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IntroductionOlder adults living with Alzheimer's disease and related dementias (ADRD) who are then diagnosed with cancer are an understudied population. While the role of cognitive impairment during and after cancer treatment have been well-studied, less is understood about patients who are living with ADRD and then develop cancer. The purpose of this study is to contribute evidence about our understanding of this vulnerable population.Materials and methodsThis was a retrospective cohort study of a linked, representative family of databases of cancer registries and Medicare administrative claims that make up the SEER-Medicare database. Older adults ages 68 and older with a first primary cancer type: breast, cervical, colorectal, lung, oral, or prostate were eligible for inclusion (N = 337,932). Prevalence estimates of ADRD across cancer types and a 5% non-cancer comparison sample were compared by patient factors.ResultsThe overall prevalence of patients who had an ADRD diagnosis anytime in the three years prior to their cancer diagnosis was 5.6%. Patients with ADRD were more likely to be female, older (over age 75), a racial/ethnic minority, single, with multiple chronic conditions, and a tumor diagnosed early (stage I) or were unstaged. Black patients with colorectal and oral cancer had the highest and second highest prevalence of ADRD compared to White patients (13.46% vs 7.95% and 12.64% vs 7.82% respectively, p  .0001).DiscussionThe higher prevalence of ADRD among Black and Latine older adults with cancer not only aligns with the trend observed in our non-cancer comparison sample, but also, these findings demonstrate the compounded risk experienced by minoritized older adults over the life course. The greater than expected prevalence of patients with ADRD who go on to develop cancer demonstrates better assessment of cognition is urgently needed. Accurate identification of these vulnerable populations is critical to improve assessment, care coordination, and address inequities in screening and treatment planning.

Clinician generated segmentation of tumor and healthy tissue regions of interest (ROIs) on medical images is crucial for radiotherapy. However, interobserver segmentation variability has long been considered a significant detriment to the implementation of high-quality and consistent radiotherapy dose delivery. This has prompted the increasing development of automated segmentation approaches. However, extant segmentation datasets typically only provide segmentations generated by a limited number of annotators with varying, and often unspecified, levels of expertise. In this data descriptor, numerous clinician annotators manually generated segmentations for ROIs on computed tomography images across a variety of cancer sites (breast, sarcoma, head and neck, gynecologic, gastrointestinal; one patient per cancer site) for the Contouring Collaborative for Consensus in Radiation Oncology challenge. In total, over 200 annotators (experts and non-experts) contributed using a standardized annotation platform (ProKnow). Subsequently, we converted Digital Imaging and Communications in Medicine data into Neuroimaging Informatics Technology Initiative format with standardized nomenclature for ease of use. In addition, we generated consensus segmentations for experts and non-experts using the Simultaneous Truth and Performance Level Estimation method. These standardized, structured, and easily accessible data are a valuable resource for systematically studying variability in segmentation applications.

BackgroundThere 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.MethodsWe 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.ResultsThe 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

ObjectiveTo analyse the effect of age at diagnosis on clinical outcomes of localized prostate cancer (PCa) treated with radiation therapy.Subjects and methodsWe identified 12 784 patients with intermediate- or high-risk localized PCa treated with radiation therapy (RT) and neoadjuvant androgen deprivation therapy (ADT) between 2000 and 2015 from nationwide Veterans Affairs data. Patients were grouped into three age categories (≤59, 60-69, and ≥70 years old). Outcomes included immediate PSA response (3-month post-RT PSA and 2-year PSA nadir, grouped into

BackgroundEarly experience with indocyanine green-based fluorescent cholangiography during laparoscopic cholecystectomy suggests the potential to improve outcomes. However, the cost-effectiveness of routine use has not been studied. Our objective was to evaluate the cost-effectiveness of fluorescent cholangiography versus standard bright light laparoscopic cholecystectomy for noncancerous gallbladder disease.MethodsA Markov model decision analysis was performed comparing fluorescent cholangiography versus standard bright light laparoscopic cholecystectomy alone. Probabilities of outcomes, survival, toxicities, quality-adjusted life-years, and associated costs were determined from literature review and pooled analysis of currently available studies on fluorescent cholangiography (n = 37). Uncertainty in the model parameters was evaluated with 1-way and probabilistic sensitivity analyses, varying parameters up to 40% of their means. Cost-effectiveness was measured with an incremental cost-effectiveness ratio expressed as the dollar amount per quality-adjusted life-year.ResultsThe model predicted that fluorescent cholangiography reduces lifetime costs by $1,235 per patient and improves effectiveness by 0.09 quality-adjusted life-years compared to standard bright light laparoscopic cholecystectomy. Reduced costs were due to a decreased operative duration (21.20 minutes, P < .0001) and rate of conversion to open (1.62% vs 6.70%, P < .0001) associated with fluorescent cholangiography. The model was not influenced by the rate of bile duct injury. Probabilistic sensitivity analysis found that fluorescent cholangiography was both more effective and less costly in 98.83% of model iterations at a willingness-to-pay threshold of $100,000/quality-adjusted life year.ConclusionThe current evidence favors routine use of fluorescent cholangiography during laparoscopic cholecystectomy as a cost-effective surgical strategy. Our model predicts that fluorescent cholangiography reduces costs while improving health outcomes, suggesting fluorescence imaging may be considered standard surgical management for noncancerous gallbladder disease. Further study with prospective trials should be considered to verify findings of this predictive model.

ObjectiveTo determine the odds of accessing telemedicine either by phone or by video during the COVID-19 pandemic.MethodsWe 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.ResultsWe 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).ConclusionWe 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.

BackgroundOncology 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.MethodsThis 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.ResultsAmong 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

BackgroundTravel 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.MethodsWe 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).ResultsOverall, 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.ConclusionThe benefit of GCT observed with increased travel times may be a 'Travel Time Paradox,' and may vary across racial/ethnic and socioeconomic groups.

Although Affordable Care Act (ACA) implementation has improved cancer outcomes, less is known about how much the improvement applies to different racial and ethnic populations. We examined changes in health insurance coverage and cancer-specific mortality rates by race/ethnicity pre- and post-ACA. We identified newly diagnosed breast (n = 117,738), colorectal (n = 38,334), and cervical cancer (n = 11,109) patients < 65 years in California 2007-2017. Hazard rate ratios (HRR) and 95% confidence intervals (CI) were calculated using multivariable Cox regression to estimate risk of cancer-specific death pre- (2007-2010) and post-ACA (2014-2017) and by race/ethnicity [American Indian/Alaska Natives (AIAN); Asian American; Hispanic; Native Hawaiian or Pacific Islander (NHPI); non-Hispanic Black (NHB); non-Hispanic white (NHW)]. Cancer-specific mortality from colorectal cancer was lower post-ACA among Hispanic (HRR = 0.82, 95% CI = 0.74 to 0.92), NHB (HRR = 0.69, 95% CI = 0.58 to 0.82), and NHW (HRR = 0.90; 95% CI = 0.84 to 0.97) but not Asian American (HRR = 0.95, 95% CI = 0.82 to 1.10) patients. We observed a lower risk of death from cervical cancer post-ACA among NHB women (HRR = 0.68, 95% CI = 0.47 to 0.99). No statistically significant differences in breast cancer-specific mortality were observed for any racial or ethnic group. Cancer-specific mortality decreased following ACA implementation for colorectal and cervical cancers for some racial and ethnic groups in California, suggesting Medicaid expansion is associated with reductions in health inequity.

