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BACKGROUND Durable palliation of advanced lung cancer is a common objective for radiation oncologists. However, there is no consensus on how to deliver the radiation course. Herein we report our experience of using split course radiotherapy and our assessment of outcomes based on planning from three-dimensional (3D) simulation before each treatment course. METHODS All lung cancer patients from 2006-2020 were identified. Of these, 52 patients received a split course treatment of 50-60 Gy in 18-25 fractions intended to provide durable palliation for disease not amenable to curative therapy. Treatment involved 3D planning with repeat computed tomography (CT) simulation prior to the second course. Survival and symptomatic response were analyzed via chart review. We categorized rapid responders versus non-rapid responders from the initial radiation course based on ≥30% gross tumor volume (GTV) reduction at the second CT simulation. We evaluated the impact of response on overall survival and palliative response. RESULTS Among our cohort treated with split course palliative radiotherapy, 33 (63%) had a rapid response to initial treatment. There was no difference in survival between groups [hazard ratio (HR) =1.30, P=0.47]. There was no significant difference in palliative response rates between rapid and non-rapid responders. On multivariable analysis, only female sex (HR =0.26, P

Symptomatic severe aortic regurgitation (ssAR) is a Class I recommendation for surgical aortic valve replacement (SAVR). We sought to evaluate the practice patterns and drivers of ssAR patients rec...

Introduction: Strategic naps are considered as efficacious means of maintaining performance and reducing the individual’s sleep debt. It can reduce subjective feelings of fatigue and improve performance and alertness. However, literature is scant on assessment of naps and associated cognitive performance in the Indian military aviation scenario. This study is an attempt to assess the nap duration and its objective assessment on gain in performance, if any. Material and Methods: In this cross-sectional observational study, sleep data were collected from 23 aviation personnel in a military flying base using actigraphy device. The actigraphic data were then fed into a software called fatigue avoidance scheduling tool. The nap duration and its effect on cognitive parameters were analyzed. Results: About 65.2% of the participant were found to be Day-Time Habitual Nappers. Of the 50 Naps logged by these participants, 11 (22%) naps were less than 30 min, 14 (28%) were between 30 and 60 min, 15 (30%) were between 60 and 120 min, and only 10 (20%) were above 120 min. Post-nap gain in the effectiveness and other cognitive parameters was found to be different in different cognitive domains. Conclusion: Naps more than 30 min had the optimal efficiency. The nap-induced gain in the task effectiveness and cognitive performance was confirmed. While the performance enhancement was significant for the naps more than 30 min, naps more than 60 min did not have any added advantages.

BACKGROUND Population-based studies demonstrate that Black men in the United States have an increased risk of death from prostate cancer. Determinants of racial disparities are multifactorial, including socioeconomic and biologic factors. METHODS The authors conducted a pooled analysis of patients derived from 152 centers within the Veterans Health Administration. The cohort included men who had nonmetastatic prostate diagnosed between 2001 and 2015 and received definitive radiation therapy. The primary endpoint was prostate cancer-specific mortality (PCSM). Secondary endpoints included all-cause mortality (ACM) and the time from a prostate-specific antigen level ≥4 ng/mL to biopsy and radiation therapy. A Cox regression model was performed to adjust for differences between clinical parameters. RESULTS Among the 31,131 patients included in the cohort, 9584 (30.8%) were Black. The 10-year cumulative incidence of death from prostate cancer was lower in Black men compared with White men (4.0% vs 4.8%; P = .004). In a competing risk model, Black race was associated with a decreased risk of PCSM (subdistribution hazard ratio, 0.79; 95% CI, 0.69-0.92; P = .002). Similarly, the 10-year cumulative incidence of death from any cause was lower in Black men (27.6% vs 31.8%; P < .001). In multivariable analysis, Black men had a 10% decreased risk of ACM (hazard ratio, 0.90; 95% CI, 0.85-0.95; P < .001). CONCLUSIONS The current results indicate relatively lower PCSM and ACM among Black men who were included in a large Veterans Health Administration cohort and received radiation therapy as primary treatment for nonmetastatic prostate cancer. There is an ongoing need to continue to understand and mitigate the factors associated with disparities in health care outcomes.

Background The safety of testosterone therapy (TT) after definitive treatment for localized prostate cancer remains undefined. We analyzed the risks of biochemical recurrence and mortality in men receiving TT after treatment for localized prostate cancer. Methods Cohort analysis using the national US Veterans Affairs Informatics and Computing Infrastructure. We identified 69,984 patients with localized prostate cancer diagnosed from 2001 to 2015 treated with surgery or radiation. We coded receipt of TT after treatment as a time-dependent covariate; used the National Death Index to identify cause of death; and defined biochemical recurrence as PSA > 0.2 ng/mL after surgery and nadir + 2 ng/mL after radiation. We analyzed recurrence and mortality using cumulative incidence curves, Fine-Gray competing risk regression, and Cox regression. Results This cohort included 28,651 surgery patients and 41,333 radiation patients, of whom 469 (1.64%) and 543 (1.31%), respectively, received TT with a median follow-up of 6.95 years. Comparing testosterone users to nonusers, there were no between-group differences in biochemical recurrence, prostate cancer-specific mortality, or overall mortality after surgery [hazard ratios (HR): 1.07; HR: 0.72 (p = 0.43); and HR: 1.11 (p = 0.43), respectively] or radiation [HR: 1.07; HR: 1.02 (p = 0.95); and HR: 1.02 (p = 0.86), respectively]. Limitations included lack of detailed data on TT duration and serum testosterone concentrations. Conclusions In this multi-ethnic national cohort, TT did not increase the risks of biochemical recurrence or prostate cancer-specific or overall mortality after surgery or radiation. These data suggest that TT is safe in appropriate men after definitive treatment of localized prostate cancer.

