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Background: Both dose and linear energy transfer (LET) could play a substantial role in adverse event (AE) initialization of cancer patients treated with pencil‐beam‐scanning (PBS) proton therapy. However, not all the voxels within the AE regions are directly induced from the dose and LET effect. It is important to study the synergistic effect of dose and LET in AE initialization by only including a subset of voxels that are dosimetrically important. Purpose: To perform exploratory investigation of the dose and LET effects upon AE initialization in PBS using seed spots analysis. Methods: A total of 113 head‐and‐neck (H&N) cancer patients receiving curative PBS were included. Among them, 20 patients experienced unanticipated CTCAEv4.0 grade ≥3 AEs (AE group) and 93 patients did not (control group). Within the AE group, 13 AE patients were included in the seed spot analysis to derive the descriptive features of AE initialization and the remaining 7 mandible osteoradionecrosis patients and 93 control patients were used to derive the feature‐based volume constraint of mandible osteoradionecrosis. The AE regions were contoured and the corresponding dose–LET volume histograms of AE regions were generated for all patients in the AE group. We selected high LET voxels (the highest 5% of each dose bin) with a range of moderate‐to‐high dose (≥∼40‐Gy relative biological effectiveness) as critical voxels. Critical voxels that were contiguous with each other were grouped into clusters. Each cluster was considered a potential independent seed spot for AE initialization. Seed spots were displayed in a 2D dose–LET plane based on their mean dose and LET to derive the descriptive features of AE initialization. A volume constraint of mandible osteoradionecrosis was then established based on the extracted features using a receiver operating characteristic curve. Results: The product of dose and LET (xBD) was found to be a descriptive feature of seed spots leading to AE initialization in this preliminary study. The derived xBD volume constraint for mandible osteoradionecrosis showed good performance with an area under curve of 0.87 (sensitivity of 0.714 and specificity of 0.807 in the leave‐one‐out cross‐validation) for the very limited patient data included in this study. Conclusion: Our exploratory study showed that both dose and LET were observed to be important in AE initializations. The derived xBD volume constraint could predict mandible osteoradionecrosis reasonably well in the very limited H&N cancer patient data treated with PBS included in this study. [ABSTRACT FROM AUTHOR]

Purpose: To develop an online graphic processing unit (GPU)‐accelerated Monte Carlo‐based adaptive radiation therapy (ART) workflow for pencil beam scanning (PBS) proton therapy to address interfraction anatomical changes in patients treated with PBS. Methods and Materials: A four‐step workflow was developed using our in‐house developed GPU‐accelerated Monte Carlo‐based treatment planning system to implement online Monte Carlo‐based ART for PBS. The first step conducts diffeomorphic demon‐based deformable image registration (DIR) to propagate contours on the initial planning CT (pCT) to the verification CT (vCT) to form a new structure set. The second step performs forward dose calculation of the initial plan on the vCT with the propagated contours after manual approval (possible modifications involved). The third step triggers a reoptimization of the plan depending on whether the verification dose meets the clinical requirements or not. A robust evaluation will be done for both the verification plan in the second step and the reopotimized plan in the third step. The fourth step involves a two‐stage (before and after delivery) patient‐specific quality assurance (PSQA) of the reoptimized plan. The before‐delivery PSQA is to compare the plan dose to the dose calculated using an independent fast open‐source Monte Carlo code, MCsquare. The after‐delivery PSQA is to compare the plan dose to the dose recalculated using the log file (spot MU, spot position, and spot energy) collected during the delivery. Jaccard index (JI), dice similarity coefficients (DSCs), and Hausdorff distance (HD) were used to assess the quality of the propagated contours in the first step. A commercial plan evaluation software, ClearCheck™, was integrated into the workflow to carry out efficient plan evaluation. 3D Gamma analysis was used during the fourth step to ensure the accuracy of the plan dose from reoptimization. Three patients with three different disease sites were chosen to evaluate the feasibility of the online ART workflow for PBS. Results: For all three patients, the propagated contours were found to have good volume conformance [JI (lowest‐highest: 0.833–0.983) and DSC (0.909–0.992)] but suboptimal boundary coincidence [HD (2.37–20.76 mm)] for organs‐at‐risk. The verification dose evaluated by ClearCheck™ showed significant degradation of the target coverage due to the interfractional anatomical changes. Reoptimization on the vCT resulted in great improvement of the plan quality to a clinically acceptable level. 3D Gamma analyses of PSQA confirmed the accuracy of the plan dose before delivery (mean Gamma index = 98.74% with a threshold of 2%/2 mm/10%), and after delivery based on the log files (mean Gamma index = 99.05% with a threshold of 2%/2 mm/10%). The average time cost for the complete execution of the workflow was around 858 s, excluding the time for manual intervention. Conclusion: The proposed online ART workflow for PBS was demonstrated to be efficient and effective by generating a reoptimized plan that significantly improved the plan quality. [ABSTRACT FROM AUTHOR]

It is well established that sea turtles are vulnerable to atmospheric and oceanographic shifts associated with climate change. However, few studies have formally projected how their seasonal marine habitat may shift in response to warming ocean temperatures. Here we used a high-resolution global climate model and a large satellite tagging dataset to project changes in the future distribution of suitable thermal habitat for loggerheads along the northeastern continental shelf of the United States. Between 2009 and 2018, we deployed 196 satellite tags on loggerheads within the Middle Atlantic Bight (MAB) of the Northwest Atlantic continental shelf region, a seasonal foraging area. Tag location data combined with depth and remotely sensed sea surface temperature (SST) were used to characterize the species' current thermal range in the MAB. The best-fitting model indicated that the habitat envelope for tagged loggerheads consisted of SST ranging from 11.0° to 29.7 °C and depths between 0 and 105.0 m. The calculated core bathythermal range consisted of SSTs between 15.0° and 28.0 °C and depths between 8.0 and 92.0 m, with the highest probability of presence occurred in regions with SST between 17.7° and 25.3 °C and at depths between 26.1 and 74.2 m. This model was then forced by a high-resolution global climate model under a doubling of atmospheric CO2 to project loggerhead probability of presence over the next 80 years. Our results suggest that loggerhead thermal habitat and seasonal duration will likely increase in northern regions of the NW Atlantic shelf. This change in spatiotemporal range for sea turtles in a region of high anthropogenic use may prompt adjustments to the localized protected species conservation measures. [ABSTRACT FROM AUTHOR]

Purpose: We propose linear energy transfer (LET)-guided robust optimization in intensity modulated proton therapy for head and neck cancer. This method simultaneously considers LET and physical dose distributions of tumors and organs at risk (OARs) with uncertainties.Methods and Materials: Fourteen patients with head and neck cancer were included in this retrospective study. Cord, brain stem, brain, and oral cavity were considered. Two algorithms, voxel-wise worst-case robust optimization and LET-guided robust optimization (LETRO), were used to generate intensity modulated proton therapy plans for each patient. The latter method directly optimized LET distributions rather than indirectly as in previous methods. LET-volume histograms (LETVHs) were generated, and high LET was redistributed from nearby OARs to tumors in a user-defined way via LET-volume constraints. Dose-volume histogram indices, such as clinical target volume (CTV) D98% and D2%-D98%, cord Dmax, brain stem Dmax, brain Dmax, and oral cavity Dmean, were calculated. Plan robustness was quantified using the worst-case analysis method. LETVH indices analogous to dose-volume histogram indices were used to characterize LET distributions. The Wilcoxon signed rank test was performed to measure statistical significance.Results: In the nominal scenario, LETRO provided higher LET distributions in the CTV (unit: keV/μm; CTV LET98%: 1.18 vs 1.08, LETRO vs RO, P = .0031) while preserving comparable physical dose and plan robustness. LETRO achieved significantly reduced LET distributions in the cord, brain stem, and oral cavity compared with RO (cord LETmax: 7.20 vs 8.20, P = .0010; brain stem LETmax: 10.95 vs 12.05, P = .0007; oral cavity LETmean: 2.11 vs 3.12, P = .0052) and had comparable physical dose and plan robustness in all OARs. In the worst-case scenario, LETRO achieved significantly higher LETmean in the CTV, reduced LETmax in the brain, and was comparable to other LETVH indices (CTV LETmean: 3.26 vs 3.35, P = .0012; brain LETmax: 24.80 vs 22.00, P = .0016).Conclusions: LETRO robustly optimized LET and physical dose distributions simultaneously. It redistributed high LET from OARs to targets with slightly modified physical dose and plan robustness. [ABSTRACT FROM AUTHOR]

