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The NCCN Guidelines for Head and Neck Cancers address tumors arising in the oral cavity (including mucosal lip), pharynx, larynx, and paranasal sinuses. Occult primary cancer, salivary gland cancer, and mucosal melanoma (MM) are also addressed. The specific site of disease, stage, and pathologic findings guide treatment (eg, the appropriate surgical procedure, radiation targets, dose and fractionation of radiation, indications for systemic therapy). The NCCN Head and Neck Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel’s most recent recommendations regarding management of HPV-positive oropharynx cancer and ongoing research in this area.

ImportanceSpine metastasis can be treated with high-dose radiation therapy with advanced delivery technology for long-term tumor and pain control.ObjectiveTo assess whether patient-reported pain relief was improved with stereotactic radiosurgery (SRS) as compared with conventional external beam radiotherapy (cEBRT) for patients with 1 to 3 sites of vertebral metastases.Design, Setting, and ParticipantsIn this randomized clinical trial, patients with 1 to 3 vertebral metastases were randomized 2:1 to the SRS or cEBRT groups. This NRG 0631 phase 3 study was performed as multi-institutional enrollment within NRG Oncology. Eligibility criteria included the following: (1) solitary vertebral metastasis, (2) 2 contiguous vertebral levels involved, or (3) maximum of 3 separate sites. Each site may involve up to 2 contiguous vertebral bodies. A total of 353 patients enrolled in the trial, and 339 patients were analyzed. This analysis includes data extracted on March 9, 2020.InterventionsPatients randomized to the SRS group were treated with a single dose of 16 or 18 Gy (to convert to rad, multiply by 100) given to the involved vertebral level(s) only, not including any additional spine levels. Patients assigned to cEBRT were treated with 8 Gy given to the involved vertebra plus 1 additional vertebra above and below.Main Outcomes and MeasuresThe primary end point was patient-reported pain response defined as at least a 3-point improvement on the Numerical Rating Pain Scale (NRPS) without worsening in pain at the secondary site(s) or the use of pain medication. Secondary end points included treatment-related toxic effects, quality of life, and long-term effects on vertebral bone and spinal cord.ResultsA total of 339 patients (mean [SD] age of SRS group vs cEBRT group, respectively, 61.9 [13.1] years vs 63.7 [11.9] years; 114 [54.5%] male in SRS group vs 70 [53.8%] male in cEBRT group) were analyzed. The baseline mean (SD) pain score at the index vertebra was 6.06 (2.61) in the SRS group and 5.88 (2.41) in the cEBRT group. The primary end point of pain response at 3 months favored cEBRT (41.3% for SRS vs 60.5% for cEBRT; difference, −19 percentage points; 95% CI, −32.9 to −5.5; 1-sided P = .99; 2-sided P = .01). Zubrod score (a measure of performance status ranging from 0 to 4, with 0 being fully functional and asymptomatic, and 4 being bedridden) was the significant factor influencing pain response. There were no differences in the proportion of acute or late adverse effects. Vertebral compression fracture at 24 months was 19.5% with SRS and 21.6% with cEBRT (P = .59). There were no spinal cord complications reported at 24 months.Conclusions and RelevanceIn this randomized clinical trial, superiority of SRS for the primary end point of patient-reported pain response at 3 months was not found, and there were no spinal cord complications at 2 years after SRS. This finding may inform further investigation of using spine radiosurgery in the setting of oligometastases, where durability of cancer control is essential.Trial RegistrationClinicalTrials.gov Identifier: NCT00922974

Adjuvant guidelines in surgically resected p16+ oropharyngeal carcinoma (OPC) with positive surgical margins (PSM) or extranodal extension (ENE) are based on randomized controlled trials predating p16 status. It remains unclear if adjuvant chemotherapy is necessary in p16+ patients with these features.The National Cancer Database was used to identify cases of nonmetastatic p16+ OPC diagnosed from 2010 to 2017. Patients treated with surgical resection followed by adjuvant radiation (aRT) or adjuvant chemoradiation (aCRT) were eligible for analysis.A total of 14 071 patients were eligible for analysis. Overall survival (OS) was not statistically different between aRT and aCRT in patients with PSM (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.56-1.28), ENE (HR 0.93, 95% CI 0.69-1.27) or both (HR 0.73, 95% CI 0.41-1.31).In patients with p16+ OPC with ENE, PSM, or both, adding chemotherapy to aRT was not associated with improved OS.

Given the poor lymphatics of the glottis, we evaluated omission of chemotherapy in patients treated definitely for T3N0M0 squamous cell carcinoma (SCC) of the glottis.We performed survival analysis of patients with T3N0M0 SCC of the glottis identified in the National Cancer Database treated with radiation alone versus chemoradiation.A total of 3785 patients were identified. Patients age ≥70 and those with comorbidities were less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI [0.25-0.37] and 0.48 [0.31-0.76], respectively). Five-year OS was lower in patients treated with radiation versus chemoradiation (33.8% [30.3%-37.2%] vs. 58.0% [55.8%-60.0%]). In patients70 with no comorbidities this difference persisted (51.0% [44.5%-57.0%] versus 66.7% [64.0%-69.3%]).Overall survival was higher in patients treated with chemoradiation compared to radiation alone, even when controlling for age and comorbidities. Radiotherapy with chemotherapy omission is not appropriate in patients with T3N0M0 SCC of the glottis.

Càncer de cap i coll; Radioteràpia; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Cáncer de cabeza y cuello; Terapia de radiación; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Head and Neck Cancer; Radiation Therapy; Coronavirus SARS-CoV-2; COVID-19; 2019-nCoV Purpose Because of the unprecedented disruption of health care services caused by the COVID-19 pandemic, the American Society of Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) identified an urgent need to issue practice recommendations for radiation oncologists treating head and neck cancer (HNC) in a time of limited resources and heightened risk for patients and staff. Methods and Materials A panel of international experts from ASTRO, ESTRO, and select Asia-Pacific countries completed a modified rapid Delphi process. Topics and questions were presented to the group, and subsequent questions were developed from iterative feedback. Each survey was open online for 24 hours, and successive rounds started within 24 hours of the previous round. The chosen cutoffs for strong agreement (≥80%) and agreement (≥66%) were extrapolated from the RAND methodology. Two pandemic scenarios, early (risk mitigation) and late (severely reduced radiation therapy resources), were evaluated. The panel developed treatment recommendations for 5 HNC cases. Results In total, 29 of 31 of those invited (94%) accepted, and after a replacement 30 of 30 completed all 3 surveys (100% response rate). There was agreement or strong agreement across a number of practice areas, including treatment prioritization, whether to delay initiation or interrupt radiation therapy for intercurrent SARS-CoV-2 infection, approaches to treatment (radiation dose-fractionation schedules and use of chemotherapy in each pandemic scenario), management of surgical cases in event of operating room closures, and recommended adjustments to outpatient clinic appointments and supportive care. Conclusions This urgent practice recommendation was issued in the knowledge of the very difficult circumstances in which our patients find themselves at present, navigating strained health care systems functioning with limited resources and at heightened risk to their health during the COVID-19 pandemic. The aim of this consensus statement is to ensure high-quality HNC treatments continue, to save lives and for symptomatic benefit.