Increasing evidence indicates an association between statins and reduced prostate cancer-specific mortality (PCSM). However, significant bias may exist in these studies. One particularly challenging bias to assess is the healthy user effect, which may be quantified by screening patterns. We aimed to evaluate the association between statin use, screening, and PCSM in a dataset with detailed longitudinal information. We used the Veterans Affairs Informatics and Computing Infrastructure to assemble a cohort of patients diagnosed with prostate cancer (PC) between 2000 and 2015. We collected patient-level demographic, comorbidity, and tumor data. We also assessed markers of preventive care utilization including cholesterol and prostate specific antigen (PSA) screening rates. Patients were considered prediagnosis statin users if they had at least one prescription one or more years prior to PC diagnosis. We evaluated PCSM using hierarchical Fine-Gray regression models and all-cause mortality (ACM) using a cox regression model. The final cohort contained 68,432 men including 40,772 (59.6%) prediagnosis statin users and 27,660 (40.4%) nonusers. Prediagnosis statin users had higher screening rates than nonusers for cholesterol (90 vs. 69%, p

Cigarette smoking is a risk factor for mortality in several genitourinary cancers, likely due to accumulation of carcinogens in urine. However, in prostate cancer (PC) the link has been less studied. We evaluated differences in prostate cancer-specific mortality (PCSM) between current smokers, past smokers, and never smokers diagnosed with PC. This was a retrospective cohort study of PCSM in men diagnosed with PC between 2000 and 2015 treated in the US Veterans Affairs health care system, using competing risk regression analyses. The cohort included 73,668 men (current smokers: 22,608 (30.7%), past smokers: 23,695 (32.1%), and never smokers: 27,365 (37.1%)). Median follow-up was 5.9 years. Current smoker patients were younger at presentation (median age current: 63, never: 66; p

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.

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.

Objectives Preoperative radiotherapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiotherapy and different radiation techniques on cardiovascular morbidity among a cohort of esophageal cancer patients. Materials and methods We identified 1125 patients aged 65 and older diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation from the Surveillance Epidemiology and End Results (SEER)-Medicare database. We used Medicare claims to identify severe perioperative and late cardiovascular events. Multivariable logistic regression and Fine-Gray models were used to determine the effect of presurgery treatment on the risk of perioperative and late cardiovascular disease. Results Preoperative chemotherapy or chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared with surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a late cardiovascular event compared with patients treated with surgery alone (subdistribution hazard ratio [SDHR]: 1.36; P=0.035). There was no significant increase in late cardiovascular events among patients treated with preoperative chemotherapy (SDHR: 1.18; P=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy had a 68% decreased risk of having a late cardiovascular event compared with patients receiving conventional radiation (SDHR: 0.32; P=0.007). Conclusions This study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as intensity modulated radiotherapy.

Importance Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective, nonrandomized design of these analyses raises questions about study validity. Objective To examine the extent to which comparative effectiveness analyses using observational cancer registry data produce results concordant with those of randomized clinical trials. Design, Setting, and Participants In this comparative effectiveness study, a total of 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types were identified. Data on participants within the National Cancer Database (NCDB) diagnosed between 2004 and 2014, matching the eligibility criteria of the randomized clinical trial, were obtained. The present study was conducted from August 1, 2017, to September 10, 2019. The trials included 85 118 patients, and the corresponding NCDB analyses included 1 344 536 patients. Three Cox proportional hazards regression models were used to determine hazard ratios (HRs) for overall survival, including univariable, multivariable, and propensity score–adjusted models. Multivariable and propensity score analyses controlled for potential confounders, including demographic, comorbidity, clinical, treatment, and tumor-related variables. Main Outcomes and Measures The main outcome was concordance between the results of randomized clinical trials and observational cancer registry data. Hazard ratios with an NCDB analysis were considered concordant if the NDCB HR fell within the 95% CI of the randomized clinical trial HR. An NCDB analysis was considered concordant if both the NCDB and clinical trialPvalues for survival were nonsignificant (P ≥ .05) or if they were both significant (P Results Analyses using the NCDB-produced HRs for survival were concordant with those of 141 randomized clinical trials in 79 univariable analyses (56%), 98 multivariable analyses (70%), and 90 propensity score models (64%). The NCDB analyses producedPvalues concordant with randomized clinical trials in 58 univariable analyses (41%), 65 multivariable analyses (46%), and 63 propensity score models (45%). No clinical trial characteristics were associated with concordance between NCDB analyses and randomized clinical trials, including disease site, type of clinical intervention, or severity of cancer. Conclusions and Relevance The findings of this study suggest that comparative effectiveness research using cancer registry data often produces survival outcomes discordant with those of randomized clinical trial data. These findings may help provide context for clinicians and policy makers interpreting observational comparative effectiveness research in oncology.

