantage of each altered fractionation schedule over CFxn was redemonstrated on comparison of PSM groups.Conclusion: Increasing utilization of HypoFxn for T2N0M0 glottic cancer is driving national practice patterns away from CFxn. Our findings support the use of altered fractionation, particularly HypoFxn, for patients undergoing definitive radiotherapy, although HyperFxn remains understudied in a prospective fashion. [ABSTRACT FROM AUTHOR]

Background: For patients with resectable gastric adenocarcinoma, perioperative chemotherapy and adjuvant chemoradiotherapy (CRT) are considered standard options. In the current study, the authors used the National Cancer Data Base to compare overall survival (OS) between these regimens.Methods: Patients who underwent gastrectomy for nonmetastatic gastric adenocarcinoma from 2004 through 2012 were divided into those treated with perioperative chemotherapy without RT versus those treated with adjuvant CRT. Survival was estimated and compared using univariate and multivariate models adjusted for patient and tumor characteristics, surgical margin status, and the number of lymph nodes examined. Subset analyses were performed for factors chosen a priori, and potential interactions between treatment and covariates were assessed.Results: A total of 3656 eligible patients were identified, 52% of whom underwent perioperative chemotherapy and 48% of whom received postoperative CRT. The median follow-up was 47 months, and the median age of the patients was 62 years. Analysis of the entire cohort demonstrated improved OS with adjuvant RT on both univariate (median of 51 months vs 42 months; P = .013) and multivariate (hazard ratio, 0.874; 95% confidence interval, 0.790-0.967 [P = .009]) analyses. Propensity score-matched analysis also demonstrated improved OS with adjuvant RT (median of 49 months vs 39 months; P = .033). On subset analysis, a significant interaction was observed between the survival impact of adjuvant RT and surgical margins, with a greater benefit of RT noted among patients with surgical margin-positive disease (hazard ratio with RT: 0.650 vs 0.952; P for interaction <.001).Conclusions: In this National Cancer Data Base analysis, the use of adjuvant RT in addition to chemotherapy was associated with a significant OS advantage for patients with resected gastric cancer. The survival advantage observed with adjuvant CRT was most pronounced among patients with positive surgical margins. Cancer 2017;123:3402-9. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Purpose Conventional prostate cancer risk stratification results in considerable heterogeneity within each prognostic group. Men with pathologic grade Group 4 (Gleason score 8) but otherwise low-risk features have been identified as a favorable subset of high-risk prostate cancer. Given recent randomized data supporting improved cancer outcome with brachytherapy in intermediate- and high-risk prostate cancer, we sought to evaluate brachytherapy utilization and overall survival (OS) for these patients. Methods and Materials We queried the National Cancer Database for clinical T1c–T2a N0 M0 prostate cancer with prostate-specific antigen <10 ng/mL and Gleason score 8 adenocarcinoma on biopsy. All patients received androgen deprivation therapy and either external beam radiation therapy (EBRT) alone, brachytherapy alone, or a combination of EBRT with brachytherapy boost (brachytherapy + EBRT). Kaplan–Meier OS estimates as well as univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score–matched analyses were performed to further control for baseline confounders. Results Four thousand four hundred ninety-six patients were identified with a median followup of 62.5 months (range, 2.3–119.8). Median age was 72 years (range, 41–90+). Utilization of brachytherapy decreased from 2004 to 2009. The odds ratio for brachytherapy by year (continuous variable) was 0.86 ( p < 0.001). Five-year OS was 84%, 88%, and 89% for the EBRT alone, brachytherapy alone, and brachytherapy + EBRT groups, respectively. On multivariate analysis, higher median income, low comorbidity score, and treatment with brachytherapy alone (hazard ratio, 0.66; p = 0.005) or brachytherapy + EBRT (hazard ratio, 0.70; p = 0.001) remained associated with longer OS. Propensity score matching confirmed longer OS associated with either brachytherapy regimen. Conclusions Of those men with World Health Organization pathologic grade Group 4 (Gleason score 8) prostate cancer and otherwise favorable prognostic features treated with androgen deprivation therapy and radiation therapy, longer OS was achieved when prostate brachytherapy was included, whether used alone or in combination with supplemental EBRT. In spite of these excellent outcomes, prostate brachytherapy utilization is declining in the United States. [ABSTRACT FROM AUTHOR]

