Carlos E. Cardenas

Out-of-field doses and neutron dose equivalents for electron beams from modern Varian and Elekta linear accelerators.

Out‐of‐field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high‐energy electron beams. To better understand the extent of these exposures, we measured out‐of‐field dose characteristics of electron applicators for high‐energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out‐of‐field dose profiles and percent depth‐dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out‐of‐field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out‐of‐field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central‐axis, which was found to be higher than typical out‐of‐field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases. PACS number(s): 87.55.N‐, 87.55.ne, 87.56.bd, 87.56.jfOut-of-field doses from radiotherapy can cause harmful side effects or eventually lead to secondary cancers. Scattered doses outside the applicator field, neutron source strength values, and neutron dose equivalents have not been broadly investigated for high-energy electron beams. To better understand the extent of these exposures, we measured out-of-field dose characteristics of electron applicators for high-energy electron beams on two Varian 21iXs, a Varian TrueBeam, and an Elekta Versa HD operating at various energy levels. Out-of-field dose profiles and percent depth-dose curves were measured in a Wellhofer water phantom using a Farmer ion chamber. Neutron dose was assessed using a combination of moderator buckets and gold activation foils placed on the treatment couch at various locations in the patient plane on both the Varian 21iX and Elekta Versa HD linear accelerators. Our findings showed that out-of-field electron doses were highest for the highest electron energies. These doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. The Elekta linear accelerator had higher electron out-of-field doses than the Varian units examined, and the Elekta dose profiles exhibited a second dose peak about 20 to 30 cm from central-axis, which was found to be higher than typical out-of-field doses from photon beams. Electron doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. With respect to neutron dosimetry, Q values and neutron dose equivalents increased with electron beam energy. Neutron contamination from electron beams was found to be much lower than that from photon beams. Even though the neutron dose equivalent for electron beams represented a small portion of neutron doses observed under photon beams, neutron doses from electron beams may need to be considered for special cases. PACS number(s): 87.55.N-, 87.55.ne, 87.56.bd, 87.56.jf.

Investigation of radiomic signatures for local recurrence using primary tumor texture analysis in oropharyngeal head and neck cancer patients

Radiomics is one such “big data” approach that applies advanced image refining/data characterization algorithms to generate imaging features that can quantitatively classify tumor phenotypes in a non-invasive manner. We hypothesize that certain textural features of oropharyngeal cancer (OPC) primary tumors will have statistically significant correlations to patient outcomes such as local control. Patients from an IRB-approved database dispositioned to (chemo)radiotherapy for locally advanced OPC were included in this retrospective series. Pretreatment contrast CT scans were extracted and radiomics-based analysis of gross tumor volume of the primary disease (GTVp) were performed using imaging biomarker explorer (IBEX) software that runs in Matlab platform. Data set was randomly divided into a training dataset and test and tuning holdback dataset. Machine learning methods were applied to yield a radiomic signature consisting of features with minimal overlap and maximum prognostic significance. The radiomic signature was adapted to discriminate patients, in concordance with other key clinical prognosticators. 465 patients were available for analysis. A signature composed of 2 radiomic features from pre-therapy imaging was derived, based on the Intensity Direct and Neighbor Intensity Difference methods. Analysis of resultant groupings showed robust discrimination of recurrence probability and Kaplan-Meier-estimated local control rate (LCR) differences between “favorable” and “unfavorable” clusters were noted.

