Immunotherapy and radiation therapy sequencing: State of the data on timing, efficacy, and safety.

Radiation therapy exerts a tumoricidal local effect as well as both local and systemic immunomodulation. Immune checkpoint blockade has become a widely used treatment modality across cancer types with a rapidly growing list of agents and US Food and Drug Administration-approved indications. Moreover, there may be synergy between radiation therapy and immune checkpoint blockade. Various strategies have been used, but the optimal sequencing of these therapies is unclear. In this review, the authors discuss the major mechanisms of available immune checkpoint inhibitors and explore the available preclinical and clinical evidence regarding treatment sequencing. They also review safety considerations and conclude with possible future directions.

Technical note: Atlas-based Auto-segmentation of masticatory muscles for head and neck cancer radiotherapy.

PURPOSE: The study aimed to use quantitative geometric and dosimetric metrics to assess the accuracy of atlas-based auto-segmentation of masticatory muscles (MMs) compared to manual drawn contours for head and neck cancer (HNC) radiotherapy (RT). MATERIALS AND METHODS: Fifty-eight patients with HNC treated with RT were analyzed. Paired MMs (masseter, temporalis, and medial and lateral pterygoids) were manually delineated on planning computed tomography (CT) images for all patients. Twenty-nine patients were used to generate the MM atlas. Using this atlas, automatic segmentation of the MMs was performed for the remaining 29 patients without manual correction. Auto-segmentation accuracy for MMs was compared using dice similarity coefficients (DSCs), Hausdorff distance (HD), HD95, and variation in the center of mass (∆COM). The dosimetric impact on MMs was calculated (∆dose) using dosimetric parameters (D99%, D95%, D50%, and D1%), and compared with the geometric indices to test correlation. RESULTS: DSCmean ranges from 0.79 ± 0.04 to 0.85 ± 0.04, HDmean from 0.43 ± 0.08 to 0.82 ± 0.26 cm, HD95mean from 0.32 ± 0.08 to 0.42 ± 0.16 cm, and ∆COMmean from 0.18 ± 0.11 to 0.33 ± 0.23 cm. The mean MM volume difference was < 15%. The correlation coefficient (r) of geometric and dosimetric indices for the four MMs ranges between -0.456 and 0.300. CONCLUSIONS: Atlas-based auto-segmentation for masticatory muscles provides geometrically accurate contours compared to manual drawn contours. Dose obtained from those auto-segmented contours is comparable to that from manual drawn contours. Atlas-based auto-segmentation strategy for MM in HN radiotherapy is readily availalbe for clinical implementation.

Role of Immunotherapy in the Management of Locally Advanced and Recurrent/Metastatic Cervical Cancer.

Despite combined therapeutic approaches, there is an unmet clinical need to identify effective strategies for improved patient outcomes in treating locally advanced and metastatic cervical cancer (CC). Immunotherapy is emerging as a novel therapeutic approach in this disease for which the causative agent, human papillomavirus (HPV), has dynamic, complex immunomodulatory effects. This review explores the biologic rational of immuno-oncology in the treatment of CC and discusses the initial clinical efficacy, ongoing clinical trials, and rationale for combined multimodal treatment approaches for locally advanced and recurrent/metastatic CC. The utility of immune checkpoint inhibitors is explored, including anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4), PD-1, and PD-L1. Preliminary data supporting the combination of radiotherapy and immunotherapy and areas of active drug development for CC are also reviewed.

Characterizing mechanical and medical imaging properties of polyvinyl chloride-based tissue-mimicking materials.

Polyvinyl chloride (PVC) is a commonly used tissue-mimicking material (TMM) for phantom construction using 3D printing technology. PVC-based TMMs consist of a mixture of PVC powder and dioctyl terephthalate as a softener. In order to allow the clinical use of a PVC-based phantom use across CT and magnetic resonance imaging (MRI) imaging platforms, we evaluated the mechanical and physical imaging characteristics of ten PVC samples. The samples were made with different PVC-softener ratios to optimize phantom bioequivalence with physiologic human tissue. Phantom imaging characteristics, including computed tomography (CT) number, MRI relaxation time, and mechanical properties (e.g., Poisson's ratio and elastic modulus) were quantified. CT number varied over a range of approximately -10 to 110 HU. The relaxation times of the T1-weighted and T2-weighted images were 206.81 ± 17.50 and 20.22 ± 5.74 ms, respectively. Tensile testing was performed to evaluate mechanical properties on the three PVC samples that were closest to human tissue. The elastic moduli for these samples ranged 7.000-12.376 MPa, and Poisson's ratios were 0.604-0.644. After physical and imaging characterization of the various PVC-based phantoms, we successfully produced a bioequivalent phantom compatible with multimodal imaging platforms for machine calibration and image optimization/benchmarking. By combining PVC with 3D printing technologies, it is possible to construct imaging phantoms simulating human anatomies with tissue equivalency.