BACKGROUND Limited data exist regarding which head and head and neck cancer (HNC) survivors will suffer from long-term dysphagia. METHODS From a population-based cohort of 1901 Utah residents with HNC and ≥3 years follow-up, we determined hazard ratio for dysphagia, aspiration pneumonia, or gastrostomy associated with various risk factors. We tested prediction models with combinations of factors and then assessed discrimination of our final model. RESULTS Cancer site in the hypopharynx, advanced tumor classification, chemoradiation, preexisting dysphagia, stroke, dementia, esophagitis, esophageal spasm, esophageal stricture, gastroesophageal reflux, thrush, or chronic obstructive pulmonary disease were associated with increased risk of long-term dysphagia. Our final prediction tool gives personalized risk calculation for diagnosis of dysphagia, aspiration pneumonia, or gastrostomy tube placement at 5, 10, and 15 years after HNC based on 18 factors. CONCLUSION We developed a clinically useful risk prediction tool to identify HNC survivors most at risk for dysphagia.

ImportancePathologic complete response (pCR) may be associated with prognosis in patients with soft tissue sarcoma (STS).ObjectiveWe sought to determine the prognostic significance of pCR on survival outcomes in STS for patients receiving neoadjuvant chemoradiotherapy (CT-RT) (Radiation Therapy Oncology Group [RTOG] 9514) or preoperative image-guided radiotherapy alone (RT, RTOG 0630) and provide a long-term update of RTOG 0630.Design, Setting, and ParticipantsRTOG has completed 2 multi-institutional, nonrandomized phase 2 clinical trials for patients with localized STS. One hundred forty-three eligible patients from RTOG 0630 (n = 79) and RTOG 9514 (n = 64) were included in this ancillary analysis of pCR and 79 patients from RTOG 0630 were evaluated for long-term outcomes.InterventionPatients in trial 9514 received CT interdigitated with RT, whereas those in trial 0630 received preoperative RT alone.Main Outcomes and MeasuresOverall and disease-free survival (OS and DFS) rates were estimated by the Kaplan-Meier method. Hazard ratios (HRs) and P values were estimated by multivariable Cox model stratified by study, where possible; otherwise, P values were calculated by stratified log-rank test. Analysis took place between December 14, 2016, to April 13, 2017.ResultsOverall there were 42 (53.2%) men; 68 (86.1%) were white; with a mean (SD) age of 59.6 (14.5) years. For RTOG 0630, at median follow-up of 6.0 years, there was 1 new in-field recurrence and 1 new distant failure since the initial report. From both studies, 123 patients were evaluable for pCR: 14 of 51 (27.5%) in trial 9514 and 14 of 72 (19.4%) in trial 0630 had pCR. Five-year OS was 100% for patients with pCR vs 76.5% (95% CI, 62.3%-90.8%) and 56.4% (95% CI, 43.3%-69.5%) for patients with less than pCR in trials 9514 and 0630, respectively. Overall, pCR was associated with improved OS (P = .01) and DFS (HR, 4.91; 95% CI, 1.51-15.93; P = .008) relative to less than pCR. Five-year local failure rate was 0% in patients with pCR vs 11.7% (95% CI, 3.6%-25.1%) and 9.1% (95% CI, 3.3%-18.5%) for patients with less than pCR in 9514 and 0630, respectively. Histologic types other than leiomyosarcoma, liposarcoma, and myxofibrosarcoma were associated with worse OS (HR, 2.24; 95% CI, 1.12-4.45).Conclusions and RelevanceThis ancillary analysis of 2 nonrandomized clinical trials found that pCR was associated with improved survival in patients with STS and should be considered as a prognostic factor of clinical outcomes for future studies.Trial RegistrationClinicalTrials.gov Identifiers: RTOG 0630 (NCT00589121); RTOG 9514 (NCT00002791)

Prolonged drought due to climate change has negatively impacted amphibians in southern California, U.S.A. Due to the severity and length of the current drought, agencies and researchers had growing concern for the persistence of the arroyo toad (

OBJECTIVES: To compare patterns of care and overall survival (OS) between stereotactic body radiotherapy (SBRT) and percutaneous local tumor ablation (LTA) for non-surgically managed early-stage non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2014 for adults with non-metastatic, node-negative invasive adenocarcinoma or squamous cell carcinoma of the lung with primary tumor size ≤5.0 cm who did not undergo surgery or chemotherapy and received SBRT or LTA. Patterns of care were assessed with multivariate logistic regression. After propensity-score weighting with generalized boosted regression, OS was assessed with univariate and doubly-robust multivariate Cox regression. RESULTS: Of 15,792 patients, 14,651 (93%) received SBRT and 1141 (7%) received LTA. Increasing age (OR 1.01, p = .035), treatment at an academic institution (OR 2.94, p < .001), increasing tumor size (OR 1.05, p < .001), and more recent year of diagnosis (OR 1.43, p < .001) were predictive of treatment with SBRT, whereas comorbidities (OR 0.74, p = .003) and treatment at a high-volume facility (OR 0.05, p < .001) were predictive for LTA. At a median follow-up of 26.2 months, SBRT was associated with improved OS relative to LTA within a propensity-score weighted doubly-robust multivariate analysis (HR 0.71, p < .001). On weighted subgroup analyses, improved OS was observed with SBRT for tumor sizes > 2.0 cm (HR 0.72, p < .001) and for those treated at high-volume facilities (HR 0.71, p < .001). No OS difference was found with SBRT or LTA in tumor sizes ≤2.0 cm (HR 0.90, p = .227). CONCLUSION: Within the NCDB, SBRT was more commonly utilized and was associated with improved OS when compared to percutaneous LTA for patients with non-surgically managed early-stage NSCLC. Patients with small tumor volumes likely represent an appropriate population for future prospective randomized comparisons between SBRT and LTA.