A prostate cancer (CaP) patient with nonmetastatic but clinical positive lymph nodes (cN+) represents a difficult clinical scenario. We compare overall survival (OS) between cN+ men that underwent radical prostatectomy (RP) and were found to have negative node status (pN) with those found to have positive nodal status (pN+), and assess predictors of discordant nodal status. We queried the National Cancer Data Base between 2004 and 2015 for patients that were cT1-3 cN+ cM0 CaP treated with RP. Patients with 0 nodes, cT4, or cM1 disease were excluded. We compared groups based on pathologic nodal status: Discordant (cN+ -> pN) & Concordant (cN+ -> pN+). Kaplan Meier estimations were used to compare OS. Logistic regression was used to determine possible predictors of nodal status. We find that of 6470 cN+ patients, 1,367 (21.1%) underwent RP, 866 (13.4%) had confirmed nodal status. Discordant status was found in 159 (18.4%) and concordant staging in 707 (81.6%). Differences exist in PSA at diagnosis (7.3 vs. 11.2), biopsy group, # of nodes examined (7 vs. 10), race, and Charlson index. Discordant staging had longer OS compared to Concordant staging (P = 0.007) and similar OS to a 3:1 matched cohort of high risk localized CaP patients used as reference (P = 0.46). Lower Gleason Score (GG1-3) was associated with an increased likelihood of discordant staging. Clinical nodal staging is associated with a substantial false positive rate. Discordant status had better OS than Concordant status and similar OS to matched patients with localized CaP. Clinical nodal staging may inappropriately lead to noncurative therapy in a substantial number of men with potentially curable disease.

BACKGROUND Pay-for-performance reimbursement ties hospital payments to standardized quality-of-care metrics. To the authors' knowledge, the impact of pay-for-performance reimbursement models on hospitals caring primarily for uninsured or underinsured patients remains poorly defined. The objective of the current study was to evaluate how standardized quality-of-care metrics vary by a hospital's propensity to care for uninsured or underinsured patients and demonstrate the potential impact that pay-for-performance reimbursement could have on hospitals caring for the underserved. METHODS The authors identified 1,703,865 patients with cancer who were diagnosed between 2004 and 2015 and treated at 1344 hospitals. Hospital safety-net burden was defined as the percentage of uninsured or Medicaid patients cared for by that hospital, categorizing hospitals into low-burden, medium-burden, and high-burden hospitals. The authors evaluated the impact of safety-net burden on concordance with 20 standardized quality-of-care measures, adjusting for differences in patient age, sex, stage of disease at diagnosis, and comorbidity. RESULTS Patients who were treated at high-burden hospitals were more likely to be young, male, Black and/or Hispanic, and to reside in a low-income and low-educated region. High-burden hospitals had lower adherence to 13 of 20 quality measures compared with low-burden hospitals (all P

Background: Cyclosporine A (CsA) is one of the systemic therapeutic options for moderate-to-severe psoriasis, based on its efficacy and rapidity of action. The current study investigated the response to CsA in patients with moderate-to-severe plaque psoriasis. Materials and Methods: TRANSITION was an observational, cross-sectional, multicentre study which evaluated the proportion of partial- and suboptimal-responders among patients with moderate-to-severe plaque psoriasis treated with continuous CsA for >= 12 weeks. Patients demonstrating a Psoriasis Area and Severity Index (PASI) response of >= 90, >= 75 and = 50 and

High-volume hospitals are associated with improved outcomes in glioblastoma (GBM). However, the impact of travel burden to high-volume centers is poorly understood. We examined post-operative outcomes between GBM patients that underwent treatment at local, low-volume hospitals with those that traveled long distances to high-volume hospitals. The National Cancer Database was queried for GBM patients that underwent surgery (2010–2014). We established two cohorts: patients in the lowest quartile of travel distance and volume (Short-travel/Low-Volume: STLV) and patients in the highest quartile of travel and volume (Long-travel/High-Volume: LTHV). Outcomes analyzed were 30-day, 90-day mortality, overall survival, 30-day readmission, and hospital length of stay. Of 35,529 cases, STLV patients (n = 3414) traveled a median of 3 miles (Interquartile range [IQR] 1.8–4.2) to low-volume centers (5 [3–7] annual cases) and LTHV patients (n = 3808) traveled a median of 62 miles [44.1–111.3] to high-volume centers (48 [42–71]). LTHV patients were younger, had lower Charlson scores, largely received care at academic centers (84.4% vs 11.9%), were less likely to be minorities (8.1% vs 17.1%) or underinsured (6.9% vs 12.1), and were more likely to receive trimodality therapy (75.6% vs 69.2%; all p

Safety-net hospitals (SNHs) provide disproportionate care for underserved patients. Prior studies have identified poor outcomes, increased costs, and reduced access to certain complex, elective surgeries at SNHs. However, it is unknown whether similar patterns exist for the management of glioblastoma (GBM). We sought to determine if patients treated at HBHs receive equitable care for GBM, and if safety-net burden status impacts post-treatment survival. The National Cancer Database was queried for GBM patients diagnosed between 2010 and 2015. Safety-net burden was defined as the proportion of Medicaid and uninsured patients treated at each hospital, and stratified as low (LBH), medium (MBH), and high-burden (HBH) hospitals. The impact of safety-net burden on the receipt of any treatment, trimodality therapy, gross total resection (GTR), radiation, or chemotherapy was investigated. Secondary outcomes included post-treatment 30-day mortality, 90-day mortality, and overall survival. Univariate and multivariate analyses were utilized. Overall, 40,082 GBM patients at 1202 hospitals (352 LBHs, 553 MBHs, and 297 HBHs) were identified. Patients treated at HBHs were significantly less likely to receive trimodality therapy (OR = 0.75, p