Background and purpose Radiotherapy (RT) to the primary nasopharyngeal tumor is frequently offered to patients with metastatic nasopharyngeal carcinoma (mNPC). However, only limited data exist to support RT in this setting. We used the National Cancer Database (NCDB) to evaluate outcomes for mNPC patients receiving chemotherapy with and without local RT. Methods The NCDB was queried for patients with mNPC with synchronous metastatic disease at diagnosis who received chemotherapy. Overall survival (OS) was analyzed using the Kaplan–Meier method, Cox proportional hazards models, and propensity score-matched analyses. Results From 2004 to 2013, 718 cases were identified (39% chemotherapy-alone, 61% chemotherapy + RT). At a median follow-up of 4.4 years, RT was associated with improved survival on univariate analysis (median OS 21.4 vs 15.5 months; 5-year OS 28% vs 10%; p < 0.001) and multivariate analyses (HR, 0.61; CI, 0.51–0.74; p < 0.001). Propensity score analysis with matched baseline characteristics demonstrated a similar OS advantage with RT (HR, 0.68; CI, 0.55–0.84; p < 0.001). The benefits of RT remained consistent in models controlling for single vs multi-organ metastases and anatomic sites of metastatic involvement. RT dose was an independent prognostic factor as both a continuous and categorical variable, with OS benefits observed among patients receiving ≥50 Gy. Long-term survival of >10 years was only observed in the RT cohort. Conclusions This analysis supports strategies incorporating local RT with chemotherapy for mNPC. Prospective trials evaluating RT integration for mNPC are warranted. [ABSTRACT FROM AUTHOR]

Purpose Implanted fiducial markers are often used in radiotherapy to facilitate accurate visualization and localization of tumors. Typically, such markers are used to aid daily patient positioning and to verify the target's position during treatment. These markers can also provide a wealth of information regarding tumor motion, yet determining their accurate position in thousands of images is often prohibitive. This work introduces a novel, automated method for identifying fiducial markers in planar x-ray imaging. Methods In brief, the method was performed as follows. First, using processed CBCT projection images, an automated routine of reconstruction, forward-projection, tracking, and stabilization generated static templates of the marker cluster at arbitrary viewing angles. Breathing data were then incorporated into the same routine, resulting in dynamic templates dependent on both viewing angle and breathing motion. Finally, marker clusters were tracked using normalized cross correlations between templates (either static or dynamic) and CBCT projection images. To quantify the accuracy of the technique, a phantom study was performed and markers were manually tracked by two users to compare the automated technique against human measurements. Then, 75 pretreatment CBCT scans of 15 pancreatic cancer patients were analyzed to test the automated technique under real-life conditions, including several challenging scenarios for tracking fiducial markers (e.g., extraneous metallic objects, field-of-view limitations, and marker migration). Results In phantom and patient studies, for both static and dynamic templates, the method automatically tracked visible marker clusters in 100% of projection images. For scans in which a phantom exhibited 0D, 1D, and 3D motion, the automated technique showed median errors of 39 μm, 53 μm, and 93 μm, respectively. Human precision was worse in comparison; median interobserver differences for single markers and for the averaged coordinates of four markers were 183 μm and 120 μm, respectively. In patient scans, the method was robust against a number of confounding factors. Automated tracking was performed accurately despite the presence of radio-opaque, nonmarker objects (e.g., metallic stents, surgical clips) in five patients. This success was attributed to the distinct appearance of clusters as a whole compared to individual markers. Dynamic templates produced higher cross-correlation scores than static templates in patients whose fiducial marker clusters exhibited considerable deformation or rotation during the breathing cycle. For other patients, no significant difference was seen between dynamic and static templates. Additionally, transient differences in the cross-correlation score identified instances where markers disappeared from view. Conclusions A novel, automated method for producing dynamic templates of fiducial marker clusters has been developed. Production of these templates automatically provides measurements of tumor motion that occurred during the CBCT scan that was used to produce them. Additionally, using these templates with intrafractional images could potentially allow for more robust real-time target tracking in radiotherapy. [ABSTRACT FROM AUTHOR]