PurposeColorectal cancer (CRC) is a leading cause of international morbidity and is the second highest cause of cancer-related mortality in the world. The purpose of this study was to investigate the relationship between international health care spending on CRC mortality over time.MethodsThis is a retrospective study using a publicly available data from the WHO Global Health Observatory database. General estimating equations were used to analyze the relationship between total health care expenditure per capita (THEpc) and CRC mortality at the country level. The primary predictors of interest were quartiles of THEpc. Other exposure variables included gross domestic product per capita (GDPpc), smoking (% of adult population smoking), physician density (per 10,000), and time.ResultsMortality decreased significantly from 2000 to 2016 (coefficient [95% CI], -2.2 [-3.3 to -1.1]; P < .001). THEpc, GDPpc, time, and percentage of adult population smoking were significant predictors of CRC mortality. Patients in the top two quartiles of THEpc had 3% higher rates of CRC mortality compared with countries in Q1 THEpc (Q3: 3.4 [1.9-4.8], P < .001; Q4: 3.2 [1.4-5.0], P = .001). Similar trends were seen in GDPpc (Q4: 3.2 [1.4-5.0], P = .001; Q3: 3.4 [1.9-4.8], P < .001; Q2: 1.7 [0.7-2.6], P < .001; Q1: reference).ConclusionOverall, mortality decreased significantly over the study period. Countries with higher health expenditures and higher gross domestic products experienced higher rates of CRC mortality. Further research will be necessary to determine the cause for this, but we postulate that it may be a result of more robust diagnostic and follow-up methods in countries with more resources.

PurposeDelivering 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 materialsEighty-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.ResultsCompared 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

BackgroundDisparities 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).MethodsWe 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.ResultsThe 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).ConclusionsRacial 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.

PurposeMinority race and lower socioeconomic status are associated with lower rates of opioid prescription and undertreatment of pain in multiple noncancer healthcare settings. It is not known whether these differences in opioid prescribing exist among patients undergoing cancer treatment.Methods and materialsThis observational cohort study involved 33,872 opioid-naive patients of age > 65 years undergoing definitive cancer treatment. We compared rates of new opioid prescriptions by race or ethnicity and socioeconomic status controlling for differences in baseline patient, cancer, and treatment factors. To evaluate downstream impacts of opioid prescribing and pain management, we also compared rates of persistent opioid use and pain-related emergency department (ED) visits.ResultsCompared with non-Hispanic White patients, the covariate-adjusted odds of receiving an opioid prescription were 24.9% (95% CI, 16.0 to 33.9, P < .001) lower for non-Hispanic Blacks, 115.0% (84.7 to 150.3, P < .001) higher for Asian-Pacific Islanders, and not statistically different for Hispanics (-1.0 to 14.0, P = .06). There was no significant association between race or ethnicity and persistent opioid use or pain-related ED visits. Patients living in a high-poverty area had higher odds (53.9% [25.4 to 88.8, P < .001]) of developing persistent use and having a pain-related ED visit (39.4% [16.4 to 66.9, P < .001]).ConclusionFor older patients with cancer, rates of opioid prescriptions and pain-related outcomes significantly differed by race and area-level poverty. Non-Hispanic Black patients were associated with a significantly decreased likelihood of receiving an opioid prescription. Patients from high-poverty areas were more likely to develop persistent opioid use and have a pain-related ED visit.

BackgroundWe assessed breast cancer mortality in older versus younger women according to race/ethnicity, neighborhood socioeconomic status (nSES), and health insurance status.MethodsThe 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 (

PurposeTo provide insight into the types of questions asked to medical physicists by patients during one-on-one physicist-patient consults at one institution.Materials and methodsMedical physicists trained in patient communication techniques met with patients to provide an overview of the treatment planning and delivery processes, discuss the patient's treatment plan, and answer any technical questions. From August 2016 to December 2019, 152 physicist-patient consults were conducted. In the initial months of the study (August 2016-December 2017), following each physicist-patient consult, all patient questions were documented by the physicists. For the remaining time period (January 2018-December 2019), any newly encountered questions were periodically added to the list. The questions were compiled into a comprehensive list and organized into categories.ResultsThere were a total of 88 unique patient questions. These questions fit into four topical categories. Fifty-four questions (61.4%) were in the "Treatment Planning and Delivery Questions" category, 15 questions (17.1%) were in the "General Radiation Questions or Concerns" category, 13 questions (14.8%) were in the "Safety and Quality Assurance Questions" category, and 6 questions (6.8%) were in the "Medical Questions" category. Overall, patients were primarily concerned about how radiation works, the treatment planning and delivery processes, and what is being done to keep them safe throughout their treatment.ConclusionPhysicist-patient consults provided an opportunity to address the technical aspects of radiation therapy with patients in greater detail. The fact that patient questions could be conveniently grouped into only four topical categories indicates that it may be straightforward for other medical physicists to prepare for effectively addressing technical questions during physicist-patient consults.

BackgroundAlthough opioids play a critical role in the management of cancer pain, the ongoing opioid epidemic has raised concerns regarding their persistent use and abuse. We lack data-driven tools in oncology to understand the risk of adverse opioid-related outcomes. This project seeks to identify clinical risk factors and create a risk score to help identify patients at risk of persistent opioid use and abuse.MethodsWithin a cohort of 106 732 military veteran cancer survivors diagnosed between 2000 and 2015, we determined rates of persistent posttreatment opioid use, diagnoses of opioid abuse or dependence, and admissions for opioid toxicity. A multivariable logistic regression model was used to identify patient, cancer, and treatment risk factors associated with adverse opioid-related outcomes. Predictive risk models were developed and validated using a least absolute shrinkage and selection operator regression technique.ResultsThe rate of persistent opioid use in cancer survivors was 8.3% (95% CI = 8.1% to 8.4%); the rate of opioid abuse or dependence was 2.9% (95% CI = 2.8% to 3.0%); and the rate of opioid-related admissions was 2.1% (95% CI = 2.0% to 2.2%). On multivariable analysis, several patient, demographic, and cancer and treatment factors were associated with risk of persistent opioid use. Predictive models showed a high level of discrimination when identifying individuals at risk of adverse opioid-related outcomes including persistent opioid use (area under the curve [AUC] = 0.85), future diagnoses of opioid abuse or dependence (AUC = 0.87), and admission for opioid abuse or toxicity (AUC = 0.78).ConclusionThis study demonstrates the potential to predict adverse opioid-related outcomes among cancer survivors. With further validation, personalized risk-stratification approaches could guide management when prescribing opioids in cancer patients.