BACKGROUND Rhinoscleroma is a chronic inflammatory condition in which deforming masses of tissue distend the nasal cavity. Klebsiella rhinoscleromatis is the causative agent. Antibiotic therapy traditionally consisted of streptomycin and tetracycline. But longterm therapy results in adverse side effects and poor patient compliance, hence this study to search alternative agents. MATERIALS AND METHODS This is a prospective study of 60 cases of rhinoscleroma visiting to the Department of ENT, KIMS, for a period of two years. RESULTS After 8 weeks treatment in the atrophic and granulomatous group, 6 (60%) became histopathologically negative and 4 (40%) remained histopathologically positive. The treatment was continued for another 4 weeks in positive cases and at the end of 12 weeks, 8 (80%) turned histopathologically negative, 2 (20%) remained positive. CONCLUSION We conclude that ciprofloxacin is a very good alternative drug compared to doxycycline in the treatment of rhinoscleroma particularly in the early stages of the disease and complete cure can be achieved by early diagnosis and treatment.

BackgroundPay-for-performance reimbursement ties hospital payments to standardized quality of care metrics. The impact of pay-for-performance reimbursement models on safety-net hospitals, which care primarily for uninsured or underinsured patients, remains poorly defined. This study evaluates how standardized quality of care metrics vary by a hospital’s safety-net status, and helps us better understand the potential impact that pay-for-performance reimbursement could have on funding of safety-net hospitals.MethodsWe identified 1,703,865 bladder, breast, cervix, colon, endometrium, gastric, lung, ovary, or rectum cancer patients treated at 1,344 hospitals diagnosed between 2004 and 2015. Safety-net burden was defined for each hospital as the percentage of uninsured or Medicaid patients cared for by that hospital. Hospitals were grouped into low-, medium-, and high-burden hospitals. We evaluated the impact of safety-net burden on concordance with 20 standardized quality of care measures, adjusting for differences in patient age, gender, stage at diagnosis, and comorbidity.ResultsPatients seen at high-burden hospitals were more likely to be young, male, black, Hispanic, and to reside in a low-income and low-educated region. High-burden hospitals had lower adherence to 13 of 20 quality measures compared to low-burden hospitals (all pDiscussionCancer care at safety-net hospitals was associated with lower concordance to standardized quality of care measures. Under a pay-for-performance reimbursement model these lower quality of care scores could decrease payments to safety-net hospitals, potentially increasing health disparities for at-risk cancer patients.

PurposePreoperative radiation therapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiation therapy and different radiation techniques on cardiovascular morbidity among a large cohort of esophageal cancer patients.MethodsWe identified 1,125 Medicare beneficiaries diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation. We used Medicare claims to identify severe adverse cardiovascular events in the perioperative and postoperative periods. Multivariable logistic regression and Fine-Gray models were used to determine the effect of pre-surgery treatment on the risk of perioperative and postoperative cardiovascular disease.ResultsPreoperative chemotherapy or preoperative chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared to surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a postoperative cardiovascular event compared to patients treated with surgery alone (subdistribution hazard ratio [SDHR] 1.36; p=0.035). There was no significant increase in cardiovascular events among patients treated with preoperative chemotherapy (SDHR 1.18; p=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy (IMRT) had a 68% decreased risk of having a cardiovascular event compared to patients receiving conventional radiation (SDHR 0.32; p=0.007).ConclusionsThis study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as IMRT.

PurposeResearchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective non-random design of these analyses raise questions about study validity. The purpose of this study was to determine the extent to which comparative effectiveness analyses using cancer registry data produces results concordant with randomized clinical trials.MethodsWe identified 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types. For each trial we identified subjects from the National Cancer Database (NCDB) matching the eligibility criteria of the randomized trial. With each trial we used three Cox regression models to determine hazard ratios (HRs) for overall survival including univariable, multivariable, and propensity score adjusted models. Multivariable and propensity score analyses controlled for potential confounders including demographic, comorbidity, clinical, treatment, and tumor-related variables. Each NCDB survival analysis was defined as discordant if the HR for the NCDB analysis fell outside the 95% confidence interval of the corresponding randomized trial.ResultsNCDB analyses produced HRs for survival discordant with randomized trials in 62 (44%) univariable analyses, 43 (30%) multivariable analyses, and 51 (36%) propensity score models. NCDB analyses produced p-values discordant with randomized trials in 83 (59%) univariable analyses, 76 (54%) multivariable analyses, and 78 (55%) propensity score models. We did not identify any clinical trial characteristic associated with discordance between NCDB analyses and randomized trials including disease site, type of clinical intervention, or severity of cancer.ConclusionComparative effectiveness research with cancer registry data often produces survival outcomes discordant to randomized clinical data. These findings help provide context for providers interpreting observational comparative effectiveness research in oncology.

This cohort study examines the association between use of 5α-reductase inhibitors and prostate cancer mortality among US Medicare beneficiaries.

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 < 0.001). Compared to RT, RP was not associated with a significant difference in PCSM (SHR 0.47, 95% CI 0.19–1.17; p = 0.1) or ACM (HR 0.88, 95% CI 0.46–1.70; p = 0.71). These data suggest that RP is associated with favorable survival outcomes that appear to be superior to those for patients who did not receive definitive therapy and comparable to those for patients receiving definitive ADT/RT. Randomized trials of surgery with multimodal therapy are needed. PATIENT SUMMARY: We found that in clinically node-positive prostate cancer, radical prostatectomy was associated with a cancer-specific and overall survival benefit compared to nondefinitive therapy. Randomized clinical trials are required to determine the best treatment approach in this patient population.