OBJECTIVE: To estimate long-term prevalence of new dysphagia-related diagnoses in in a large cohort of head and neck cancer survivors. STUDY DESIGN: Retrospective cohort SETTING: Population-based SUBJECTS AND METHODS: 1901 adults diagnosed with head and neck cancer between 1997 and 2012 with at least 3 years of follow up were compared with 7,796 controls matched for age, sex and birth state. Prevalence of new dysphagia-related diagnoses and procedures and hazard ratio compared to controls were evaluated in patients 2–5 years and 5 years and beyond after diagnosis. Risk factors for the development of these diagnoses were analyzed. RESULTS: Prevalence of new diagnosis and hazard ratio compared to controls remained elevated for all diagnoses throughout the time periods investigated. The rate of aspiration pneumonia was 3.13% at 2–5 years increasing to 6.75% at 5 or more years, with hazard ratios of 9.53 (95% CI 5.08 −17.87) and 12.57 (7.17–22.04) respectively. Rate of gastrostomy tube placement increased from 2.82% to 3.32% with hazard ratio remaining elevated from 51.51 (13.45 – 197.33) to 35.2 (7.81–158.72) over the same time period. The rate of any dysphagia-related diagnosis or procedure increased from 14.9% to 26% with hazard ratio remaining elevated from 3.32 (2.50–4.42) to 2.12 (1.63–2.75). Treatment with radiation therapy and age over 65 were associated with increased hazard ratio for dysphagia-related diagnoses. CONCLUSION: Our data supports our hypothesis that new dysphagia-related diagnoses continue to occur at clinically meaningful levels in long-term head and neck cancer survivors beyond 5 years after diagnosis.

Avian egg production demands resources such as lipids and proteins. Relative egg size and mass varies across species, reflecting differences in maternal investment. This variability may affect the maternal transfer of anthropogenic pollutants including lipophilic polychlorinated biphenyls (PCBs) and protein-associated per- and polyfluoroalkyl substances (PFASs) and mercury (Hg). We conducted a meta-analysis on seabirds and investigated whether interspecies variation in maternal investment contributes toward skewed pollutant concentration ratios between males and females, as C

For patients treated with SBRT for spinal metastases in the cervical area, a thermoplastic mask is the usual immobilization technique. This project investigates the impact of shoulder position variability on target coverage for such cases. Eight HN patients treated in a suite equipped with a CT-on-rails system (CTOR) were randomly chosen. Of these, three were treated with shoulder depressors. For each patient, their planning CT was used to contour spine targets at the C5, C6 and C7 levels for which two VMAT plans were developed to deliver 18 Gy to each target per the RTOG 0631 protocol. One plan used full arcs while the other used avoidance sectors around the lateral positions. For each patient, IGRT CTOR images were used to recalculate doses that would have been delivered from these plans. Target coverage and dose to the spinal cord were compared for four scenarios: full and partial arcs, with or without depressors. A Dunn test showed significant differences between groups with and without shoulder depressors, but not between those with full versus partial arcs. For most of the investigated cases, the coverage ended up being higher than planned due to the shoulder position being inferior at treatment compared to simulation. In some cases, this led to higher spinal cord doses than allowed per protocol. The results of this study confirm that, when treating lower cervical spine lesions with SBRT, special care should be taken to ensure that the shoulders are positioned as they were during planning CT acquisition.

The Antarctic ecosystem represents a remote region far from point sources of pollution. Still, Antarctic marine predators, such as seabirds, are exposed to organohalogen contaminants (OHCs) which may induce adverse health effects. With increasing restrictions and regulations on OHCs, the levels and exposure are expected to decrease over time. We studied south polar skua (Catharacta maccormiciki), a top predator seabird, to compare OHC concentrations measured in whole blood from 2001/2002 and 2013/2014 in Dronning Maud Land. As a previous study found increasing organochlorine concentrations with sampling day during the 2001/2002 breeding season, suggesting dietary changes, we investigated if this increase was repeated in the 2013/2014 breeding season. In addition to organochlorines, we analyzed hydroxy-metabolites, brominated contaminants and per- and polyfluoroalkyl substances (PFAS) in 2013/2014, as well as dietary descriptors of stable isotopes of carbon and nitrogen, to assess potential changes in diet during breeding. Lipid normalized concentrations of individual OHCs were 63%, 87% and 105% higher for hexachlorobenzene (HCB), 1,1-dichloro-2,2-bis (p- chlorophenyl)ethylene (p,p’-DDE), and ∑Polychlorinated biphenyls (PCBs), respectively, in 2013/2014 compared to 2001/2002. South polar skuas males in 2013/2014 were in poorer body condition than in 2001/ 2002, and with higher pollutant levels. Poorer body condition may cause the remobilization of contaminants from stored body reserves, and continued exposure to legacy contaminants at overwintering areas may explain the unexpected higher OHC concentrations in 2013/2014 than 2001/2002. Concentrations of protein-associated PFAS increased with sampling day during the 2013/2014 breeding season, whereas the lipid-soluble chlorinated pesticides, PCBs and polybrominated diphenyl ether (PBDEs) showed no change. OHC occurrence was not correlated with stable isotopes. The PFAS biomagnification through the local food web at the colony should be investigated further. Organic pollutants Seabirds PFAS PCB HCB Mirex Catharacta maccormicki

Early stage lung cancer is increasingly being treated using stereotactic body radiation therapy (SBRT). Several advanced treatment planning algorithms are now available in various commercial treatment planning systems. This work compares the dose distributions calculated for the same treatment plan using, five algorithms, in three different treatment planning systems. All plans were normalized to ensure the prescription dose covers 95% of the planning target volume (PTV). Dose to the planning target volume (PTV) was compared using near-minimum dose (D(98%)), near-maximum dose (D(2%)) and dose homogeneity, while dose fall-off was compared using D(2cm) and R(50). Dose to the lung was compared using V(5Gy), V(20Gy) and mean lung dose. Statistical analysis shows that dose distributions calculated using Eclipse’s Acuros XB and RayStation’s Monte Carlo were significantly different from the other dose distributions for the PTV dose parameters investigated. For lung dosimetric parameters, this difference persisted for volumetric modulated arc therapy (VMAT) plans but not for conformal arc plans. While normal tissue complication probability (NTCP) differences were significant for some of the algorithms for VMAT delivery approaches, they were not significantly different for any algorithm for conformal arc plans. All parameters investigated here were within 5% between all algorithms. The results show that, while some small dosimetric differences can be expected around the PTV, the dose distribution to the rest of the treatment area, especially the lungs, should not be clinically-relevant when switching between one of the five algorithms investigated.