PurposeOlder patients undergoing radiation therapy (RT) for pelvic malignancies are at increased risk for pelvic fracture, which is associated with significant morbidity and mortality. RT techniques such as brachytherapy or intensity modulated RT (IMRT) allow for more conformal dose distributions, but it is not known whether the risk for pelvic fracture varies by RT modality.Methods and materialsThis observational cohort study involved 28,354 patients ≥65 years old, treated with RT for pelvic malignancies. We evaluated the relative risk of pelvic fracture by type of RT when accounting for baseline factors. To test for nonspecific effects, we also evaluated risk of nonpelvic fractures in the same population.ResultsThe 5-year incidence of pelvic fractures was 12.7% (95% confidence interval [CI], 11.6%-13.8%), 11.8% (10.8%-12.8%), and 3.7% (3.4%-4.0%) for patients with gastrointestinal, gynecologic, and prostate cancer, respectively. On multivariable analysis, being treated with IMRT (hazard ratio, 0.85; 95% CI, 0.73-0.99) or brachytherapy therapy alone (hazard ratio, 0.43; 95% CI, 0.34-0.54) was associated with a reduced hazard for pelvic fractures compared with 3D conformal radiation therapy in female patients. In contrast, there was no association with RT modality and the hazard for nonpelvic fractures among females. There was no significant association between pelvic fractures and IMRT or brachytherapy for male patients. White race, advanced age, and higher comorbidity were associated with an increased hazard for pelvic fracture.ConclusionsIMRT and brachytherapy were associated with a reduced risk of pelvic fractures in older women undergoing RT for pelvic malignancies. Pelvic insufficiency fracture risk should be considered when treating with pelvic RT.

Purpose of reviewAdverse effects of sedative-hypnotic medications on cognition are concerning. Past studies have examined benzodiazepine (BZD) use and cognitive outcomes; however, few studies have examined newer non-BZD hypnotic agents (nBHs; e.g. zolpidem). This systematic review examined observational studies assessing the association between nBH use and cognitive outcomes.Recent findingsFive studies met eligibility requirements and were included in the review. Most studies did not find an association between nBH use and dementia diagnosis; however, we found no studies assessing other cognitive outcomes such as cognitive performance (e.g., word recall tasks). Characterization of nBH use mostly consisted of incident new use; one study assessed nBH dosing; none examined duration of use. Studies included were of strong quality.SummaryThis review found no association between nBH use and dementia diagnosis, although there is a need for more research on more cognitive outcomes and nBH use patterns.

ObjectiveThe cost-effectiveness of exercise interventions in lung cancer survivors is unknown. We performed a model-based cost-effectiveness analysis of an exercise intervention in lung cancer survivors.DesignWe used Markov modeling to simulate the impact of the Lifestyle Interventions and Independence for Elders exercise intervention compared with usual care for stage I-IIIA lung cancer survivors after curative-intent treatment. We calculated and considered incremental cost-effectiveness ratios of less than US $100,000/quality-adjusted life-year as cost-effective and assessed model uncertainty using sensitivity analyses.ResultsThe base-case model showed that the Lifestyle Interventions and Independence for Elders exercise program would increase overall cost by US $4740 and effectiveness by 0.06 quality-adjusted life-years compared with usual care and have an incremental cost-effectiveness ratio of US $79,504/quality-adjusted life-year. The model was most sensitive to the cost of the exercise program, probability of increasing exercise, and utility benefit related to exercise. At a willingness-to-pay threshold of US $100,000/quality-adjusted life-year, Lifestyle Interventions and Independence for Elders had a 71% probability of being cost-effective compared with 27% for usual care. When we included opportunity costs, Lifestyle Interventions and Independence for Elders had an incremental cost-effectiveness ratio of US $179,774/quality-adjusted life-year, exceeding the cost-effectiveness threshold.ConclusionsA simulation of the Lifestyle Interventions and Independence for Elders exercise intervention in lung cancer survivors demonstrates cost-effectiveness from an organization but not societal perspective. A similar exercise program for lung cancer survivors may be cost-effective.

Evidence supporting radical prostatectomy (RP) for men with clinically node-positive (cN+) prostate cancer (PC) is limited. In a US national database, we identified 741 men with cN+ nonmetastatic PC diagnosed during 2000-2015 who underwent definitive local therapy with RP (n=78), radiotherapy (RT) with neoadjuvant androgen deprivation therapy (ADT) (n=193), or nondefinitive therapy with ADT alone (n=445) or observation (n=25). We compared PC-specific mortality (PCSM) and all-cause mortality (ACM) using multivariable Fine-Gray competing risk regression and Cox regression, respectively. Compared to nondefinitive therapy, RP was associated with significantly better PCSM (subdistribution hazard ratio [SHR] 0.32, 95% confidence interval [CI] 0.16-0.66; p=0.002) and ACM (HR 0.36, 95% CI 0.21-0.61; p

ObjectiveTo conduct an anatomic site-specific case-control study of candidate colorectal cancer (CRC) risk factors.DesignCase-control study of US veterans with >1 colonoscopy during 1999-2011. Cases had cancer registry-identified CRC at colonoscopy, while controls were CRC free at colonoscopy and within 3 years of colonoscopy. Primary outcome was CRC, stratified by anatomic site: proximal, distal, or rectal. Candidate risk factors included age, sex, race/ethnicity, body mass index, height, diabetes, smoking status, and aspirin exposure summarised by adjusted ORs and 95% CIs.Results21 744 CRC cases (n=7017 rectal; n=7039 distal; n=7688 proximal) and 612 646 controls were included. Males had significantly higher odds relative to females for rectal cancer (OR=2.84, 95% CI 2.25 to 3.58) than distal cancer (OR=1.84, 95% CI 1.50 to 2.24). Relative to whites, blacks had significantly lower rectal cancer odds (OR=0.88, 95% CI 0.82 to 0.95), but increased distal (OR=1.27, 95% CI 1.19 to 1.37) and proximal odds (OR=1.62, 95% CI 1.52 to 1.72). Diabetes prevalence was more strongly associated with proximal (OR=1.29, 95% CI 1.22 to 1.36) than distal (OR=1.15, 95% CI 1.08 to 1.22) or rectal cancer (OR=1.12, 95% CI 1.06 to 1.19). Current smoking was more strongly associated with rectal cancer (OR=1.81, 95% CI 1.68 to 1.95) than proximal cancer (OR=1.53, 95% CI 1.43 to 1.65) or distal cancer (OR=1.46, 95% CI 1.35 to 1.57) compared with never smoking. Aspirin use was significantly more strongly associated with reduced rectal cancer odds (OR=0.71, 95% CI 0.67 to 0.76) than distal (OR=0.85, 95% CI 0.81 to 0.90) or proximal (OR=0.91, 95% CI 0.86 to 0.95).ConclusionCandidate CRC risk factor associations vary significantly by anatomic site. Accounting for site may enable better insights into CRC pathogenesis and cancer control strategies.

BackgroundChimeric antigen receptor T-cell (CAR-T) therapy is a promising new class of cancer therapy but has a high up-front cost. We evaluated the cost-effectiveness of CAR-T therapy among pediatric patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).MethodsWe built a microsimulation model for pediatric patients with relapsed/refractory B-ALL receiving either CAR-T therapy or standard of care. Outcomes included costs, quality of life (health utility), complications, and survival. We measured cost-effectiveness with the incremental cost-effectiveness ratio (ICER), with ICERs under $100 000 per quality-adjusted life-year (QALY) considered cost effective. One-way and probabilistic sensitivity analyses were used to test model uncertainty.ResultsCompared to standard of care, CAR-T therapy increased overall cost by $528 200 and improved effectiveness by 8.18 QALYs, resulting in an ICER of $64 600/QALY. The model was sensitive to assumptions about long-term CAR-T survival, the complete remission rate of CAR-T patients, and the health utility of long-term survivors. The base model assumed a 76.0% one-year survival with CAR-T, although if this decreased to 57.8%, then CAR-T was no longer cost effective. If the complete remission rate of CAR-T recipients decreased from 81% to 56.2%, or if the health utility of disease-free survivors decreased from 0.94 to 0.66, then CAR-T was no longer cost effective. Probabilistic sensitivity analysis found that CAR-T was cost effective in 94.8% of iterations at a willingness to pay of $100 000/QALY.ConclusionCAR-T therapy may represent a cost-effective option for pediatric relapsed/refractory B-ALL, although longer follow-up of CAR-T survivors is required to confirm validity of these findings.