Estimation of daily interfractional larynx residual setup error after isocentric alignment for head and neck radiotherapy: quality assurance implications for target volume and organs-at-risk margination using daily CT on- rails imaging.

Larynx may alternatively serve as a target or organs at risk (OAR) in head and neck cancer (HNC) image-guided radiotherapy (IGRT). The objective of this study was to estimate IGRT parameters required for larynx positional error independent of isocentric alignment and suggest population-based compensatory margins. Ten HNC patients receiving radiotherapy (RT) with daily CT on-rails imaging were assessed. Seven landmark points were placed on each daily scan. Taking the most superior-anterior point of the C5 vertebra as a reference isocenter for each scan, residual displacement vectors to the other six points were calculated postisocentric alignment. Subsequently, using the first scan as a reference, the magnitude of vector differences for all six points for all scans over the course of treatment was calculated. Residual systematic and random error and the necessary compensatory CTV-to-PTV and OAR-to-PRV margins were calculated, using both observational cohort data and a bootstrap-resampled population estimator. The grand mean displacements for all anatomical points was 5.07 mm, with mean systematic error of 1.1 mm and mean random setup error of 2.63 mm, while bootstrapped POIs grand mean displacement was 5.09 mm, with mean systematic error of 1.23 mm and mean random setup error of 2.61 mm. Required margin for CTV-PTV expansion was 4.6 mm for all cohort points, while the bootstrap estimator of the equivalent margin was 4.9 mm. The calculated OAR-to-PRV expansion for the observed residual setup error was 2.7 mm and bootstrap estimated expansion of 2.9 mm. We conclude that the interfractional larynx setup error is a significant source of RT setup/delivery error in HNC, both when the larynx is considered as a CTV or OAR. We estimate the need for a uniform expansion of 5 mm to compensate for setup error if the larynx is a target, or 3 mm if the larynx is an OAR, when using a nonlaryngeal bony isocenter.

Evaluating Automatic Segmentation for Swallowing-Related Organs for Head and Neck Cancer.

Purpose: To evaluate the accuracy of deep-learning-based auto-segmentation of the superior constrictor, middle constrictor, inferior constrictor, and larynx in comparison with a traditional multi-atlas-based method. Methods and Materials: One hundred and five computed tomography image datasets from 83 head and neck cancer patients were retrospectively collected and the superior constrictor, middle constrictor, inferior constrictor, and larynx were analyzed for deep-learning versus multi-atlas-based segmentation. Eighty-three computed tomography images (40 diagnostic computed tomography and 43 planning computed tomography) were used for training the convolutional neural network, and for atlas-based model training. The remaining 22 computed tomography datasets were used for validation of the atlas-based auto-segmentation versus deep-learning-based auto-segmentation contours, both of which were compared with the corresponding manual contours. Quantitative measures included Dice similarity coefficient, recall, precision, Hausdorff distance, 95th percentile of Hausdorff distance, and mean surface distance. Dosimetric differences between the auto-generated contours and manual contours were evaluated. Subjective evaluation was obtained from 3 clinical observers to blindly score the autosegmented structures based on the percentage of slices that require manual modification. Results: The deep-learning-based auto-segmentation versus atlas-based auto-segmentation results were compared for the superior constrictor, middle constrictor, inferior constrictor, and larynx. The mean Dice similarity coefficient values for the 4 structures were 0.67, 0.60, 0.65, and 0.84 for deep-learning-based auto-segmentation, whereas atlas-based auto-segmentation has Dice similarity coefficient results at 0.45, 0.36, 0.50, and 0.70, respectively. The mean 95th percentile of Hausdorff distance (cm) for the 4 structures were 0.41, 0.57, 0.59, and 0.54 for deep-learning-based auto-segmentation, but 0.78, 0.95, 0.96, and 1.23 for atlas-based auto-segmentation results, respectively. Similar mean dose differences were obtained from the 2 sets of autosegmented contours compared to manual contours. The dose-volume discrepancies and the average modification rates were higher with the atlas-based auto-segmentation contours. Conclusion: Swallowing-related structures are more accurately generated with DL-based versus atlas-based segmentation when compared with manual contours.