Funding: J.H. is supported by a PhD scholarship funded by the School of Biology, University of St Andrews. A.G. is supported by a Natural Environment Research Council Independent Research Fellowship (grant no. NE/ K009524/1) and a European Research Council Consolidator grant (no. 771387). Females and males may face different selection pressures. Accordingly, alleles that confer a benefit for one sex often incur a cost for the other. Classic evolutionary theory holds that the X chromosome, whose sex-biased transmission sees it spending more time in females, should value females more than males, whereas autosomes, whose transmission is unbiased, should value both sexes equally. However, recent mathematical and empirical studies indicate that male-beneficial alleles may be more favoured by the X chromosome than by autosomes. Here we develop a gene's-eye-view approach that reconciles the classic view with these recent discordant results, by separating a gene's valuation of female versus male fitness from its ability to induce fitness effects in either sex. We use this framework to generate new comparative predictions for sexually antagonistic evolution in relation to dosage compensation, sex-specific mortality and assortative mating, revealing how molecular mechanisms, ecology and demography drive variation in masculinization versus feminization across the genome. Publisher PDF

Treatment is complex for patients with head and neck (H&N) cancers with specific site of disease, stage, and pathologic findings guiding treatment decision-making. Treatment planning for H&N cancers involves a multidisciplinary team of experts. This article describes supportive care recommendations in the NCCN Guidelines for Head and Neck Cancers, as well as the rationale supporting a new section on imaging recommendations for patients with H&N cancers. This article also describes updates to treatment recommendations for patients with very advanced H&N cancers and salivary gland tumors, specifically systemic therapy recommendations.

Parotid tumors are rare, and no clinical trial data exists to guide postoperative radiation therapy (PORT) usage. We sought to determine the impact of PORT on the overall survival (OS) of patients with parotid malignancies. Patient data was queried from the National Cancer Database. Patients with surgical resection of parotid gland carcinomas from 2004 to 2012 were analyzed. Kaplan-Meier and Cox proportional hazards were used to assess OS among those receiving PORT or not. Additionally, variables affecting OS and use of PORT were evaluated. A total of 12,439 patients were identified for analysis. Increasing T stage, N stage, tumor grade, and positive margin status were predictive of PORT. Survival for patients receiving PORT versus surgery only at 5 and 10 years was 65.5% and 50.3% versus 74.4% and 61.2% for surgery only (p ≤ 0.001). After multivariable adjustment, PORT improved OS (adjusted hazard ratio 0.79, 95% confidence interval 0.70–0.89). In subgroup analysis, PORT provided benefit for certain histologic subtypes and all other patient groups except those with T1 tumors and undifferentiated/anaplastic tumor grades. Our data suggests that PORT was associated with improved survival. Additionally, some subgroups may receive additional benefit and patients with small (T1), low-grade disease may be able to forgo PORT.

Genes can behave in ways that are conditional upon their parent-of-origin. The best understood form of this is genomic imprinting (GI), which typically involves the silencing of a gene originating from one parent and the expression of its homologue originating from the other parent. A number of hypotheses have been proposed to explain GI, which may be grouped into those based on asymmetries of genetic interest versus those based on asymmetries of genetic information. Dispersal patterns can drive both of these asymmetries and modulate the costs and benefits of imprinting. GI may also have consequences for dispersal of individuals and genes, by driving imprinting of loci underpinning dispersal, altering the fitness consequences of dispersal, and affecting rates of introgression.

Adult head and neck (HN) sarcomas are a rare malignancy with limited data delineating the role of postoperative radiotherapy (PORT), particularly for a positive surgical margin. There are no randomized trials supporting the use of PORT, therefore treatment trends vary between institutions. A positive margin predicts recurrence and poor survival outcomes. This study uses the National Cancer Database (NCDB) to investigate whether PORT improves overall survival (OS) in adult HN sarcomas with a positive margin and how utilization has changed.Patients (n = 1142) in the NCDB from 2004-2013 with adult HN sarcomas who underwent resection and had a positive margin.Factors significantly associated with increased utilization of PORT were: having insurance, salivary gland primary site, high-risk histology, poor differentiation, and a macroscopic positive margin. Treatment with PORT was associated with improved 5-year OS for all patients with a positive margin (57% vs 48%; P = .002), both microscopic (57% vs 49%; P = .010) and macroscopic (57% vs 41%; P = .036). Improved OS was significant after controlling for other known covariates on multivariate analysis (HR: 0.76; [0.64-0.90]; P = .002). Treatment at a community-based facility was an independent predictor for reduced OS (HR: 1.37; [1.15-1.64]; P .001). The percentage utilization (53%) of PORT for these patients did not change significantly over time.PORT provides a significant survival benefit for adult HN sarcoma patients with either a microscopic or macroscopic positive margin; however, PORT is underutilized. Treatment at academic/research cancer programs was associated with increased utilization of PORT and improved survival outcomes.

Background Primary prostate sarcomas (PPS) are rare. Outcomes for this cancer have not been well characterized. Materials and methods Subjects with a PPS diagnosed between 1973 and 2014 were identified in the SEER database. Subjects were stratified by disease stage and types of therapies received. Disease-specific survival (DSS) and Overall survival (OS) was estimated by Kaplan-Meier analysis and cohorts were compared with a univariate and multivariable Cox regression. Results The incidence of PPS among all prostate cancer diagnoses was 0.02%. Subjects younger than age 26 years at diagnosis represented 29% of cases, and 32% of primary prostate sarcomas were rhabdomyosarcoma histology. Rhabdomyosarcoma histologies The median age at diagnosis was 9 years. Between age 0-25 years rhabdomyosarcoma accounted for 96.4% of primary prostate sarcoma diagnoses, after age 25 rhabdomyosarcoma represented 15% of new diagnoses. The 10-year DSS and OS for rhabdomyosarcoma was 47% and 44%. Non-rhabdomyosarcoma histologies The median age at diagnosis was 71 years. The most common diagnoses were leiomyosarcoma (33%) and carcinosarcoma (28%). Localized, regional, or distant disease occurred in 40%, 34%, and 26% of cases. The 10-year DSS and OS were 26% and 14%. In locally advanced cases, RT added to surgery trended toward improved DSS (P = 0.10). Conclusions Disease-specific survival and OS for non-rhabdomyosarcoma histologies appear inferior to those of rhabdomyosarcoma. The addition of RT to surgical resection may improve DSS in locally advanced non-rhabdomyosarcoma. This is the largest report of the incidence, stage distribution, and survival for this extremely rare urologic malignancy providing valuable prognostic information.

