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There is no current standard-of-care follow-up strategy for patients who receive palliative radiotherapy (PRT) for bone metastases. Within our institution there is currently a heterogenous practice in which some providers schedule routine follow up 1-3 months after initial PRT while others do follow up only as needed (PRN). Our study aims to compare rates of retreatment based on follow-up strategies (planned vs. PRN), explore factors that potentially affect retreatment, and evaluate whether provider follow-up strategy correlates with measurable differences in quality of care. In a retrospective chart review, PRT courses for bone metastases at our single institution were divided by follow-up strategies (planned vs. PRN). Demographic, clinical, and PRT data were collected and analyzed via descriptive statistics. The relationship between planned follow-up appointment and subsequent retreatment was studied. More patients received retreatment within one year of initial PRT in the planned follow-up group than in the PRN follow-up group (40.4% vs. 14.4%, p<0.001). Retreatment was achieved sooner in the planned follow-up group than in the PRN follow-up group (137 days vs. 156 days). When accounting for other variables, having a planned follow-up appointment remains the most important factor in establishing retreatment (OR = 3.32, 2.11-5.29, p<0.001). Having a planned follow-up appointment after the initial course of PRT improves identification of patients who would benefit from additional treatment, thus improving patient experience and quality of care. [ABSTRACT FROM AUTHOR]

Context: Research shows an increased symptom burden in young adult (YA) cancer patients compared with their older adult counterpart. Objectives: The purpose of this study was to identify differences in clinical characteristics and related outcomes between YA and older adult cancer patients admitted for cancer-related pain. Materials and Methods: We retrospectively identified 190 hospitalized patients in a single academic center with admissions for cancer-related pain. Patients were grouped into either "young adult" (18–39) or "older adult" (>40) cohorts. We compared differences in patient characteristics and pain regimens. Results: Median oral morphine equivalent per 24 hours was higher in the YA group (194 mg vs. 70 mg, p = 0.010). Younger patients received patient-controlled analgesia (PCA) more frequently (p = 0.023). The number of palliative care consults and adjuvants prescribed did not differ between groups (p > 0.05), although YAs more frequently had an inpatient pain anesthesia consult (p = 0.047). Conclusion: Findings show increased opioid requirements and PCA use in YAs being treated for malignancy compared with their older adult counterpart. [ABSTRACT FROM AUTHOR]

BACKGROUND Most gastrointestinal stromal tumors (GISTs) are considered nonhereditary or sporadic. However, single-institution studies suggest that GIST patients develop additional malignancies at increased frequencies. It was hypothesized that greater insight could be gained into possible associations between GISTs and other malignancies with a national cancer database inquiry. METHODS Patients diagnosed with GISTs (2001-2011) in the Surveillance, Epidemiology, and End Results database were included. Standardized prevalence ratios (SPRs) and standardized incidence ratios (SIRs) were used to quantify cancer risks incurred by GIST patients before and after GIST diagnoses, respectively, in comparison with the general US population. RESULTS There were 6112 GIST patients, and 1047 (17.1%) had additional cancers. There were significant increases in overall cancer rates: 44% (SPR, 1.44) before the GIST diagnosis and 66% (SIR, 1.66) after the GIST diagnosis. Malignancies with significantly increased occurrence both before and after diagnoses included other sarcomas (SPR, 5.24; SIR, 4.02), neuroendocrine-carcinoid tumors (SPR, 3.56; SIR, 4.79), non-Hodgkin lymphoma (SPR, 1.69; SIR, 1.76), and colorectal adenocarcinoma (SPR, 1.51; SIR, 2.16). Esophageal adenocarcinoma (SPR, 12.0), bladder adenocarcinoma (SPR, 7.51), melanoma (SPR, 1.46), and prostate adenocarcinoma (SPR, 1.20) were significantly more common only before the GIST diagnosis. Ovarian carcinoma (SIR, 8.72), small intestine adenocarcinoma (SIR, 5.89), papillary thyroid cancer (SIR, 5.16), renal cell carcinoma (SIR, 4.46), hepatobiliary adenocarcinoma (SIR, 3.10), gastric adenocarcinoma (SIR, 2.70), pancreatic adenocarcinoma (SIR, 2.03), uterine adenocarcinoma (SIR, 1.96), non-small cell lung cancer (SIR, 1.74), and transitional cell carcinoma of the bladder (SIR, 1.65) were significantly more common only after the GIST diagnosis. CONCLUSIONS This is the first population-based study to characterize the associations and temporal relations between GISTs and other cancers by both site and histological type. These associations may carry important clinical implications for future cancer screening and treatment strategies. Cancer 2015;121:2960-2967. © 2015 American Cancer Society. [ABSTRACT FROM AUTHOR]

Our purpose was to investigate the effect of physicist-patient consults on patient anxiety and patient satisfaction with a randomized prospective phase III clinical trial. Sixty-six patients were randomly assigned to the physics direct patient care (PDPC) arm or the control arm of the trial. Patients assigned to the PDPC arm received 2 physicist-patient consults to educate them on the technical aspects of their radiation therapy, while patients assigned to the control arm received the standard of care (ie, standard radiation therapy workflow without any additional physicist-patient consults). Questionnaires were administered to all patients at 4 time points (after enrollment, after the simulation, after the first treatment, and after the last treatment) to assess anxiety and satisfaction. The decrease in anxiety for the PDPC arm, compared with the control arm, was statistically significant at the first treatment (P =.027) time point. The increase in technical satisfaction for the PDPC arm, compared with the control arm, was statistically significant at the simulation (P =.005), first treatment (P <.001), and last treatment (P =.002) time points. The increase in overall satisfaction for the PDPC arm, compared with the control arm, was statistically significant at the first treatment (P =.014) and last treatment (P =.001) time points. Physicist-patient consults improved the patient experience by decreasing anxiety and increasing satisfaction. Future work is needed to modify current radiation oncology workflows and medical physics responsibilities to allow all patients to benefit from this advancement in patient care. [ABSTRACT FROM AUTHOR]

Purpose: Concerns have been raised about the potential for worse treatment outcomes because of dosimetric inaccuracies related to tumor motion and increased toxicity caused by the spread of low-dose radiation to normal tissues in patients with locally advanced non-small cell lung cancer (NSCLC) treated with intensity modulated radiation therapy (IMRT). We therefore performed a population-based comparative effectiveness analysis of IMRT, conventional 3-dimensional conformal radiation therapy (3D-CRT), and 2-dimensional radiation therapy (2D-RT) in stage III NSCLC. Methods and Materials: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare database to identify a cohort of patients diagnosed with stage III NSCLC from 2002 to 2009 treated with IMRT, 3D-CRT, or 2D-RT. Using Cox regression and propensity score matching, we compared survival and toxicities of these treatments. Results: The proportion of patients treated with IMRT increased from 2% in 2002 to 25% in 2009, and the use of 2D-RT decreased from 32% to 3%. In univariate analysis, IMRT was associated with improved overall survival (OS) (hazard ratio [HR] 0.90, P=.02) and cancer-specific survival (CSS) (HR 0.89, P=.02). After controlling for confounders, IMRT was associated with similar OS (HR 0.94, P=.23) and CSS (HR 0.94, P=.28) compared with 3D-CRT. Both techniques had superior OS compared with 2D-RT. IMRT was associated with similar toxicity risks on multivariate analysis compared with 3D-CRT. Propensity score matched model results were similar to those from adjusted models. Conclusions: In this population-based analysis, IMRT for stage III NSCLC was associated with similar OS and CSS and maintained similar toxicity risks compared with 3D-CRT. [Copyright &y& Elsevier]

Purpose: Approximately one half of the radiotherapy (RT) prescribed in the United States is delivered with palliative intent. The purpose of this study was to investigate the patterns of delivery of palliative RT across the United States. Methods: Using the Surveillance, Epidemiology, and End Results-Medicare linked database, 51,610 patients were identified with incident stage IV breast, prostate, lung, or colorectal cancer diagnosed between 2000 and 2007 and observed through 2009. Multivariate logistic regression determined predictors of palliative RT. Results: Forty-one percent of the study population received palliative RT, including 53% of patients with lung cancer, followed by those with breast (42%), prostate (40%), and colorectal cancers (12%). Multivariate analysis revealed that older patients (P = .001) and those with higher Charlson comorbidity scores (P = .001) were less likely to receive palliative RT. Black patients with prostate cancer were 20% less likely (P = .001), and black patients with colorectal cancer were 28% less likely (P = .001), than white patients to receive palliative RT. Among those treated with RT, 23% of patients with lung cancer died within 2 weeks of completing treatment, followed by those with colorectal (12%), breast (11%), and prostate cancers (8%). In addition to tumor site, significant predictors (P = .05) of death within 2 weeks of receiving RT included increased age, increased comorbidity, and male sex. Conclusion: Inequality in the receipt of palliative RT exists among the elderly and patients with comorbid conditions and varies with race. In addition, a significant number of patients die shortly after receiving RT. Understanding these patterns of care, along with further research into the underlying causes, will improve access and quality of palliative RT. [ABSTRACT FROM AUTHOR]