Contemporary image-guided cervical cancer brachytherapy: Consensus imaging recommendations from the Society of Abdominal Radiology and the American Brachytherapy Society.

PURPOSE: To present recommendations for the use of imaging for evaluation and procedural guidance of brachytherapy for cervical cancer patients. METHODS: An expert panel comprised of members of the Society of Abdominal Radiology Uterine and Ovarian Cancer Disease Focused Panel and the American Brachytherapy Society jointly assessed the existing literature and provide data-driven guidance on imaging protocol development, interpretation, and reporting. RESULTS: Image-guidance during applicator implantation reduces rates of uterine perforation by the tandem. Postimplant images may be acquired with radiography, computed tomography (CT), or magnetic resonance imaging (MRI), and CT or MRI are preferred due to a decrease in severe complications. Pre-brachytherapy T2-weighted MRI may be used as a reference for contouring the high-risk clinical target volume (HR-CTV) when CT is used for treatment planning. Reference CT and MRI protocols are provided for reference. CONCLUSIONS: Image-guided brachytherapy in locally advanced cervical cancer is essential for optimal patient management. Various imaging modalities, including orthogonal radiographs, ultrasound, computed tomography, and magnetic resonance imaging, remain integral to the successful execution of image-guided brachytherapy.

Fitting experimental transcription data with a comprehensive template-dependent modular kinetic model.

In the companion article, we developed a modular scheme for representing the kinetics of transcription elongation by RNA polymerase. As an example of how to use these approaches, in this article we use a comprehensive modular model of this sort to fit experimental transcript elongation results obtained on the canonical tR2 template of phage λ by means of complementary bulk gel electrophoresis and surface plasmon resonance assays. The gel electrophoresis results, obtained in experiments quenched at various times after initiation of transcription, provide distributions of RNA lengths as a function of time. The surface plasmon resonance methods were used to monitor increases and decreases in the total mass of transcription elongation complexes in the same experiments. The different measures of transcription dynamics that these methods provide allow us to use them in combination to obtain a set of largely robust and well-defined kinetic parameters. The results show that our modular approach can be used to develop and test predictive kinetic schemes that can be fit to real transcription elongation data. They also suggest that these approaches can be extended to simulate the kinetics of other processes that involve the processive extension or shortening of nucleic acid chains and related systems of sequential branching reaction events.

Management of locally advanced mesonephric carcinoma of the cervix in the setting of Mullerian Duct anomaly spectrum and unilateral renal agenesis: A case report and review of the literature.

Cervical mesonephric adenocarcinoma is a rare histologic cervical carcinoma variant arising from remnants of the mesonephric duct. Few clinical cases have been reported in the literature, and given the low rate of occurrence, the optimal management strategy is unknown. Most reported cases involve patients with either early stage (FIGO I) or metastatic disease. Herein, we report the only known case of locally advanced, node-positive cervical mesonephric carcinoma in a 55-year old woman with Mullerian duct anomaly of the uterus, obstructed hemivagina, and ipsilateral renal agenesis. To our knowledge, this would be the first case report with the concurrence of both rare entities. We review the treatment paradigm in this patient, and the literature, including radiotherapy and brachytherapy techniques.

The Case for Brachytherapy: Why It Deserves a Renaissance.

The recent global events related to the coronavirus disease of 2019 pandemic have significantly changed the medical landscape and led to a shift in oncologic treatment perspectives. There is a renewed focus on preserving treatment outcomes while maintaining medical accessibility and decreasing medical resource utilization. Brachytherapy, which is a vital part of the treatment course of many cancers (particularly prostate and gynecologic cancers), has the ability to deliver hypofractionated radiation and thus shorten treatment time. Studies in the early 2000s demonstrated a decline in brachytherapy usage despite data showing equivalent or even superior treatment outcomes for brachytherapy in disease sites, such as the prostate and cervix. However, newer data suggest that this trend may be reversing. The renewed call for shorter radiation courses based on data showing equivalent outcomes will likely establish hypofractionated radiation as the standard of care across multiple disease sites. With shifting reimbursement, brachytherapy represents the pinnacle in hypofractionated, conformal radiation therapy, and with extensive long-term data in support of the treatment modality brachytherapy is primed for a renaissance.