ObjectiveThis study evaluates the impact of individual surgeons and institutions on the use of mastectomy or breast conserving surgery (BCS) among elderly women with breast cancer.Summary of background dataCurrent literature characterizes patient clinical and demographic factors that increase likelihood of mastectomy use. However, the impact of the individual provider or institution is not well understood, and could provide key insights to biases in the decision-making process.MethodsA retrospective cohort study of 29,358 women 65 years or older derived from the SEER-Medicare linked database with localized breast cancer diagnosed from 2000 to 2009. Multilevel, multivariable logistic models were employed, with odds ratios (ORs) used to describe the impact of demographic or clinical covariates, and the median OR (MOR) used to describe the relative impact of the surgeon and institution.ResultsSix thousand five hundred ninety-four women (22.4%) underwent mastectomy. Unadjusted rates of mastectomy ranged from 0% in the bottom quintile of surgeons to 58.0% in the top quintile. On multivariable analysis, the individual surgeon (MOR 1.97) had a greater impact on mastectomy than did the institution (MOR 1.71) or all other clinical and demographic variables except tumor size (OR 3.06) and nodal status (OR 2.95). Surgeons with more years in practice, or those with a lower case volume were more likely to perform mastectomy (P < 0.05).ConclusionThe individual surgeon influences the likelihood of mastectomy for the treatment of localized breast cancer. Further research should focus on physician-related biases that influence this decision to ensure patient autonomy.

Background: A recent meta-analysis affirmed the benefit of medicinal cannabis for chronic neuropathic pain, a disabling and difficult-to-treat condition. As medicinal cannabis use is becoming increasingly prevalent among Americans, an exploration of its economic feasibility is warranted. We present this cost-effectiveness analysis of adjunctive cannabis pharmacotherapy for chronic peripheral neuropathy. Materials and Methods: A published Markov model comparing conventional therapies for painful diabetic neuropathy was modified to include arms for augmenting first-line, second-line (if first-line failed), or third-line (if first- and second-line failed) therapies with smoked cannabis. Microsimulation of 1,000,000 patients compared the cost (2017 U.S. dollars) and effectiveness (quality-adjusted life years [QALYs]) of usual care with and without adjunctive cannabis using a composite of third-party and out-of-pocket costs. Model efficacy inputs for cannabis were adapted from clinical trial data. Adverse event rates were derived from a prospective study of cannabis for chronic noncancer pain and applied to probability inputs for conventional therapies. Cannabis cost was derived from retail market pricing. Parameter uncertainty was addressed with one-way and probabilistic sensitivity analysis. Results: Adding cannabis to first-line therapy was incrementally less effective and costlier than adding cannabis to second-line and third-line therapies. Third-line adjunctive cannabis was subject to extended dominance, that is, the second-line strategy was more effective with a more favorable incremental cost-effectiveness ratio of $48,594 per QALY gained, and therefore, third-line adjunctive cannabis was not as cost-effective. At a modest willingness-to-pay threshold of $100,000/QALY gained, second-line adjunctive cannabis was the strategy most likely to be cost-effective. Conclusion: As recently proposed willingness-to-pay thresholds for the United States health marketplace range from $110,000 to $300,000 per QALY, cannabis appears cost-effective when augmenting second-line treatment for painful neuropathy. Further research is warranted to explore the long-term benefit of smoked cannabis and standardization of its dosing for chronic neuropathic pain.

BackgroundBreast cancer in younger patients is reported to be more aggressive and associated with lower survival; however, factors associated with age-specific mortality differences have not been adequately assessed.MethodsWe used data from the population-based California Cancer Registry for 38,509 younger (18-49 years) and 121,573 older (50 years and older) women diagnosed with stage I to III breast cancer, 2005-2014. Multivariable Cox regression models were used to estimate breast cancer-specific mortality rate ratios (MRR) and 95% confidence intervals (CI), stratified by tumor subtype, guideline treatment, and care at an NCI-designated cancer center (NCICC).ResultsOlder breast cancer patients at diagnosis experienced 17% higher disease-specific mortality than younger patients, after multivariable adjustment (MRR = 1.17; 95% CI, 1.11-1.23). Higher MRRs (95% CI) were observed for older versus younger patients with hormone receptor (HR)+/HER2- (1.24; 1.14-1.35) and HR+/HER2+ (1.38; 1.17-1.62), but not for HR-/HER2+ (HR = 0.94; 0.79-1.12) nor triple-negative breast cancers (1.01; 0.92-1.11). The higher mortality in older versus younger patients was diminished among patients who received guideline-concordant treatment (MRR = 1.06; 95% CI, 0.99-1.14) and reversed among those seen at an NCICC (MRR = 0.86; 95% CI, 0.73-1.01).ConclusionsAlthough younger women tend to be diagnosed with more aggressive breast cancers, adjusting for these aggressive features results in older patients having higher mortality than younger patients, with variations by age, tumor subtype, receipt of guideline treatment, and being cared for at an NCICC.ImpactHigher breast cancer mortality in older compared with younger women could partly be addressed by ensuring optimal treatment and comprehensive patient-centered care.

Anatomic subsite risk factors for gastric cancer differ substantially, and subsite-specific distribution of risk factors (such as Helicobacter pylori) can vary by race and ethnicity and neighborhood socioeconomic status (nSES). We examined differences in gastric cancer incidence by subsite, stratified by race and ethnicity and nSES, using Surveillance Epidemiology and End Results Program 2000-2014 data for 77,881 incident gastric cancer cases (cardia, n = 23,651; non-cardia, n = 35,825; overlapping or unspecified, n = 18,405). Compared with non-Hispanic whites, cardia cancer multivariable-adjusted incidence rate ratios were 35%-47% lower for blacks, Hispanics, Asian or Pacific Islanders, and American Indian or Alaska Natives; conversely, non-cardia incidence rate ratios were 1.7- to 3.9-fold higher for blacks, Hispanics, Asian or Pacific Islanders, and American Indian or Alaska Natives. Higher adjusted incidence rate ratios with decreasing nSES (lowest vs highest nSES quintile) were observed for all gastric (1.3-fold) and non-cardia (1.3-fold) cancers but were borderline significant for cardia cancers (1.1-fold). In conclusion, non-cardia cancer incidence is higher in minorities and varies by nSES, but cardia cancer incidence is higher in non-Hispanic whites and does not vary substantially by nSES. Clarifying reasons for higher cardia risk in non-Hispanic whites and targeted interventions to address non-cardia cancer risk in minorities could lessen the burden of gastric cancer.