Abstract Since 2009, we have deployed 167 satellite tags on loggerheads within the U.S. Mid-Atlantic Bight of the Northwest Atlantic Ocean. These tags collect and transmit location, temperature and depth information and have yielded 18,790 temperature-depth profiles during the highly stratified season (01 June –04 October) for the region. This includes 16,371 profiles exceeding the mixed-layer depth, and, of those, 11,591 full water column profiles reaching the ocean floor. The US MAB is a dynamic ecosystem that is difficult to model due to a combination of complex seasonal water masses and currents and a limited set of tools for taking in situ measurements. This region is also prime foraging habitat for loggerhead sea turtles during the late-spring to summer months. Here we suggest that the habitat usage of loggerhead turtles in the Mid-Atlantic Bight make them good ocean observers within this difficult to model, highly stratified region. The use of turtle-borne telemetry devices has the potential to improve resolution of in situ temperature through depth data and in turn improve oceanographic model outputs. It is imperative that model outputs are continuously updated, as they are regularly used to inform management and conservation decisions. Highlights • Data loggers on turtles collected 18,790 temperature-depth profiles. • Profiles were collected during the highly stratified season within the US MAB. • This is a replicable method to study the oceanography of mid-latitude shelf seas. [ABSTRACT FROM AUTHOR]

Sea turtles are vulnerable to climate change impacts in both their terrestrial (nesting beach) and oceanic habitats. From 1982 to 2012, air and sea surface temperatures at major high use foraging and nesting regions (n = 5) of loggerhead turtles (Caretta caretta) nesting in Greece have steadily increased. Here, we update the established relationships between sea surface temperature and nesting data from Zakynthos (latitude: 37.7°N), a major nesting beach, while also expanding these analyses to include precipitation and air temperature and additional nesting data from two other key beaches in Greece: Kyparissia Bay (latitude: 37.3°N) and Rethymno, Crete (latitude: 35.4°N). We confirmed that nesting phenology at Zakynthos has continued to be impacted by breeding season temperature; however, temperature has no consistent relationship with nest numbers, which are declining on Zakynthos and Crete but increasing at Kyparissia. Then using statistically downscaled outputs of 14 climate models assessed by the Intergovernmental Panel on Climate Change (IPCC), we projected future shifts in nesting for these populations. Based on the climate models, we projected that temperature at the key foraging and breeding sites (Adriatic Sea, Aegean Sea, Crete, Gulf of Gabès and Zakynthos/Kyparissia Bay; overall latitudinal range: 33.0°—45.8°N) for loggerhead turtles nesting in Greece will rise by 3–5°C by 2100. Our calculations indicate that the projected rise in air and ocean temperature at Zakynthos could cause the nesting season in this major rookery to shift to an earlier date by as much as 50–74 days by 2100. Although an earlier onset of the nesting season may provide minor relief for nest success as temperatures rise, the overall climatic changes to the various important habitats will most likely have an overall negative impact on this population. [ABSTRACT FROM AUTHOR]

This study represents the first documented use of a remotely operated vehicle (ROV) to actively track sea turtles in situ. From 2008 to 2014, an ROV was deployed to track the at-sea behavior of loggerhead turtles in the Northwest Atlantic Ocean. Seventy turtles were tracked, totaling 44.7 h of direct turtle footage. For all attempts, usable video with a turtle retained in view for a minimum of 30 s, was produced at a rate of 43.5% of effort. Turtles were first spotted from the boat, and then when the turtle was within ~ 50 m of the boat, the ROV was deployed to track the turtle for as long as possible. Tracking durations reached up to 426.1 min. Tracked turtles often remained within ~ 10 m of the surface; however loggerheads were tracked to the seafloor on 12 occasions. Turtles were filmed foraging both pelagically and benthically, even though bottom temperatures reached as low as 7.1 °C. A range of inter- and intra-species interactions were also captured. Several varieties of fish remained associated with individual turtles for extended periods of time, even during benthic foraging dives. Additionally, a variety of social interactions between loggerheads were documented. Generally these interactions were filmed occurring near the ocean surface. Overall, using the ROV provided great insight into loggerhead at-sea behavior, otherwise unattainable using previously established techniques. [ABSTRACT FROM AUTHOR]

Background: Malignant tumours arising within the nasal cavity and paranasal sinuses are rare and composed of several histological types, rendering controlled clinical trials to establish the best treatment impractical. We undertook a systematic review and meta-analysis to compare the clinical outcomes of patients treated with charged particle therapy with those of individuals receiving photon therapy. Methods: We identified studies of nasal cavity and paranasal sinus tumours through searches of databases including Embase, Medline, Scopus, and the Cochrane Collaboration. We included treatment-naive cohorts (both primary and adjuvant radiation therapy) and those with recurrent disease. Primary outcomes of interest were overall survival, disease-free survival, and locoregional control, at 5 years and at longest follow-up. We used random-effect models to pool outcomes across studies and compared event rates of combined outcomes for charged particle therapy and photon therapy using an interaction test. Findings: 43 cohorts from 41 non-comparative observational studies were included. Median follow-up for the charged particle therapy group was 38 months (range 5-73) and for the photon therapy group was 40 months (14-97). Pooled overall survival was significantly higher at 5 years for charged particle therapy than for photon therapy (relative risk 1·51, 95% CI 1·14-1·99; p=0·0038) and at longest follow-up (1·27, 1·01-1·59; p=0·037). At 5 years, disease-free survival was significantly higher for charged particle therapy than for photon therapy (1·93, 1·36-2·75, p=0·0003) but, at longest follow-up, this event rate did not differ between groups (1·51, 1·00-2·30; p=0·052). Locoregional control did not differ between treatment groups at 5 years (1·06, 0·68-1·67; p=0·79) but it was higher for charged particle therapy than for photon therapy at longest follow-up (1·18, 1·01-1·37; p=0·031). A subgroup analysis comparing proton beam therapy with intensity-modulated radiation therapy showed significantly higher disease-free survival at 5 years (relative risk 1·44, 95% CI 1·01-2·05; p=0·045) and locoregional control at longest follow-up (1·26, 1·05-1·51; p=0·011). Interpretation: Compared with photon therapy, charged particle therapy could be associated with better outcomes for patients with malignant diseases of the nasal cavity and paranasal sinuses. Prospective studies emphasising collection of patient-reported and functional outcomes are strongly encouraged. Funding: Mayo Foundation for Medical Education and Research. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated relapse patterns after transoral laser microsurgery (TLM) in squamous cell carcinoma (SCC) of the tonsil and tongue base and evaluated the indications for adjuvant irradiation. Methods: Between December 1, 1996, and December 31, 2005, 79 patients with previously untreated SCC of the tonsil or tongue base underwent TLM with or without neck dissection. Thirty-eight patients (48%) underwent postoperative irradiation (median, 62 Gy) to the primary site and the neck. Analysis of relapse patterns was performed on the basis of adverse risk factors and the presence or absence of adjuvant irradiation. Results: The median follow-up for living patients was 47 months (range, 10 to 107 months), and patients were monitored for at least 2 years or until recurrence or death. Local, regional, and distant treatment failures numbered 4, 6, and 4 for surgery alone (n = 41) and 0, 2, and 6 for adjuvant irradiation (n = 38), respectively. Patients with high-risk features (extracapsular extension or at least 2 adverse factors) had locoregional control rates at 2 or more years of 66% and 94% for TLM alone and TLM plus adjuvant irradiation, respectively. Conclusions: Adjuvant irradiation after TLM resection of oropharyngeal SCC with intermediate- or high-risk features improves locoregional control compared with TLM alone. [ABSTRACT FROM AUTHOR]