BACKGROUND African American (AA) men in the general US population are more than twice as likely to die of prostate cancer (PC) compared with non-Hispanic white (NHW) men. The authors hypothesized that receiving care through the Veterans Affairs (VA) health system, an equal-access medical system, would attenuate this disparity. METHODS A longitudinal, centralized database of >20 million veterans was used to assemble a cohort of 60,035 men (18,201 AA men [30.3%] and 41,834 NHW men [69.7%]) who were diagnosed with PC between 2000 and 2015. RESULTS AA men were more likely to live in regions with a lower median income ($40,871 for AA men vs $48,125 for NHW men; P

Background:Patients with advanced esophageal cancer often experience pain and dysphagia, yet the optimal palliative management remains unclear. This retrospective study evaluated outcomes and adverse effects of palliative radiotherapy (RT) compared with esophageal stenting among a cohort of U.S. veterans with metastatic esophageal cancer.Patients and Methods:We identified 1,957 veterans in the United States with metastatic esophageal cancer who received palliative RT to the esophagus or esophageal stenting, and assessed the risks of severe adverse effects, including esophageal fistula formation, perforation, obstruction, hemorrhage, and esophagitis. We determined palliative efficacy by evaluating pain and dysphagia scores before and after intervention. Multivariable analyses were used to control for potential confounding factors.Results:In our cohort, 1,593 patients underwent RT and 364 underwent esophageal stenting. The cumulative incidence of any severe adverse effect at 6 months was higher among patients who received stents compared with those who received RT (21.7% vs 12.4%;PPPP=.1029).Conclusions:Compared with esophageal stenting, RT was associated with a decreased risk of adverse effects, greater pain relief, and equivalent relief of moderate to severe dysphagia over time. Unmeasured patient- or tumor-related factors could have influenced the choice of intervention, thereby impacting our study outcomes. To our knowledge, this is the largest study to date analyzing the comparative risks and benefits of palliative RT and esophageal stenting among patients with metastatic esophageal cancer.

IMPORTANCE: 5α-Reductase inhibitors (5-ARIs), commonly used to treat benign prostatic hyperplasia, reduce serum prostate-specific antigen (PSA) concentrations by 50%. The association of 5-ARIs with detection of prostate cancer in a PSA-screened population remains unclear. OBJECTIVE: To test the hypothesis that prediagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease at diagnosis, and higher risk of prostate cancer–specific mortality and all-cause mortality than use of other or no PSA-decreasing drugs. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study linked the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records for 80 875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from January 1, 2001, to December 31, 2015. Patients were followed up until death or December 31, 2017. Data analysis was performed from March 2018 to May 2018. EXPOSURES: Prediagnostic 5-ARI use. MAIN OUTCOMES AND MEASURES: The primary outcome was prostate cancer–specific mortality (PCSM). Secondary outcomes included time from first elevated PSA (defined as PSA≥4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and all-cause mortality (ACM). Prostate-specific antigen levels for 5-ARI users were adjusted by doubling the value, consistent with previous clinical trials. RESULTS: Median (interquartile range [IQR]) age at diagnosis was 66 (61-72) years; median [IQR] follow-up was 5.90 (3.50-8.80) years. Median time from first adjusted elevated PSA to diagnosis was significantly greater for 5-ARI users than 5-ARI nonusers (3.60 [95% CI, 1.79-6.09] years vs 1.40 [95% CI, 0.38-3.27] years; P

Objective The primary aim of this study was to evaluate the effect of increased frequency of dialysis (FHD) on change in fluid status and body composition using segmental bioimpedance. Approach Twelve stable HD patients were switched from 3 times/week to 6 times/week HD (FHD). Systolic blood pressure (SBP), body mass and body mass index (BMI) were measured pre- and post-HD. Calf resistance (R 5) at 5 kHz was measured using a multifrequency bioimpedance device (Hydra 4200). Calf resistivity (ρ = R 5 * area/length), normalized resistivity (CNR = ρ/BMI) and calf extracellular volume (cECV) were calculated. Fat mass was measured by Futrex body composition analyzers (Futrex 6100, Futrex Tech, Inc.). All measurements were performed at baseline (BL) and monthly for up to one year. Main results Nine patients completed one year of FHD. Compared to BL, body weight and cECV decreased, and CNR increased significantly by the first month but did not change thereafter. SBP pre-HD decreased significantly by the end of the first month with further reduction until month 12. Additionally, antihypertensive medication decreased significantly from baseline by month 4 and remained stable from month 6 throughout the rest of the study. The post-HD CNR in five of nine patients reached the range of normal (>18.5 10-2 * Ohm * m3 kg-1 for males and >19.1 10-2 * Ohm * m3 kg-1 for females) after 1 year FHD. In patients who returned to 3 times/week dialysis, CNR decreased significantly in the first week, and this was associated with increases in body weight and SBP. Significance Reduction of fluid overload with no alteration of body composition was observed in this study. Accordingly, improving fluid status was confirmed by reducing BP and use of antihypertensive drugs together with increase in CNR. Measurement of fluid status by CNR in hemodialysis patients is a new method to quantitatively assess hydration potentially creating a target for volume of fluid removal.