Patterns-of-failure guided biological target volume definition for head and neck cancer patients: FDG-PET and dosimetric analysis of dose escalation candidate subregions

BACKGROUND To identify the radio-resistant subvolumes in pretreatment FDG-PET by mapping the spatial location of the origin of tumor recurrence after IMRT for head-and-neck squamous cell cancer to the pretreatment FDG-PET/CT. METHODS Patients with local/regional recurrence after IMRT with available FDG-PET/CT and post-failure CT were included. For each patient, both pre-therapy PET/CT and recurrence CT were co-registered with the planning CT (pCT). A 4-mm radius was added to the centroid of mapped recurrence growth target volumes (rGTVs) to create recurrence nidus-volumes (NVs). The overlap between boost-tumor-volumes (BTV) representing different SUV thresholds/margins combinations and NVs was measured. RESULTS Forty-seven patients were eligible. Forty-two (89.4%) had type A central high dose failure. Twenty-six (48%) of type A rGTVs were at the primary site and 28 (52%) were at the nodal site. The mean dose of type A rGTVs was 71Gy. BTV consisting of 50% of the maximum SUV plus 10mm margin was the best subvolume for dose boosting due to high coverage of primary site NVs (92.3%), low average relative volume to CTV1 (41%), and least average percent voxels outside CTV1 (19%). CONCLUSIONS The majority of loco-regional recurrences originate in the regions of central-high-dose. When correlated with pretreatment FDG-PET, the majority of recurrences originated in an area that would be covered by additional 10mm margin on the volume of 50% of the maximum FDG uptake.

Guidelines and experience using imaging biomarker explorer (IBEX) for radiomics

Imaging Biomarker Explorer (IBEX) is an open-source tool for medical imaging radiomics work. The purpose of this paper is to describe how to use IBEXs graphical user interface (GUI) and to demonstrate how IBEX calculated features have been used in clinical studies. IBEX allows for the import of DICOM images with DICOM radiation therapy structure files or Pinnacle files. Once the images are imported, IBEX has tools within the Data Selection GUI to manipulate the viewing of the images, measure voxel values and distances, and create and edit contours. IBEX comes with 27 preprocessing and 132 feature choices to design feature sets. Each preprocessing and feature category has parameters that can be altered. The output from IBEX is a spreadsheet that contains: 1) each feature from the feature set calculated for each contour in a data set, 2) image information about each contour in a data set, and 3) a summary of the preprocessing and features used with their selected parameters. Features calculated from IBEX have been used in studies to test the variability of features under different imaging conditions and in survival models to improve current clinical models.

Prospective in silico study of the feasibility and dosimetric advantages of MRI-guided dose adaptation for human papillomavirus positive oropharyngeal cancer patients compared with standard IMRT

Highlights • The average dose to 95% of initial PTV volume was 70.7 Gy for standard plans vs. 58.5 Gy for adaptive plans.• MRI-guided adaptive approach resulted in decrease dose to normal tissue compared with standard plans.• NTCP of post-treatment dysphagia, feeding tube, and hypothyroidism were reduced using the adaptive approach.

TU-F-CAMPUS-T-04: An Evaluation of Out-Of-Field Doses for Electron Beams From Modern Varian and Elekta Linear Accelerators

Purpose: Accurately determining out-of-field doses when using electron beam radiotherapy is of importance when treating pregnant patients or patients with implanted electronic devices. Scattered doses outside of the applicator field in electron beams have not been broadly investigated, especially since manufacturers have taken different approaches in applicator designs. Methods: In this study, doses outside of the applicator field were measured for electron beams produced by a 10×10 applicator on two Varian 21iXs operating at 6, 9, 12, 16, and 20 MeV, a Varian TrueBeam operating at 6, 9, 12, 16, and 20 MeV, and an Elekta Versa HD operating at 6, 9, 12 and 15 MeV. Peripheral dose profiles and percent depth doses were measured in a Wellhofer water phantom at 100 cm SSD with a Farmer ion chamber. Doses were compared to peripheral photon doses from AAPM’s Task Group #36 report. Results: Doses were highest for the highest electron energies. Doses typically decreased with increasing distance from the field edge but showed substantial increases over some distance ranges. Substantial dose differences were observed between different accelerators; the Elekta accelerator had much higher doses than any Varian unit examined. Surprisingly, doses were often similar to, and could be much higher than, doses from photon therapy. Doses decreased sharply with depth before becoming nearly constant; the dose was found to decrease to a depth of approximately E(MeV)/4 in cm. Conclusion: The results of this study indicate that proper shielding may be very important when utilizing electron beams, particularly on a Versa HD, while treating pregnant patients or those with implanted electronic devices. Applying a water equivalent bolus of Emax(MeV)/4 thickness (cm) on the patient would reduce fetal dose drastically for all clinical energies and is a practical solution to manage the potentially high peripheral doses seen from modern electron beams. Funding from NIH Grant number: #CA180803