Objectives: This study identifies clinical characteristics associated with HPV-positive oropharynx squamous cell carcinoma (OPSCC) and evaluates predictors of overall survival (OS) in HPV-positive patients undergoing definitive treatment within the National Cancer Data Base (NCDB).Material and Methods: The NCDB was queried for patients ⩾18years old with OPSCC and known HPV status who underwent definitive treatment: surgery, radiation (RT), chemotherapy-RT (CRT), surgery+RT, surgery+CRT (S-CRT). Cox proportional hazards model was used for multivariate analysis (MVA) to evaluate predictors of OS by HPV status.Results: 3952 patients were included: 2454 (62%) were HPV-positive. Median follow up was 23.7months (range, 1.0-54.5). Unadjusted 2-year OS rates for HPV-positive vs. negative were 93.1% vs. 77.8% (p<0.001) with an adjusted hazard ratio of 0.44 (95% CI, 0.36-0.53; p<0.001). MVA identified multimodality treatment including CRT (HR, 0.42; p=0.024) and S-RT (HR, 0.30; p=0.024), but not S-CRT (HR, 0.51; p=0.086), as predictors for improved OS in HPV-positive stage III-IVB disease. Multimodality treatment including S-CRT was associated with longer OS in HPV-negative OPSCC. Nodal stage was poorly associated with OS in HPV-positive cancers. The presence of positive margins and/or extracapsular extension was associated with worse OS in HPV-negative (HR, 2.11; p=0.008) but not HPV positive OPSCC (HR, 1.61; p=0.154).Conclusion: The established demographic and clinical features of HPV-positive OPSCC were corroborated in the NCDB. Population analysis suggests that AJCC staging is poorly associated with OS in HPV-positive cancer, and traditional high-risk features may be less impactful. Bimodality therapy appears beneficial in HPV-positive HNSCC. [ABSTRACT FROM AUTHOR]

Background: Primary mediastinal B cell lymphoma (PMBCL) is an uncommon lymphoma for which trials are few with small patient numbers. The role of radiation therapy (RT) after standard immunochemotherapy for early-stage disease has never been studied prospectively. We used the Surveillance, Epidemiology, and End Results (SEER) database to evaluate PMBCL and the impact of RT on outcomes.Methods and Materials: We queried the SEER database for patients with stage I-II PMBCL diagnosed from 2001 to 2011. Retrievable data included age, gender, race (white/nonwhite), stage, extranodal disease, year of diagnosis, and use of RT as a component of definitive therapy. Kaplan-Meier overall survival (OS) estimates, univariate (UVA) log-rank and multivariate (MVA) Cox proportional hazards regression analyses were performed.Results: Two hundred fifty patients with stage I-II disease were identified, with a median follow-up time of 39 months (range, 3-125 months). The median age was 36 years (range, 18-89 years); 61% were female; 76% were white; 45% had stage I disease, 60% had extranodal disease, and 55% were given RT. The 5-year OS for the entire cohort was 86%. On UVA, OS was improved with RT (hazard ratio [HR] 0.446, P=.029) and decreased in association with nonwhite race (HR 2.70, P=.006). The 5-year OS was 79% (no RT) and 90% (RT). On MVA, white race and RT remained significantly associated with improved OS (P=.007 and .018, respectively). The use of RT decreased over time: 61% for the 67 patients whose disease was diagnosed from 2001 to 2005 and 53% in the 138 patients treated from 2006 to 2010.Conclusion: This retrospective population-based analysis is the largest PMBCL dataset to date and demonstrates a significant survival benefit associated with RT. Nearly half of patients treated in the United States do not receive RT, and its use appears to be declining. In the absence of phase 3 data, the use of RT should be strongly considered for its survival benefit in early-stage disease. [ABSTRACT FROM AUTHOR]