Prognostic Value of Computed Tomography and/or 18F-Fluorodeoxyglucose Positron Emission Tomography Radiomics Features in Locally Advanced Non-small Cell Lung Cancer.

INTRODUCTION: We investigated whether adding computed tomography (CT) and/or 18F-fluorodeoxyglucose (18F-FDG) PET radiomics features to conventional prognostic factors (CPFs) improves prognostic value in locally advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We retrospectively identified 39 cases with stage III NSCLC who received chemoradiotherapy and underwent planning CT and staging 18F-FDG PET scans. Seven CPFs were recorded. Feature selection was performed on 48 CT and 49 PET extracted radiomics features. A penalized multivariate Cox proportional hazards model was used to generate models for overall survival based on CPFs alone, CPFs with CT features, CPFs with PET features, and CPFs with CT and PET features. Linear predictors generated and categorized into 2 risk groups for which Kaplan-Meier survival curves were calculated. A log-rank test was performed to quantify the discrimination between the groups and calculated the Harrell's C-index to quantify the discriminatory power. A likelihood ratio test was performed to determine whether adding CT and/or PET features to CPFs improved model performance. RESULTS: All 4 models significantly discriminated between the 2 risk groups. The discriminatory power was significantly increased when CPFs were combined with PET features (C-index 0.82; likelihood ratio test P < .01) or with both CT and PET features (0.83; P < .01) compared with CPFs alone (0.68). There was no significant improvement when CPFs were combined with CT features (0.68). CONCLUSION: Adding PET radiomics features to CPFs yielded a significant improvement in the prognostic value in locally advanced NSCLC; adding CT features did not.

Current Status of Clinical Trials for Cervical and Uterine Cancer Using Immunotherapy Combined With Radiation.

Novel therapies combined with radiation continue to be of significant interest in the developmental treatment paradigm of gynecologic cancers. Clinical implementation of immunotherapy in oncology has rapidly changed the treatment landscape, options, paradigm, and outcomes through clinical trials. Immunotherapy has emerged as a therapeutic pillar in the treatment of solid tumors with demonstrable synergistic activity when combined with radiation therapy and chemoradiotherapy by an alteration or enhancement of the immune system. In solid tumors, radiation therapy induces migration of dendritic cells, T cell activation, and proliferation, and increases in tumor-infiltrating lymphocytes. These immunomodulatory effects in conjunction with immune checkpoint blockade are currently under active investigation in the adjuvant, definitive, and metastatic settings. Results from early phase trials demonstrate promising efficacy and overall tolerable toxicity profiles of combined modality treatment. There is significant interest in optimizing the treatment for patients with locally advanced cervical cancer beyond the standard of care-chemoradiation-which has been in place for the last 30 years. The majority of cervical cancer emerges after persistent infection with a high-risk subtype of the human papillomavirus, where viral oncoproteins lead to cellular changes and immortalization. As a result, immune tolerance can develop, resulting in cancer. Knowledge of the mechanism of human papillomavirus-related oncogenesis suggests that immune therapy or checkpoint blockade can reinvigorate an antitumor immune response. Current clinical trials are exploring the therapeutic potential of these approaches. Uterine cancers have been grouped into 4 molecular subclasses by their driver mutations, mutational burden, and copy-number alterations. Of these subgroups, the polymerase epsilon-mutated and microsatellite-unstable may represent up to 40% of endometrial cancers, and they have been shown to be immunogenic. Because of the inherent immunogenicity of these MSI-high tumors, combined immune modulation strategies, including chemotherapy, radiation, and immunotherapy and immune checkpoint inhibitor therapy, are being explored to improve treatment outcomes. In this review, we explore current immunomodulatory and multimodality therapeutic approaches in the treatment of cervical and uterine cancer through ongoing clinical trials investigating the combination of immunotherapy and radiation therapy.

Simulation-based learning for enhanced gynecologic brachytherapy training among radiation oncology residents.