PurposeGeneralized competing event (GCE) models improve stratification of patients according to their risk of cancer events relative to competing causes of mortality. The potential impact of such methods on clinical trial power and cost, however, is uncertain. We sought to test the hypothesis that GCE models can reduce estimated clinical trial cost in elderly patients with cancer.MethodsPatients with nonmetastatic head and neck (n = 9,677), breast (n = 22,929), or prostate cancer (n = 51,713) were sampled from the SEER-Medicare database. Using multivariable Cox proportional hazards models, we compared risk scores for all-cause mortality (ACM) and cancer-specific mortality (CSM) with GCE-based risk scores for each disease. We applied a cost function to estimate the cost and duration of clinical trials with a primary end point of overall survival in each population and in high-risk subpopulations. We conducted sensitivity analyses to examine model uncertainty.ResultsFor the purpose of enriching subpopulations, GCE models reduced estimated clinical trial cost compared with Cox models of ACM and CSM in all disease sites. The relative cost reductions with GCE models compared with ACM and CSM models, respectively, were -68.4% and -14.4% in prostate cancer, -38.8% and -18.3% in breast cancer, and -17.1% and -4.1% in head and neck cancer. Cost savings in breast and prostate cancers were on the order of millions of dollars. The GCE model also reduced relative clinical trial duration compared with CSM and ACM models for all disease sites. The optimal risk score cutoff for clinical trial enrollment occurred near the top tertile for all disease sites.ConclusionGCE models have significant potential to improve clinical trial efficiency and reduce cost, with a potentially large impact in prostate and breast cancers.

PurposeCancer ascertainment using large-scale electronic health records is a challenge. Our aim was to propose and apply a structured approach for evaluating multiple candidate approaches for cancer ascertainment using colorectal cancer (CRC) ascertainment within the US Department of Veterans Affairs (VA) as a use case.MethodsThe proposed approach for evaluating cancer ascertainment strategies includes assessment of individual strategy performance, comparison of agreement across strategies, and review of discordant diagnoses. We applied this approach to compare three strategies for CRC ascertainment within the VA: administrative claims data consisting of International Classification of Diseases, Ninth Revision (ICD9) diagnosis codes; the VA Central Cancer Registry (VACCR); and the newly accessible Oncology Domain, consisting of cases abstracted by local cancer registrars. The study sample consisted of 1,839,043 veterans with index colonoscopy performed from 1999 to 2014. Strategy-specific performance was estimated based on manual record review of 100 candidate CRC cases and 100 colonoscopy controls. Strategies were further compared using Cohen's κ and focused review of discordant CRC diagnoses.ResultsA total of 92,197 individuals met at least one CRC definition. All three strategies had high sensitivity and specificity for incident CRC. However, the ICD9-based strategy demonstrated poor positive predictive value (58%). VACCR and Oncology Domain had almost perfect agreement with each other (κ, 0.87) but only moderate agreement with ICD9-based diagnoses (κ, 0.51 and 0.57, respectively). Among discordant cases reviewed, 15% of ICD9-positive but VACCR- or Oncology Domain-negative cases had incident CRC.ConclusionEvaluating novel strategies for identifying cancer requires a structured approach, including validation against manual record review, agreement among candidate strategies, and focused review of discordant findings. Without careful assessment of ascertainment methods, analyses may be subject to bias and limited in clinical impact.

BackgroundPrevious studies have reported conflicting information regarding the prognostic role of p16 in nonoropharyngeal head and neck squamous cell carcinoma (HNSCC).MethodsUsing the US Veterans Affairs database, we analyzed 1448 patients with locoregionally advanced HNSCC and known p16 status diagnosed between 2005 and 2015 and treated with surgery, radiotherapy, or chemoradiotherapy. Tumor p16 status was determined through manual review of pathology reports of primary tumor specimens. Oropharyngeal (n = 1061) or nonoropharyngeal (n = 387; hypopharyngeal, laryngeal, or oral cavity) tumor site was determined from tumor registry data and manually reviewed for accuracy. We used multivariable Cox regression to analyze the effect of p16 status on overall survival (OS), cancer-specific survival (CSS), and competing mortality (CM) for oropharyngeal or nonoropharyngeal tumor sites. All statistical tests were two-sided.ResultsIn multivariable models adjusting for treatment, stage, age, comorbidity, and body mass index, patients with p16-positive tumors had improved OS, CSS, and CM compared with patients with p16-negative tumors in both oropharyngeal (OS: hazard ratio [HR] = 0.53, 95% confidence interval [CI] = 0.40 to 0.71, P < .001; CSS: HR = 0.50, 95% CI = 0.35 to 0.73, P < .001; CM: HR = 0.59, 95% CI = 0.38 to 0.93, P = .02) and nonoropharyngeal primary sites (OS: HR = 0.41, 95% CI = 0.25 to 0.69, P < .001; CSS: HR = 0.37, 95% CI = 0.18 to 0.77, P = .008; CM: HR = 0.46, 95% CI = 0.23 to 0.95, P = .04). The prognostic impact of p16 status did not statistically significantly differ by primary tumor site for OS, CSS, or CM (Pinteraction > .05).ConclusionsOur findings support the hypothesis that p16 has a similar prognostic role in both nonoropharyngeal and oropharyngeal cancer. Consideration should be given to increased testing for p16 in laryngeal, hypopharyngeal, and oral cavity primaries.

ObjectivesTo develop a training program designed to meet the specific needs of medical physicists as they transition into a clinical role with direct patient care responsibilities.Materials and methodsThe training program was designed in collaboration with the faculty at the UC San Diego School of Medicine and incorporates training techniques that have been shown to be effective in improving communication skills. The program emphasizes experiential, practice-based learning over didactic presentations.ResultsThe training program is comprised of 5 components: 1) a 1-day Clinician-Patient Communication Workshop run by the UC San Diego School of Medicine, 2) Communication Strategies for Radiation Oncology, which consists of two, 2-hour sessions designed to provide trainees with patient communication skills that are specific to patient interactions in radiation oncology, 3) Simulated Patient Interactions, in which trainees perform mock physicist-patient consults with trained patient actors, 4) Faculty-Observed Patient Consults, and 5) a Case-Based Treatment Toxicity Course. A competency assessment mechanism was also developed to provide a clear set of objectives and to guide trainer feedback. [Correction added after first online publication on November 7, 2018: The phrase ", which consists of two, 2-hour" was added above.] CONCLUSIONS: The training program that we have developed incorporates an array of established education techniques and provides a comprehensive, accessible, means of improving medical physicists' patient communication skills.