Purpose: Radiation pneumonitis remains a major limitation in the radiation therapy treatment of patients with lung cancer. Functional avoidance radiation therapy uses functional imaging to reduce pulmonary toxic effects by designing radiation therapy plans that reduce doses to functional regions of the lung. Lung functional imaging has been developed that uses 4-dimensional computed tomography (4DCT) imaging to calculate 4DCT-based lung ventilation (4DCT-ventilation). A phase 2 multicenter study was initiated to evaluate 4DCT-ventilation functional avoidance radiation therapy. The study hypothesis was that functional avoidance radiation therapy could reduce the rate of grade ≥2 radiation pneumonitis to 12% compared with a 25% historical rate, with the trial being positive if ≤16.4% of patients experienced grade ≥2 pneumonitis.Methods and Materials: Lung cancer patients receiving curative-intent radiation therapy (prescription doses of 45-75 Gy) and chemotherapy were accrued. Patient 4DCT scans were used to generate 4DCT-ventilation images. The 4DCT-ventilation images were used to generate functional avoidance plans that reduced doses to functional portions of the lung while delivering the prescribed tumor dose. Pneumonitis was evaluated by a clinician at 3, 6, and 12 months after radiation therapy.Results: Sixty-seven evaluable patients were accrued between April 2015 and December 2019. The median prescription dose was 60 Gy (range, 45-66 Gy) delivered in 30 fractions (range, 15-33 fractions). The average reduction in the functional volume of lung receiving ≥20 Gy with functional avoidance was 3.5% (range, 0%-12.8%). The median follow-up was 312 days. The rate of grade ≥2 radiation pneumonitis was 10 of 67 patients (14.9%; 95% upper CI, 24.0%), meeting the phase 2 criteria.Conclusions: 4DCT-ventilation offers an imaging modality that is convenient and provides functional imaging without an extra procedure necessary. This first report of a multicenter study of 4DCT-ventilation functional avoidance radiation therapy provided data showing that the trial met phase 2 criteria and that evaluation in a phase 3 study is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Real‐time visualization of target motion using fiducial markers during radiation therapy treatment will allow for more accurate dose delivery. The purpose of this study was to optimize techniques for online fiducial marker tracking by detecting the scattered treatment beam through coded aperture imaging (CAI). Coded aperture imaging is a novel imaging technique that can allow target tracking in real time during treatment, and do so without adding any additional radiation dose, by making use of the scattered treatment beam radiation. Methods: Radiotherapy beams of various energies, incident on phantoms containing gold fiducial markers were modeled using MCNP6.2 Monte Carlo transport code. Orthogonal scatter radiographs were collected through a CAI geometry. After decoding the simulated radiograph data, the centroid location and FWHM/SNR of the fiducial signals were analyzed. The effects of properties related to the CA (rank, pattern, and physical dimensions), detector (dimensions and pixel count), position (CA and phantom), and the incident beam (spectrum and direction) were investigated. These variables were evaluated by quantifying the positional accuracy, resolution, and SNR of the fiducials' signal. The effects of phantom scatter and decoding artifacts were reduced via Fourier filtering to avoid treatment interruption and physical interaction with the coded mask. Results: The method was able to accurately localize the markers to within 1 pixel of a simulated radiograph. A 10 × 10 × 2 cm tungsten mask was chosen to attenuate >99 % of incident scatter through opaque elements, while minimizing collimation artifacts which arise from vignetting of the coded radiograph. Clear separation of centroids from fiducial signals with 2.5 mm separation was maintained, and initial optimization of parameters has produced an aperture which decodes the location of multiple fiducial markers inside a human phantom properly with a high SNR in the final radiograph image. Conclusion: Current results show a proof of concept for a novel real‐time imaging method. Coded aperture imaging is a promising technique for extracting the fiducial scatter signal from a broader Compton‐scatter background. These results can be used to further optimize the CAI parameter space and guide fabrication and testing of a clinical device. [ABSTRACT FROM AUTHOR]

Purpose: Three‐dimensional in‐vivo dose verification is one of the standing challenges in radiation therapy. X‐ray‐induced acoustic tomography has recently been proposed as an imaging method for use in in‐vivo dosimetry. The aim of this study was to investigate the accuracy of reconstructing three‐dimensional (3D) absolute dose using x‐ray‐induced acoustic tomography. We performed this investigation using two different tomographic dose reconstruction techniques. Methods: Two examples of 3D dose reconstruction techniques for x‐ray acoustic imaging are investigated. Dose distributions are calculated for varying field sizes using a clinical treatment planning system. The induced acoustic pressure waves which are generated by the increase in temperature due to the absorption of pulsed MV x‐rays are simulated using an advanced