PURPOSE: Brachytherapy is an irreplaceable component of gynecologic cancer treatment. Resident training has declined, and procedural exposure is variable. We evaluated whether simulation-based gynecologic brachytherapy training among radiation oncology residents could improve knowledge, confidence, and interest. METHODS AND MATERIALS: Before a brachytherapy workshop, radiation oncology residents without prior gynecologic brachytherapy experience completed a survey on brachytherapy knowledge, procedural confidence, plan evaluation, and quality/safety. Residents then participated in a gynecologic brachytherapy workshop. Lectures covered brachytherapy imaging and physics principles/quality assurance, followed by hands-on and individualized feedback regarding applicator selection and placement, target segmentation, and physics quality assurance. Afterward, preworkshop questions were recollected. Descriptive statistics and Fisher's exact tests were used for data analysis. RESULTS: After the workshop, resident responses regarding the learning environment and baseline knowledge questions improved overall. There was a 30% improvement in favorable responses to the learning environment statement "My residency has a formal process/curriculum to teach brachytherapy" and for baseline knowledge the greatest improvement was seen for "I am familiar with the anatomy and placement of the applicators in relation to the anatomy". "Lack of didactic or procedural training exposure" was identified as the main reason for declining brachytherapy use. Initially, 1/8 residents correctly completed the knowledge questions, and after the workshop, 6/7 (p < 0.001) residents correctly completed the questions. CONCLUSIONS: Domain-specific knowledge, procedural confidence, and brachytherapy interest improved after a gynecologic brachytherapy workshop. Integrated didactic and simulation-based brachytherapy training may serve as a valuable learning tool to augment resident knowledge, introduce practical skills, and spark resident interest in brachytherapy.

Deep learning vs. atlas-based models for fast auto-segmentation of the masticatory muscles on head and neck CT images.

BACKGROUND: Impaired function of masticatory muscles will lead to trismus. Routine delineation of these muscles during planning may improve dose tracking and facilitate dose reduction resulting in decreased radiation-related trismus. This study aimed to compare a deep learning model with a commercial atlas-based model for fast auto-segmentation of the masticatory muscles on head and neck computed tomography (CT) images. MATERIAL AND METHODS: Paired masseter (M), temporalis (T), medial and lateral pterygoid (MP, LP) muscles were manually segmented on 56 CT images. CT images were randomly divided into training (n = 27) and validation (n = 29) cohorts. Two methods were used for automatic delineation of masticatory muscles (MMs): Deep learning auto-segmentation (DLAS) and atlas-based auto-segmentation (ABAS). The automatic algorithms were evaluated using Dice similarity coefficient (DSC), recall, precision, Hausdorff distance (HD), HD95, and mean surface distance (MSD). A consolidated score was calculated by normalizing the metrics against interobserver variability and averaging over all patients. Differences in dose (∆Dose) to MMs for DLAS and ABAS segmentations were assessed. A paired t-test was used to compare the geometric and dosimetric difference between DLAS and ABAS methods. RESULTS: DLAS outperformed ABAS in delineating all MMs (p < 0.05). The DLAS mean DSC for M, T, MP, and LP ranged from 0.83 ± 0.03 to 0.89 ± 0.02, the ABAS mean DSC ranged from 0.79 ± 0.05 to 0.85 ± 0.04. The mean value for recall, HD, HD95, MSD also improved with DLAS for auto-segmentation. Interobserver variation revealed the highest variability in DSC and MSD for both T and MP, and the highest scores were achieved for T by both automatic algorithms. With few exceptions, the mean ∆D98%, ∆D95%, ∆D50%, and ∆D2% for all structures were below 10% for DLAS and ABAS and had no detectable statistical difference (P > 0.05). DLAS based contours had dose endpoints more closely matched with that of the manually segmented when compared with ABAS. CONCLUSIONS: DLAS auto-segmentation of masticatory muscles for the head and neck radiotherapy had improved segmentation accuracy compared with ABAS with no qualitative difference in dosimetric endpoints compared to manually segmented contours.

Clinical feasibility of MR-assisted CT-based cervical brachytherapy using MR-to-CT deformable image registration.

PURPOSE: The purpose of this study is to evaluate the feasibility of using deformable image registration algorithms to improve high-dose-rate high-risk clinical target volume (HR-CTV) delineation between preapplicator implantation MRI (pre-MRI) and postapplicator implantation CT (post-CT) in the treatment of locally advanced cervical cancer (LACC). METHOD AND MATERIALS: Twenty-six patients were identified for the study. Regions of interest were segmented on MRI and CT. A HR-CTV was delineated on pre-MRI and compared with the previously contoured HR-CTV on the post-CT. Two commercially available algorithms, ANACONDA (anatomically constrained) and MORFEUS (biomechanical model based) with various controlling structure settings, including the cervix, uterus, etc., were used to deform pre-MRI to post-CT. MRI-to-CT deformed targets are denoted as HR-CTV'. Quantitative deformation metrics include Dice index, distance to agreement, and center of mass displacement. Qualitative clinical usefulness of deformations was scored based on HR-CTV identification on CT images. RESULTS: For ANACONDA and MORFEUS deformations, using a cervix controlling region of interest resulted in the highest Dice, lowest distance to agreement, and lowest center of mass displacement for HR-CTV'. With MORFEUS deformations, the deformed HR-CTV' proved clinically useful in 23 patients. CONCLUSIONS: Prebrachytherapy implantation MRI can aid target contours for CT-based brachytherapy through ANACONDA or MORFEUS algorithms with appropriate parameter selection for LACC patients.