Background: Travel time to treatment facilities may impede the receipt of guideline-concordant treatment (GCT) among patients diagnosed with early-stage non-small cell lung cancer (ES-NSCLC). We investigated the relative contribution of travel time in the receipt of GCT among ES-NSCLC patients. Methods: We included 22,821 ES-NSCLC patients diagnosed in California from 2006–2015. GCT was defined using the 2016 National Comprehensive Cancer Network guidelines, and delayed treatment was defined as treatment initiation >6 versus ≤6 weeks after diagnosis. Mean-centered driving and public transit times were calculated from patients' residential block group centroid to the treatment facilities. We used logistic regression to estimate risk ratios and 95% confidence intervals (CIs) for the associations between patients' travel time and receipt of GCT and timely treatment, overall and by race/ethnicity and neighborhood socioeconomic status (nSES). Results: Overall, a 15-minute increase in travel time was associated with a decreased risk of undertreatment and delayed treatment. Compared to Whites, among Blacks, a 15-minute increase in driving time was associated with a 24% (95%CI = 8%-42%) increased risk of undertreatment, and among Filipinos, a 15-minute increase in public transit time was associated with a 27% (95%CI = 13%-42%) increased risk of delayed treatment. Compared to the highest nSES, among the lowest nSES, 15-minute increases in driving and public transit times were associated with 33% (95%CI = 16%-52%) and 27% (95%CI = 16%-39%) increases in the risk of undertreatment and delayed treatment, respectively. Conclusion: The benefit of GCT observed with increased travel times may be a 'Travel Time Paradox,' and may vary across racial/ethnic and socioeconomic groups. [ABSTRACT FROM AUTHOR]

Purpose: To determine how the respiratory phase impacts dose to normal organs during stereotactic body radiation therapy (SBRT) for pancreatic cancer. Methods and Materials: Eighteen consecutive patients with locally advanced, unresectable pancreatic adenocarcinoma treated with SBRT were included in this study. On the treatment planning 4-dimensional computed tomography (CT) scan, the planning target volume (PTV), defined as the gross tumor volume plus 3-mm margin, the duodenum, and the stomach were contoured on the end-expiration (CTexp) and end-inspiration (CTinsp) phases for each patient. A separate treatment plan was constructed for both phases with the dose prescription of 33 Gy in 5 fractions with 95% coverage of the PTV by the 100% isodose line. The dose-volume histogram (DVH) endpoints, volume of duodenum that received 20 Gy (V20), V25, and V30 and maximum dose to 5 cc of contoured organ (D5cc), D1cc, and D0.1cc, were evaluated. Results: Dosimetric parameters for the duodenum, including V25, V30, D1cc, and D0.1cc improved by planning on the CTexp compared to those on the CTinsp. There was a statistically significant overlap of the PTV with the duodenum but not the stomach during the CTinsp compared to the CTexp (0.38 ± 0.17 cc vs 0.01 ± 0.01 cc, P=.048). A larger expansion of the PTV, in accordance with a Danish phase 2 trial, showed even more overlapping volume of duodenum on the CTinsp compared to that on the CTexp (5.5 ± 0.9 cc vs 3.0 ± 0.8 cc, P=.0003) but no statistical difference for any stomach dosimetric DVH parameter. Conclusions: Dose to the duodenum was higher when treating on the inspiratory than on the expiratory phase. These data suggest that expiratory gating may be preferable to inspiratory breath-hold and free breathing strategies for minimizing risk of toxicity. [Copyright &y& Elsevier]

Abstract: Background and Purpose: To test whether 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) imaging metrics correlate with outcomes in patients with stage I non-small cell lung cancer (NSCLC) treated with stereotactic ablative radiotherapy (SABR). Material and Methods: Fifty-four patients with stage I NSCLC underwent pre-SABR PET at simulation and/or post-SABR PET within 6 months. We analyzed maximum standardized uptake value (SUVmax) and metabolic tumor volume defined using several thresholds (MTV50%, or MTV2, 4, 7, and 10). Endpoints included primary tumor control (PTC), progression-free survival (PFS), overall survival (OS) and cancer-specific survival (CSS). We performed Kaplan–Meier, competing risk, and Cox proportional hazards survival analyses. Results: Patients received 25–60Gy in 1 to 5 fractions. Median follow-up time was 13.2 months. The 1-year estimated PTC, PFS, OS and CSS were 100, 83, 87 and 94%, respectively. Pre-treatment SUVmax (p =0.014), MTV7 (p =0.0077), and MTV10 (p =0.0039) correlated significantly with OS. In the low-MTV7 vs. high-MTV7 sub-groups, 1-year estimated OS was 100 vs. 78% (p =0.0077) and CSS was 100 vs. 88% (p =0.082). Conclusions: In this hypothesis-generating study we identified multiple pre-treatment PET-CT metrics as potential predictors of OS and CSS in patients with NSCLC treated with SABR. These could aid risk-stratification and treatment individualization if validated prospectively. [Copyright &y& Elsevier]

Purpose: We have previously reported that metabolic tumor volume (MTV) obtained from pretreatment 18F-fluorodeoxydeglucose positron emission tomography (FDG PET)/ computed tomography (CT) predicted outcome in patients with head-and-neck cancer (HNC). The purpose of this study was to validate these results on an independent dataset, determine whether the primary tumor or nodal MTV drives this correlation, and explore the interaction with p16INK4a status as a surrogate marker for human papillomavirus (HPV). Methods and Materials: The validation dataset in this study included 83 patients with squamous cell HNC who had a FDG PET/CT scan before receiving definitive radiotherapy. MTV and maximum standardized uptake value (SUVmax) were calculated for the primary tumor, the involved nodes, and the combination of both. The primary endpoint was to validate that MTV predicted progression-free survival and overall survival. Secondary analyses included determining the prognostic utility of primary tumor vs. nodal MTV. Results: Similarly to our prior findings, an increase in total MTV of 17 cm3 (difference between the 75th and 25th percentiles) was associated with a 2.1-fold increase in the risk of disease progression (p = 0.0002) and a 2.0-fold increase in the risk of death (p = 0.0048). SUVmax was not associated with either outcome. Primary tumor MTV predicted progression-free (hazard ratio [HR] = 1.94; p < 0.0001) and overall (HR = 1.57; p < 0.0001) survival, whereas nodal MTV did not. In addition, MTV predicted progression-free (HR = 4.23; p < 0.0001) and overall (HR = 3.21; p = 0.0029) survival in patients with p16INK4a-positive oropharyngeal cancer. Conclusions: This study validates our previous findings that MTV independently predicts outcomes in HNC. MTV should be considered as a potential risk-stratifying biomarker in future studies of HNC. [ABSTRACT FROM AUTHOR]

Purpose: We previously showed that metabolic tumor volume (MTV) on positron emission tomography—computed tomography (PET-CT) predicts for disease recurrence and death in head-and-neck cancer (HNC). We hypothesized that increases in MTV over time would correlate with tumor growth and biology, and would predict outcome. We sought to examine tumor growth over time in serial pretreatment PET-CT scans. Methods and Materials: From 2006 to 2009, 51 patients had two PET-CT scans before receiving HNC treatment. MTV was defined as the tumor volume ≥50% of maximum SUV (SUVmax). MTV was calculated for the primary tumor, nodal disease, and composite (primary tumor + nodes). MTV and SUV velocity were defined as the change in MTV or SUVmax over time, respectively. Cox regression analyses were used to examine correlations between SUV, MTV velocity, and outcome (disease progression and overall survival). Results: The median follow-up time was 17.5 months. The median time between PET-CT scans was 3 weeks. Unexpectedly, 51% of cases demonstrated a decrease in SUVmax (average, −0.1 cc/week) and MTV (average, −0.3 cc/week) over time. Despite the variability in MTV, primary tumor MTV velocity predicted disease progression (hazard ratio 2.94; p = 0.01) and overall survival (hazard ratio 1.85; p = 0.03). Conclusions: Primary tumor MTV velocity appears to be a better prognostic indicator of disease progression and survival in comparison to nodal MTV velocity. However, substantial variability was found in PET-CT biomarkers between serial scans. Caution should be used when PET-CT biomarkers are integrated into clinical protocols for HNC. [ABSTRACT FROM AUTHOR]

BACKGROUND: Radiotherapy may improve the outcome of patients with pancreatic cancer but at an increased cost. In this study, the authors evaluated the cost-effectiveness of modern radiotherapy techniques in the treatment of locally advanced pancreatic cancer. METHODS: A Markov decision-analytic model was constructed to compare the cost-effectiveness of 4 treatment regimens: gemcitabine alone, gemcitabine plus conventional radiotherapy, gemcitabine plus intensity-modulated radiotherapy (IMRT); and gemcitabine with stereotactic body radiotherapy (SBRT). Patients transitioned between the following 5 health states: stable disease, local progression, distant failure, local and distant failure, and death. Health utility tolls were assessed for radiotherapy and chemotherapy treatments and for radiation toxicity. RESULTS: SBRT increased life expectancy by 0.20 quality-adjusted life years (QALY) at an increased cost of $13,700 compared with gemcitabine alone (incremental cost-effectiveness ratio [ICER] = $69,500 per QALY). SBRT was more effective and less costly than conventional radiotherapy and IMRT. An analysis that excluded SBRT demonstrated that conventional radiotherapy had an ICER of $126,800 per QALY compared with gemcitabine alone, and IMRT had an ICER of $1,584,100 per QALY compared with conventional radiotherapy. A probabilistic sensitivity analysis demonstrated that the probability of cost-effectiveness at a willingness to pay of $50,000 per QALY was 78% for gemcitabine alone, 21% for SBRT, 1.4% for conventional radiotherapy, and 0.01% for IMRT. At a willingness to pay of $200,000 per QALY, the probability of cost-effectiveness was 73% for SBRT, 20% for conventional radiotherapy, 7% for gemcitabine alone, and 0.7% for IMRT. CONCLUSIONS: The current results indicated that IMRT in locally advanced pancreatic cancer exceeds what society considers cost-effective. In contrast, combining gemcitabine with SBRT increased clinical effectiveness beyond that of gemcitabine alone at a cost potentially acceptable by today's standards. Cancer 2012;. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To explore the relationship between pathologic tumor volume and volume estimated from different tumor segmentation techniques on 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) in oral cavity cancer. Materials and methods: Twenty-three patients with squamous cell carcinoma of the oral tongue had PET–CT scans before definitive surgery. Pathologic tumor volume was estimated from surgical specimens. Metabolic tumor volume (MTV) was defined from PET–CT scans as the volume of tumor above a given SUV threshold. Multiple SUV thresholds were explored including absolute SUV thresholds, relative SUV thresholds, and gradient-based techniques. Results: Multiple MTV’s were associated with pathologic tumor volume; however the correlation was poor (R 2 range 0.29–0.58). The ideal SUV threshold, defined as the SUV that generates an MTV equal to pathologic tumor volume, was independently associated with maximum SUV (p =0.0005) and tumor grade (p =0.024). MTV defined as a function of maximum SUV and tumor grade improved the prediction of pathologic tumor volume (R 2 =0.63). Conclusions: Common SUV thresholds fail to predict pathologic tumor volume in head and neck cancer. The optimal technique that allows for integration of PET–CT with radiation treatment planning remains to be defined. Future investigation should incorporate biomarkers such as tumor grade into definitions of MTV. [Copyright &y& Elsevier]