As the number of high-conflict separation cases continues to rise, mental health counselors are increasingly called upon to assist courts with child custody evaluations. Counselors can provide family courts with invaluable services either as treating or as forensic experts. Because each of these roles is unique, however, it is imperative that counselors who provide services to family courts understand the differences. Ethical, legal, and malpractice risks also increase considerably for counselors who provide courts with expert testimony. The purpose of this paper is to (a) discuss the central differences between the roles of counselor and of child custody evaluator, and (b) describe best practices for conducting child custody evaluations. [ABSTRACT FROM AUTHOR]

Mental health counselors encounter numerous complex situations when working with children and adolescent's in anger management groups. This study promotes the use of Social Cognitive Theory to reduce cognitive distortions and aggressive behavior in youth. Specifically, it highlights Leadership Implementation Training (LIT), a youth-oriented model that integrates leadership skills into school-based anger management groups with the intent of reducing aggression in angry youth. Initial data suggest that doing so is an effective tool for mental health counselors who facilitate groups in schools. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the anti-inflammatory effect of antiplatelet agent, clopidogrel, in experimentally induced inflammatory bowel disease (IBD). Materials and Methods: TNBS induced Crohn's disease model and oxazolone induced ulcerative colitis model were used to evaluate the role of clopidogrel in IBD. Spargue Dawley female and Wistar male rats were used respectively. The colitis was induced by a single intra-colonic application of TNBS (0.25 ml, 120 mg/ml in 50% ethanol) and oxazolone (450 μl 5% oxazolone in 50% ethanol). Rats were divided into four groups (n=6) in each model namely normal control, sham control, test and standard group. Drug treatment was carried out for 21 days. After 21 days, animals were sacrificed and evaluated for weight change, colon mucosal damage index (CMDI), disease activity Index (DAI) and myeloperoxidase (MPO) activity. Results: Results showed that clopidogrel provided significant protection against mucosal damage in both the models of IBD. It significantly reduced (P<0.05) the decrease in body weight and CMDI, DAI and MPO scores. Conclusion: The results indicate that clopidogrel may be effective in treatment of Crohn's disease and ulcerative colitis. Platelet inhibition may be one of the mechanism for effectiveness of clopidogrel in the treatment of IBD. [ABSTRACT FROM AUTHOR]

In the past 30 years high-conflict families seeking resolution of child custody disputes have inundated family courts. Custody-related evaluations conducted by mental health counselors provide family courts with a thorough and unbiased assessment about the functionality of a family and offer recommendations about custody issues. The authors present (a) a description of mental health evaluations in child custody disputes; (b) ethical considerations involved in the evaluation process; (c) recommendations for conducting custody-related mental health evaluations; and (d) a format for the written report. [ABSTRACT FROM AUTHOR]

Purpose: To examine the dosimetric impact of margin reduction and quantify residual error after three-dimensional (3D) image registration using daily cone-beam computed tomography (CBCT) for prostate cancer patients. Methods and Materials: One hundred forty CBCTs from 5 prostate cancer patients were examined. Two intensity-modulated radiotherapy plans were generated on CT simulation on the basis of two planning target volume (PTV) margins: 10 mm all around the prostate and seminal vesicles except 6 mm posteriorly (10/6) and 5 mm all around except 3 mm posteriorly (5/3). Daily CBCT using the Varian On-Board Imaging System was acquired. The 10/6 and 5/3 simulation plans were overlaid onto each CBCT, and each CBCT plan was calculated. To examine residual error, PlanCT/CBCT intensity-based 3D image registration was performed for prostate localization using center of mass and maximal border displacement. Results: Prostate coverage was within 2% between the 10/6 and 5/3 plans. Seminal vesicle coverage was reduced with the 5/3 plan compared with the 10/6 plan, with coverage difference within 7%. The 5/3 plan allowed 30–50% sparing of bladder and rectal high-dose regions. For residual error quantification, center of mass data show that 99%, 93%, and 96% of observations fall within 3 mm in the left–right, anterior–posterior, and superior–inferior directions, respectively. Maximal border displacement observations range from 79% to 99%, within 5 mm for all directions. Conclusion: Cone-beam CT dosimetrically validated a 10/6 margin when soft-tissue localization is not used. Intensity-based 3D image registration has the potential to improve target localization and to provide guidelines for margin definition. [Copyright &y& Elsevier]

Juvenile sex offenders (JSOs) often appear unmotivated to change, which thus necessitates a therapeutic approach that matches "resistant" client characteristics. In this article, the authors review common traits of JSOs, introduce motivational counseling as an effective treatment modality, and offer a case illustration. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer patients, especially long-distance patients, often struggle to receive timely and precise medical information and support for their symptom management and survivorship care. ChatGPT-4's responses to queries concerning head and neck (HN) cancer remain questionable. The purpose of this study was to develop and validate a retrained large language model (LLM) for HN cancer patients. In this cross-sectional study, the presented LLM was retrained with a high-quality user-defined knowledge base. The responses from the LLM to patients' questions were validated against human responses, and the model showed a superior performance, with average scores of 4.25 for accuracy, 4.35 for clarity, 4.22 for completeness, and 4.32 for relevance, on a 5-point scale. The confined-trained LLM with a high-quality user-defined knowledge base demonstrates high accuracy, clarity, completeness, and relevance in offering evidence-based information and guidance on the symptom management and survivorship care for head and neck cancer patients. Purpose: This study aimed to develop a retrained large language model (LLM) tailored to the needs of HN cancer patients treated with radiotherapy, with emphasis on symptom management and survivorship care. Methods: A comprehensive external database was curated for training ChatGPT-4, integrating expert-identified consensus guidelines on supportive care for HN patients and correspondences from physicians and nurses within our institution's electronic medical records for 90 HN patients. The performance of our model was evaluated using 20 patient post-treatment inquiries that were then assessed by three Board certified radiation oncologists (RadOncs). The rating of the model was assessed on a scale of 1 (strongly disagree) to 5 (strongly agree) based on accuracy, clarity of response, completeness s, and relevance. Results: The average scores for the 20 tested questions were 4.25 for accuracy, 4.35 for clarity, 4.22 for completeness, and 4.32 for relevance, on a 5-point scale. Overall, 91.67% (220 out of 240) of assessments received scores of 3 or higher, and 83.33% (200 out of 240) received scores of 4 or higher. Conclusion: The custom-trained model demonstrates high accuracy in providing support to HN patients offering evidence-based information and guidance on their symptom management and survivorship care. [ABSTRACT FROM AUTHOR]

Implementing professional support systems that are beneficial to the professional needs of faculty of color (FOC) have been found to promote positive work environments. Using a Critical Race Theory lens, the results of this qualitative study yielded two important themes related to support for counselor educators of color (a) culturally responsive mentoring and (b) purposeful support toward tenure and promotion. Culturally relevant implications that addresses programs and systems have been provided. [ABSTRACT FROM AUTHOR]

Background: Communication and interpersonal skills are essential medical components of oncology patient care. Patients and families rely on physicians for treatment, expertise, guidance, hope, meaning, and compassion throughout a life-threatening illness. A provider's inability to empathize with patients is linked to physician-related fatigue and burnout. Because oncology training programs focus on teaching evidence-based medicine and clinical acumen, little time may be dedicated to professional development and acquisition of interactive skills. Traditional communication courses typically include two components: formal, knowledge-based learning skills, which are gained from didactic lectures, and role-playing, which usually occurs in small groups. We report the implementation of a novel longitudinal communication curriculum for trainees in Oncology. Materials and Methods: At a single-center institution, an innovative communication curriculum titled "REFLECT" (Respect, Empathy, Facilitate Effective Communication, Listen, Elicit Information, Compassion, and Teach Others) was implemented for radiation oncology residents and medical oncology fellows to improve and refine physician/patient interactions. All oncology specialty residents and fellows were eligible to participate in this communication curriculum. The curriculum emphasized a reflective process to guide trainees through challenging scenarios. Results: Since October 2018, this comprehensive course consisted of quarterly (four hour) workshops comprising assigned reading, knowledge assessments, didactic lectures, expert guest lecturers, standardized patient simulations, role-playing, patient/expert panels, coaching, reflective writing, and debriefing/feedback sessions. The curriculum provided longitudinal communication training integrated with the learners' daily physician/patient encounters rather than occasional isolated experiences. Fifteen workshops have been completed. Each focused on navigating challenging situations with patients, loved ones, or colleagues. Conclusions: Future directions of the curriculum will entail improving the communication skills of oncology trainees and gathering communication improvement data to assess the program's success formally. [ABSTRACT FROM AUTHOR]