PurposeCompared with conventional radiation therapy, intensity modulated radiation therapy (IMRT) may reduce acute toxicity from anal cancer treatment, potentially leading to improved long-term outcomes. We analyze the effect of IMRT on short- and long-term outcomes among a large sample of US veterans.Methods and materialsFrom a national Veterans Affairs database, we identified 779 patients (n = 403 conventional radiation therapy, n = 376 IMRT) with locally advanced anal squamous cell carcinoma diagnosed between 2000 and 2015 and treated with concurrent chemoradiation therapy. Radiation treatment planning and dosimetric constraints were not standardized across patients. We analyzed the effect of IMRT on short-term outcomes (acute toxicity, treatment breaks, and incomplete chemotherapy) and long-term outcomes (survival and ostomy placement) in multivariable logistic regression, Fine-Gray, and frailty models, adjusting for potential confounders.ResultsIMRT was associated with decreased radiation treatment breaks ≥5 days (odds ratio [OR] 0.58; 95% confidence interval [CI] 0.37-0.91; P = .02), increased rates of receiving 2 cycles of mitomycin C chemotherapy (OR 2.04; 95% CI 1.22-3.45; P = .007), increased rates of receiving 2 cycles of any chemotherapy (OR 3.45; 95% CI 1.82-6.25; P < .001), and decreased risk of ostomy related to tumor recurrence or progression (subdistribution hazard ratio 0.60; 95% CI 0.37-0.99; P = .045). IMRT was not associated with a decrease in grade 3 to 4 hematologic toxicity (P = .79), hospitalization for gastrointestinal toxicity (P = .59), or cancer-specific survival (P = 0.18).ConclusionsAmong a large sample of US veterans with anal cancer, IMRT was associated with higher rates of receiving 2 chemotherapy cycles, decreased radiation treatment breaks, and decreased rates of ostomy placement. IMRT appears to offer substantial benefits over conventional radiation therapy for patients undergoing concurrent chemoradiation therapy for anal cancer.

PurposeThe survival benefit of combined radiation therapy (RT) and androgen deprivation therapy (ADT) compared with ADT alone for clinically lymph node-positive prostate cancer remains controversial.Methods and materialsWe identified patients with clinically node-positive, nonmetastatic prostate cancer diagnosed between 2000 and 2015 and treated with ADT (n = 450) or ADT-RT (n = 198) from a national Veterans Affairs database. We compared prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM) between treatment groups using multivariable competing-risks regression and Cox regression, respectively. An interaction term between ADT-RT and prostate-specific antigen (PSA) level (dichotomized about the median) was included in the multivariable models.ResultsADT-RT was associated with improved PCSM among patients with PSA levels less than the median of 26 ng/mL (sub-distribution hazard ratio, 0.50; 95% confidence interval [CI] 0.28-0.88; P = .02) but not greater than the median (hazard ratio [HR], 1.15; 95% CI 0.67-1.96; P = .62) (P = .038 for interaction). ADT-RT was also associated with improved ACM among patients with PSA levels less than the median (HR, 0.38; 95% CI 0.25-0.57; P

A positive surgical margin (PSM) following cancer resection oftentimes necessitates adjuvant treatments and carries significant financial and prognostic implications. We sought to compare PSM rates for the ten most common solid cancers in the United States, and to assess trends over time. Over 10 million patients were identified in the National Cancer Data Base from 1998-2012, and 6.5 million had surgical margin data. PSM rates were compared between two time periods, 1998-2002 and 2008-2012. PSM was positively correlated with tumor category and grade. Ovarian and prostate cancers had the highest PSM prevalence in women and men, respectively. The highest PSM rates for cancers affecting both genders were seen for oral cavity tumors. PSM rates for breast cancer and lung and bronchus cancer in both men and women declined over the study period. PSM increases were seen for bladder, colon and rectum, and kidney and renal pelvis cancers. This large-scale analysis appraises the magnitude of PSM in the United States in order to focus future efforts on improving oncologic surgical care with the goal of optimizing value and improving patient outcomes.

The NCCN Guidelines for Colon Cancer provide recommendations regarding diagnosis, pathologic staging, surgical management, perioperative treatment, surveillance, management of recurrent and metastatic disease, and survivorship. These NCCN Guidelines Insights summarize the NCCN Colon Cancer Panel discussions for the 2018 update of the guidelines regarding risk stratification and adjuvant treatment for patients with stage III colon cancer, and treatment of BRAF V600E mutation-positive metastatic colorectal cancer with regimens containing vemurafenib.

PURPOSE:To study the effects of immunosuppression on treatment toxicity, long-term cancer recurrence risk, and survival among human immunodeficiency virus (HIV)-positive anal cancer patients. METHODS AND MATERIALS:From a nationwide retrospective cohort of veterans with anal cancer we identified 142 HIV-positive patients with stage I-III disease, diagnosed between 2000 and 2015 and treated with definitive-intent chemotherapy and radiation. We used regression models to study the impact of pretreatment CD4 counts and longitudinal posttreatment CD4 counts on outcomes including acute toxicity, long-term ostomy rates, cancer recurrence, cancer-specific survival, and overall survival. All models were adjusted for potential confounders. RESULTS:The median pretreatment CD4 count was 375 cells/mm3, which dropped to 157 cells/mm3 after treatment. Each 100-cell/mm3 decrease in pretreatment CD4 count was associated with an increased risk of acute hematologic toxicity (odds ratio 1.19, 95% confidence interval [CI] 1.01-1.42, P=.04) and hospitalization for hematologic toxicity (odds ratio 1.24, 95% CI 1.00-1.54, P=.049) but not gastrointestinal toxicity, tumor recurrence, or cancer-specific mortality (P>.05). Each 100-cells/mm3 decrease in posttreatment CD4 count increased the risk of recurrence by 54% (hazard ratio 1.54, 95% CI 1.09-2.17, P=.01) and cancer mortality by 46% at a trend level (hazard ratio 1.46, 95% CI 0.99-2.14, P=.06). Neither pre- nor posttreatment CD4 count influenced long-term ostomy rates or overall survival (all P>.05). CONCLUSIONS:Lower pretreatment CD4 counts were associated with acute hematologic toxicity, and lower posttreatment CD4 count levels were associated with an increased risk of tumor recurrence. These results suggest that immune surveillance may play an important role in long-term disease control in anal cancer.

Purpose: Treatments for locoregionally advanced head and neck cancer (LAHNC) negatively impact swallowing function, but the long-term incidence of severe toxicity requiring esophageal dilation is not well-documented in the population. The aim of this study was to compare the incidence of long-term esophageal dilation across varying treatments for LAHNC. Methods and Materials: We identified 5,223 patients with LAHNC diagnosed from 2000 to 2009 in the SEER-Medicare database. We compared the incidence of esophageal dilation for surgery alone vs. surgery plus adjuvant radiotherapy (RT) and chemoradiotherapy (CRT) vs. definitive RT or CRT. Results: The cumulative incidence of esophageal dilation for all sites at 10 years, according to treatment group were as follows: CRT, 14% (95% confidence interval (CI), 12-17%); definitive RT, 13% (95% CI, 10-16%); surgery alone, 5% (95% CI, 3-7%); surgery and CRT, 15% (95% CI, 11-19%); surgery and adjuvant RT: 10% (95% CI, 8-13%). There was no significant difference in the incidence of esophageal dilation between surgery plus adjuvant RT/CRT or definitive RT/CRT (p = 0.37), but the incidence was significantly increased in both groups compared to surgery alone (p = 0.003). On multivariable analysis, chemotherapy was associated with significantly increased incidence of esophageal dilation (HR 2.9, 95% CI 1.5-5.5, p < 0.001) in oropharyngeal cancers. Conclusions: The incidence of esophageal dilation is similar in LAHNC patients undergoing RT with or without surgery. Chemoradiotherapy increases the long-term risk of esophageal dilation events over surgery alone.