The relationship between posterior pharyngeal wall thickness and swallowing function after radiation therapy.

Background: Dysphagia is a complication following radiation therapy (RT) for head and neck cancers (HNC). Radiologic findings of posterior pharyngeal wall thickening (PPWT) after RT has not been quantified and correlated to swallowing outcomes.Aims/objective: To evaluate PPWT and its impact on swallowing function following RT.Material and methods: Retrospective analysis of pre- and three-month post-RT PPWT, demographics, oncologic history, and swallowing parameters of patients undergoing RT for HNC. Multivariate analysis of variance was performed to evaluate the effect of PPWT on swallowing outcomes.Results: The mean age of the cohort (n = 207) was 61.8 (± 11.29) years. The mean PPWT increased by 0.28 (± 0.19) cm (p = .00) three-months after RT. A significant difference in PPWT score between tumor subsites, χ2(2) = 45.883, p = .00, with the highest mean rank score of 135.97 for nasopharynx and 103.46 for oropharynx. PPWT was significantly associated with increased pyriform sinus retention, higher Penetration-Aspiration Scale (PAS) scores and post-deglutitive aspiration (p < .05).Conclusions and significance: PPWT increase significantly after RT for HNC. Increased PPWT was associated with mean radiation dose to the nasopharynx and oropharynx and was an independent risk factor for increased pharyngeal residue, higher PAS scores, and timing of aspiration (p < .05).

Characterization and clinical validation of patient-specific three-dimensional printed tissue-equivalent bolus for radiotherapy of head and neck malignancies involving skin.

PURPOSE: Megavoltage radiotherapy to irregular superficial targets is challenging due to the skin sparing effect. We developed a three-dimensional bolus (3DB) program to assess the clinical impact on dosimetric and patient outcomes. MATERIALS AND METHODS: Planar commercial bolus (PCB) and 3DB density, clarity, and net bolus effect were rigorously evaluated prior to clinical implementation. After IRB approval, patients with cutaneous or locally advanced malignancies deemed to require bolus for radiotherapy treatment were treated with custom 3DB. RESULTS: The mean density of 3DB and PCB was of 1.07 g/cm 3 and 1.12 g/cm3, respectively. 3DB optic clarity was superior versus PCB at any material thickness. Phantom measurements of superficial dose with 3DB and PCB showed excellent bolus effect for both materials. 3DB reduced air gaps compared with PCB - particularly in irregular areas such as the ear, nose, and orbit. A dosimetric comparison of 3DB and PCB plans showed equivalent superficial homogeneity for 3DB and PCB (3DB median HI 1.249, range 1.111-1.300 and PCB median HI 1.165, range 1.094-1.279), but better conformity with 3DB (3DB median CI 0.993, range 0.962-0.993) versus PCB (PCB median CI 0.977, range 0.601-0.991). Patient dose measurements using 3DB confirm the delivered superficial dose was within 1% of the intended prescription (95% CI 97-102%; P = 0.11). CONCLUSIONS: 3DB improves radiotherapy plan conformity, reduces air gap volume in irregular superficial areas which could affect superficial dose delivery, and provides excellent dose coverage to irregular superficial targets.

Clinical Enhancement in AI-Based Post-processed Fast-Scan Low-Dose CBCT for Head and Neck Adaptive Radiotherapy.