Simple Summary: Approximately 75% of all head and neck cancer patients are treated with radiotherapy. Radiotherapy to the oral cavity results in acute and late adverse events which can be severe depending on the outcome measured and intensity of the treatment. These adverse events are detrimental to the patient's quality of life and function and are costly to manage. The aim of this retrospective study was to evaluate the association between radiotherapy dose to a defined oral cavity organ-at-risk avoidance structure and prospectively obtained validated provider- and patient-reported outcomes, opioid use, and hospitalization in 196 patients treated with radiotherapy for tumors in the head and neck region. We identified a statistically significant association between radiotherapy dose to the oral cavity organ-at-risk structure, opioid use, and hospitalization. This association provides valuable information for radiotherapy treatment planning to allow for reduction in adverse events. Background: Approximately 75% of all head and neck cancer patients are treated with radiotherapy (RT). RT to the oral cavity results in acute and late adverse events which can be severe and detrimental to a patient's quality of life and function. The purpose of this study was to explore associations between RT dose to a defined oral cavity organ-at-risk (OAR) avoidance structure, provider- and patient-reported outcomes (PROs), opioid use, and hospitalization. Methods: This was a retrospective analysis of prospectively obtained outcomes using multivariable modeling. The study included 196 patients treated with RT involving the oral cavity for a head and neck tumor. A defined oral cavity OAR avoidance structure was used in all patients for RT treatment planning. Validated PROs were collected prospectively. Opioid use and hospitalization were abstracted electronically from medical records. Results: Multivariable modeling revealed the mean dose to the oral cavity OAR was significantly associated with opioid use (p = 0.0082) and hospitalization (p = 0.0356) during and within 30 days of completing RT. Conclusions: The findings of this study may be valuable in RT treatment planning for patients with tumors of the head and neck region to reduce the need for opioid use and hospitalization during treatment. [ABSTRACT FROM AUTHOR]

Purpose We propose a robust treatment planning model that simultaneously considers proton range and patient setup uncertainties and reduces high linear energy transfer (LET) exposure in organs at risk (OARs) to minimize the relative biological effectiveness (RBE) dose in OARs for intensity-modulated proton therapy (IMPT). Our method could potentially reduce the unwanted damage to OARs. Methods We retrospectively generated plans for 10 patients including two prostate, four head and neck, and four lung cancer patients. The 'worst-case robust optimization' model was applied. One additional term as a 'biological surrogate (BS)' of OARs due to the high LET-related biological effects was added in the objective function. The biological surrogate was defined as the sum of the physical dose and extra biological effects caused by the dose-averaged LET. We generated nine uncertainty scenarios that considered proton range and patient setup uncertainty. Corresponding to each uncertainty scenario, LET was obtained by a fast LET calculation method developed in-house and based on Monte Carlo simulations. In each optimization iteration, the model used the worst-case BS among all scenarios and then penalized overly high BS to organs. The model was solved by an efficient algorithm (limited-memory Broyden-Fletcher-Goldfarb-Shanno) in a parallel computing environment. Our new model was benchmarked with the conventional robust planning model without considering BS. Dose-volume histograms (DVHs) of the dose assuming a fixed RBE of 1.1 and BS for tumor and organs under nominal and uncertainty scenarios were compared to assess the plan quality between the two methods. Results For the 10 cases, our model outperformed the conventional robust model in avoidance of high LET in OARs. At the same time, our method could achieve dose distributions and plan robustness of tumors assuming a fixed RBE of 1.1 almost the same as those of the conventional robust model. Conclusions Explicitly considering LET in IMPT robust treatment planning can reduce the high LET to OARs and minimize the possible toxicity of high RBE dose to OARs without sacrificing plan quality. We believe this will allow one to design and deliver safer proton therapy. [ABSTRACT FROM AUTHOR]

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5), requires that symptoms of ADHD must be developmentally inappropriate in order for an ADHD diagnosis to be considered. Because the DSM-5 does not specifically outline procedure for determining developmental inappropriateness of behaviors, practitioners do not have guidance for making this consideration. To explore the relationship between mental age and behavior ratings of ADHD symptoms, the cognitive and behavioral data from 50 children who were evaluated in a school or clinic were compiled for this study. Cognitive ability scores were used to calculate mental age and behavior rating scores were then recalculated using the assessed mental age. Using the recalculated behavior ratings, scores based on mental age decreased significantly on the Attention Problems, Hyperactivity, and Atypicality scales of the BASC-2. Additionally, as the discrepancy between mental and chronological age increased, larger differences in scores were found. [ABSTRACT FROM AUTHOR]

Our objective was to report the prospective results of mucosal sparing radiation therapy in human papillomavirus–related oropharyngeal squamous cell carcinoma. From March 2016 through May 2019, patients were enrolled in this institutional review board–approved prospective cohort study at a multisite institution. Inclusion criteria included p16+ American Joint Committee on Cancer seventh edition pathologic T1 or T2, N1 to N3, and M0 oropharyngeal cancers. Proton therapy (PT) was delivered to at-risk nodal regions, excluding the primary mucosal site. Secondary to insurance denial for PT, intensity modulated radiation therapy (IMRT) was allowed. European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Head and Neck Module and Patient-Reported Outcomes Measurement Information System surveys (quality of life [QOL]) and modified barium swallowing impairment profiles (MBSImP) were obtained at baseline before radiation therapy, then 3 and 12 months after radiation therapy. Kaplan-Meier estimates were calculated for time-to-event clinical outcomes, and repeated measures mixed models were used to explore changes in QOL over time. A comparison of QOL and swallowing outcomes with standard-of-care treatment was analyzed. There were 61 evaluable patients with a median follow-up of 38 months (range, 10-64); 44 (72%) were treated with PT and 17 (28%) were treated with IMRT. The 2-year local control, locoregional control, distant metastasis–free survival, and overall survival were 98%, 97%, 98%, and 100%, respectively. There were 6 grade ≥3 events related to treatment. Two IMRT patients required percutaneous endoscopic gastrostomy tube placement during treatment secondary to significant nausea due to dysgeusia. Patients noted significant QOL improvement over time in the pain, swallowing, speech, social eating, social contact, mouth opening, and use of pain medication domains (all P <.02). The MBSImP overall severity score as well as oral and pharyngeal impairment scores showed stability with no significant change over time. For the 44 patients treated with PT, the mean D95 to the primary target was 10.7 Gy (standard deviation = 12.5 Gy). Mucosal sparing radiation is well tolerated in select resected human papillomavirus–related oropharyngeal squamous cell carcinoma with a low risk of recurrence at the mucosal primary site, a low rate of percutaneous endoscopic gastrostomy tube placement, and few radiation-related grade ≥3 adverse events. [ABSTRACT FROM AUTHOR]