numerical modeling package for acoustic wave propagation in the time domain. Two imaging techniques, back projection and iterative time reversal, are used to reconstruct the 3D dose distribution in a water phantom with open fields. Image analysis is performed and reconstructed depth dose curves from x‐ray acoustic imaging are compared to the depth dose curves calculated from the treatment planning system. Calculated field sizes from the reconstructed dose profiles by back projection and time reversal are compared to the planned field size to determine their accuracy. The iterative time reversal imaging technique is also used to reconstruct dose in an example clinical dose distribution. Image analysis of this clinical test case is performed using the gamma passing rate. In addition, gamma passing rates are used to validate the stopping criteria in the iterative time reversal method. Results: Water phantom simulations showed that back projection does not adequately reconstruct the shape and intensity of the depth dose. When compared to the depth of maximum dose calculated by a treatment planning system, the maximum dose depth by back projection is shifted deeper by 55 and 75 mm for 4 × 4 cm and 10 × 10 cm field sizes, respectively. The reconstructed depth dose by iterative time reversal accurately agrees with the planned depth dose for a 4 × 4 cm field size and is shifted deeper by 12 mm for the 10 × 10 cm field size. When reconstructing field sizes, the back projection method leads to 18% and 35% larger sizes for the 4 × 4 cm and 10 × 10 cm fields, respectively, whereas the iterative time reversal method reconstructs both field sizes with < 2% error. For the clinical dose distribution, we were able to reconstruct the dose delivered by a 1 degree sub‐arc with a good accuracy. The reconstructed and planned doses were compared using gamma analysis, with> 96% gamma passing rate at 3%/2 mm. Conclusions: Our results show that the 3D x‐ray acoustic reconstructed dose by iterative time reversal is considerably more accurate than the dose reconstructed by back projection. Iterative time reversal imaging has a potential for use in 3D absolute dosimetry. [ABSTRACT FROM AUTHOR]

• The study aimed to evaluate which clinical, dose, and dose-function factors predict pulmonary function test (PFT) changes for patients with lung cancer treated with 4DCT-ventilation functional avoidance radiotherapy. • Results showed that only dose-function metrics and the presence of COPD were significant in predicting FEV1 decline through univariate analysis. • Multivariate analysis identified a combination of clinical factors and dose-function metrics in predicting FEV1 and FEV1/FVC changes. • The study validated the significance of reducing dose to functional lung to mitigate decline in pulmonary function and provided guidance for future clinical trials. Functional avoidance radiotherapy uses functional imaging to reduce pulmonary toxicity by designing radiotherapy plans that reduce doses to functional regions of the lung. A phase-II, multi-center, prospective study of 4DCT-ventilation functional avoidance was completed. Pre and post-treatment pulmonary function tests (PFTs) were acquired and assessed pulmonary function change. This study aims to evaluate which clinical, dose and dose-function factors predict PFT changes for patients treated with 4DCT-ventilation functional avoidance radiotherapy. 56 patients with locally advanced lung cancer receiving radiotherapy were accrued. PFTs were obtained at baseline and three months following radiotherapy and included forced expiratory volume in 1-second (FEV1), forced vital capacity (FVC), and FEV1/FVC. The ability of patient, clinical, dose (lung and heart), and dose-function metrics (metrics that combine dose and 4DCT-ventilation-based function) to predict PFT changes were evaluated using univariate and multivariate linear regression. Univariate analysis showed that only dose-function metrics and the presence of chronic obstructive pulmonary disease (COPD) were significant (p<0.05) in predicting FEV1 decline. Multivariate analysis identified a combination of clinical (immunotherapy status, presence of thoracic comorbidities, smoking status, and age), along with lung dose, heart dose, and dose-function metrics in predicting FEV1 and FEV1/FVC changes. The current work evaluated factors predicting PFT changes for patients treated in a prospective functional avoidance radiotherapy study. The data revealed that lung dose- function metrics could predict PFT changes, validating the significance of reducing the dose to the functional lung to mitigate the decline in pulmonary function and providing guidance for future clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: Internal organ motion reduces the accuracy and efficacy of radiation therapy. However, there is a lack of tools to objectively (based on a medical or scientific task) assess the dosimetric consequences of motion, especially on an individual basis. We propose to use therapy operating characteristic (TOC) analysis to quantify the effects of motion on treatment efficacy for individual patients. We demonstrate the application of this tool with pancreatic stereotactic body radiation therapy (SBRT) clinical data and explore the origin of motion sensitivity. Methods: The technique is described as follows. (a) Use tumor‐motion data measured from patients to calculate the motion‐convolved dose of the gross tumor volume (GTV) and the organs at risk (OARs). (b) Calculate tumor control probability (TCP) and normal tissue complication probability (NTCP) from the motion‐convolved dose–volume histograms. (c) Construct TOC curves from TCP and NTCP models. (d) Calculate the area under the TOC curve (AUTOC) and use it as a figure of merit for treatment efficacy. We used tumor motion data measured from patients to calculate the relation between AUTOC and motion magnitude for 25 pancreatic SBRT treatment plans. Furthermore, to explore the driving factor of motion sensitivity of a given plan, we compared the dose distribution of motion‐sensitive plans and motion‐robust plans and studied the dependence of motion sensitivity to motion directions. Results: Our technique is able to recognize treatment plans that are sensitive to motion. Under the presence of motion, the treatment efficacy of some plans changes from providing high tumor control and low risks of complications to providing no tumor control and high risks of side effects. Several treatment plans experience falloffs in AUTOC at a smaller magnitude of motion than other plans. In our dataset, a potential indicator of a motion‐sensitive treatment plan is that the duodenum is in proximity to the tumor in the SI direction. Conclusions: The TOC framework can serve as a tool to quantify the effects of internal organ motion in radiation therapy. With pancreatic SBRT clinical data, we applied this tool to study the change in treatment efficacy induced by motion for individual treatment plans. This framework could potentially be used clinically to understand the effects of motion in an individual patient and to design a patient‐specific motion management plan. This framework could also be used in research to evaluate different components of the treatment process, such as motion‐management techniques, treatment‐planning algorithms, and treatment margins. [ABSTRACT FROM AUTHOR]

Purpose: Motion often hinders the safe delivery of ablative doses of radiation in the treatment of pancreatic tumors. Real-time tumor-tracking methods are an emerging technique to increase the accuracy of delivery. In this study, we report on a large, retrospective cohort of pancreatic patients treated with real-time, fiducial-based, kV-image guidance of stereotactic body radiation therapy (SBRT). The purpose of our study was to determine the impact of real-time tracking on treatment accuracy, tumor dose, and clinical workflow.Methods and Materials: Real-time tracking data from 68 patients treated with pancreatic SBRT were analyzed. The kV images orthogonal to the treatment beam were acquired in real time during treatment to visualize the location of implanted fiducial markers. Positional corrections were made if the fiducial markers were observed >3 mm from the expected reference position. We recorded the frequency and nature of treatment interventions resulting from real-time tracking and derived a neural network-based dosimetric model to calculate the impact of these in-treatment interventions on target dose.Results: Treatment pauses that required patient realignment because of real-time tumor tracking occurred during 32% of all fractions. The median magnitude of realignment shifts was 5.2 mm (range, 2.1-18.9 mm). Forty-five percent of shifts resulted in dosimetric differences to the tumor; of these, the median point dose difference was 23% ± 22% of prescription dose (maximum, 94%). The number of pauses per fraction was significantly higher in patients treated with respiratory gating (vs abdominal compression) and in patients with greater treatment time.Conclusion: Fiducial-based, real-time target tracking is clinically feasible for pancreatic SBRT treatment. Our data indicate that real-time tumor tracking leads to patient realignment in 32% of cases and results in significant benefits to target coverage. The increased accuracy of real-time target tracking may potentially enable safe dose escalation in pancreatic SBRT. [ABSTRACT FROM AUTHOR]