Radiotherapy dose–volume parameters predict videofluoroscopy-detected dysphagia per DIGEST after IMRT for oropharyngeal cancer: Results of a prospective registry

PURPOSE Our primary aim was to prospectively validate retrospective dose-response models of chronic radiation-associated dysphagia (RAD) after intensity modulated radiotherapy (IMRT) for oropharyngeal cancer (OPC). The secondary aim was to validate a grade ≥2 cut-point of the published videofluoroscopic dysphagia severity (Dynamic Imaging Grade for Swallowing Toxicity, DIGEST) as radiation dose-dependent. MATERIAL AND METHODS Ninety-seven patients enrolled on an IRB-approved prospective registry protocol with stage I-IV OPC underwent pre- and 3-6 month post-RT videofluoroscopy. Dose-volume histograms (DVH) for swallowing regions of interest (ROI) were calculated. Dysphagia severity was graded per DIGEST criteria (dichotomized with grade ≥2 as moderate/severe RAD). Recursive partitioning analysis (RPA) and Bayesian Information Criteria (BIC) were used to identify dose-volume effects associated with moderate/severe RAD. RESULTS 31% developed moderate/severe RAD (i.e. DIGEST grade ≥2) at 3-6 months after RT. RPA found DVH-derived dosimetric parameters of geniohyoid/mylohyoid (GHM), superior pharyngeal constrictor (SPC), and supraglottic region were associated with DIGEST grade ≥2 RAD. V61 ≥ 18.57% of GHM demonstrated optimal model performance for prediction of DIGEST grade ≥2. CONCLUSION The findings from this prospective longitudinal registry validate prior observations that dose to submental musculature predicts for increased burden of dysphagia after oropharyngeal IMRT. Findings also support dichotomization of DIGEST grade ≥2 as a dose-dependent split for use as an endpoint in trials or predictive dose-response analysis of videofluoroscopy results.

Auto-delineation of oropharyngeal clinical target volumes using three-dimensional convolutional neural networks

Accurate clinical target volume (CTV) delineation is essential to ensure proper tumor coverage in radiation therapy. This is a particularly difficult task for head-and-neck cancer patients where detailed knowledge of the pathways of microscopic tumor spread is necessary. This paper proposes a solution to auto-segment these volumes in oropharyngeal cancer patients using a two-channel 3D U-Net architecture. The first channel feeds the network with the patients CT image providing anatomical context, whereas the second channel provides the network with tumor location and morphological information. Radiation therapy simulation computer tomography scans and their corresponding manually delineated CTV and gross tumor volume (GTV) delineations from 285 oropharyngeal patients previously treated at MD Anderson Cancer Center were used in this study. CTV and GTV delineations underwent rigorous group peer-review prior to the start of treatment delivery. The convolutional networks parameters were fine-tuned using a training set of 210 patients using 3-fold cross-validation. During hyper-parameter selection, we use a score based on the overlap (dice similarity coefficient (DSC)) and missed volumes (false negative dice (FND)) to minimize any possible under-treatment. Three auto-delineated models were created to estimate tight, moderate, and wide CTV margin delineations. Predictions on our test set (75 patients) resulted in auto-delineations with high overlap and close surface distance agreement (DSC  >  0.75 on 96% of cases for tight and moderate auto-delineation models and 97% of cases having mean surface distance  ⩽  5.0 mm) to the ground-truth. We found that applying a 5 mm uniform margin expansion to the auto-delineated CTVs would cover at least 90% of the physician CTV volumes for a large majority of patients; however, determination of appropriate margin expansions for auto-delineated CTVs merits further investigation.