Purpose: To explore the prognostic value of metabolic tumor volume measured on postradiation 18F-fluorodeoxyglucose positron emission tomography (PET) imaging in patients with head-and-neck cancer. Methods and Materials: Forty-seven patients with head-and-neck cancer who received pretreatment and posttreatment PET/computed tomography (CT) imaging along with definitive chemoradiotherapy were included in this study. The PET/CT parameters evaluated include the maximum standardized uptake value, metabolic tumor volume (MTV2.0–MTV4.0; where MTV2.0 refers to the volume above a standardized uptake value threshold of 2.0), and integrated tumor volume. Kaplan-Meier and Cox regression models were used to test for association between PET endpoints and disease-free survival and overall survival. Results: Multiple postradiation PET endpoints correlated significantly with outcome; however, the most robust predictor of disease progression and death was MTV2.0. An increase in MTV2.0 of 21cm3 (difference between 75th and 25th percentiles) was associated with an increased risk of disease progression (hazard ratio [HR] = 2.5, p = 0.0001) and death (HR = 2.0, p = 0.003). In patients with nonnasopharyngeal carcinoma histology (n = 34), MTV2.0 <18 cm3 and MTV2.0 ≥18 cm3 yielded 2-year disease-free survival rates of 100% and 63%, respectively (p = 0.006) and 2-year overall survival rates of 100% and 81%, respectively (p = 0.009). There was no correlation between MTV2.0 and disease-free survival or overall survival with nasopharyngeal carcinoma histology (n = 13). On multivariate analysis, only postradiation MTV2.0 was predictive of disease-free survival (HR = 2.47, p = 0.0001) and overall survival (HR = 1.98, p = 0.003). Conclusions: Postradiation metabolic tumor volume is an adverse prognostic factor in head-and-neck cancer. Biomarkers such as MTV are important for risk stratification and will be valuable in the future with risk-adapted therapies. [Copyright &y& Elsevier]

Introduction: Dose escalation for pancreas cancer is limited by the tolerance of adjacent normal tissues, especially with stereotactic body radiotherapy (SBRT). The duodenum is generally considered to be the organ at greatest risk. This study reports on the dosimetric determinants of duodenal toxicity with single-fraction SBRT. Methods and Materials: Seventy-three patients with locally advanced unresectable pancreatic adenocarcinoma received 25Gy in a single fraction. Dose–volume histogram (DVH) endpoints evaluated include V5 (volume of duodenum that received 5Gy), V10, V15, V20, V25, and Dmax (maximum dose to 1cm3). Normal tissue complication probability (NTCP) was evaluated with a Lyman model. Univariate and multivariate analyses were conducted with Kaplan-Meier and Cox regression models. Results: The median time to Grade 2–4 duodenal toxicity was 6.3 months (range, 1.6–11.8 months). The 6- and 12-month actuarial rates of toxicity were 11% and 29%, respectively. V10–V25 and Dmax all correlated significantly with duodenal toxicity (p <0.05). In particular, V15 ≥9.1cm3 and V15 <9.1cm3 yielded duodenal toxicity rates of 52% and 11%, respectively (p =0.002); V20 ≥3.3cm3 and V20 <3.3cm3 gave toxicity rates of 52% and 11%, respectively (p =0.002); and Dmax ≥23Gy and Dmax <23Gy gave toxicity rates of 49% and 12%, respectively (p =0.004). Lyman NTCP model optimization generated the coefficients m =0.23, n =0.12, and TD50 =24.6Gy. Only the Lyman NTCP model remained significant in multivariate analysis (p =0.001). Conclusions: Multiple DVH endpoints and a Lyman NTCP model are strongly predictive of duodenal toxicity after SBRT for pancreatic cancer. These dose constraints will be valuable in future abdominal SBRT studies. [Copyright &y& Elsevier]

Abstract: A wildfire burned through previously established research plots, allowing comparisons of pre- and post-fire nutrient pools and fluxes. The Gondola fire resulted in the loss of 30.9mgha−1 of C and 510kgha−1 of N, mostly by the combustion of forest floor and vegetation. Mineral N leaching was accelerated for 3 years after the fire, but accounted for only 19kgha−1 of the total N loss. Potential inputs of P by ash were small relative to soil extractable pools and no significant changes in soil extractable P were noted. No changes in exchangeable K+ were noted, even though inputs by ash could have been detected, suggesting that K was lost either during or after the fire. Similarly, decreases in soil exchangeable Mg2+ were noted even though ash inputs should have caused notable increases, suggesting Mg loss either during or after the fire. The increases in soil-exchangeable Ca2+ were large, but only marginally significant (P =0.09) and fell within the error bounds of what could have been input from ash. Comparisons with a nearby site that burned >20 years previously suggest that ecosystem C pools will not be made up for until trees are re-established at the Gondola fire, whereas N losses could be more than made up for within 20 years if N-fixing vegetation colonized the site. [Copyright &y& Elsevier]

Purpose: Full-dose gemcitabine and concurrent radiotherapy is a promising treatment approach in unresectable pancreatic cancer. This study was conducted to assess the pattern of failure and toxicity associated with the use of conformal treatment volumes, omitting prophylactic lymph node irradiation. Methods and Materials: Seventy-four patients with locally advanced pancreatic cancer were treated between 1997 and 2005 with full-dose (1000 mg/m2, Days 1, 8, and 15) gemcitabine and concurrent radiotherapy (36 Gy [median] in 15 daily fractions). The planning target volume (PTV) was limited to the gross tumor volume (GTV) plus 1-cm margin. Patient computed tomography (CT) scans were systematically reviewed to determine the pattern of failure. Kaplan-Meier and Cox-regression models were used to analyze freedom from local progression (FFLP), distant failure, overall survival (OS), and toxicity. Results: With a median follow-up of 10.6 months (20.6 months in living patients), the 1-year and 2-year FFLP rates were 64% and 38%, respectively. Four patients (5%) failed in the peripancreatic lymph nodes (3 in-field and 1 marginal failure). Median OS was 11.2 months. Analyzed as a time-dependent covariate, local failure was a significant predictor of OS (p = 0.0074). Sixteen patients (22%) had significant gastrointestinal (GI) toxicity (≥ Grade 3). PTV correlated with significant GI toxicity (p = 0.007). Conclusions: Freedom from local progression in unresectable pancreatic cancer is suboptimal. In conjunction with full-dose gemcitabine, the use of conformal fields encompassing only the GTV helps reduce toxicity and does not result in marginal failures. Our findings provide rationale for intensification of local therapy in conjunction with more effective systemic therapy. [Copyright &y& Elsevier]

PURPOSE: The quality of radiotherapy auto-segmentation training data, primarily derived from clinician observers, is of utmost importance. However, the factors influencing the quality of clinician-derived segmentations are poorly understood; our study aims to quantify these factors. METHODS: Organ at risk (OAR) and tumor-related segmentations provided by radiation oncologists from the Contouring Collaborative for Consensus in Radiation Oncology data set were used. Segmentations were derived from five disease sites: breast, sarcoma, head and neck (H&N), gynecologic (GYN), and GI. Segmentation quality was determined on a structure-by-structure basis by comparing the observer segmentations with an expert-derived consensus, which served as a reference standard benchmark. The Dice similarity coefficient (DSC) was primarily used as a metric for the comparisons. DSC was stratified into binary groups on the basis of structure-specific expert-derived interobserver variability (IOV) cutoffs. Generalized linear mixed-effects models using Bayesian estimation were used to investigate the association between demographic variables and the binarized DSC for each disease site. Variables with a highest density interval excluding zero were considered to substantially affect the outcome measure. RESULTS: Five hundred seventy-four, 110, 452, 112, and 48 segmentations were used for the breast, sarcoma, H&N, GYN, and GI cases, respectively. The median percentage of segmentations that crossed the expert DSC IOV cutoff when stratified by structure type was 55% and 31% for OARs and tumors, respectively. Regression analysis revealed that the structure being tumor-related had a substantial negative impact on binarized DSC for the breast, sarcoma, H&N, and GI cases. There were no recurring relationships between segmentation quality and demographic variables across the cases, with most variables demonstrating large standard deviations. CONCLUSION: Our study highlights substantial uncertainty surrounding conventionally presumed factors influencing segmentation quality relative to benchmarks. Common radiation oncologist demographic factors are not associated with segmentation performance. [ABSTRACT FROM AUTHOR]