Background: In proton therapy dose calculation, Monte Carlo (MC) simulations are superior in accuracy but more time consuming, compared to analytical calculations. Graphic processing units (GPUs) are effective in accelerating MC simulations but may suffer thread divergence and racing condition in GPU threads that degrades the computing performance due to the generation of secondary particles during nuclear reactions. Purpose: A novel concept of virtual particle (VP) MC (VPMC) is proposed to avoid simulating secondary particles in GPU‐accelerated proton MC dose calculation and take full advantage of the computing power of GPU. Methods: Neutrons and gamma rays were ignored as escaping from the human body; doses of electrons, heavy ions, and nuclear fragments were locally deposited; the tracks of deuterons were converted into tracks of protons. These particles, together with primary and secondary protons, are considered to be the realistic particles. Histories of primary and secondary protons were replaced by histories of multiple VPs. Each VP corresponded to one proton (either primary or secondary). A continuous‐slowing‐down‐approximation model, an ionization model, and a large angle scattering event model corresponding to nuclear interactions were developed for VPs by generating probability distribution functions (PDFs) based on simulation results of realistic particles using MCsquare. For efficient calculations, these PDFs were stored in the Compute Unified Device Architecture textures. VPMC was benchmarked with TOPAS and MCsquare in phantoms and with MCsquare in 13 representative patient geometries. Comparisons between the VPMC calculated dose and dose measured in water during patient‐specific quality assurance (PSQA) of the selected 13 patients were also carried out. Gamma analysis was used to compare the doses derived from different methods and calculation efficiencies were also compared. Results: Integrated depth dose and lateral dose profiles in both homogeneous and inhomogeneous phantoms all matched well among VPMC, TOPAS, and MCsquare calculations. The 3D–3D gamma passing rates with a criterion of 2%/2 mm and a threshold of 10% was 98.49% between MCsquare and TOPAS and 98.31% between VPMC and TOPAS in homogeneous phantoms, and 99.18% between MCsquare and TOPAS and 98.49% between VPMC and TOPAS in inhomogeneous phantoms, respectively. In patient geometries, the 3D–3D gamma passing rates with 2%/2 mm/10% between dose distributions from VPMC and MCsquare were 98.56 ± 1.09% in patient geometries. The 2D–3D gamma analysis with 3%/2 mm/10% between the VPMC calculated dose distributions and the 2D measured planar dose distributions during PSQA was 98.91 ± 0.88%. VPMC calculation was highly efficient and took 2.84 ± 2.44 s to finish for the selected 13 patients running on four NVIDIA Ampere GPUs in patient geometries. Conclusion: VPMC was found to achieve high accuracy and efficiency in proton therapy dose calculation. [ABSTRACT FROM AUTHOR]

Purpose: Patients with human papillomavirus oropharyngeal cancer are highly curable but risk significant long-term toxic effects with standard therapy. This study investigated a de-escalation strategy of decreased adjuvant radiation therapy and chemotherapy after transoral robotic surgery, and reports on long-term functional and quality of life (QOL) outcomes.Methods and Materials: Eligible patients had a p16-positive oropharyngeal cancer and ≤10 pack-year smoking history and underwent surgery followed by treatment with either 30 Gy delivered in 1.5-Gy fractions twice per day over 2 weeks with weekly docetaxel (15 mg/m2) if they had intermediate pathologic risk factors or 36 Gy in 1.8-Gy fractions twice per day over 2 weeks with the same chemotherapy if they had extranodal extension. Toxic effects, swallow function, and QOL were measured longitudinally.Results: Seventy-nine patients (89.9% male) were treated and eligible for toxic effect and functional evaluation. Dry mouth was the most common grade 1 toxic effect at 1 year (55.6%), 2 years (53.3%), and 3 years (49.2%). The cumulative rates of grade 2 toxic effects at 1, 2, and 3 years were 1.4%, 6.7%, and 6.8%, respectively. There were only 2 grade 3 toxic effects at ≥1 year, including a grade 3 fatigue at 2.5 years, and a grade 3 superficial soft tissue fibrosis at 4 years. There were no grade 4 to 5 toxic effects. No patients were percutaneous endoscopic gastrostomy-dependent. Swallow function improved by 12 months posttreatment. QOL improved over time by all measurement tools and most patients returned to baseline level of function and QOL.Conclusions: De-escalated adjuvant therapy for select patients with human papillomavirus oropharyngeal cancer resulted in low rates of long-term toxic effects, excellent swallow outcomes, and preservation of global and xerostomia-related QOL. [ABSTRACT FROM AUTHOR]

Understanding the surfacing behavior of marine wildlife is an important component for improving abundance estimates derived from visual surveys. We monitored the behavior of 18 leatherback sea turtles (Dermochelys coriacea) in coastal habitats off Massachusetts, USA, using a high-resolution camera and satellite tag package (HiCAS - High Resolution Camera and Satellite) that we assembled from commercially available components which work independently. We used nine data streams derived from the multiple sensors and a video camera to explore four different depth thresholds defining surface zones. We compared classification of video images by a human to classification of those images by a machine learning algorithm. We calculated four metrics to describe surface behavior for each of the nine data streams. The mean percent time at the surface was the only behavior metric that changed systematically as data streams were used to assess different visible depth thresholds, increasing as the depth threshold increased. Other behavior metrics (mean surface duration, mean dive duration and number of surfacing events per hour) were less similar across data streams, making them unreliable for estimating surface availability. This study highlights the need for sustained data collection to better inform the availability bias estimates used to calculate abundance from visual observations. [Display omitted] • A novel animal-born tag was developed to better understand surface behavior. • High resolution video, multiple sensors, and different parameterizations were used. • Machine learning was evaluated for automated data retrieval from video. • Percent time at surface was the most reliable metric describing surface behavior. • Observed variability suggests caution needed when estimating surface behavior. [ABSTRACT FROM AUTHOR]

Successful management strategies are important for conservation and allow accurate surveying and monitoring of populations for presence, abundance, and trend. This becomes challenging for cryptic, low‐density species, and for animals that have complicated life histories where not every stage of the life cycle can be surveyed effectively. We used information from animal‐borne data loggers to characterize the dive‐surfacing behavior of cryptic loggerhead turtles (Caretta caretta) in the northwest Atlantic from 2009–2018. Our data covered a large geographic area off the east coast of North America, and allowed us to present estimates for and variation in 3 metrics that can be used to assess availability bias affecting visual surveys: average dive duration, average surface duration, and the proportion of time at the surface. We used a stochastic partial differential equation approach to construct spatiotemporal regression models for the availability bias metrics. Model predictions showed pronounced individual, spatial, and spatiotemporal (seasonal) variation among the 245 turtles. Overall, we estimated an average dive duration of 14.5 ± 1.36 minutes (SE), an average surface duration of 15.1 ± 2.77 minutes, and an average proportion of time at the surface of 0.50 (95% CI = 0.41–0.59). We made predictions of the 3 availability bias metrics on a 20‐km × 20‐km grid and further used predictions to explore seasonal variations. Our results contribute new insights into loggerhead turtle behavior and provide information that enables survey counts to be translated into more accurate abundance estimates. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the accuracy of the RayStation Monte Carlo dose engine (RayStation MC) in modeling small‐field block apertures in proton pencil beam scanning. Furthermore, we evaluate the suitability of MCsquare as a second check for RayStation MC. Methods: We have enhanced MCsquare to model block apertures. To test the accuracy of both RayStation MC and the newly enhanced MCsquare, we compare the dose predictions of each to in‐water dose measurements obtained using diode detectors and radiochromic film. Nine brass apertures with openings of 1, 2, 3, 4, and 5 cm and either 2 cm or 4 cm thickness were used in the irradiation of a water phantom. Two measurement setups were used, one with a range shifter and 119.7 MeV proton beam energy and the other with no range shifter and 147 MeV proton beam energy. To further test the validity of RayStation MC and MCsquare in modeling block apertures and to evaluate MCsquare as a second check tool, 10 small‐field (average target volume 8.3 cm3) patient treatment plans were calculated by each dose engine followed by a statistical comparison. Results: Comparing to the absolute dose measurements in water, RayStation MC differed by 1.2% ± 1.0% while MCsquare differed by −1.8% ± 3.7% in the plateau region of a pristine Bragg peak. Compared to the in‐water film measurements, RayStation MC and MCsquare both performed well with an average 2D‐3D gamma passing rate of 99.4% and 99.7% (3%/3 mm), respectively. A t‐test comparing the agreement with the film measurements between RayStation MC and MCsquare suggested that the relative spatial dose distributions calculated by MCsquare and RayStation MC were statistically indistinguishable. Directly comparing the dose calculations between MCsquare and RayStation MC over 10 patients resulted in an average 3D‐3D gamma passing rates of 98.5% (3%/3 mm) and 94.1% (2%/2 mm), respectively. Conclusion: The validity of RayStation MC algorithm for use with patient‐specific apertures has been expanded to include small apertures. MCsquare has been enhanced to model apertures and was found to be an adequate second check of RayStation MC in this scenario. [ABSTRACT FROM AUTHOR]

