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Background: Patients with brain metastases (BrMs) from esophageal cancer have poor prognosis, the incidence of which is expected to rise due to improved survival from the primary tumor and increased neuroimaging. We aimed to identify patient and esophageal cancer characteristics associated with shorter survival in patients with BrMs and, secondly, to compare the prognosis of patients with HER2 overexpression., Methods: We retrospectively reviewed patients with BrMs from esophageal cancer at a single institution from 2008-2021. We collected patient demographics, primary tumor and BrM characteristics, and treatment. Our primary outcome was median survival from the time of BrM., Results: The median age at primary diagnosis was 66.5 years and 86% were male. Of the 49 patients, 71% had adenocarcinoma, 20% squamous cell carcinoma and 8% other. In this group, 71% of patients presented with stage III or IV disease, including 16% with synchronous primary metastatis and BrM. The median time to BrM was 10.1 months (interquartile range 1.7-22.8) and the median survival from BrM was 8.4 months (95% CI 4.8-16.8 months). On multivariable analysis, treatment with stereotactic radiosurgery (hazard ratio [HR] = 0.19; P = 0.04), surgical resection (HR 0.24; P = 0.03), and immunotherapy (HR 0.19; P = 0.04) were associated with increased survival while Karnofsky Performance Status (KPS) ≤70 (HR = 13.2; P < 0.001) was associated with decreased survival. HER2 overexpression was found in 22% of patients, but we noted no survival difference (5.2 months HER2+ vs. 9.8 months HER2neg; P = 0.95)., Conclusions: The median survival from esophageal-to-brain metastasis was 8.4 months. Patients with a single lesion, KPS score >70, and treatment with surgical resection was correlated with improved survival. Further, HER2+ patients had distinct patient and BrM characteristics., (Copyright © 2024. Published by Elsevier Inc.)

Introduction: Hypogonadism is associated with frailty, lower health-related quality of life, decreased muscle mass, and premature mortality, which may predispose patients to poor postoperative outcomes. We aimed to determine the prevalence of hypogonadism in men undergoing radical cystectomy (RC) and whether hypogonadism and frailty are associated with adverse postoperative outcomes., Materials and Methods: The IBM MarketScan database was used to identify men who underwent RC between 2012 and 2021. Frailty was determined using published Hospital Frailty Risk Score ranges. Patients were considered to have hypogonadism if diagnosed within 5 years prior to RC. Length of stay (LOS), complications, emergency department (ED) visits and inpatient readmissions were compared. Sub-group analysis of men with hypogonadism was performed to determine the effect of testosterone replacement therapy (TRT) on clinical outcomes., Results: Among 3,727 men who underwent RC, 226 (6.1%) had a diagnosis of hypogonadism. Overall, 565 (15.2%) men were low-risk frailty, 2,214 (59.4%) intermediate-risk frailty, and 948 (25.4%) were high-risk frailty, and men with hypogonadism were significantly more frail compared to men without hypogonadism (P = 0.027). There was no significant difference in LOS, complications, or rate of ED visits and inpatient readmissions between cohorts (P > 0.05). However, high-risk frailty was associated with an increased risk of 90-day ED visit (HR 1.19, 95%CI 1.00-1.41, P = 0.049) and 90-day readmission (HR 1.60, 95%CI 1.29-1.97, P < 0.001) after RC. Among men with hypogonadism, 58 (25.7%) were on TRT. There was no significant difference in frailty, LOS, complications, or 90-day ED visits or 90-day inpatient readmissions between patient with hypogonadism prescribed TRT and those without TRT., Conclusions: These findings suggest that hypogonadism and preoperative frailty may be important to evaluate prior to undergoing RC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Reduction of opioids is an important goal in the care of patients undergoing radical cystectomy (RC). Liposomal bupivacaine (LB) has been shown to be a safe and effective pain reliever in the immediate postoperative period and has been reported to reduce postoperative opioid requirements. Since the liposomal formulation is predicated on slow systemic absorption, the amount of bupivacaine administered is notably higher than that typically used with standard bupivacaine (SB) formulations. In addition, LB is costly, not universally available, and studies comparing this formulation to SB are lacking. We sought to determine if there is a difference in postoperative opioid requirements in patients who receive LB vs. high dose SB at the time of RC., Methods: In May 2019 we transitioned to administration of high-volume SB injected intraoperatively at the time of RC. This prospective cohort was compared to a historical cohort of patients who received injection of LB at the time of surgery. Primary endpoints included postsurgical opioid use measured in morphine equivalent dose (MED) and patient-reported Numeric Rating Scale (NRS) pain scores and length of stay. All patients were managed using principles of enhanced recovery after surgery (ERAS)., Results: From May 2019 through August 2019, 28 patients underwent RC and met eligibility criteria to receive SB at the time of surgery. They were compared to a historical cohort of 34 patients who received LB between November 2017 and July 2018. There was no difference in MED exposure either in the postanesthesia care unit (SB 9.0 ± 8.9 MED vs. LB 6.5 ± 9.4 MED, P= 0.29) or during the remainder of the hospital stay (SB 36.8 ± 56.9 MED vs. LB 42.1 ± 102.5 MED, P= 0.81), no difference in NRS pain scores on postoperative day 1 (SB 2.6 ± 1.6 vs. LB 2.1 ± 1.7, P= 0.23), day 2 (SB 2.4 ± 1.8 vs. LB 1.9 ± 1.6, P= 0.19), or day 3 (SB 1.9 ± 1.8 vs. LB 1.7 ± 1.7, P= 0.69) and no difference in