INTRODUCTION AND OBJECTIVES:The safety of testosterone replacement therapy in men who have undergone radical prostatectomy (RP) for localized prostate cancer remains undefined.METHODS:In a large na...

INTRODUCTION AND OBJECTIVES:5α-Reductase inhibitors (5-ARIs), commonly used to treat benign prostatic hyperplasia, reduce serum prostate-specific antigen (PSA) concentrations by 50%. The effect of 5-ARIs on prostate cancer detection in a PSA-screened population remains unclear. We tested the hypothesis that pre-diagnostic 5-ARI use is associated with a delayed diagnosis, more advanced disease, and higher risk of prostate cancer-specific mortality and all-cause mortality.METHODS:We linked the Veterans Affairs Informatics and Computing Infrastructure with the National Death Index to obtain patient records. The cohort included 80,875 men with American Joint Committee on Cancer stage I-IV prostate cancer diagnosed from 2001-2015. The exposure was pre-diagnostic 5-ARI use. The main outcomes were time from initial PSA elevation (defined as PSA ≥ 4 ng/mL) to diagnostic prostate biopsy, cancer grade and stage at time of diagnosis, and prostate cancer-specific and all-cause mortality. PSA was adjusted by doubling ...

INTRODUCTION AND OBJECTIVES:The safety of testosterone replacement therapy in men who have undergone radiation therapy (RT) for localized prostate cancer remains undefined.METHODS:In a large nation...

Background Intraoperative MRI has been shown to improve gross-total resection of high-grade glioma. However, to the knowledge of the authors, the cost-effectiveness of intraoperative MRI has not been established. Purpose To construct a clinical decision analysis model for assessing intraoperative MRI in the treatment of high-grade glioma. Materials and Methods An integrated five-state microsimulation model was constructed to follow patients with high-grade glioma. One-hundred-thousand patients treated with intraoperative MRI were compared with 100 000 patients who were treated without intraoperative MRI from initial resection and debulking until death (median age at initial resection, 55 years). After the operation and treatment of complications, patients existed in one of three health states: progression-free survival (PFS), progressive disease, or dead. Patients with recurrence were offered up to two repeated resections. PFS, valuation of health states (utility values), probabilities, and costs were obtained from randomized controlled trials whenever possible. Otherwise, national databases, registries, and nonrandomized trials were used. Uncertainty in model inputs was assessed by using deterministic and probabilistic sensitivity analyses. A health care perspective was used for this analysis. A willingness-to-pay threshold of $100 000 per quality-adjusted life year (QALY) gained was used to determine cost efficacy. Results Intraoperative MRI yielded an incremental benefit of 0.18 QALYs (1.34 QALYs with intraoperative MRI vs 1.16 QALYs without) at an incremental cost of $13 447 ($176 460 with intraoperative MRI vs $163 013 without) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio of $76 442 per QALY. Because of parameter distributions, probabilistic sensitivity analysis demonstrated that intraoperative MRI had a 99.5% chance of cost-effectiveness at a willingness-to-pay threshold of $100 000 per QALY. Conclusion Intraoperative MRI is likely to be a cost-effective modality in the treatment of high-grade glioma. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Bettmann in this issue.

PURPOSE Treatment decisions about localized prostate cancer depend on accurate estimation of the patient’s life expectancy. Current cancer and noncancer survival models use a limited number of predefined variables, which could restrict their predictive capability. We explored a technique to create more comprehensive survival prediction models using insurance claims data from a large administrative data set. These data contain substantial information about medical diagnoses and procedures, and thus may provide a broader reflection of each patient’s health. METHODS We identified 57,011 Medicare beneficiaries with localized prostate cancer diagnosed between 2004 and 2009. We constructed separate cancer survival and noncancer survival prediction models using a training data set and assessed performance on a test data set. Potential model inputs included clinical and demographic covariates, and 8,971 distinct insurance claim codes describing comorbid diseases, procedures, surgeries, and diagnostic tests. We used a least absolute shrinkage and selection operator technique to identify predictive variables in the final survival models. Each model’s predictive capacity was compared with existing survival models with a metric of explained randomness (ρ2) ranging from 0 to 1, with 1 indicating an ideal prediction. RESULTS Our noncancer survival model included 143 covariates and had improved survival prediction (ρ2 = 0.60) compared with the Charlson comorbidity index (ρ2 = 0.26) and Elixhauser comorbidity index (ρ2 = 0.26). Our cancer-specific survival model included nine covariates, and had similar survival predictions (ρ2 = 0.71) to the Memorial Sloan Kettering prediction model (ρ2 = 0.68). CONCLUSION Survival prediction models using high-dimensional variable selection techniques applied to claims data show promise, particularly with noncancer survival prediction. After further validation, these analyses could inform clinical decisions for men with prostate cancer.