Purpose: Due to the employment of quadratic programming using soft constraints to implement dose volume constraints and the "trial‐and‐error" procedure needed to achieve a clinically acceptable plan, conventional dose volume constraints (upper limit) are not adequately effective in controlling small and isolated hot spots in the dose/linear energy transfer (LET) distribution. Such hot spots can lead to adverse events. In order to mitigate the risk of brain necrosis, one of the most clinically significant adverse events in patients receiving intensity‐modulated proton therapy (IMPT) for base of skull (BOS) cancer, we propose per‐voxel constraints to minimize hot spots in LET‐guided robust optimization. Methods and materials: Ten BOS cancer patients treated with IMPT were carefully selected by meeting one of the following conditions: (1) diagnosis of brain necrosis during follow‐up; and (2) considered high risk for brain necrosis by not meeting dose constraints to the brain. An optimizing structure (BrainOPT) and an evaluating structure (BrainROI) that both contained the aforementioned hot dose regions in the brain were generated for optimization and evaluation, respectively. Two plans were generated for every patient: one using conventional dose‐only robust optimization, the other using LET‐guided robust optimization. The impact of LET was integrated into the optimization via a term of extra biological dose (xBD). A novel optimization tool of per‐voxel constraints to control small and isolated hot spots in either the dose, LET, or combined (dose/LET) distribution was developed and used to minimize dose/LET hot spots of the selected structures. Indices from dose‐volume histogram (DVH) and xBD dose‐volume histogram (xBDVH) were used in the plan evaluation. A newly developed tool of the dose‐LET‐volume histogram (DLVH) was also adopted to illustrate the underlying mechanism. Wilcoxon signed‐rank test was used for statistical comparison of the DVH and xBDVH indices between the conventional dose‐only and the LET‐guided robustly optimized plans. Results: Per‐voxel constraints effectively and efficiently minimized dose hot spots in both dose‐only and LET‐guided robust optimization and LET hot spots in LET‐guided robust optimization. Compared to the conventional dose‐only robust optimization, the LET‐guided robust optimization could generate plans with statistically lower xBD hot spots in BrainROI (VxBD,50 Gy[RBE], p = 0.009; VxBD,60 Gy[RBE], p = 0.025; xBD1cc, p = 0.017; xBD2cc, p = 0.022) with comparable dose coverage, dose hot spots in the target, and dose hot spots in BrainROI. DLVH analysis indicated that LET‐guided robust optimization could either reduce LET at the same dose level or redistribute high LET from high dose regions to low dose regions. Conclusion: Per‐voxel constraint is a powerful tool to minimize dose/LET hot spots in IMPT. The LET‐guided robustly optimized plans outperformed the conventional dose‐only robustly optimized plans in terms of xBD hot spots control. [ABSTRACT FROM AUTHOR]

Purpose: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273.Methods and Materials: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods.Results: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03).Conclusions: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273. [ABSTRACT FROM AUTHOR]

• PBT is associated with decreased radiation dose to the contralateral neck. • PBT contralateral neck failure rate was comparable to photon irradiation. • Subgroup analysis demonstrates comparable control rates in de novo and recurrent subgroups. Unilateral radiation therapy is appropriate for select patients with oropharyngeal squamous cell carcinoma (OPSCC). The use of proton beam therapy (PBT) in the unilateral setting decreases the dose to the contralateral neck and organs at risk. This study aims to evaluate contralateral recurrences in patients who received ipsilateral PBT. We evaluated the Proton Collaborative Group database for patients treated with PBT for head and neck squamous cell carcinoma between the years 2015–2020 at 12 institutions. Dosimetric analysis was performed in five cases. Our analysis included 41 patients that received ipsilateral PBT with a mean follow-up of 14.7 months. 37% patients (n = 15) were treated for recurrent disease, and 63% (n = 26) were treated for de novo disease. Oropharyngeal sites included tonsillar fossa (n = 30) and base of tongue (n = 11). The median dose and BED delivered were 69.96 CGE and 84 Gy, respectively. Eight (20%) patients experienced at least one grade 3 dysphagia (n = 4) or esophagitis (n = 4) toxicity. No grade ≥ 4 toxicities were reported. There was one (2.4%) failure in the contralateral neck. The 1-year locoregional control was 88.9% and the freedom from distant metastasis was 95.5% (n = 2). The dosimetric analysis demonstrated similar ipsilateral level II cervical nodal region doses, whereas contralateral doses were higher with photon plans, mean: 15.5 Gy and 0.7 CGE, D5%: 25.1 Gy and 6.6 CGE. Our series is the first to report outcomes for patients with OPSCC receiving unilateral PBT. The contralateral neck failure rate was excellent and comparable to failure rates with photon irradiation. [ABSTRACT FROM AUTHOR]

• Compared to VMAT, IMPT is associated with less PEG placement for the treatment of OPC. • IMPT is associated with decreased acute hospitalizations compared to VMAT. • Provider-reported acute toxicities show less mucositis, dysphagia, and pain with IMPT. • Patient-reported outcomes improved with IMPT included cough and dysgeusia. • Benefits were predominantly seen in those treated definitively or with adjuvant CRT. IMPT improves normal tissue sparing compared to VMAT in treating oropharyngeal cancer (OPC). Our aim was to assess if this translates into clinical benefits. OPC patients treated with definitive or adjuvant IMPT or VMAT from 2013 to 2018 were included. All underwent prospective assessment using patient-reported-outcomes (PROs) (EORTC-QLQ-H&N35) and provider-assessed toxicities (CTCAEv4.03). End-of-treatment and pretreatment scores were compared. PEG-tube use, hospitalization, and narcotic use were retrospectively collected. Statistical analysis used the Wilcoxon Rank-Sum Test with propensity matching for PROs/provider-assessed toxicities, and t -tests for other clinical outcomes. 46 IMPT and 259 VMAT patients were included; median follow-up was 12 months (IMPT) and 30 months (VMAT). Baseline characteristics were balanced except for age (p = 0.04, IMPT were older) and smoking (p < 0.01, 10.9% IMPT >20PYs, 29.3% VMAT). IMPT was associated with lower PEG placement (OR = 0.27; 95% CI: 0.12–0.59; p = 0.001) and less hospitalization ≤60 days post-RT (OR = 0.21; 95% CI:0.07–0.6, p < 0.001), with subgroup analysis revealing strongest benefits in patients treated definitively or with concomitant chemoradiotherapy (CRT). IMPT was associated with a relative risk reduction of 22.3% for end-of-treatment narcotic use. Patients reported reduced cough and dysgeusia with IMPT (p < 0.05); patients treated definitively or with CRT also reported feeling less ill, reduced feeding tube use, and better swallow. Provider-assessed toxicities demonstrated less pain and mucositis with IMPT, but more mucosal infection. IMPT is associated with improved PROs, reduced PEG-tube placement, hospitalization, and narcotic requirements. Mucositis, dysphagia, and pain were decreased with IMPT. Benefits were predominantly seen in patients treated definitively or with CRT. [ABSTRACT FROM AUTHOR]

Purpose: The dose‐averaged linear energy transfer (LETd) for intensity‐modulated proton therapy (IMPT) calculated by one‐dimensional (1D) analytical models deviates from more accurate but time‐consuming Monte Carlo (MC) simulations. We developed a fast hybrid three‐dimensional (3D) analytical LETd calculation that is more accurate than 1D analytical model. Methods: We used the Geant4 MC code to generate 3D LETd distributions of monoenergetic proton beams in water for all energies and used a customized error function to fit the LETd lateral profiles at various depths to the MC simulation. The 3D LETd calculation kernel was a lookup table of these fitted coefficients, and LETd was determined directly from spot energies and voxel coordinates during analytical dose calculations. We validated our new method by comparing the calculated LETd distributions to MC results using 3D Gamma index analysis with 3%/2 mm criteria in 12 patient geometries. The significance of the improvement in Gamma index analysis passing rates over the 1D analytical model was determined using the Wilcoxon rank‐sum test. Results: The passing rate of 3D Gamma analysis comparing LETd distributions from the hybrid 3D method and the 1D method to MC simulations was significantly improved from 94.0% ± 2.5% to 98.0% ± 1.0% (P = 0.0003). The typical time to calculate dose and LETd simultaneously using an Intel Xeon E5‐2680 2.50 GHz workstation was approximately 2.5 min. Conclusions: Our new method significantly improved the LETd calculation accuracy compared to the 1D method while maintaining significantly shorter calculation time even comparing with the GPU‐based fast MC code. [ABSTRACT FROM AUTHOR]