To estimate the effect of platinum-based chemotherapy on live birth (LB) and infertility after cancer, in order to address a lack of treatment-specific fertility risks for female survivors of adolescent and young adult cancer, which limits counseling on fertility preservation decisions. Retrospective cohort study. US administrative database. We identified incident breast, colorectal, and ovarian cancer cases in females aged 15–39 years who received platinum-based chemotherapy or no chemotherapy and matched them to females without cancer. Platinum-based chemotherapy. We estimated the effect of chemotherapy on the incidence of LB and infertility after cancer, overall, and after accounting for competing events (recurrence, death, and sterilizing surgeries). There were 1,287 survivors in the chemotherapy group, 3,192 in the no chemotherapy group, and 34,147 women in the no cancer group, with a mean age of 33 years. Accounting for competing events, the overall 5-year LB incidence was lower in the chemotherapy group (3.9%) vs. the no chemotherapy group (6.4%). Adjusted relative risks vs. no chemotherapy and no cancer groups were 0.61 (95% confidence interval [CI] 0.42–0.82) and 0.70 (95% CI 0.51–0.93), respectively. The overall 5-year infertility incidence was similar in the chemotherapy group (21.8%) compared with the no chemotherapy group (20.7%). The adjusted relative risks vs. no chemotherapy and no cancer groups were 1.05 (95% CI 0.97–1.15) and 1.42 (95% CI 1.31–1.53), respectively. Cancer survivors treated with platinum-based chemotherapy experienced modestly increased adverse fertility outcomes. The estimated effects of platinum-based chemotherapy were affected by competing events, suggesting the importance of this analytic approach for interpretations that ultimately inform clinical fertility preservation decisions. [ABSTRACT FROM AUTHOR]

Background Opioid tapering in the general population is linked to increases in hospitalizations or emergency department visits related to psychiatric or drug-related diagnoses. Cancer survivors represent a unique population with different opioid indications, prescription patterns, and more frequent follow-up care. This study sought to describe patterns of opioid tapering among older cancer survivors and to test the hypothesis of whether older cancer survivors face increased risks of adverse events with opioid tapering. Methods Using the Surveillance, Epidemiology and End Results Medicare–linked database, we identified 15 002 Medicare-beneficiary cancer survivors diagnosed between 2010 and 2017 prescribed opioids consistently for at least 6 months after their cancer diagnosis. Tapering was defined as a binary time-varying event occurring with any monthly oral morphine equivalent reduction of 15% or more from the previous month. Primary diagnostic billing codes associated with emergency room or hospital admissions were used for the composite endpoint of psychiatric- or drug-related event(s). Results There were 3.86 events per 100 patient-months, with 97.8% events being mental health emergencies, 1.91% events being overdose emergencies, and 0.25% involving both. Using a generalized estimating equation for repeated measure time-based analysis, opioid tapering was not statistically associated with acute events in the 3-month posttaper period (odds ratio [OR] = 1.02; P  = .62) or at any point in the future (OR = 0.96; P  = .46). Conclusions Opioid tapering in older cancer survivors does not appear to be linked to a higher risk of acute psychiatric- or drug-related events, in contrast to prior research in the general population. [ABSTRACT FROM AUTHOR]

Presents several correspondence on medical care in Great Britain. Importance of the Independent Living Fund; Comments on the association of backache with epidural anesthesia following childbirth; Treatment of avulsed incisor teeth.

Background: This study was done to determine the representation of minorities, women, and the elderly in National Cancer Institute (NCI) clinical trials. Methods: This is an analysis in the NCI Clinical Data Update System. Patients were evaluated in breast, colorectal, lung, and prostate cancer trials from 2000 to 2019. Representation in a trial was determined by race/ethnicity, sex, and age. Secondarily, the change in trial participation by multivariable analysis by comparing years 2000 through 2004 to 2015 through 2019 was evaluated. Results: The cohort included 242,720 participants: 197,320 Non‐Hispanic White (81.3%), 21,190 Black (8.7%), 11,587 Hispanic (4.8%), and 6880 Asian/Pacific Islander (2.8%). Black and Hispanic patients were underrepresented for colorectal (odds ratio [OR], 0.58; 95% confidence interval [CI], 0.50‐0.67; P <.001 and OR, 0.74; 95% CI, 0.64‐0.87; P <.001, respectively), lung (OR, 0.83; 95% CI, 0.76‐0.91; P <.001 and 0.66; 95% CI, 0.57‐0.77; P <.001, respectively), and prostate cancer trials (OR, 0.85; 95% CI, 0.79‐0.92; P <.001 and OR, 0.58; 95% CI, 0.51‐0.66; P <.001) between 2015 and 2019. The odds of participation in 2015 to 2019 increased among Black patients in breast (OR, 2.19; 95% CI, 2.07‐%2.32; P <.001), lung (OR, 1.54; 95% CI, 1.38‐1.73; P <.001), and prostate cancer trials (OR, 1.14; 95% CI, 1.04‐1.26; P <.001). The odds of participation in a trial among Hispanic patients increased for breast (OR, 3.32; 95% CI, 3.09‐3.56; P <.001), colorectal (OR, 2.46; 95% CI, 2.04‐2.96; P <.001), lung (OR, 3.88; 95% CI, 3.20‐4.69; P <.001), and prostate cancer (OR, 1.70; 95% CI, 1.42‐2.04; P =.005). Conclusions: This study identified that Black and Hispanic patients remain underrepresented in trials, but in recent years, participation has increased. These findings indicate that minority participation has increased over time, but further efforts are needed. Minorities, women, and the elderly have remained underrepresented in clinical trials in recent years. However, some minority participation has increased in recent years. [ABSTRACT FROM AUTHOR]

Background: Increased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single‐institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC. Methods: This work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US‐population‐based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population. Results: A total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs. Conclusions: Our findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies. [ABSTRACT FROM AUTHOR]

Background: We assessed breast cancer mortality in older versus younger women according to race/ethnicity, neighborhood socioeconomic status (nSES), and health insurance status.Methods: The study included female breast cancer cases 18 years of age and older, diagnosed between 2005 and 2015 in the California Cancer Registry. Multivariable Cox proportional hazards modeling was used to generate hazard ratios (HR) of breast cancer specific deaths and 95% confidence intervals (CI) for older (60+ years) versus younger (< 60 years) patients separately by race/ethnicity, nSES, and health insurance status.Results: Risk of dying from breast cancer was higher in older than younger patients after multivariable adjustment, which varied in magnitude by race/ethnicity (P-interaction< 0.0001). Comparing older to younger patients, higher mortality differences were shown for non-Hispanic White (HR = 1.43; 95% CI, 1.36-1.51) and Hispanic women (HR = 1.37; 95% CI, 1.26-1.50) and lower differences for non-Hispanic Blacks (HR = 1.17; 95% CI, 1.04-1.31) and Asians/Pacific Islanders (HR = 1.15; 95% CI, 1.02-1.31). HRs comparing older to younger patients varied by insurance status (P-interaction< 0.0001), with largest mortality differences observed for privately insured women (HR = 1.51; 95% CI, 1.43-1.59) and lowest in Medicaid/military/other public insurance (HR = 1.18; 95% CI, 1.10-1.26). No age differences were shown for uninsured women. HRs comparing older to younger patients were similar across nSES strata.Conclusion: Our results provide evidence for the continued disparity in Black-White breast cancer mortality, which is magnified in younger women. Moreover, insurance status continues to play a role in breast cancer mortality, with uninsured women having the highest risk for breast cancer death, regardless of age. [ABSTRACT FROM AUTHOR]

The authors sought to determine the impact of selected social determinants of health (SDoH) on psychological health and well-being (defined as depression, cognition, and self-rated health) among Black and Hispanic/Latinx adults relative to White adults 51–89 years of age. Disparities in depressive symptomatology, cognition, and self-rated health were measured among 2,306 non–Hispanic/Latinx Black, 1,593 Hispanic/Latinx, and 7,244 non–Hispanic/Latinx White adults who participated in the Health and Retirement Study (N=11,143). Blinder-Oaxaca decomposition was used to examine whether differences in selected SDoH explained a larger share of the disparities than age, sex, measures of health, health behaviors, and health care utilization. Selected SDoH included education, parental education, number of years worked, marital status, veteran status, geographic residence, nativity status, income, and insurance coverage. Black and Hispanic/Latinx adults reported worse depressive symptomatology, cognition, and self-rated health than White adults. Selected SDoH were associated with a larger proportion of the Black–White disparities in depressive symptomatology (51%), cognition (39%), and self-rated health (37%) than were age, sex, measures of health, health behaviors, and health care utilization. SDoH were associated with a larger proportion of the Hispanic/Latinx–White disparity in cognition (76%) and self-rated health (75%), but age and physical health correlated with the disparity in depressive symptomatology (28%). Education, parental education, years worked, income, and insurance parity were SDoH associated with these disparities. Differences in SDoH underlie racial/ethnic disparities in depression, cognition, and self-rated health among older adults. Education, income, number of years worked, and insurance parity are key SDoH. [ABSTRACT FROM AUTHOR]