Purpose: To assess image quality and uncertainty in organ-at-risk segmentation on cone beam computed tomography (CBCT) enhanced by deep-learning convolutional neural network (DCNN) for head and neck cancer. Methods: An in-house DCNN was trained using forty post-operative head and neck cancer patients with their planning CT and first-fraction CBCT images. Additional fifteen patients with repeat simulation CT (rCT) and CBCT scan taken on the same day (oCBCT) were used for validation and clinical utility assessment. Enhanced CBCT (eCBCT) images were generated from the oCBCT using the in-house DCNN. Quantitative imaging quality improvement was evaluated using HU accuracy, signal-to-noise-ratio (SNR), and structural similarity index measure (SSIM). Organs-at-risk (OARs) were delineated on o/eCBCT and compared with manual structures on the same day rCT. Contour accuracy was assessed using dice similarity coefficient (DSC), Hausdorff distance (HD), and center of mass (COM) displacement. Qualitative assessment of users' confidence in manual segmenting OARs was performed on both eCBCT and oCBCT by visual scoring. Results: eCBCT organs-at-risk had significant improvement on mean pixel values, SNR (p < 0.05), and SSIM (p < 0.05) compared to oCBCT images. Mean DSC of eCBCT-to-rCT (0.83 ± 0.06) was higher than oCBCT-to-rCT (0.70 ± 0.13). Improvement was observed for mean HD of eCBCT-to-rCT (0.42 ± 0.13 cm) vs. oCBCT-to-rCT (0.72 ± 0.25 cm). Mean COM was less for eCBCT-to-rCT (0.28 ± 0.19 cm) comparing to oCBCT-to-rCT (0.44 ± 0.22 cm). Visual scores showed OAR segmentation was more accessible on eCBCT than oCBCT images. Conclusion: DCNN improved fast-scan low-dose CBCT in terms of the HU accuracy, image contrast, and OAR delineation accuracy, presenting potential of eCBCT for adaptive radiotherapy.

COVID-19 impact on timing of brachytherapy treatment and strategies for risk mitigation.

PURPOSE: The purpose of this study was to highlight the importance of timely brachytherapy treatment for patients with gynecologic, breast, and prostate malignancies, and provide a framework for brachytherapy clinical practice and management in response to the COVID-19 pandemic. METHODS AND MATERIALS: We review amassing evidence to help guide the management and timing of brachytherapy for gynecologic, breast, and prostate cancers. Where concrete data could not be found, peer-reviewed expert opinion is provided. RESULTS: There may be a significant negative impact on oncologic outcomes for patients with gynecologic malignancies who have a delay in the timely completion of therapy. Delay of prostate or breast cancer treatment may also impact oncologic outcomes. If a treatment delay is expected, endocrine therapy may be an appropriate temporizing measure before delivery of radiation therapy. The use of shorter brachytherapy fractionation schedules will help minimize patient exposure and conserve resources. CONCLUSIONS: Brachytherapy remains a critical treatment for patients and may shorten treatment time and exposure for some. Reduced patient exposure and resource utilization is important during COVID-19. Every effort should be made to ensure timely brachytherapy delivery for patients with gynecologic malignancies, and endocrine therapy may help temporize treatment delays for breast and prostate cancer patients. Physicians should continue to follow developing institutional, state, and federal guidelines/recommendations as challenges in delivering care during COVID-19 will continue to evolve.

Integrated skin flash planning technique for intensity-modulated radiation therapy for vulvar cancer prevents marginal misses and improves superficial dose coverage.

INTRODUCTION: Radiation therapy (RT) plays a definitive role in locally advanced vulvar cancer, and in the adjuvant setting with high risk postoperative features after wide local excision. There is significant morbidity associated with traditional, large RT fields using 2D or 3D techniques, and the use of intensity-modulated radiation therapy (IMRT) in vulvar cancer is increasing. However, there remains a paucity of technical information regarding the prevention of a marginal miss during the treatment planning process. The use of an integrated skin flash (ISF) during RT planning can be used to account for anatomic variation, and intra- and interfraction motion seen during treatment. CASE DESCRIPTION: Herein we present the case of a patient with a T1aN0M0, Stage IA vulva cancer to illustrate the progressive vulvar swelling and lymph edema seen during treatment and retrospectively evaluate the dosimetric effects of using an ISF RT plan vs standard RT planning techniques. CONCLUSIONS: Standard planning techniques to treat vulvar cancer patients with IMRT do not sufficiently account for the change in patient anatomy and can lead to a marginal miss. ISF is an RT planning technique that can decrease the risk of a marginal miss and the technique is easily implemented during the planning stages of RT treatment. Furthermore, use of an ISF technique can improve vulvar clinical target volume coverage and plan homogeneity. Based on our experience, and this study, a 2-cm ISF is suggested to account for variations in daily clinical setup and changes in patient anatomy during treatment.