Malignant melanoma of the lacrimal sac is an exceptionally rare tumor with a poor prognosis. We report two cases of malignant melanoma of the lacrimal sac: a 73 year-old female treated with primary surgical resection and a 75 year-old male treated with surgical resection, adjuvant proton beam radiotherapy, and adjuvant immunotherapy. We discuss the role of post-operative proton beam therapy and recent advancements in immunotherapy. These cases highlight the importance of early diagnosis and multi-modality treatment in this aggressive malignancy. [ABSTRACT FROM AUTHOR]

In order to better spare organs at risk in the head and neck, the application of proton beam therapy is of great interest. In this study we report the clinical utilization of a novel and robust scanning proton beam therapy treatment planning method called Individual Field Simultaneous Optimization (IFSO) that incorporates the advantages of field patching technique integrated with simultaneous optimization of multiple fields. A treatment planning intercomparison between a conventional Intensity Modulated Proton Therapy Treatment Plan with single target volume vs a split target volume utilizing IFSO method demonstrates superiority of IFSO with regards to sparing of organs at risk and plan robustness. [ABSTRACT FROM AUTHOR]

• Regional metastases are most common in ipsilateral neck level II-IV. • The distribution of lymph node metastases is similar in HPV(+) and HPV(-) • Regional recurrence is uncommon in HPV(+) disease. • Frequent levels involved in recurrent disease are ipsi- and contralateral II and ipsilateral V. To investigate and describe the patterns of regional metastases and recurrences after surgical treatment of oropharyngeal squamous cell cancer (OPSCC). Retrospective study of patients diagnosed with OPSCC from 2006 to 2021 at a tertiary referral center. Only patients treated with surgery including a neck dissection were included. Patients with unknown human papillomavirus (HPV) status, prior head and neck cancer, distant metastases, or synchronous head and neck cancer were excluded. A total of 928 patients were included. 89% were males, the average age was 58.6 years (range: 25.2–87.5), 874 (94%) were HPV(+), and 513 (55.3%) had a tonsil cancer. Among cN + patients, the most commonly involved levels at presentation were level II (85.2%), level III (33.3%), and level IV (9.4%). In cN0 patients, metastases were only observed in level II (16.2%) and level III (9.2%). Nodal recurrence occurred in 48 (5.2%) patients after a median time of 1.0 years (interquartile range: 0.6–2.0). Nodal recurrence incidence was similar in HPV(+) and HPV(-) patients (5.0% vs. 7.4%, p = 0.44). The most common levels for regional recurrence were ipsilateral level II (45.8%), contralateral level II (43.8%), and ipsilateral level V (25.0%). Multivariable analysis revealed that pN was a significant predictor for regional recurrence (p = 0.02). There is no difference in the distribution of regional metastases and recurrences in HPV(+) and HPV(-) OPSCC patients. Our findings align with the established understanding that regional metastases predominantly manifest in the ipsilateral level II-IV at presentation. Moreover, the data support the clinical recommendation to restrict elective neck dissection in cN0 patients to ipsilateral levels IIa and III, excluding level IIb. Regional recurrence is significantly associated with pN status. [ABSTRACT FROM AUTHOR]

Objectives: The natural history of squamous cell carcinoma (SCC) of the oral cavity (OC) in young adults is unknown. We sought to provide an updated report on treatment outcomes of patients with OC SCC who were 40 years or younger.Materials and Methods: We performed a retrospective analysis of 124 consecutive patients with primary OC SCC treated at Mayo Clinic (1980-2014). Patient and tumor characteristics and treatment approach were abstracted from patient charts.Results: Median patient age was 35 years (range, 19-40 years). The most common primary site was oral tongue (107 patients; 86.3%). Most patients (101; 81.5%) underwent wide local excision. Surgery alone was curative in 77 patients (62.1%); 47 (37.9%) received radiotherapy, and 26 (21%) received chemotherapy. Five-year overall survival (OS) was 78.1%; 10-year OS was 76.9%. Five-year disease-free survival (DFS) was 66.6%; 5-year local control was 87.6%; and 5-year locoregional control was 78.5%. On multivariable analysis, factors associated with worse OS and DFS were higher pathologic T stage (P = .008), lymph node positivity (P < .001), and disease recurrence (P < .001).Conclusion: Young adults with primary OC SCC may be treated with a similar treatment approach as older adults. [ABSTRACT FROM AUTHOR]

Objective: To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/- chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC).Methods: From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen.Results: All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22-6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240-67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540-12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%.Conclusions: AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension. [ABSTRACT FROM AUTHOR]

Purpose: To characterize quality of life (QOL) using real-time, electronic patient-reported outcomes (ePROs) and to evaluate adverse events (AEs) and supportive care during head-and-neck radiotherapy (RT) and concurrent chemoradiotherapy (CCRT).Methods: Sixty-five patients undergoing head-and-neck RT completed electronic, real-time, 12-item linear analog self-assessments (LASA) at baseline, before biweekly appointments, and at the last week of RT. Changes in QOL domains between time points were calculated. Clinical data were collected from the institutional medical record. AEs were recorded at the same time points as the LASA and graded.Results: During head-and-neck RT, most patients had clinically meaningful decreases in all QOL domains except level of support, financial concerns, and legal concerns. QOL domains with the most prevalent, clinically meaningful decreases were fatigue (75.4% of patients; 95% CI, 62.9-84.9%), social activity (70.8%; 95% CI, 58.0-81.1%), and overall QOL (70.8%; 95% CI, 58.0-81.1%). All patients had grade 2 AEs; 35.4% had grade 3 (50.0%, CCRT; 12.0%, RT; P = .002). Weight loss averaged 5.5 kg (6.9 kg, CCRT; 2.8 kg, RT; P < .001). Intravenous hydration was needed in 52.3% (77.5%, CCRT; 12.0%, RT; P < .001); feeding tube placement 40.0% (57.5%, CCRT; 12.0%, RT; P = .001); emergency department visits without hospitalization, 10.8%; and emergent hospitalization, 27.7% (37.5%, CCRT; 12.0%, RT; P = .04).Conclusions: Head-and-neck RT, particularly CCRT, negatively impacts patients' overall QOL, social activity, and fatigue, with frequent grade 3 AEs, weight loss, intravenous hydration, feeding tube placement, ED visits, and hospitalization. Real-time ePROs allow providers to monitor QOL at multiple time points during RT, potentially allowing early intervention to improve QOL and mitigate AEs. [ABSTRACT FROM AUTHOR]

Purpose: To report the outcomes of patients with favorable risk oropharyngeal cancer that underwent adjuvant radiation therapy with omission of the primary site from the clinical target volume (CTV). Material/Methods: A retrospective study of 40 patients treated with transoral surgery (TOS) followed by neck only radiation using intensity modulated radiation therapy (IMRT) with exclusion of the primary site. For all patients, a CTV of the primary surgical bed was contoured to obtain the estimated incidental dose to the primary site. Results: Median follow-up was 51 months (range, 13-155 months). The median radiation therapy (RT) dose to the neck was 6000 cGy (range, 5400-6400 cGy). The mean incidental dose to the primary tonsillar site was 4320 cGy (SD ± 480 cGy) and to the primary base of tongue site was 4060 cGy (SD ± 420 cGy). There were no local failures and only 1 regional failure, resulting in 97.5% locoregional control rate at 4 years. Two patients developed distant metastases, without evidence of locoregional recurrence, for a 4-year overall survival rate of 97%. Conclusions: Our analysis suggests that mucosal sparing RT after TOS in favorable risk oropharyngeal cancer patients may provide comparable oncologic and improved functional outcomes compared to conventional treatment in selected patients. [ABSTRACT FROM AUTHOR]