Evaluation of diffusion weighted imaging for tumor delineation in head-and-neck radiotherapy by comparison with automatically segmented 18F-fluorodeoxyglucose positron emission tomography

Background and purpose Diffusion weighted (DW) MRI may facilitate target volume delineation for head-and-neck (HN) radiation treatment planning. In this study we assessed the use of a dedicated, geometrically accurate, DW-MRI sequence for target volume delineation. The delineations were compared with semi-automatic segmentations on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) images and evaluated for interobserver variation. Methods and materials Fifteen HN cancer patients underwent both DW-MRI and FDG-PET for RT treatment planning. Target delineation on DW-MRI was performed by three observers, while for PET a semi-automatic segmentation was performed using a Gaussian mixture model. For interobserver variation and intermodality variation, volumes, overlap metrics and Hausdorff distances were calculated from the delineations. Results The median volumes delineated by the three observers on DW-MRI were 10.8, 10.5 and 9.0 cm3 respectively, and was larger than the median PET volume (8.0 cm3). The median conformity index of DW-MRI for interobserver variation was 0.73 (range 0.38–0.80). Compared to PET, the delineations on DW-MRI by the three observers showed a median dice similarity coefficient of 0.71, 0.69 and 0.72 respectively. The mean Hausdorff distance was small with median (range) distances between PET and DW-MRI of 2.3 (1.5–6.8), 2.5 (1.6–6.9) and 2.0 (1.35–7.6) mm respectively. Over all patients, the median 95th percentile distances were 6.0 (3.0–13.4), 6.6 (4.0–24.0) and 5.3 (3.4–26.0) mm. Conclusion Using a dedicated DW-MRI sequence, target volumes could be defined with good interobserver agreement and a good overlap with PET. Target volume delineation using DW-MRI is promising in head-and-neck radiotherapy, combined with other modalities, it can lead to more precise target volume delineation.

Three-dimensional imaging assessment of anatomic invasion and volumetric considerations for chemo/radiotherapy-based laryngeal preservation in T3 larynx cancer

OBJECTIVES To investigate the impact of 3-Diminsional (3D) tumor volume (TV) and extent of involvement of primary tumor on treatment outcomes in a large uniform cohort of T3 laryngeal carcinoma patients treated with nonsurgical laryngeal preservation strategies. MATERIALS AND METHODS The pretreatment contrast-enhanced computed tomography images of 90 patients with T3 laryngeal carcinoma were reviewed. Primary gross tumor volume (GTVp) was delineated to calculate the 3D TV and define the extent of invasion. Cartilage and soft tissue involvement was coded. The extent of invasion was dichotomized into non/limited invasion versus multiple invasion extension (MIE), and was subsequently correlated with survival outcomes. RESULTS The median TV was 6.6 cm3. Sixty-five patients had non/limited invasion, and 25 had MIE. Median follow-up for surviving patients was 52 months. The 5-year local control and overall survival rates for the whole cohort were 88% and 68%, respectively. There was no correlation between TV and survival outcomes. However, patients with non/limited invasion had better 5-year local control (LC) than those with MIE (95% vs 72%, p = .009) but did not have a significantly higher rate of overall survival (OS) (74% vs 67%, p = .327). In multivariate correlates of LC, MIE maintained statistical significance whereas baseline airway status showed a statistically significance trend with poor LC (p = .0087 and 0.06, respectively). Baseline good performance status was an independent predictor of improved OS (p = .03) in multivariate analysis. CONCLUSION The extent of primary tumor invasion is an independent prognostic factor of LC of the disease after definitive radiotherapy in T3 larynx cancer.