Background: Open cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is associated with high morbidity, which limits the degree to which patients may benefit from this therapy. This study aimed to determine the feasibility of laparoscopic CRS/HIPEC. Methods: This was a single institution prospective clinical trial and comparative study using historical controls. Patients with histologically confirmed peritoneal surface malignancy (PSM) of appendiceal, colorectal, ovarian, or primary peritoneal origin, peritoneal carcinomatosis index (PCI) ≤ 10 were eligible. Results: Clinical trial: 18 patients (median age 57 years, 39% female) with appendiceal (15) or colorectal (3) primary PSM underwent laparoscopic CRS/HIPEC. Median and range outcomes were: operative time 219 min (134–378), EBL 10 mL (0–100), time to return to bowel function 3 days (1–7), duration IV narcotic use 3 days (1–8), length of stay 6 days (3–11). All patients had a complete cytoreduction (CC-score 0). Three (17%) experienced minor morbidity, with no major morbidity or mortality. Median DFS and OS were not reached with median follow-up of 48 months. Comparative analysis: Laparoscopic approach associated with reduced time to return of bowel function (3 versus 4 days, p = 0.001), length of stay (8 versus 5 days, p < 0.001), and morbidity (16% versus 42%, p = 0.008). Independent predictors of DFS included prior chemotherapy (HR 5.07, 95% CI 1.85, 13.89; p = 0.002), and CC-score > 0 (HR 3.31, 95% CI 1.19, 9.41; p = 0.025), but not surgical approach. CC-score > 0 was the only independent predictor of OS (HR 10.12, 95% CI 2.16, 47.30, p = 0.003). Conclusions and relevance: Laparoscopic CRS/HIPEC should be considered for patients with PSM with low-volume disease, including those with adenocarcinoma histology. Trial registration: Clinicaltrials.gov; NCT02463877. [ABSTRACT FROM AUTHOR]

Purpose: To investigate a new clinical role for medical physicists in direct patient care with a prospective phase 2 clinical trial.Materials and Methods: Medical physicists participated in the Physics Direct Patient Care (PDPC) protocol, establishing independent professional relationships with radiation oncology patients. After attending a dedicated patient communication training program, medical physicists routinely met with patients for 2 physicist-patient consults to explain the treatment planning and delivery process, review the patient's treatment plan, and answer all technical questions. The first physicist-patient consult took place immediately before the computed tomography simulation, and the second took place immediately before the first treatment. Questionnaires were administered to each patient on the PDPC protocol at 3 time points to assess both anxiety and satisfaction. The first questionnaire was given shortly after the first physicist-patient consult, the second questionnaire was given shortly after the second physicist-patient consult, and the third questionnaire was given after the last treatment appointment, with no associated physicist-patient consult.Results: The mean patient anxiety score was considered to be low at all questionnaire time points. There was a statistically significant decrease (P < .0001) in anxiety from the simulation time point to the first treatment time point. The mean patient technical satisfaction score was considered to be high at all measurement time points. There was a statistically significant increase (P = .0012) in technical satisfaction from the simulation time point to the first treatment time point. There was a statistically significant decrease (P < .023) in technical satisfaction from the first treatment time point to the last treatment time point.Conclusions: Establishing a new clinical role for medical physicists and investigating its effects on patient anxiety and satisfaction have created the foundation for future studies. Based on the results of this trial, the PDPC protocol will be expanded to a larger group of medical physicists, radiation oncologists, and patient disease sites and investigated with a randomized phase 3 clinical trial. [ABSTRACT FROM AUTHOR]

Background: The 2018 US Preventive Services Task Force guidelines recommend individualizing prostate cancer screening in 55‐ to 69‐year‐old men. Given the higher incidence of prostate cancer in African American (AA) compared to non‐Hispanic White (NHW) men, this study compared reported rates of prostate‐specific antigen (PSA) screening hypothesizing that it would not be commensurate with the relative risk between these two groups. Methods: Using the 2020 Behavioral Risk Factor Surveillance System, we identified 43,685 men (40,301 NHW and 3384 AA) interviewed about PSA screening. Results: AA men had an odds ratio (OR) of 0.80 (95% confidence interval [CI], 0.69–0.93; p =.004) of reporting PSA screening; sequentially correcting for access to care, smoking, and age had minimal effect on this finding, but when correcting for income significantly attenuated this difference (OR, 0.95; 95% CI, 0.81–1.12). Further adding education level eliminated the effect size of AA race entirely with OR, 0.99 (95% CI, 0.84–1.17; p =.91). Further analysis found significant interaction between education and race, with college‐educated AA men having 1.42 OR of receiving screening compared to college‐educated NHW men. Conclusions: Despite prostate cancer being more common and having higher population‐level mortality in AA than NHW men, PSA screening and education patterns do not reflect this increased risk even when adjusting for health access disparities. The authors' findings of significant effect from both income and education suggest that systemic racism is an important factor in the observed difference in PSA screening between AA men and NHW men. Lay summary: In the United States, prostate cancer is more common in African American menNew guidelines from 2018 encourage physicians to consider risk factors in deciding whether or not to recommend screening, but overall African American men continue to be screened at a lower rate than non‐Hispanic White menThis effect disappears when correcting for income and education level, suggesting that several factors including systemic racism, medical mistrust, and self‐advocacy may impact this observed difference African American men continue to report lower rates of PSA screening compared to non‐Hispanic White men in a nationwide survey. This effect appears to be mediated by income and education, suggesting that systemic racism as well as self‐advocacy and medical mistrust may be responsible for this observed difference. [ABSTRACT FROM AUTHOR]

Purpose: To report the outcomes and toxicities in patients treated with intensity-modulated radiotherapy (IMRT) for pancreatic adenocarcinoma. Methods and Materials: Forty-seven patients with pancreatic adenocarcinoma were treated with IMRT between 2003 and 2008. Of these 47 patients, 29 were treated adjuvantly and 18 definitively. All received concurrent 5-fluorouracil chemotherapy. The treatment plans were optimized such that 95% of the planning target volume received the prescription dose. The median delivered dose for the adjuvant and definitive patients was 50.4 and 54.0 Gy, respectively. Results: The median age at diagnosis was 63.9 years. For adjuvant patients, the 1- and 2-year overall survival rate was 79% and 40%, respectively. The 1- and 2-year recurrence-free survival rate was 58% and 17%, respectively. The local-regional control rate at 1 and 2 years was 92% and 80%, respectively. For definitive patients, the 1-year overall survival, recurrence-free survival, and local-regional control rate was 24%, 16%, and 64%, respectively. Four patients developed Grade 3 or greater acute toxicity (9%) and four developed Grade 3 late toxicity (9%). Conclusions: Survival for patients with pancreatic cancer remains poor. A small percentage of adjuvant patients have durable disease control, and with improved therapies, this proportion will increase. Systemic therapy offers the greatest opportunity. The present results have demonstrated that IMRT is well tolerated. Compared with those who received three-dimensional conformal radiotherapy in previously reported prospective clinical trials, patients with pancreatic adenocarcinoma treated with IMRT in our series had improved acute toxicity. [ABSTRACT FROM AUTHOR]

Background: It has been observed that married cancer patients have lower mortality rates than unmarried patients, but data for different racial/ethnic groups are scarce. The authors examined the risk of overall mortality associated with marital status across racial/ethnic groups and sex in data from the California Cancer Registry.Methods: California Cancer Registry data for all first primary invasive cancers diagnosed from 2000 through 2009 for the 10 most common sites of cancer-related death for non-Hispanic whites (NHWs), blacks, Asians/Pacific Islanders (APIs), and Hispanics were used to estimate multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for marital status in relation to overall mortality by race/ethnicity and sex. The study cohort included 393,470 male and 389,697 female cancer patients and 204,007 and 182,600 deaths from all causes, respectively, through December 31, 2012.Results: All-cause mortality was higher in unmarried patients than in married patients, but there was significant variation by race/ethnicity. Adjusted HRs (95% CIs) ranged from 1.24 (95% CI, 1.23-1.26) in NHWs to 1.11 (95% CI, 1.07-1.15) in APIs among males and from 1.17 (95% CI, 1.15-1.18) in NHWs to 1.07 (95% CI, 1.04-1.11) in APIs among females. All-cause mortality associated with unmarried status compared with married status was higher in US-born API and Hispanic men and women relative to their foreign-born counterparts.Conclusions: For patients who have the cancers that contribute most to mortality, being unmarried is associated with worse overall survival compared with being married, with up to 24% higher mortality among NHW males but only 6% higher mortality among foreign-born Hispanic and API females. Future research should pursue the identification of factors underlying these associations to inform targeted interventions for unmarried cancer patients. Cancer 2016;122:1570-8. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

PURPOSE: Older hospitalized cancer patients face high risks of hospital mortality. Improved risk stratification could help identify high-risk patients who may benefit from future interventions, although we lack validated tools to predict in-hospital mortality for patients with cancer. We evaluated the ability of a high-dimensional machine learning prediction model to predict inpatient mortality and compared the performance of this model to existing prediction indices. METHODS: We identified patients with cancer older than 75 years from the National Emergency Department Sample between 2016 and 2018. We constructed a high-dimensional predictive model called Cancer Frailty Assessment Tool (cFAST), which used an extreme gradient boosting algorithm to predict in-hospital mortality. cFAST model inputs included patient demographic, hospital variables, and diagnosis codes. Model performance was assessed with an area under the curve (AUC) from receiver operating characteristic curves, with an AUC of 1.0 indicating perfect prediction. We compared model performance to existing indices including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score. RESULTS: We identified 2,723,330 weighted emergency department visits among older patients with cancer, of whom 144,653 (5.3%) died in the hospital. Our cFAST model included 240 features and demonstrated an AUC of 0.92. Comparator models including the Modified 5-Item Frailty Index, Charlson comorbidity index, and Hospital Frailty Risk Score achieved AUCs of 0.58, 0.62, and 0.71, respectively. Predictive features of the cFAST model included acute conditions (respiratory failure and shock), chronic conditions (lipidemia and hypertension), patient demographics (age and sex), and cancer and treatment characteristics (metastasis and palliative care). CONCLUSION: High-dimensional machine learning models enabled accurate prediction of in-hospital mortality among older patients with cancer, outperforming existing prediction indices. These models show promise in identifying patients at risk of severe adverse outcomes, although additional validation and research studying clinical implementation of these tools is needed. [ABSTRACT FROM AUTHOR]