OBJECT: High-grade gliomas (HGGs) have poor survival and high treatment costs. Intraoperative MRI (ioMRI) improves gross-total resection (GTR) rates and prolongs progression-free survival (PFS) in HGGs, but questions regarding its cost-effectiveness persist. To date, no clinical decision analysis models assessing ioMRI in the treatment of HGG exist. METHODS: An integrated 5-state microsimulation model was constructed to follow patients with HGG. Patients treated with ioMRI were compared to those without ioMRI from initial resection/debulking until death. Following surgery and treatment of complications, patients existed in one of 3 health states: PFS, progressive disease, or dead. Patients with recurrence were offered up to two repeat resections. PFS, health utility values, probabilities, and costs were obtained from randomized-controlled trials whenever possible. Otherwise, national databases, registries, and non-randomized trials were used. Uncertainty in model inputs was assessed using deterministic and probabilistic sensitivity analyses. A healthcare perspective was taken for this analysis. A willingness to pay (WTP) threshold of $100,000/QALY gained was used to determine cost-efficacy. RESULTS: IoMRI yielded an incremental benefit of 0.18 QALYs (1.16 QALYs without ioMRI vs. 1.34 with) at an incremental cost of $13,447 ($157,000 without vs. $170,447 with) in microsimulation modeling, resulting in an incremental cost-effectiveness ratio (ICER) of $76,442 per QALY. Given our parameter distributions, probabilistic sensitivity analysis demonstrated that ioMRI had a 99.5% chance of cost-effectiveness at a WTP threshold of $100,000/QALY. CONCLUSION: Intra-operative MRI is likely a cost-effective modality in the treatment of HGGs.

AIM Chronic radiation proctitis (CRP) develops in 5-15% of patients after pelvic radiation therapy, with rectal bleeding being the main symptom. Reports suggest that argon plasma coagulation (APC) can be an effective therapy for CRP following radiotherapy for prostate cancer, but there is less information about how useful it is after radiotherapy for gynaecological malignancy. The aim of this work therefore was to study the efficacy of APC for CRP after radiotherapy for gynaecological malignancy. METHOD This was a prospective study of consecutive patients with CRP following radiotherapy for gynaecological malignancy at IPGMER symptoms included rectal bleeding grade (RBG) ≥ 2. APC was performed at monthly intervals to a maximum of four treatment sessions. Severity of disease at baseline was graded (endoscopically) by the total colonoscopic severity score (TCSS) and treatment response was assessed by reduction in RBG from ≥ 2 to ≤ 1 measured at > 6 months after cessation of APC. RESULTS Seventy patients [90% with cervical cancer, 10% with endometrial cancer; mean age 51.93 ± 9.15 years; median RBG 3 (range 2-4)] received APC. Seven patients died due to underlying malignancy and seven patients were lost to follow-up. Fifty-six (85.7%) patients responded to therapy after a median of 2 (range 1-4) treatment sessions. Multivariate analysis demonstrated that a lower haemoglobin at the start of treatment predicted failure of therapy (P < 0.05). CONCLUSION APC is an effective management option for CRP in female patients with gynaecological malignancy. However, the more anaemic the patient the less likely it is to be successful.

Background: Pancreatic cancer is an aggressive disease characterized by early and relentless tumor spread, thus leading healthcare providers to consider it a “distant disease.” However, local pancreatic tumor progression can lead to substantial morbidity. This study defines the long-term morbidity from local and nonlocal disease progression in a large population-based cohort. Methods: A total of 21,500 Medicare beneficiaries diagnosed with pancreatic cancer in 2000 through 2011 were identified. Hospitalizations were attributed to complications of either local disease (eg, biliary disorder, upper gastrointestinal ulcer/bleed, pain, pancreas-related, radiation toxicity) or nonlocal/distant disease (eg, thromboembolic events, cytopenia, dehydration, nausea/vomiting/motility problem, malnutrition and cachexia, ascites, pathologic fracture, and chemotherapy-related toxicity). Competing risk analyses were used to identify predictors of hospitalization. Results: Of the total cohort, 9,347 patients (43.5%) were hospitalized for a local complication and 13,101 patients (60.9%) for a nonlocal complication. After adjusting for the competing risk of death, the 12-month cumulative incidence of hospitalization from local complications was highest in patients with unresectable disease (53.1%), followed by resectable (39.5%) and metastatic disease (33.7%) at diagnosis. For nonlocal complications, the 12-month cumulative incidence was highest in patients with metastatic disease (57.0%), followed by unresectable (56.8%) and resectable disease (42.8%) at diagnosis. Multivariable analysis demonstrated several predictors of hospitalization for local and nonlocal complications, including age, race/ethnicity, location of residence, disease stage, tumor size, and diagnosis year. Radiation and chemotherapy had minimal impact on the risk of hospitalization. Conclusions: Despite the widely known predilection of nonlocal/distant disease spread in pancreatic cancer, local tumor progression also leads to substantial morbidity and frequent hospitalization.

Objective MRI and CT scans are usually normal in mild traumatic brain injury (mTBI) although 15–20% of such patients suffer for months from fatigue, headache, anxiety, sleep and other disorders. mTBI is suspected to be a cerebrovascular injury, similar to moderate and severe TBI. Brain SPECT is more sensitive and shows perfusion abnormalities immediately after mTBI. This work explores the perfusion abnormalities for young patients suffering from fatigue several months after mTBI. Patients and methods Twelve mTBI patients (age:8–36 yr, 4 male) with no history of fatigue prior to trauma were prospectively studied following onset of fatigue 6–12 months after mTBI utilizing 99 m-Tc ECD brain SPECT with early and delayed radiotracer imaging. Results The perfusion pattern in the mTBI + fatigue group included left hemispheric deficits in frontal lobes (early phase: 15.2 ± 4.2%, delayed phase: 9.9 ± 2.2%) and medial temporal lobes (early phase 11.2 ± 3.7%, delayed phase: 9.0 ± 2.3%). Seven patients additionally showed excess tracer accumulation in the parenchyma surrounding internal jugular bulb inferior to temporal lobe. This was modeled as due to increased cellular permeability from TBI induced oxidative stress affecting endothelial tight junctions and consequent tracer leakage across jugular bulbs. Prolonged posture changes from erect to supine position during imaging increase jugular cross-sectional area and venous wall pressure as has been observed in other disease processes and seem to be responsible for tracer leakage from jugular bulbs in our study. Conclusion This work supports an oxidative stress and BBB disruption model for mTBI. The frontal and temporal lobe perfusion deficits are attributed to anatomical vulnerabilities of these lobes. During a mild TBI both of these lobes are susceptible to grazing impacts with underlying bony ridges. We propose a relation between mTBI and fatigue arising from oxidative stress in mTBI affecting ATP generation and altering endothelial homeostasis for both micro-and-large vasculatures. The tracer leakage observed around jugular veins is due to posture induced changes in venous cross-sections and wall pressure as well as from compromised endothelium post TBI induced oxidative stress.