Background and purposePre- and mid-radiotherapy FDG-PET metrics have been proposed as biomarkers of recurrence and survival in patients treated for stage III non-small cell lung cancer. We evaluated these metrics in patients treated with definitive radiation therapy (RT). We also evaluated outcomes after progression on mid-radiotherapy PET/CT.Material and methodsSeventy-seven patients treated with RT with or without chemotherapy were included in this retrospective study. Primary tumor and involved nodes were delineated. PET metrics included metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUVmax. For mid-radiotherapy PET, both absolute value of these metrics and percentage decrease were analyzed. The influence of PET metrics on time to death, local recurrence, and regional/distant recurrence was assessed using Cox regression.Results91% of patients had concurrent chemotherapy. Median follow-up was 14months. None of the PET metrics were associated with overall survival. Several were positively associated with local recurrence: pre-radiotherapy MTV, and mid-radiotherapy MTV and TLG (p=0.03-0.05). Ratio of mid- to pre-treatment SUVmax was associated with regional/distant recurrence (p=0.02). 5/77 mid-radiotherapy scans showed early out-of-field progression. All of these patients died.ConclusionsSeveral PET metrics were associated with risk of recurrence. Progression on mid-radiotherapy PET/CT was a poor prognostic factor.

OBJECTIVE Rupture of large or giant intracranial aneurysms leads to significant morbidity, mortality, and health care costs. Both coiling and the Pipeline embolization device (PED) have been shown to be safe and clinically effective for the treatment of unruptured large and giant intracranial aneurysms; however, the relative cost-to-outcome ratio is unknown. The authors present the first cost-effectiveness analysis to compare the economic impact of the PED compared with coiling or no treatment for the endovascular management of large or giant intracranial aneurysms. METHODS A Markov model was constructed to simulate a 60-year-old woman with a large or giant intracranial aneurysm considering a PED, endovascular coiling, or no treatment in terms of neurological outcome, angiographic outcome, retreatment rates, procedural and rehabilitation costs, and rupture rates. Transition probabilities were derived from prior literature reporting outcomes and costs of PED, coiling, and no treatment for the management of aneurysms. Cost-effectiveness was defined, with the incremental cost-effectiveness ratios (ICERs) defined as difference in costs divided by the difference in quality-adjusted life years (QALYs). The ICERs < $50,000/QALY gained were considered cost-effective. To study parameter uncertainty, 1-way, 2-way, and probabilistic sensitivity analyses were performed. RESULTS The base-case model demonstrated lifetime QALYs of 12.72 for patients in the PED cohort, 12.89 for the endovascular coiling cohort, and 9.7 for patients in the no-treatment cohort. Lifetime rehabilitation and treatment costs were $59,837.52 for PED; $79,025.42 for endovascular coiling; and $193,531.29 in the no-treatment cohort. Patients who did not undergo elective treatment were subject to increased rates of aneurysm rupture and high treatment and rehabilitation costs. One-way sensitivity analysis demonstrated that the model was most sensitive to assumptions about the costs and mortality risks for PED and coiling. Probabilistic sampling demonstrated that PED was the cost-effective strategy in 58.4% of iterations, coiling was the cost-effective strategy in 41.4% of iterations, and the no-treatment option was the cost-effective strategy in only 0.2% of iterations. CONCLUSIONS The authors' cost-effective model demonstrated that elective endovascular techniques such as PED and endovascular coiling are cost-effective strategies for improving health outcomes and lifetime quality of life measures in patients with large or giant unruptured intracranial aneurysm.

Background: Although the number of cancer survivors has increased substantially over the past several decades, the composition of survivors treated with radiotherapy is not well defined. Radiotherapy carries unique long-term toxicity risks for cancer survivors. This study describes the current estimates and future projections of the epidemiology of 5-year cancer survivors who receive radiation therapy.Methods: We used cancer incidence and survival data from the Surveillance, Epidemiology, and End-Results (SEER) database linked to U.S. Census data to estimate the number of 5-year cancer survivors treated with radiation between 2000 and 2030. Future projections assumed continuing incidence and survival trends based on historical rates.Results: In 2016, there were an estimated 3.05 million cancer survivors treated with radiation, accounting for 29% of all cancer survivors. The number of radiation-treated cancer survivors is projected to reach 3.38 million by 2020 and 4.17 million by 2030. In 2016, breast (40%) and prostate cancer (23%) composed the majority of radiation-treated survivors, followed by head and neck cancer (5.8%), lymphoma (5.6%), uterine (3.9%), and rectal cancer (3.8%). The percentage of 70 years or older radiation-treated survivors steadily increased between 2000 and 2030.Conclusions: The next several years are projected to see a large increase in the number of cancer survivors treated with radiation.Impact: This group of cancer survivors has unique needs given the long-term risks of radiation, and increased research and awareness are required to optimize health of this growing population. Cancer Epidemiol Biomarkers Prev; 26(6); 963-70. ©2017 AACR.

PurposeDespite multiple randomized trials showing the efficacy of hypofractionated radiation therapy in early-stage breast cancer, the United States has been slow to adopt this treatment. The goal of this study was to evaluate the impact of individual radiation oncologists on the early adoption of hypofractionated radiation therapy for early-stage breast cancer.MethodsWe identified 22,233 Medicare beneficiaries with localized breast cancer that was diagnosed from 2004 to 2011 who underwent breast-conserving surgery with adjuvant radiation. Multilevel, multivariable logistic models clustered by radiation oncologist and geographic practice area were used to determine the impact of the provider and geographic region on the likelihood of receiving hypofractionated compared with standard fractionated radiation therapy while controlling for a patient's clinical and demographic covariates. Odds ratios (OR) describe the impact of demographic or clinical covariates, and the median OR (MOR) describes the relative impact of the individual radiation oncologist and geographic region on the likelihood of undergoing hypofractionated radiation therapy.ResultsAmong the entire cohort, 2333 women (10.4%) were treated with hypofractionated radiation therapy, with unadjusted rates ranging from 0.0% in the bottom quintile of radiation oncologists to 30.4% in the top quintile. Multivariable analysis found that the individual radiation oncologist (MOR 3.08) had a greater impact on the use of hypofractionation than did geographic region (MOR 2.10) or clinical and demographic variables. The impact of the provider increased from the year 2004 to 2005 (MOR 2.82) to the year 2010 to 2011 (MOR 3.16) despite the publication of long-term randomized trial results in early 2010. Male physician and radiation oncologists treating the highest volume of breast cancer patients were less likely to perform hypofractionation (P

BackgroundAbout 10-15% of adult, and most pediatric, gastrointestinal stromal tumors (GIST) lack mutations in KIT, PDGFRA, SDHx, or RAS pathway components (KRAS, BRAF, NF1). The identification of additional mutated genes in this rare subset of tumors can have important clinical benefit to identify altered biological pathways and select targeted therapies.MethodsWe performed comprehensive genomic profiling (CGP) for coding regions in more than 300 cancer-related genes of 186 GISTs to assess for their somatic alterations.ResultsWe identified 24 GIST lacking alterations in the canonical KIT/PDGFRA/RAS pathways, including 12 without SDHx alterations. These 24 patients were mostly adults (96%). The tumors had a 46% rate of nodal metastases. These 24 GIST were more commonly mutated at 7 genes: ARID1B, ATR, FGFR1, LTK, SUFU, PARK2 and ZNF217. Two tumors harbored FGFR1 gene fusions (FGFR1-HOOK3, FGFR1-TACC1) and one harbored an ETV6-NTRK3 fusion that responded to TRK inhibition. In an independent sample set, we identified 5 GIST cases lacking alterations in the KIT/PDGFRA/SDHx/RAS pathways, including two additional cases with FGFR1-TACC1 and ETV6-NTRK3 fusions.ConclusionsUsing patient demographics, tumor characteristics, and CGP, we show that GIST lacking alterations in canonical genes occur in younger patients, frequently metastasize to lymph nodes, and most contain deleterious genomic alterations, including gene fusions involving FGFR1 and NTRK3. If confirmed in larger series, routine testing for these translocations may be indicated for this subset of GIST. Moreover, these findings can be used to guide personalized treatments for patients with GIST. Trial registration NCT 02576431. Registered October 12, 2015.