Purpose Stereotactic body radiation therapy ( SBRT) for pancreatic cancer requires a skillful approach to deliver ablative doses to the tumor while limiting dose to the highly sensitive duodenum, stomach, and small bowel. Here, we develop knowledge-based artificial neural network dose models ( ANN- DMs) to predict dose distributions that would be approved by experienced physicians. Methods Arc-based SBRT treatment plans for 43 pancreatic cancer patients were planned, delivering 30-33 Gy in five fractions. Treatments were overseen by one of two physicians with individual treatment approaches, with variations in prescribed dose, target volume delineation, and primary organs at risk. Using dose distributions calculated by a commercial treatment planning system ( TPS), physician-approved treatment plans were used to train ANN- DMs that could predict physician-approved dose distributions based on a set of geometric parameters (vary from voxel to voxel) and plan parameters (constant across all voxels for a given patient). Patient datasets were randomly allocated, with two-thirds used for training, and one-third used for validation. Differences between TPS and ANN- DM dose distributions were used to evaluate model performance. ANN- DM design, including neural network structure and parameter choices, was evaluated to optimize dose model performance. Results Remarkable improvements in ANN- DM accuracy (i.e., from > 30% to < 5% mean absolute dose error, relative to the prescribed dose) were achieved by training separate dose models for the treatment style of each physician. Increased neural network complexity (i.e., more layers, more neurons per layer) did not improve dose model accuracy. Mean dose errors were less than 5% at all distances from the PTV, and mean absolute dose errors were on the order of 5%, but no more than 10%. Dose-volume histogram errors (in cm3) demonstrated good model performance above 25 Gy, but much larger errors were seen at lower doses. Conclusions ANN- DM dose distributions showed excellent overall agreement with TPS dose distributions, and accuracy was substantially improved when each physician's treatment approach was taken into account by training their own dedicated models. In this manner, one could feasibly train ANN- DMs that could predict the dose distribution desired by a given physician for a given treatment site. [ABSTRACT FROM AUTHOR]

Purpose: Presently no reported prospective, randomized trials have clearly defined the role of androgen-deprivation therapy (ADT) for patients with intermediate-risk prostate cancer in the setting of radiation therapy (RT) dose escalation. This study׳s objective was to evaluate the survival benefit of adding ADT to high-dose RT for patients with intermediate-risk prostate cancer using the National Cancer Data Base.Materials and Methods: The National Cancer Data Base was queried for patients with intermediate-risk prostate cancer treated from 2004 to 2006, with available data for Gleason Score, prostate-specific antigen, TNM staging, and receipt of radiation and ADT. Start of RT was within 1 to 180 days of ADT; radiation included external beam alone (≥70Gy) or external beam RT plus brachytherapy boost. Overall survival was evaluated using multivariate (MVA) Cox regression and propensity score-matched (PSM) analyses.Results: A total of 14,126 patients were included of which 7,568 (53.6%) received no ADT and 6,558 (46.4%) received ADT. Median follow-up was 85.8 months (6.0-119.9mo). Median RT dose was 75.6Gy in 42 fractions. Under MVA, the addition of ADT for patients with intermediate-risk prostate cancer had no overall survival benefit compared with RT alone (hazard ratio [HR] = 0.97, P = 0.316). PSM also confirmed no survival benefit with the addition of ADT for the entire intermediate-risk cohort (HR = 0.98, P = 0.560). On subset analysis, those with 3 intermediate-risk factors had a survival benefit with the addition of ADT on both MVA (HR = 0.69, P = 0.037) and PSM (HR = 0.61, P = 0.026). Limitations include retrospective design and incomplete data on the type of ADT and duration.Conclusions: With the exception of men who present with all 3 intermediate-risk factors, a significant association with decreased all-cause mortality risk and ADT was not observed for patients with intermediate-risk prostate cancer. [ABSTRACT FROM AUTHOR]

We report the first whole-genome sequences for five strains, two carried and three pathogenic, of the emerging pathogen Haemophilus haemolyticus. Preliminary analyses indicate that these genome sequences encode markers that distinguish H. haemolyticus from its closest Haemophilus relatives and provide clues to the identity of its virulence factors. [ABSTRACT FROM AUTHOR]