Objectives To investigate clinicopathologic and treatment factors associated with survival in adult head and neck sarcomas in the National Cancer Database (NCDB). To analyze whether treatment settings and therapies received influence survival outcomes and to compare trends in utilization via an aggregated national data set. Study Design Prospectively gathered data. Setting NCDB. Subjects and Methods The study comprised a total of 6944 adult patients treated for a head and neck sarcoma from January 2004 to December 2013. Overall survival (OS) was the primary outcome. Results Increased age and tumor size, nodal involvement, and poorly differentiated histology had significantly reduced OS ( P < .001). Angiosarcoma, malignant nerve sheath tumor, malignant fibrous histiocytoma, osteosarcoma, and rhabdomyosarcoma histologic subtypes had significantly reduced OS, while liposarcoma, chondrosarcoma, and chordoma had improved OS ( P < .001). Utilization of surgical therapy was associated with improved OS, while positive surgical margins were associated with treatment at a community-based cancer program and had reduced OS ( P < .001). On multivariate analysis, treatment with radiation and/or chemotherapy was not significantly associated with OS; however, primary treatment with definitive chemoradiotherapy had significantly reduced OS. Patients treated at academic/research cancer programs (n = 3874) had significantly improved 5- and 10-year OS (65% and 54%, respectively) when compared with patients treated at community-based cancer programs (n = 3027; 49% and 29%; P < .001). The percentage utilization of these programs (56% vs 44%) did not change over the study period. Conclusion For adult head and neck sarcomas, treatment at an academic/research cancer program was associated with improved survival; however, despite increasing medical specialization, the percentage utilization of these programs for this rare tumor remains constant.

Purpose Although several feasibility studies have demonstrated the safety of adjuvant concurrent chemoradiotherapy (CRT) for locally advanced or incompletely resected non–small-cell lung cancer (NSCLC), it remains uncertain whether this approach is superior to sequential chemotherapy followed by postoperative radiotherapy (C→PORT). We sought to determine the most effective treatment sequence. Patients and Methods Using the National Cancer Database, we selected two cohorts of patients with nonmetastatic NSCLC who had received at least a lobectomy followed by multiagent chemotherapy and radiotherapy; cohort one included patients with R0 resection and pN2 disease, whereas cohort two included patients with R1-2 resection regardless of nodal status. Overall survival (OS) was examined using a propensity score–matched analysis with a shared frailty Cox regression. Results A total of 747 patients in cohort one and 277 patients in cohort two were included, with a median follow-up of 32.8 and 27.9 months, respectively. The median OS was 58.8 months for patients who received C→PORT versus 40.4 months for patients who received CRT in cohort one (log-rank P < .001). For cohort two, the median OS was 42.6 months for patients who received C→PORT versus 38.5 months for patients who received CRT (log-rank P = .42). After propensity score matching, C→PORT remained associated with improved OS compared with CRT in cohort one (hazard ratio, 1.35; P = .019), and there was no statistical difference in OS between the sequencing groups for cohort two (hazard ratio, 1.35; P = .19). Conclusion Patients with NSCLC who undergo R0 resection and are found to have pN2 disease have improved outcomes when adjuvant chemotherapy is administered before, rather than concurrently with, radiotherapy. For patients with positive margins after surgery, there is not a clear association between treatment sequencing and survival.

Background To assess the effectiveness and outcomes of adjuvant radiotherapy regimens for nonmelanoma skin cancers (NMSC) of the head and neck, particularly for elderly patients. Methods A retrospective review of patients with head and neck NMSC was conducted. Radiotherapy dose per fraction regimens included ≤200, 240–250, 300–400, and 500–600 cGy. Demographics, tumor characteristics, local control (LC), regional control (RC), and survival outcomes were analyzed. Results Of the 90 patients with 140 disease sites, 76.6% were squamous cell carcinoma, 15.5% were basal cell carcinoma, and 7.7% were other histologies. The mean age at diagnosis was 72.1 years old. The most common location was preauricular (20.0%), followed by temple, scalp, cheek, and forehead. The overall LC and RC rates were 88.8% and 88.8%, respectively by patients, and 92.8% and 86.4%, respectively by treatment sites. Age, primary tumor location, T classification, N classification, overall stage, perineural invasion, comorbid disease, skull base invasion, and radiotherapy subgroup were significantly associated with disease-free and overall survival (P < 0.05). LC and RC were not significantly different among the radiotherapy dose subgroups. The mean survival was longer in patients treated with 240–250 cGy/fraction (50.3 months). There was no significant difference in radiotherapy toxicity between the subgroups. Conclusion Short-term radiotherapy regimens for patients with locally or regionally advanced head and neck NMSC appear feasible and effective, particularly in elderly patients or those that cannot tolerate the length of standard regimens.

PURPOSE/OBJECTIVE(S) Laryngeal preservation with definitive chemoradiation (CRT) in patients with advanced laryngeal cancer has been established through various prospective randomized trials. However, it is unclear what the optimal treatment approach for patients with T3N0M0 glottic cancer is and whether chemotherapy is needed in conjunction with radiation. We sought to evaluate survival differences in patients with T3N0M0 glottic cancer treated with radiation alone (RT) versus chemoradiation. MATERIALS/METHODS Patients with T3N0M0 glottic cancer diagnosed from 2004 through 2017 were identified from the National Cancer Database. Patients treated definitively with RT or CRT were selected. Patients receiving adjuvant RT or CRT were excluded. Baseline differences among treatment groups were identified. Overall survival was estimated with the Kaplan-Meier method and reported as median survival (MS). A multivariable cox proportional hazards model was constructed to identify variables associated with survival. RESULTS A total of 3785 patients were included in the cohort, with 942 (25%) patients who received RT alone and 2843 (75%) who received CRT. With a median follow up of 75.2 months, median survival was significantly longer in patients treated with CRT than in patients treated with RT alone (82 months [m], 95% CI 76-87m vs 29m, 95% CI 25-33m). On multivariable cox model, patient factors associated with decreased overall survival (OS) included omission of chemo (hazard ratio [HR] 1.69, 95% CI 1.52-1.87), age > 70 (HR 1.66, 95% CI 1.15-2.42), comorbidities (HR 1.66, 95% CI 1.15-2.42, and treatment at non-tertiary academic cancer centers (HR 1.24, 95% CI 1.04-1.48). Patients age > 70 and those with multiple comorbidities were significantly less likely to receive chemotherapy (odds ratio [OR] 0.30, 95% CI 0.25-0.37 and OR 0.48 95% CI 0.31-0.76, respectively). When limiting analysis to patients under 70 with no comorbidities, the survival benefit persisted in favor of CRT (MS 113m, 95% CI 102-124m vs. MS 65, 95% CI 47-85m). CONCLUSION Optimal treatment for T3N0M0 glottic cancer has not fully been established in prospective clinical trials. This is the first study to evaluate survival outcomes in this group of patients comparing RT to CRT. Median survival appears to be significantly increased with the use of CRT, and this benefit persists when controlling for age and performance status. This study supports the use of definitive CRT for appropriately selected patients with T3N0M0 glottic cancer.