Background: To test whether nomograms developed by NRG Oncology for oropharyngeal squamous cell carcinoma (OPSCC) patients could be validated in an independent population‐based sample. Methods: The authors tested nomograms for estimating progression‐free survival (PFS) and overall survival (OS) in patients from the Veterans Health Administration with previously untreated locoregionally advanced OPSCC, diagnosed between 2008 and 2017, managed with definitive radiotherapy with or without adjuvant systemic therapy. Covariates were age, performance status, p16 status, T/N category, smoking history, education history, weight loss, marital status, and anemia. We used multiple imputation to handle missing data and performed sensitivity analyses on complete cases. Validation was assessed via Cox proportional hazards models, log‐rank tests, and c‐indexes. Results: A total of 4007 patients met inclusion criteria (658 patients had complete data). Median follow‐up time was 3.20 years, with 967 progression events and 471 noncancer deaths. Each risk score was associated with poorer outcomes per unit increase (PFS score, hazard ratio [HR], 1.42 [1.37‐1.47]; OS score, HR, 1.40 [1.34‐1.45]). By risk score quartile, 2‐year PFS estimates were 89.2%, 78.5%, 65.8%, and 48.3%; OS estimates were 92.6%, 83.6%, 73.9%, and 51.3%, respectively (P <.01 for all comparisons). C‐indices for models of PFS and OS were 0.65 and 0.67, for all patients, respectively (0.69 and 0.73 for complete cases). The nomograms slightly overestimated PFS and OS in the overall cohort but exhibited high agreement in complete cases. Conclusions: NRG nomograms were effective for predicting PFS and OS for patients with OPSCC, supporting their broader applicability in the OPSCC population undergoing definitive radiotherapy. Nomograms, including ones created by the Radiation Therapy Oncology Group (RTOG), can significantly refine prognostication, but previous attempts at external validation have been unsuccessful, possibly related to the handling of missing data. The RTOG nomograms generally performed well for prediction and risk‐stratification, especially in patients without missing data, but slightly overestimated progression‐free survival and overall survival in the overall population. [ABSTRACT FROM AUTHOR]

Background: There is limited research on how the opioid epidemic and consequent risk reduction policies have affected pain management among cancer patients. The purpose of this study was to analyze how the Opioid Safety Initiative (OSI) implemented at the Veterans Health Administration affected opioid prescribing patterns and opioid-related toxicity.Methods: We performed an interrupted time series analysis of 42 064 opioid-naïve patients treated at the Veterans Health Administration for prostate, lung, breast, and colorectal cancer from 2011 to 2016. Segmented regression was used to evaluate the impact of the OSI on the incidence of any new opioid prescriptions, high-risk prescriptions, persistent use, and pain-related emergency department (ED) visits. We compared the cumulative incidence of adverse opioid events including an opioid-related admission or diagnosis of misuse before and after the OSI. All statistical tests were 2-sided.Results: The incidence of new opioid prescriptions was 26.7% (95% confidence interval [CI] = 25.0% to 28.4%) in 2011 and increased to 50.6% (95% CI = 48.3% to 53.0%) by 2013 before OSI implementation (monthly rate of change: +3.3%, 95% CI = 1.3% to 4.2%, P < .001). After the OSI, there was a decrease in the monthly rate of change for new prescriptions (-3.4%, 95% CI = -3.9 to -2.9%, P < .001). The implementation of the OSI was associated with a decrease in the monthly rate of change of concomitant benzodiazepines and opioid prescriptions (-2.5%, 95% CI = -3.2% to -1.8%, P < .001), no statistically significant change in high-dose opioids (-1.2%, 95% CI = -3.2% to 0.9%, P = .26), a decrease in persistent opioid use (-5.7%, 95% CI = -6.8% to -4.7%, P < .001), and an increase in pain-related ED visits (+3.0%, 95% CI = 1.0% to 5.0%, P = .003). The OSI was associated with a decreased incidence of opioid-related admissions (3-year cumulative incidence: 0.9% [95% CI = 0.7% to 1.0%] vs 0.5% [95% CI = 0.4% to 0.6%], P < .001) and no statistically significant change in the incidence of opioid misuse (3-year cumulative incidence: 1.2% [95% CI = 1.0% to 1.3%] vs 1.2% [95% CI = 1.1% to 1.4%], P = .77).Conclusions: The OSI was associated with a relative decline in the rate of new, persistent, and certain high-risk opioid prescribing as well as a slight increase in the rate of pain-related ED visits. Further research on patient-centered outcomes is required to optimize opioid prescribing policies for patients with cancer. [ABSTRACT FROM AUTHOR]

Objective: To compare antimüllerian hormone (AMH) patterns by cancer status and treatment exposures across 6 years after incident breast cancer using administrative data.Design: In a cross-sectional design, AMH levels in patients who developed incident breast cancer between ages 15-39 years during 2005-2019 were matched 1:10 to levels in females without cancer in the OptumLabs Data Warehouse. Modeled AMH patterns were compared among cyclophosphamide-based chemotherapy, non-cyclophosphamide-based chemotherapy, no chemotherapy, and no breast cancer groups.Setting: Commercially insured females in the United States.Patient(s): Females with and without breast cancer.Exposure(s): Breast cancer, cyclophosphamide- and non-cyclophosphamide-based chemotherapy.Main Outcome Measure(s): AMH levels.Result(s): A total of 233 patients with breast cancer (mean age, 34 years; standard deviation, 3.7 years) contributed 278 AMH levels over a median of 2 years (range, 0-6.7 years) after diagnosis; 52% received cyclophosphamide-based chemotherapy, 17% received non-cyclophosphamide-based chemotherapy (80% platinum-based), and 31% received no chemotherapy. A total of 2,777 matched females without cancer contributed 2,780 AMH levels. The pattern of AMH levels differed among the 4 groups. Among females without cancer and breast cancer survivors who did not undergo chemotherapy, AMH declined linearly over time. In contrast, among those who received cyclophosphamide-based and noncyclophosphamide-based chemotherapy, a nonlinear pattern of AMH level of initial fall during chemotherapy, followed by an increase over 2-4 years, and then by a plateau over 1-2 years before a decline was observed.Conclusion(s): In breast cancer survivors, AMH levels from administrative data supported ovarian toxicity of non-cyclophosphamide-based chemotherapy in breast cancer and efficiently depicted the timing and duration of changes in ovarian reserve to reflect the residual reproductive lifespan. [ABSTRACT FROM AUTHOR]

Objective: To determine the odds of accessing telemedicine either by phone or by video during the COVID-19 pandemic.Methods: We performed a retrospective study of patients who were seen at a single academic institution for a urologic condition between March 15, 2020 and September 30, 2020. The primary outcome was to determine characteristics associated with participating in a telemedicine appointment (video or telephone) using logistic regression multivariable analysis. We used a backward model selection and variables that were least significant were removed. We adjusted for reason for visit, patient characteristics such as age, sex, ethnicity, race, reason for visit, preferred language, and insurance. Variables that were not significant that were removed from our final model included median income estimated by zip code, clinic location, provider age, provider sex, and provider training.Results: We reviewed 4234 visits: 1567 (37%) were telemedicine in the form of video 1402 (33.1%) or telephone 164 (3.8%). The cohort consisted of 2516 patients, Non-Hispanic White (n = 1789, 71.1%) and Hispanic (n = 417, 16.6%). We performed multivariable logistic regression analysis and demonstrated that patients who were Hispanic, older, or had Medicaid insurance were significantly less likely to access telemedicine during the pandemic. We did not identify differences in telemedicine utilization when stratifying providers by their age, sex, or training type (physician or advanced practice provider).Conclusion: We conclude that there are differences in the use of telemedicine and that this difference may compound existing disparities in care. Additionally, we identified that these differences were not associated with provider attributes. Further study is needed to overcome barriers in access to telemedicine. [ABSTRACT FROM AUTHOR]

• In this study the authors present 20 years of National Cancer Institute data on clinical trial enrollment for Kidney and Bladder cancer. • The authors found that compared to cancer incidence, Black, Hispanic and Female patients were underrepresented in Bladder and Kidney Cancer trials. • Lastly, Black and female patient participation was consistently unchanged throughout the 20 year period. To determine the representation of women, minorities, and the elderly groups in clinical trials and whether participation has changed over time. Retrospective study in the National Cancer Institute (NCI) Clinical Data Update System and Center for Disease Control and Prevention United States Cancer Statistics 2000 to 2019. We compared cancer incidence proportion to proportion of patients enrolled in an NCI trial when stratified by race/ethnicity, sex, and age. We performed multivariable analysis to determine the odds of participating in a clinical trial in 2015 to 2019 when compared to 2000 to 2004. This study included 14,094 patients, 12,169 (86.3%) non-Hispanic White patients, 662 (4.7%) Black patients, and 660 (4.7%) Hispanic patients. There were 3,701 (26.3%) female patients and 10,393 (73.7%) male patients. For bladder cancer clinical trials, Black patients and Hispanic patients were underrepresented in clinical trials compared to Non-Hispanic White patients (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.57–0.88, P = 0.002) and (OR 0.69, 95%CI 0.54–0.88, P = 0.003), respectively. For kidney cancer trials, Black and Hispanic patients were underrepresented in clinical trials compared to Non-Hispanic White patients (OR 0.42, OR 0.33–0.54, P < 0.001) and (OR 0.68, 95% CI 0.55–0.83, P < 0.001), respectively. Women were underrepresented in kidney cancer trials compared to men (OR 0.80, 95% CI 0.72–0.89) and similarly for bladder cancer trials (OR 0.72, 95% CI 0.64–0.81, P < 0.001). For bladder cancer trials, the participation of Black patients over time (OR 1.04, P = 0.814) and female patients over time (OR 1.03, P = 0.741) were unchanged. For kidney cancer trials, the participation of Black patients over time (OR 1.17, P = 0.293) and female patients over time (OR 1.03, P = 0.663) participation was also unchanged. In this study of clinical trials in bladder and kidney cancer, we identified that Blacks, Hispanics, and females were underrepresented. Additionally, Black and female participation was unchanged over the span of 20 years. [ABSTRACT FROM AUTHOR]