Purpose Recently, a large randomized trial found a survival advantage among patients who received elective neck dissection in conjunction with primary surgery for clinically node-negative oral cavity cancer compared with those receiving primary surgery alone. However, elective neck dissection comes with greater upfront cost and patient morbidity. We present a cost-effectiveness analysis of elective neck dissection for the initial surgical management of early-stage oral cavity cancer. Methods We constructed a Markov model to simulate primary, adjuvant, and salvage therapy; disease recurrence; and survival in patients with T1/T2 clinically node-negative oral cavity squamous cell carcinoma. Transition probabilities were derived from clinical trial data; costs (in 2015 US dollars) and health utilities were estimated from the literature. Incremental cost-effectiveness ratios, expressed as dollar per quality-adjusted life-year (QALY), were calculated with incremental cost-effectiveness ratios less than $100,000/QALY considered cost effective. We conducted one-way and probabilistic sensitivity analyses to examine model uncertainty. Results Our base-case model found that over a lifetime the addition of elective neck dissection to primary surgery reduced overall costs by $6,000 and improved effectiveness by 0.42 QALYs compared with primary surgery alone. The decrease in overall cost despite the added neck dissection was a result of less use of salvage therapy. On one-way sensitivity analysis, the model was most sensitive to assumptions about disease recurrence, survival, and the health utility reduction from a neck dissection. Probabilistic sensitivity analysis found that treatment with elective neck dissection was cost effective 76% of the time at a willingness-to-pay threshold of $100,000/QALY. Conclusion Our study found that the addition of elective neck dissection reduces costs and improves health outcomes, making this a cost-effective treatment strategy for patients with early-stage oral cavity cancer.

BackgroundAlthough married cancer patients have more favorable survival than unmarried patients, reasons underlying this association are not fully understood. The authors evaluated the role of economic resources, including health insurance status and neighborhood socioeconomic status (nSES), in a large California cohort.MethodsFrom the California Cancer Registry, we identified 783,167 cancer patients (386,607 deaths) who were diagnosed during 2000 through 2009 with a first primary, invasive cancer of the 10 most common sites of cancer-related death for each sex and were followed through 2012. Age-stratified and stage-stratified Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for all-cause mortality associated with marital status, adjusted for cancer site, race/ethnicity, and treatment.ResultsCompared with married patients, unmarried patients had an elevated risk of mortality that was higher among males (HR, 1.27; 95% CI, 1.26-1.29) than among females (HR, 1.19; 95% CI, 1.18-1.20; Pinteraction < .001). Adjustment for insurance status and nSES reduced the marital status HRs to 1.22 for males and 1.15 for females. There was some evidence of synergistic effects of marital status, insurance, and nSES, with relatively higher risks observed for unmarried status among those who were under-insured and living in high nSES areas compared with those who were under-insured and living in low nSES areas (Pinteraction = 6.8 × 10(-9) among males and 8.2 × 10(-8) among females).ConclusionsThe worse survival of unmarried than married cancer patients appears to be minimally explained by differences in economic resources. Cancer 2016;122:1618-25. © 2016 American Cancer Society.

BackgroundIt 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.MethodsCalifornia 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.ResultsAll-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.ConclusionsFor 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.

PurposeTo compare a novel generalized competing event (GCE) model versus the standard Cox proportional hazards regression model for stratifying elderly patients with cancer who are at risk for competing events.MethodsWe identified 84,319 patients with nonmetastatic prostate, head and neck, and breast cancers from the SEER-Medicare database. Using demographic, tumor, and clinical characteristics, we trained risk scores on the basis of GCE versus Cox models for cancer-specific mortality and all-cause mortality. In test sets, we examined the predictive ability of the risk scores on the different causes of death, including second cancer mortality, noncancer mortality, and cause-specific mortality, using Fine-Gray regression and area under the curve. We compared how well models stratified subpopulations according to the ratio of the cumulative cause-specific hazard for cancer mortality to the cumulative hazard for overall mortality (ω) using the Akaike Information Criterion.ResultsIn each sample, increasing GCE risk scores were associated with increased cancer-specific mortality and decreased competing mortality, whereas risk scores from Cox models were associated with both increased cancer-specific mortality and competing mortality. GCE models created greater separation in the area under the curve for cancer-specific mortality versus noncancer mortality (P < .001), indicating better discriminatory ability between these events. Comparing the GCE model to Cox models of cause-specific mortality or all-cause mortality, the respective Akaike Information Criterion scores were superior (lower) in each sample: prostate cancer, 28.6 versus 35.5 versus 39.4; head and neck cancer, 21.1 versus 29.4 versus 40.2; and breast cancer, 24.6 versus 32.3 versus 50.8.ConclusionCompared with standard modeling approaches, GCE models improve stratification of elderly patients with cancer according to their risk of dying from cancer relative to overall mortality.

PurposeOver the past decade, intensity-modulated radiation therapy (IMRT) has replaced conventional radiation techniques in the management of head-and-neck cancers (HNCs). We conducted this population-based study to evaluate the influence of radiation oncologist experience on outcomes in patients with HNC treated with IMRT compared with patients with HNC treated with conventional radiation therapy.MethodsWe identified radiation providers from Medicare claims of 6,212 Medicare beneficiaries with HNC treated between 2000 and 2009. We analyzed the impact of provider volume on all-cause mortality, HNC mortality, and toxicity end points after treatment with either conventional radiation therapy or IMRT. All analyses were performed by using either multivariable Cox proportional hazards or Fine-Gray regression models controlling for potential confounding variables.ResultsAmong patients treated with conventional radiation, we found no significant relationship between provider volume and patient survival or any toxicity end point. Among patients receiving IMRT, those treated by higher-volume radiation oncologists had improved survival compared with those treated by low-volume providers. The risk of all-cause mortality decreased by 21% for every additional five patients treated per provider per year (hazard ratio [HR], 0.79; 95% CI, 0.67 to 0.94). Patients treated with IMRT by higher-volume providers had decreased HNC-specific mortality (subdistribution HR, 0.68; 95% CI, 0.50 to 0.91) and decreased risk of aspiration pneumonia (subdistribution HR, 0.72; 95% CI, 0.52 to 0.99).ConclusionPatients receiving IMRT for HNC had improved outcomes when treated by higher-volume providers. These findings will better inform patients and providers when making decisions about treatment, and emphasize the critical importance of high-quality radiation therapy for optimal treatment of HNC.