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Head and Neck Cancers provide treatment recommendations for cancers of the lip, oral cavity, pharynx, larynx, ethmoid and maxillary sinuses, and salivary glands. Recommendations are also provided for occult primary of the head and neck (H&N), and separate algorithms have been developed by the panel for very advanced H&N cancers. These NCCN Guidelines Insights summarize the panel's discussion and most recent recommendations regarding the increase in human papillomavirus-associated oropharyngeal cancer and the availability of immunotherapy agents for treatment of patients with recurrent or metastatic H&N cancer.

Facial nerve (FN) palsy and perineural invasion (PNI) are adverse features in carcinomas of the parotid gland. FN sacrifice at the time of surgery is associated with significant morbidity. The role of adjuvant radiotherapy in patients with high-risk features, including FN involvement, remains unclear. Analyze the disease-free survival (DFS) and overall survival (OS) and the impact of tumor characteristics, including FN involvement, for patients treated with surgical resection for carcinoma of the parotid gland. This is a retrospective chart review. University of Utah and Intermountain Healthcare, Utah. A total of 129 patients who were treated with primary surgery for nonmetastatic primary malignancies of the parotid gland from 1988 to 2006. Parotidectomy with or without adjuvant therapy. Kaplan-Meier analysis was used to obtain 5-year estimates of DFS and OS. Recurrence risk factors, particularly the impact of FN involvement, were analyzed. Five-year DFS and OS rates were 79% and 78%, respectively. Thirty-two (28%) patients developed recurrent disease. Disease recurrence occurred in 64% of patients with both FN palsy and PNI, in 43% with FN palsy without PNI, in 27% with only PNI, and in 16% without either feature. FN involvement, particularly FN palsy, is a predictor of increased risk of recurrence and death. Radiotherapy cannot substitute for FN sacrifice in high-risk patients.

In marine mammals such as pinnipeds (seals, sea lions and walruses), reproductive strategies reveal how species acquire, store and allocate energy to offspring. During lactation, females can allocate energy acquired from concurrent resources (income breeding); or utilize energy stored prior to reproduction (capital breeding). Mothers transfer a large proportion of energy to their pups via lipid rich milk, meaning that pollutants such as polychlorinated biphenyls (PCBs) and mercury (Hg) will also transfer, raising concern for negative health effects. To quantify the effect of reproductive strategy on maternal pollutant transfer in pinnipeds, we developed a proxy for income and capital breeding by focusing on the lactational component of reproduction, and arranged species along this gradient. We found a strong positive relationship between lipid content in milk and degree of capital breeding. We tested this gradient against maternal pollutant transfer expressed as a concentration ratio by meta-analysis. In mother-pup pairs, the concentration ratio of PCBs was one order of magnitude higher than for mercury. PCB concentrations in pups and juveniles were similar to adult females, but mercury was always lower in young offspring than in females. We found no effect of reproductive strategy between studies investigating mother-pup pairs and non-related females and juveniles (< 1 year old), however data were strongly biased towards capital breeders. Our results suggest that either: 1) reproductive strategy does not affect pollutant bioaccumulation; or 2) a lack of income breeder data prevents us from testing the overall effect of reproductive strategy on maternal pollutant transfer. The finding that PCB concentrations in juveniles are similar to females is of concern due to early life stage exposure. We recommend data collection from income breeding species such as the sea lions to elucidate whether reproductive strategy, and potentially other life history traits, has an overall effect on maternal pollutant transfer.

We appreciate the comments from Zhao and Ng (1) regarding our recent National Cancer Database (NCDB) study comparing survival outcomes after postoperative adjuvant concurrent chemoradiotherapy (CRT) versus sequential chemotherapy followed by postoperative radiotherapy (C→PORT) for locally advanced or incompletely resected non-small cell lung cancer (NSCLC).

Purpose To present our preliminary experience with the recently released Calypso lung beacons to track lung tumor location during stereotactic body radiation therapy (SBRT). Materials/methods Five recent lung SBRT patients had Calypso lung beacons implanted for tumor tracking during treatment. Beacons were placed by a pulmonologist using fluoroscopic navigation within 1 week prior to planning four-dimensional computed tomography (4DCT) acquisition. Patients were immobilized in a full-body double-vacuum bag. For the first three patients, a verification 4DCT was obtained prior to the first fraction with the patient in the treatment position to assess both beacon migration and motion of tumor and beacons relative to planning day. For each treatment fraction, Calypso was used to position the patient. A verification cone-beam CT (CBCT) confirmed the Calypso-defined target position was appropriate. Real-time Calypso tracking information was also acquired and compared to an action level that was used to determine if the tumor migrated outside of the planning target volume. Results For four patients, the implant procedure was well tolerated, with average CBCT-based shifts being within 0.2 mm of the shifts reported by Calypso at the time of imaging. The other patient had a small pneumothorax due to very peripheral tumor location and experienced beacon migration. However, the patient quickly recovered from the pneumothorax, and after deactivating that beacon, motion tracking was possible throughout his treatment. Conclusions All patients were successfully treated with SBRT using the newly released Calypso lung beacons, with initial positioning confirmed by this clinic's current clinical standard of CBCT. The system allowed us to validate, with real-time confirmation, that the planned internal target volumes were appropriate to each day's extent of actual tumor motion. An efficient and effective workflow for utilizing the new lung beacons for SBRT treatments was developed.

Surgical management of external ear melanoma presents unique technical challenges based on the unique anatomy and reconstruction concerns. Surgical technique, including preservation of cartilage, is variable and impact on recurrence is unclear. Our goal was to investigate surgical approach, including extent of surgical resection and sentinel lymph node biopsy (SLNB), and the impact on recurrence. In this retrospective review of primary clinical stage 1/2 external ear melanoma, demographics, tumor characteristics, surgical resection technique (including cartilage-sparing vs. cartilage removal), and SLNB results were evaluated for recurrence risk. One hundred and fifty-six patients total had an average follow-up of 5.6 years. Twenty-nine (18.6%) patients underwent cartilage-sparing surgery and 99 (63.5%) patients underwent SLNB, 14.1% of whom had micrometastatic disease. Ten (6.4%) patients recurred loco-regionally. Recurrence was associated with Breslow depth, initial stage at diagnosis, and SLNB status. Cartilage-sparing surgery was not associated with increased recurrence. Sentinel lymph node identification rate was 100% based on clinical detection with use of lymphoscintigraphy. In addition to confirming established risk factors for melanoma recurrence, we confirm the feasibility of SLNB in stratifying recurrence risk. Although we did not see an increased recurrence risk with surgical technique and cartilage-sparing approaches, these findings are limited by small sample size.