Purpose/Objectives(s): Early-stage endometrial cancer patients are at higher risk of noncancer mortality than of cancer mortality. Competing event models incorporating comorbidity could help identify women most likely to benefit from treatment intensification. Methods and Materials: 67,397 women with stage I-II endometrioid adenocarcinoma after total hysterectomy diagnosed from 1988 to 2009 were identified in Surveillance, Epidemiology, and End Results (SEER) and linked SEER-Medicare databases. Using demographic and clinical information, including comorbidity, we sought to develop and validate a risk score to predict the incidence of competing mortality. Results: In the validation cohort, increasing competing mortality risk score was associated with increased risk of noncancer mortality (subdistribution hazard ratio [SDHR], 1.92; 95% confidence interval [CI], 1.60-2.30) and decreased risk of endometrial cancer mortality (SDHR, 0.61; 95% CI, 0.55-0.78). Controlling for other variables, Charlson Comorbidity Index (CCI) = 1 (SDHR, 1.62; 95% CI, 1.45-1.82) and CCI >1 (SDHR, 3.31; 95% CI, 2.74-4.01) were associated with increased risk of noncancer mortality. The 10-year cumulative incidences of competing mortality within low-, medium-, and high-risk strata were 27.3% (95% CI, 25.2%-29.4%), 34.6% (95% CI, 32.5%-36.7%), and 50.3% (95% CI, 48.2%-52.6%), respectively. With increasing competing mortality risk score, we observed a significant decline in omega (ω), indicating a diminishing likelihood of benefit from treatment intensification. Conclusion: Comorbidity and other factors influence the risk of competing mortality among patients with early-stage endometrial cancer. Competing event models could improve our ability to identify patients likely to benefit from treatment intensification. [Copyright &y& Elsevier]

Background: Oncology rapidly shifted to telemedicine in response to the COVID-19 pandemic. Telemedicine can increase access to healthcare, but recent research has shown disparities exist with telemedicine use during the pandemic. This study evaluated health disparities associated with telemedicine uptake during the COVID-19 pandemic among cancer patients in a tertiary care academic medical center. Methods: This retrospective cohort study evaluated telemedicine use among adult cancer patients who received outpatient medical oncology care within a tertiary care academic healthcare system between January and September 2020. We used multivariable mixed-effects logistic regression models to determine how telemedicine use varied by patient race/ethnicity, primary language, insurance status, and income level. We assessed geospatial links between zip-code level COVID-19 infection rates and telemedicine use. Results: Among 29,421 patient encounters over the study period, 8,541 (29%) were delivered via telemedicine. Several groups of patients were less likely to use telemedicine, including Hispanic (adjusted odds ratio [aOR] 0.86, p = 0.03), Asian (aOR 0.79, p = 0.002), Spanish-speaking (aOR 0.71, p = 0.0006), low-income (aOR 0.67, p < 0.0001), and those with Medicaid (aOR 0.66, p < 0.0001). Lower rates of telemedicine use were found in zip codes with higher rates of COVID-19 infection. Each 10% increase in COVID-19 infection rates was associated with an 8.3% decrease in telemedicine use (p = 0.002). Conclusions: This study demonstrates racial/ethnic, language, and income-level disparities with telemedicine use, which ultimately led patients with the highest risk of COVID-19 infection to use telemedicine the least. Additional research to better understand actionable barriers will help improve telemedicine access among our underserved populations. [ABSTRACT FROM AUTHOR]

Abstract: Objective: Primary squamous cell carcinoma (SCCA) of the vagina is a rare malignancy with limited data to guide treatment. We evaluated prognostic factors and outcomes for patients with primary vaginal SCCA treated with definitive radiation therapy at a single institution. Methods: A retrospective analysis was performed on patients treated for primary vaginal SCCA from 1959 to 2011. Results: Ninety-one patients with primary vaginal SCCA were treated with definitive radiation therapy. Thirty-eight patients had FIGO stage I, 28 stage II, 13 stage III, and 12 stage IV disease. The mean total dose was 70.1Gy. Two-year overall survival (OS), locoregional control rate (LRC), and distant metastasis-free survival by stage were, respectively: stage I: 96.2%, 80.6%, 87.5%; stage II: 92.3%, 64.7%, 84.6%; stage III: 66.6%, 44.4%, 50.0%; and stage IV: 25.0%, 14.3%, 25.0%. Treatment with total dose over 70Gy was associated with improved OS (p=0.0956) and LRC (p=0.055). There was a significant difference in median dose received by patients who developed grade 3/4 toxicity compared to those who did not (82.9Gy versus 70.0Gy, p=0.0019). None of the 10 patients treated with IMRT experienced locoregional recurrence or grade 3/4 toxicity. Tumor size larger than 4cm was associated with worse OS (p=0.0034) and LRC (p=0.006). Conclusions: Our analysis suggests that the optimal dose for definitive treatment of SCCA of the vagina lies between 70 and 80Gy. Treatment with IMRT may allow for dose escalation with reduced toxicity and excellent LRC. Tumor size over 4cm is associated with inferior outcomes and may require additional treatment modalities. [Copyright &y& Elsevier]

Purpose: Cancer patients frequently utilize the emergency department (ED) for a variety of diagnoses both related to and unrelated to their cancer, yet ED outcomes for cancer patients are not well documented. This study sought to define risks and identify predictors for inpatient admission and hospital mortality among cancer patients presenting to the ED. Patients and Methods: We utilized the National Emergency Department Sample to identify patients with and without a diagnosis of cancer presenting to the ED between January 2016 and December 2018. We used multivariable mixed-effects logistic regression models to assess the influence of cancer on outcomes of hospital admission after the ED visit and hospital mortality for the whole patient cohort and individual presenting diagnoses. Results: There were 340 million weighted ED visits, of which 8.3 million (2.3%) were associated with a cancer diagnosis. Compared to non-cancer patients, patients with cancer had an increased risk of inpatient admission (64.7% vs. 14.8%; p < 0.0001) and hospital mortality (4.6% vs. 0.5%; p < 0.0001). For each of the top 15 presenting diagnoses, cancer patients had increased risks of hospitalization (odds ratio [OR] range 2.0-13.2) or death (OR range 2.1-14.4). Although our dataset does not contain reliable estimation of stage, cancer site was the most robust individual predictor associated with the risk of hospitalization or death compared to other clinical or system-related factors. Conclusions: Cancer patients in the ED have high risks for hospital admission and death when compared to patients without cancer. Cancer patients represent a distinct population and may benefit from cancer-specific risk stratification or focused interventions to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Delivering linguistically competent care is critical to serving patients who have limited English proficiency (LEP) and represents a key national strategy to help reduce health disparities. Current acceptable standards of communication with patients who have LEP include providers communicating through professional interpretive services or bilingual providers speaking the patients' preferred language directly. This randomized clinical trial tests the effect of patient-provider language concordance on patient satisfaction.Methods and Materials: Eighty-three adult Spanish-speaking patients with cancer were randomly assigned to receive care from either (1) 1 of 2 bilingual physicians speaking to the patient directly in Spanish or (2) the same physicians speaking English and using a professional interpreter service. Validated questionnaires were administered to assess patient-reported satisfaction with both provider communication and overall care. Transcripts of initial consultations were analyzed for content variations.Results: Compared with patients receiving care through professional interpretive services, patients cared for in direct Spanish reported significantly improved general satisfaction, technical quality of care (mean composite score [MCS], 4.41 vs 4.06; P = .005), care team interpersonal manner (MCS, 4.37 vs 3.88; P = .004), communication (MCS, 4.50 vs 4.25; P = .018), and time spent with patient,(MCS, 4.30 vs 3.92; P = .028). Specific to physician communication, patients rated direct-Spanish care more highly in perceived opportunity to disclose concerns (MCS 4.91 vs 4.62; P = .001), physician empathy (MCS, 4.94 vs 4.59; P <.001), confidence in physician abilities (MCS, 4.84 vs 4.51; P = .001), and general satisfaction with their physician (MCS, 4.88 vs 4.59; P <.001). Analyzing the content of consultation encounters revealed differences between study arms, with the direct-Spanish arm having more physician speech related to patient history verification (mean number of utterances, 13 vs 9; P = .01) and partnering activities (mean utterances, 16 vs 5; P <.001). Additionally, patients in the direct-Spanish arm were more likely to initiate unprompted speech (mean utterances, 11 vs 3; P <.001) and asked their providers more questions (mean utterances, 11 vs 4; P = .007).Conclusions: This study shows improved patient-reported satisfaction among patients with cancer who had LEP and were cared for in direct Spanish compared with interpreter-based communication. Further research into interventions to mitigate the patient-provider language barrier is necessary to optimize care for this population. [ABSTRACT FROM AUTHOR]