Objective: To report a single institutional series of high-grade neuroendocrine carcinoma of the larynx (NCL), a very rare yet aggressive tumor. To review the management of NCL, including discussion of clinical behavior, treatment outcome, and prognosis. Method: A retrospective chart review of high-grade laryngeal neuroendocrine carcinomas at a single institution, including small- and large-cell neuroendocrine carcinomas. A total of 8 patients with high-grade NCL treated at our institution from 1992 to 2014 were identified. Results: The median age at diagnosis was 65.5 years (range, 43-80). Five patients were male. Two patients had a known smoking history. Primary tumor location was supraglottic in 7 patients and glottic in 1 patient. Primary treatment consisted of surgery alone (3 patients), radiotherapy alone (1 patient), combination of chemotherapy and radiotherapy (1 patient), and surgery followed by postoperative chemoradiotherapy (3 patients). Locoregional recurrence followed by distant metastasis occurred in 6 patients. Median overall survival was 44.0 months (95% CI, 3-62.0). Conclusion: High-grade NCL is a rare diagnosis. Compared to well- and moderately differentiated NCL, high-grade NCL has a far more aggressive clinical course and associated with a worse prognosis. To our knowledge, this is the largest series of patients with high-grade NCL treated at a single institution. Prompt diagnosis and multimodality therapy including elective neck dissection may improve survival. [ABSTRACT FROM AUTHOR]

Background: We reviewed outcomes of patients with loco-regionally recurrent (LRR) or new primary (NP) squamous cell carcinoma of the head and neck (SCCHN) treated at our institution with reirradiation (RRT).Methods: Patients received definitive RRT (DRRT) or post-operative RRT following salvage surgery (PRRT) from 2003 to 2011. Measured survival outcomes included loco-regional relapse free survival (LRFS) and overall survival (OS).Results: Among 81 patients (PRRT, 42; DRRT, 39), median PRRT and DRRT doses were 60 Gy (12-70 Gy) and 69.6 Gy (48-76.8 Gy). The majority of patients received IMRT-based RRT (n = 77, 95 %). With median follow-up of 78.1 months (95 % CI, 56-96.8 months), 2-year OS was 53 % with PRRT and 48 % with DRRT (p = 0.12); 23 % of patients were alive at last follow-up. LRFS at 2 years was 60 %, and did not differ significantly between PRRT and DRRT groups. A trend toward inferior LRFS was noted among patients receiving chemotherapy with RRT versus RRT alone (p = 0.06). Late serious toxicities were uncommon, including osteoradionecrosis (2 patients) and carotid artery bleeding (1 patient, non-fatal).Conclusions: OS of PRRT- and DRRT-treated patients in this series appears superior to the published literature. We used IMRT for the majority of patients, in contrast to several series and trials previously reported, which may account in part for this difference. Future studies should seek to improve outcomes among patients with LRR/NP SCCHN via alternative therapeutic modalities such as proton radiotherapy and by incorporating novel systemic agents. [ABSTRACT FROM AUTHOR]

Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Pretreatment evaluation is performed to determine the number, location, and size of the brain metastases and magnetic resonance imaging (MRI) is the recommended imaging technique, particularly in patients being considered for surgery or stereotactic radiosurgery. A contiguous thin-cut volumetric MRI with gadolinium with newer gadolinium-based agents can improve detection of small brain metastases. A systemic workup and medical evaluation are important, given that subsequent treatment for the brain metastases will also depend on the extent of the extracranial disease and on the age and performance status of the patient. Patients with hydrocephalus or impending brain herniation should be started on high doses of corticosteroids and evaluated for possible neurosurgical intervention. Patients with moderate symptoms should receive approximately 4-8 mg/d of dexamethasone in divided doses. The routine use of corticosteroids in patients without neurologic symptoms is not necessary. There is no proven benefit of anticonvulsants in patient without seizures. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Purpose: During image-guided radiosurgery, it is common to account only for translational shifts while leaving rotational deviations uncorrected. The aim of this study is to investigate the rotational setup deviations and estimate the dosimetric impact in spinal radiosurgery. Materials and methods: Stereoscopic image registrations of 711 spine radiosurgery procedures (546 patients) were retrospectively reviewed and classified to cervical (C), thoracic (T), and lumbar (L) spines. The probability of rotational deviations were estimated in three orthogonal axis. In order to investigate the dosimetric impact, the original simulation CT images were rotated in the range of ±5 deg in each axis. Then, the dosimetric changes were recorded; including the coverage (V90) and minimum dose (Dmin) to the target, and the dose of 10% volume (D10) and maximum dose (Dmax) to the spinal cord. Results: Target rotations of >5 deg and >3 deg occurred respectively in 1% and 8% of cases. The mean rotations were small (|µ|<0.6 deg) with no axis and site dependent trends. The standard deviations (σ) of different sites and axes ranged from 1.4 to 2.0 deg (mean σ=1.7 deg). The overall dosimetric changes of the target coverage(V90) and cord D10 were small. Five degree rotation resulted in a target V90 decrease of 1±1%, 2±2% and 3±1%, respectively in the lateral, vertical, and longitudinal axes. The corresponding cord D10 increased by 3±6%, 2±2%, and 6±5%. The changes in cord Dmax ranged from 92% to 138% of the original reference spinal cord. Corresponding changes in target Dmin were 59~106%. Conclusion: Large target rotations occurred in a small percentage of patients. The overall dosimetric impact on target coverage and cord D10 was small. However larger effects were observed on the target Dmin and cord Dmax. Special care must be taken for targets of elongated shapes involving multiple vertebrae. [ABSTRACT FROM AUTHOR]

Research indicates that highly educated individuals endure hardships in finding suitable romantic partners. Romantic hardships affect social and emotional adjustment levels, leading to low self-efficacy in relationship decision making. To address the need for research pertaining to this topic, the authors explored the experiences of eight individuals purposively chosen. Conducting interviews based in qualitative methods, the authors discuss thematic patterns emerging from the study. Constraints such as lack of time and social outlets were barriers to meeting highly desirable mates. [ABSTRACT FROM AUTHOR]

Purpose/objectives: Extranodal extension (ENE) and more than 4 pathologically involved lymph nodes (pN2) are critical prognostic factors in HPV-associated oropharyngeal cancer (HPV(+) OPSCC). We analyze a patient cohort with HPV(+) OPSCC to determine the sensitivity and specificity of CT and PET/CT in identifying involvement of more than 4 lymph nodes (rN2) compared to pN2 and radiographic ENE (rENE) compared to pathologic ENE (pENE).Materials/methods: The dataset consisted of 261 patients enrolled in two prospective clinical trials. All imaging studies were independently reviewed by a blinded neuroradiologist, classifying the presence or absence of rENE and rN2. Secondary analyses included correlations of imaging accuracy and pathologic size of the primary tumor.Results: CT demonstrated sensitivity of 59%, specificity of 92%, positive predictive value (PPV) of 53%, negative predictive value (NPV) of 94%, and accuracy of 88% for pN2. PET/CT showed similar results. Patients with up to 4 involved lymph nodes (rN0-1) had a 93-94% chance of remaining pN0-1. CT and PET/CT identified an equal number of involved nodes in 81% of patients. CT demonstrated sensitivity of 54%, specificity of 71%, PPV of 72%, NPV of 53%, and accuracy of 62% for pENE. PET/CT showed similar outcomes. Notably, when multiple radiographic criteria were used to identify rENE, PPV increased for both CT (84%) and PET/CT (79%).Conclusion: Patients with rN0-1 had a 93-94% chance of remaining pN0-1, suggesting rN0-1 could effectively stratify patients for clinical trials and treatment de-escalation. While CT and PET/CT were highly correlated, both showed low sensitivity for identifying pENE. [ABSTRACT FROM AUTHOR]