Toxic leadership is associated with a number of negative consequences to the long-term health and welfare of people in organizations. Destructive leader styles redirect employee efforts from mission accomplishment to self-protection and survival behaviors, undermining the organization. Increased demand and decreased funding are characteristic of the nonprofit sector. Therefore, successful nonprofit organizations tend to rely on creativity and irrnovation to ensure their communities are appropriately and sufficiently sustained. Supportive, not toxic, leadership helps foster organizational environments that encourage prudent risk-taking and innovation. This concurrent mixed methods study explored the relationship between toxic leadership and organizational citizenship and turnover behaviors among 471 survey respondents from a sample of San Diego nonprofit paid staff, and considered the influence commitment has on those relationships. An open ended question for those who reported experiencing toxic leadership provided additional context and depth as to why employees stayed in an organization in spite of abusive supervision. The findings of the study are of interest to leaders and managers of nonprofit organizations to develop policies and training processes as they strive to recruit, retain and develop talented employees. Toxic supervision was found to exist in San Diego nonprofit organizations. However, its effect on organizational citizenship (OCB) and turnover behaviors was inconclusive, as was the influencing effect of commitment, in this study. However, both commitment and OCB-like ideas emerged as stated reasons that participants did not leave the organization, as did career, resilience and opportunity concepts. These identified variables suggest complex relationships that act in concert to influence staff retention indicating possible important opportunities for future research. ACKNOWLEDGEMENTS As noted by my USD colleague, COL James Dobbs, the process of completing this course of study is not possible without help, support and guidance from many. To all of you who have done so for me over the last many years, thank you all. Particularly, I must thank my Chair, Dr. George Reed for his enthusiasm and balanced approach to the myriad aspects ofleadership, Dr. Fred Galloway, a truly supportive and encouraging educator, who inspires all of us, his students, to think and consider rather than react and repeat, Dr. Zachary Green who engages my unfocussed excitement about leadership, its connections and applications, elevates my thinking and challenges me to bring forward my underlying reasoning a skill not easily taught (or learned) and always superbly offered, and Dr. Linnea Axman a good friend whose gentle guidance helped me understand this work at a much deeper level. Thank you all for your steadfast support. I owe a special debt of gratitude to my advisor, Dr. Robert Donmoyer, who brought me into research in the nonprofit sector and opened up a new path for me. Mostly, though, he reminded me what I could and should bring to the table. For that, I will always be grateful. A special thank you to Lenore Lowe and Stephanie McCullers, this study could not have happened without them, and for recognizing good leadership is important to the sector. This process can have many barriers to progress. No one helped me break them down as well as Dr. Mary McDonald a gifted and gentle teacher There are many friends and colleagues at USD who have supported, helped and inspired me through a very long journey, especially, Dr. Owen Smith who made me think harder and everything more fun, Dr. Nathaniel Dunigan, a stalwart friend and supporter, Dr. Lyn Taylor Peyton Roberts who makes "the data" an exciting dive every time, Elaine Lewis, a good friend, who gives me my own advice when I need it better than I do, Elizabeth Castillo who has an inspiring message and started me in my new career thank you, Alma Ortega whose unique approach to the subject helps me stretch my understanding, and, Heather Gibb, who has endless patience and such good humor. I want to thank those from the The Caster Family Center for Nonprofit and Philanthropic Research where my many passionate colleagues led me to the third sector, particularly Dr. Laura Deitrich, Dr. Heather Carpenter, Dr. Audrey Barrett, Dr. Jennifer Jones, Dr. Lindsey McDougle, Bethan Theunissen, Jennifer Y ebba and Pat Libby. I also greatly appreciate my many United Way colleagues and friends who have had such great confidence in me, especially my boss, Ryan Morris, who with such good grace gave me time to finish this, talk about it and supported me throughout. I also

OBJECTIVES Positive margins can increase the risk of local recurrence of soft tissue sarcomas (STS). Utilizing a national registry, we investigated patterns of care and overall survival (OS) of patients with margin-positive non-retroperitoneal STS who received preoperative radiation therapy, adjuvant radiation therapy, or both. METHODS Adult patients with non-retroperitoneal STS who underwent resection and RT from 2004 to 2015 were included. Kaplan-Meier, log-rank analysis, and Cox regression analysis were performed. RESULTS We identified 5726 patients. Most had a tumor size >5 cm (60%), grade 3 disease (67%), and microscopically positive margins (57%). Compared to ≤50.4 Gy, a dose of 66 to 69.99 Gy was associated with decreased risk of death on multivariate analysis (HR 0.69, 95%; CI, 0.50-0.94). Receipt of a boost was associated with decreased risk of death on univariate analysis (HR 0.54, 95%; CI, 0.29-0.99). In patients with grade 2 to 3 tumors without the gross disease, there was an OS benefit associated with a boost on multivariate analysis (HR 0.39, 95%; CI, 0.16-0.97). CONCLUSION This analysis appears to show an OS benefit of dose escalation to 66 to 69 Gy for margin-positive non-retroperitoneal STS. A Postoperative boost is associated with higher OS in grade 2 to 3 STS without the gross disease.

Background National guidelines support both surgical and radiotherapy (RT) as initial treatment options for early-stage oral cavity squamous cell carcinoma (SCC). There remains limited data evaluating the survival outcomes of RT and the current practice patterns for these lesions. Methods We conducted a retrospective review of 8274 patients in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2008 with T1 to T2N0M0 oral cavity SCC. Primary outcomes were 5-year overall survival (OS) and disease-specific survival (DSS). Results Surgical therapy had significantly improved OS (140 months; p < .001) and DSS (217 months; p < .001) compared to surgery with adjuvant RT (104 and 163 months, respectively) and definitive RT (68 and 136 months, respectively). The use of radiation alone was associated with an increased T classification, hard palate, retromolar trigone primary site lesions, and advanced patient age. Conclusion Primary radiation without surgery continues to be used in a subset of early-stage oral cavity SCCs, in which it is associated with decreased OS and DSS. © 2017 Wiley Periodicals, Inc. Head Neck 39: 876–880, 2017

Importance The benefit of adjuvant radiation in surgically treated T1-2N1 oropharyngeal cancer without adverse pathologic features remains unclear Objectives To compare population-level survival outcomes in surgically-treated T1-2N1 oropharyngeal squamous cell carcinoma (OPSCC) with and without the use of adjuvant radiation. Study Design Retrospective population-based study using the Surveillance, Epidemiology, and End Results (SEER) registry data from 1998–2011. Setting Population-level study. Participants Patients with T1-2N1 OPSCC treated with surgical resection and neck dissection with or without adjuvant radiation. Intervention(s) for Clinical Trials or Exposure(s) for observational studies The use of postoperative adjuvant radiation. Main Outcome(s) and Measures Overall and disease-specific survival. Results Radiation was utilized in 74% of patients and was positively associated with extracapsular extension and well-differentiated histology. The use of radiation was associated with improved mean overall survival (124 v. 108 months, p=0.023) and a non-significant increase in mean disease-specific survival (138 v. 131 months, p=0.053). Conclusions and Relevance The use of adjuvant radiation is associated with improved survival in surgically-treated T1-2N1 squamous cell carcinoma of the oropharynx with unknown HPV status. Level of Evidence IV