Purpose: Our purpose was to investigate the effect of automated knowledge-based planning (KBP) on real-world clinical workflow efficiency, assess whether manual refinement of KBP plans improves plan quality across multiple disease sites, and develop a data-driven method to periodically improve KBP automated planning routines.Methods and Materials: Using clinical knowledge-based automated planning routines for prostate, prostatic fossa, head and neck, and hypofractionated lung disease sites in a commercial KBP solution, workflow efficiency was compared in terms of planning time in a pre-KBP (n = 145 plans) and post-KBP (n = 503) patient cohort. Post-KBP, planning was initialized with KBP (KBP-only) and subsequently manually refined (KBP +human). Differences in planning time were tested for significance using a 2-tailed Mann-Whitney U test (P < .05, null hypothesis: planning time unchanged). Post-refinement plan quality was assessed using site-specific dosimetric parameters of the original KBP-only plan versus KBP +human; 2-tailed paired t test quantified statistical significance (Bonferroni-corrected P < .05, null hypothesis: no dosimetric difference after refinement). If KBP +human significantly improved plans across the cohort, optimization objectives were changed to create an updated KBP routine (KBP'). Patients were replanned with KBP' and plan quality was compared with KBP +human as described previously.Results: KBP significantly reduced planning time in all disease sites: prostate (median: 7.6 hrs → 2.1 hrs; P < .001), prostatic fossa (11.1 hrs → 3.7 hrs; P = .001), lung (9.9 hrs → 2.0 hrs; P < .001), and head and neck (12.9 hrs → 3.5 hrs; P <.001). In prostate, prostatic fossa, and lung disease sites, organ-at-risk dose changes in KBP +human versus KBP-only were minimal (<1% prescription dose). In head and neck, KBP +human did achieve clinically relevant dose reductions in some parameters. The head and neck routine was updated (KBP'HN) to incorporate dose improvements from manual refinement. The only significant dosimetric differences to KBP +human after replanning with KBP'HN were in favor of the new routine.Conclusions: KBP increased clinical efficiency by significantly reducing planning time. On average, human refinement offered minimal dose improvements over KBP-only plans. In the single disease site where KBP +human was superior to KBP-only, differences were eliminated by adjusting optimization parameters in a revised KBP routine. [ABSTRACT FROM AUTHOR]

Background: Despite guideline recommendations, utilization of low‐dose computed tomography (LDCT) for lung cancer screening remains low. The driving factors behind these low rates and the real‐world effect of LDCT utilization on lung cancer outcomes remain limited. Methods: We identified patients diagnosed with non‐small cell lung cancer (NSCLC) from 2015 to 2017 within the Veterans Health Administration. Multivariable logistic regression assessed the influence of LDCT screening on stage at diagnosis. Lead time correction using published LDCT lead times was performed. Cancer‐specific mortality (CSM) was evaluated using Fine–Gray regression with non‐cancer death as a competing risk. A lasso machine learning model identified important predictors for receiving LDCT screening. Results: Among 4664 patients, mean age was 67.8 with 58‐month median follow‐up, 95% CI = [7–71], and 118 patients received ≥1 screening LDCT before NSCLC diagnosis. From 2015 to 2017, LDCT screening increased (0.1%–6.6%, mean = 1.3%). Compared with no screening, patients with ≥1 LDCT were more than twice as likely to present with stage I disease at diagnosis (odds ratio [OR] 2.16 [95% CI 1.46–3.20]) and less than half as likely to present with stage IV (OR 0.38 [CI 0.21–0.70]). Screened patients had lower risk of CSM even after adjusting for LDCT lead time (subdistribution hazard ratio 0.60 [CI 0.42–0.85]). The machine learning model achieved an area under curve of 0.87 and identified diagnosis year and region as the most important predictors for receiving LDCT. White, non‐Hispanic patients were more likely to receive LDCT screening, whereas minority, older, female, and unemployed patients were less likely. Conclusions: Utilization of LDCT screening is increasing, although remains low. Consistent with randomized data, LDCT‐screened patients were diagnosed at earlier stages and had lower CSM. LDCT availability appeared to be the main predictor of utilization. Providing access to more patients, including those in diverse racial and socioeconomic groups, should be a priority. [ABSTRACT FROM AUTHOR]

Background: Disparities in prostate cancer-specific mortality (PCSM) between African American and non-Hispanic White (White) patients have been attributed to biological and systemic factors. We evaluated drivers of these disparities in the Surveillance, Epidemiology, and End Results (SEER) national registry and an equal-access system, the Veterans Health Administration (VHA).Methods: We identified African American and White patients diagnosed with prostate cancer between 2004 and 2015 in SEER (n = 311 691) and the VHA (n = 90 749). We analyzed the association between race and metastatic disease at presentation using multivariable logistic regression adjusting for sociodemographic factors and PCSM using sequential competing-risks regression adjusting for disease and sociodemographic factors.Results: The median follow-up was 5.3 years in SEER and 4.7 years in the VHA. African American men were more likely than White men to present with metastatic disease in SEER (adjusted odds ratio = 1.23, 95% confidence interval [CI] = 1.17 to 1.30) but not in the VHA (adjusted odds ratio = 1.07, 95% CI = 0.98 to 1.17). African American vs White race was associated with an increased risk of PCSM in SEER (subdistribution hazard ratio [SHR] = 1.32, 95% CI = 1.10 to 1.60) but not in the VHA (SHR = 1.00, 95% CI = 0.93 to 1.08). Adjusting for disease extent, prostate-specific antigen, and Gleason score eliminated the association between race and PCSM in SEER (aSHR = 1.04, 95% CI = 0.93 to 1.16).Conclusions: Racial disparities in PCSM were present in a nationally representative registry but not in an equal-access health-care system, because of differences in advanced disease at presentation. Strategies to increase health-care access may bridge the racial disparity in outcomes. Longer follow-up is needed to fully assess mortality outcomes. [ABSTRACT FROM AUTHOR]

Background: Adjuvant ipilimumab was found to improve the overall survival and reduce toxicity compared to high‐dose interferon (HDI) in patients with resected, high‐risk melanoma. However, the cost of ipilimumab is substantially higher than HDI. This study evaluates the cost‐effectiveness of ipilimumab as an adjuvant treatment in melanoma from a healthcare perspective. Methods: We designed a Markov model simulating resected, high‐risk melanoma patients receiving either ipilimumab or HDI. Transition probabilities, including risks of survival, disease progression, and toxicity, were ascertained from clinical trial data. Costs and quality of life measurements (health utilities) were extracted from the literature. Incremental cost‐effectiveness ratios (ICERs), defined as incremental costs divided by incremental quality‐adjusted life‐years (QALYs), assessed cost‐effectiveness. ICERs <$100,000/QALY were deemed cost‐effective. We measured model uncertainty with one‐way and probabilistic sensitivity analyses. Results: In our base case model, ipilimumab increased costs by $107,100 and increased effectiveness by 0.43 QALY, yielding an ICER of $392,600/QALY. Our model was moderately sensitive to the costs of ipilimumab, though the cost of ipilimumab would need to decrease by 44% for ipilimumab to become cost‐effective compared to HDI. The model was not sensitive to survival, toxicity, or other costs. Probabilistic sensitivity analysis showed that HDI would remain the cost‐effective treatment option 96.2% of the time at a willingness‐to‐pay threshold of $100,000/QALY. Conclusions: Adjuvant ipilimumab increases the survival and decreases the toxicity compared to HDI in resected, high‐risk melanoma patients, though this would not be considered cost‐effective due to the high price of ipilimumab. [ABSTRACT FROM AUTHOR]

Purpose: To report outcomes in patients treated with intensity-modulated radiotherapy (IMRT) for tumors of the paranasal sinuses and nasal cavity (PNS/NC). Methods/Materials: Between June 2000 and December 2009, 52 patients with tumors of the PNS/NC underwent postoperative or definitive radiation with IMRT. Twenty-eight (54%) patients had squamous cell carcinoma (SCC). Twenty-nine patients (56%) received chemotherapy. The median follow-up was 26.6 months (range, 2.9–118.4) for all patients and 30.9 months for living patients. Results: Eighteen patients (35%) developed local-regional failure (LRF) at median time of 7.2 months. Thirteen local failures (25%) were observed, 12 in-field and 1 marginal. Six regional failures were observed, two in-field and four out-of-field. No patients treated with elective nodal radiation had nodal regional failure. Two-year local-regional control (LRC), in-field LRC, freedom from distant metastasis (FFDM), and overall survival (OS) were 64%, 74%, 71%, and 66% among all patients, respectively, and 43%, 61%, 61%, and 53% among patients with SCC, respectively. On multivariate analysis, SCC and >1 subsite involved had worse LRC (p = 0.0004 and p = 0.046, respectively) and OS (p = 0.003 and p = 0.046, respectively). Cribriform plate invasion (p = 0.005) and residual disease (p = 0.047) also had worse LRC. Acute toxicities included Grade ≥3 mucositis in 19 patients (37%), and Grade 3 dermatitis in 8 patients (15%). Six patients had Grade ≥3 late toxicity including one optic toxicity. Conclusions: IMRT for patients with PNS/NC tumors has good outcomes compared with historical series and is well tolerated. Patients with SCC have worse LRC and OS. LRF is the predominant pattern of failure. [Copyright &y& Elsevier]