Background: The high prevalence of distant metastatic disease among patients with pancreatic cancer often draws attention away from the local pancreatic tumor. This study aimed to define the complications and hospitalizations from local versus distant disease progression among a retrospective cohort of patients with pancreatic cancer. Methods: Records of 298 cases of pancreatic cancer treated at a single institution from 2004 through 2015 were retrospectively reviewed, and cancer-related symptoms and complications requiring hospitalization were recorded. Hospitalizations related to pancreatic cancer were attributed to either local or distant progression. Cumulative incidence analyses were used to estimate the incidence of hospitalization, and multivariable Fine-Gray regression models were used to identify factors predictive of hospitalizations. Results: The 1-year cumulative incidences of hospitalization due to local versus distant disease progression were 31% and 24%, respectively. Among 509 recorded hospitalizations, leading local etiologies included cholangitis (10%), biliary obstruction (7%), local procedure complication (7%), and gastrointestinal bleeding (7%). On multivariable analysis, significant predictors of hospitalization from local progression included unresectable disease (subdistribution hazard ratio [SDHR], 2.42; P

During the last few decades, traumatic injuries of the hip joint have significantly increased in number, and traffic accidents have also increased. Depending on the speed, direction of the forces and the position of the femur at the moment of impact, different patterns of injury occur. Basically, they are classified as hip dislocations, dislocation fractures and acetabular fractures. These injuries have in common a high rate of concomitant lesions. Several classification systems have been developed for these injuries. Commonly, Stewart and Milford's or Levin's classification is used for dislocations and dislocation fractures. For acetabular fractures, Judet and Letournel's classification and its newer version developed by Helfet (AO classification) are generally accepted. Fractures of the femoral head, though included in these classifications, are typically described by separate classifications like the one presented in 1957 by Pipkin. The multitude of injuries occuring in the hip joint requires vast knowledge of various operative approaches. No single approach exists that would permit the treatment of all injuries in an ideal fashion. Approaches are either considered limited (Kocher-Langenbeck, ilioinguinal iliofemoral) when they permit access only to a restricted segment of the joint, or extended (extended iliofemoral, Maryland, Ruedi) when they allow all-around visualization of the hip joint. The choice of the best approach for an individual patient depends on the type of injury and also on patient variables like age, preexisting disease, and concomitant injuries. The decision is further influenced by the timing of surgery, the kind of fracture stabilization intended and by complications typically seen with certain approaches. The indication for extended procedures is only seen in patients with complex injury patterns involving both the anterior and the posterior column or in delayed cases undergoing surgery more than 3 weeks after trauma. Extended approaches permit excellent visualization of the fracture, but the extent of the soft tissue trauma is reflected in a high rate of postoperative complications. After a phase in which extended procedures were favored, recently a trend towards more limited approaches can be recognized because of their lower complication rate. This is facilitated by modern fracture-reduction methods using indirect techniques.

BACKGROUND AND PURPOSE MRI appearance of subthalamic nucleus (STN) boundaries in Parkinson's patients is often unreliable and not well understood. An objective comparison between FSE T2 and inversion recovery (FSTIR) sequences for stereotactic placement of deep brain stimulators is presented to advance current understanding of STN tissue contrast for refractory Parkinson's disease (PD). METHODS We imaged 12 PD (age 53-82) and 12 control patients (age 48-77) using T2 and FSTIR sequences at 1.5T. To avoid MR contrast variation from hardware and patient dependent sources we used an internal thalamic tissue standard to normalize STN signal intensity and correlated it with patient age for these two groups. RESULTS Normalized FSTIR-weighted STN contrast decreased with increasing age for PD patients (Spearman Rank correlation = −.5) while remained virtually unchanged for controls with age (Spearman Rank coefficient ≈0). T2-weighted STN contrast did not show appreciable changes with age for both the groups (Spearman correlation ≈ −.1). CONCLUSIONS STN, a common stimulation target, shows an age dependent trend for normalized FSTIR MRI contrast. Although larger patient pools are needed, our work points to tissue relaxation-based changes in STN that may provide insight in early stages of brain pathology involving DBS targets in medically refractory Parkinson's disease.

The molecular basis of chordoma is still poorly understood, particularly with respect to differentially expressed genes involved in the primary origin of chordoma. In this study, therefore, we compared the transcriptional expression profile of one sacral chordoma recurrence, two chordoma cell lines (U-CH1 and U-CH2) and one chondrosarcoma cell line (U-CS2) with vertebral disc using a high-density oligonucleotide array. The expression of 65 genes whose mRNA levels differed significantly (p