We aimed to evaluate if use of brachytherapy (BT) is associated with improved survival in patients with oral cavity cancer who do not receive surgery and to analyze patterns of care.We queried the Surveillance, Epidemiology, and End Results database for patients who received radiation therapy for squamous cell carcinoma of the oral cavity between 1973 and 2012. Patients were grouped by treatment modality: external beam radiotherapy alone vs. external beam radiotherapy + BT. Surgical patients were excluded. Trends in BT utilization over the study period and patterns of care were analyzed. Propensity scores were generated, and a nearest-neighbor matching algorithm was used to balance the 2 groups. Cox regression modeling was used to estimate the effect of BT on overall survival. Sensitivity analysis was conducted to estimate the effect of unmeasured confounders on the analysis.Of 5,161 patients with squamous cell carcinoma of the oral cavity who received radiotherapy, 12% of patients received BT. The rate of BT use has decreased by 0.58% per year (p 0.001). Factors that predicted for omission of radiation therapy included age ≥ 65 years (adjusted odds ratio [aOR], 0.56; p0.001), regional nodal disease (aOR, 0.57; p0.001), and black race (aOR, 0.45; p0.001). Use of BT was associated with a decreased risk of death (hazard ratio, 0.75; p0.001).The use of BT is associated with improved survival in oral cavity tumors treated with definitive radiotherapy. Rates of BT utilization have declined by 0.58% per year and are currently very low.

Opsoclonus is a pathological eye movement phenomenon in hich the eyes experience involuntary, arrhythmic, rapid, multidiectional, conjugate movements. It occurs in all eye positions and uring smooth pursuit, and can also persist during sleep. It is diferentiated from nystagmus in that there is no slow eye movement hase, and it differs from ocular flutter because the eye movement s multidirectional and not confined to the horizontal. Opsoclonus an be accompanied by tremors, cerebellar ataxia, myoclonic jerks, r encephalopathy. In addition to paraneoplastic etiologies, it is ometimes autoimmune, but frequently without an identifiable ntibody [1].

Background National guidelines support surgical-based treatment and offer nonsurgical therapy as an alternative for advanced-stage oral cavity squamous cell carcinoma (SCC). There are limited data evaluating current utilization of these therapies and their survival outcomes. Methods A total of 5856 patients were found in the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2008 with resectable advanced-stage oral cavity SCC tumors. Outcomes were disease-specific survival (DSS) and overall survival (OS). Results Surgical therapy had significantly improved mean DSS and OS (115 and 71 months, respectively) compared to nonsurgical therapy (63 and 35 months, respectively; p < .001). The use of nonsurgical therapy was significantly associated with the hard palate, and patients who were single, divorced, and black, with T3, T4, and N3 tumors, and the percent utilization has significantly increased from 12% to 20% (p < .05). Conclusion Utilization of nonsurgical therapy for advanced-stage oral cavity SCC is increasing and is independently associated with a reduction in survival, as well as patient factors traditionally associated with reduced access to medical care and advanced T and N classifications. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

The low concentrations of most contaminants in the aquatic environment individually may not affect the normal function of the organisms on their own. However, when combined, complex mixtures may provoke unexpected effects even at low amounts. Selected aquatic micropollutants such as chlorpyrifos, bis-(2-ethylhexyl)-phthalate (DEHP), perfluorooctanoic acid (PFOA) and 17α-ethinylestradiol (EE2) were tested singly and in mixtures at nM to μM concentrations using precision-cut liver slices (PCLS) of Atlantic cod (Gadus morhua). Fish liver is a target organ for contaminants due to its crucial role in detoxification processes. In order to understand the effects on distinct key liver metabolic pathways, transcription levels of various genes were measured, including cyp1a1 and cyp3a, involved in the metabolism of organic compounds, including toxic ones, and the catabolism of bile acids and steroid hormones; cyp7a1, fabp and hmg-CoA, involved in lipid and cholesterol homeostasis; cyp24a1, involved in vitamin D metabolism; and vtg, a key gene in xenoestrogenic response. Only EE2 had significant effects on gene expression in cod liver slices when exposed singly at the concentrations tested. However, when exposed in combinations, effects not detected in single exposure conditions arose, suggesting complex interactions between studied pollutants that could not be predicted from the results of individual exposure scenarios. Thus, the present work highlights the importance of assessing mixtures when describing the toxic effects of micropollutants to fish liver metabolism.

Purpose Six imaging modalities were used in Radiation Therapy Oncology Group (RTOG) 0630, a study of image guided radiation therapy (IGRT) for primary soft tissue sarcomas of the extremity. We analyzed all daily patient-repositioning data collected in this trial to determine the impact of daily IGRT on clinical target volume–to–planning target volume (CTV-to-PTV) margin. Methods and materials Daily repositioning data, including shifts in right-left (RL), superior-inferior (SI), and anterior-posterior (AP) directions and rotations for 98 patients enrolled in RTOG 0630 from 18 institutions were analyzed. Patients were repositioned daily on the basis of bone anatomy by using pretreatment images, including kilovoltage orthogonal images (KVorth), megavoltage orthogonal images (MVorth), KV fan-beam computed tomography (KVCT), KV cone beam CT (KVCB), MV fan-beam CT (MVCT), and MV cone beam CT (MVCB). Means and standard deviations (SDs) for each shift and rotation were calculated for each patient and for each IGRT modality. The Student's t tests and F-tests were performed to analyze the differences in the means and SDs. Necessary CTV-to-PTV margins were estimated. Results The repositioning shifts and day-to-day variations were large and generally similar for the 6 imaging modalities. Of the 2 most commonly used modalities, MVCT and KVorth, there were no statistically significant differences in the shifts and rotations ( P = .15 and .59 for the RL and SI shifts, respectively; and P = .22 for rotation), except for shifts in AP direction ( P = .002). The estimated CTV-to-PTV margins in the RL, SI, and AP directions would be 13.0, 10.4, and 11.7 mm from MVCT data, respectively, and 13.1, 8.6, and 10.8 mm from KVorth data, respectively, indicating that margins substantially larger than 5 mm used with daily IGRT would be required in the absence of IGRT. Conclusions The observed large daily repositioning errors and the large variations among institutions imply that daily IGRT is necessary for this tumor site, particularly in multi-institutional trials. Otherwise, a CTV-to-PTV margin of 1.5 cm is required to account for daily setup variations.