length of stay (SB 5.0 ± 1.7 days, LB 4.9 ± 3.3 days, P= 0.93). Subgroup analysis of open RC and robotic-assisted RC showed no significant difference in MED or pain scores between LB and SB patients., Conclusions: Among patients undergoing RC under ERAS protocol there was no significant difference in postoperative opioid consumption, NRS pain scores, or length of stay among patients receiving SB compared to LB., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Though testicular cancer is the most common cancer in young men, there is a paucity of epidemiologic studies examining sociodemographic disparities in adjuvant therapy and outcomes. We examined the associations of sociodemographic factors with retroperitoneal lymph node dissection (RPLND) and survival among patients with nonseminomatous germ cell tumors (NSGCTs)., Methods: Within the Surveillance Epidemiology and End Results database (2005-2015), we identified 8,573 patients with nonseminomatous germ cell tumors. Multivariable logistic regression and Fine-Gray competing-risks regression models were constructed to examine the association of sociodemographic factors (neighborhood SES (nSES), race, and insurance) with, respectively, adjuvant RPLND within 1 year of diagnosis and cancer-specific mortality., Results: Patients in the lowest nSES quintile (OR 0.59, 95% CI = 0.40-0.88, P = 0.01) and Black patients (OR 0.41, 95% CI = 0.15-1.00, P= 0.058) with stage II disease were less likely to receive RPLND compared to those in the highest quintile and White patients, respectively. Stage III patients with Medicaid (OR 0.64, 95% CI = 0.46-0.89, P= 0.009) or without insurance (OR 0.46, 95% CI = 0.27-0.76, P= 0.003) were less likely to receive RPLND compared to patients with private insurance. Lowest quintile nSES patients of all disease stages and Black patients with stage I disease (HR = 2.64, 95% CI = 1.12-6.20, P = 0.026) or stage II disease (HR=4.93, 95% CI = 1.48-16.44, P = 0.009) had higher risks of cancer-specific mortality compared to highest quintile nSES and White patients, respectively., Conclusions: This national study found multilevel, stage-specific sociodemographic disparities in receipt of RPLND and survival., Competing Interests: Conflict of interest The authors declare no potential conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: When exploring survival outcomes for patients with bladder cancer, most studies rely on conventional statistical methods such as proportional hazards models. Given the successful application of machine learning to handle big data in many disciplines outside of medicine, we sought to determine if machine learning could be used to improve our ability to predict survival in bladder cancer patients. We compare the performance of artificial neural networks (ANN), a type of machine learning algorithm, with that of multivariable Cox proportional hazards (CPH) models in the prediction of 5-year disease-specific survival (DSS) and overall survival (OS) in patients with bladder cancer., Subjects and Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) 18 program database was queried to identify adult patients with bladder cancer diagnosed between 1995 and 2010, yielding 161,227 patients who met our inclusion criteria. ANNs were trained and tested on an 80/20 split of the dataset. Multivariable CPH models were developed in parallel. Variables used for prediction included age, sex, race, grade, SEER stage, tumor size, lymph node involvement, degree of extension, and surgery received. The primary outcomes were 5-year DSS and 5-year OS. Receiver operating characteristic curve analysis was conducted, and ANN models were tested for calibration., Results: The area under the curve for the ANN models was 0.81 for the OS model and 0.80 for the DSS model. Area under the curve for the CPH models was 0.70 for OS and 0.81 for DSS. The ANN OS model achieved a calibration slope of 1.03 and a calibration intercept of -0.04, while the ANN DSS model achieved a calibration slope of 0.99 and a calibration intercept of -0.04., Conclusions: Machine learning algorithms can improve our ability to predict bladder cancer prognosis. Compared to CPH models, ANNs predicted OS more accurately and DSS with similar accuracy. Given the inherent limitations of administrative datasets, machine learning may allow for optimal interpretation of the complex data they contain., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brain metastases from endometrial cancer are rare and poorly described. We aimed to estimate the proportion of brain metastases at our institution that arose from endometrial cancer, and to detail clinicopathologic features and survival outcomes., Methods: We retrospectively identified and reviewed the charts of 30 patients with brain metastases from endometrial cancer seen at Stanford Hospital from 2008 to 2018., Results: Among all patients with brain metastases, the proportion arising from endometrial cancer was 0.84%. The median age at diagnosis was 62 years (range, 39-79 years), and the median overall survival from brain metastasis diagnosis was 6.8 months (range, 1.0-58.2 months). Most patients harbored endometrioid histology (53.3%), and some had concurrent metastases to lung (50.0%), bone (36.7%), and liver (20.0%). The median time from endometrial cancer diagnosis to brain metastasis development was 20.8 months (range, 1.4 months to 11.2 years), and the median number of brain metastases was 2 (range, 1-20). Patients with non-endometrioid histologies had more brain metastases than those with endometrioid histology (6.21 vs. 2.44, P = 0.029). There was no difference in overall survival by histology., Conclusions: We describe the largest cohort to date of patients with brain metastases originating from endometrial cancer. These patients represent a small fraction of all patients with brain metastases and have poor prognoses. These data enable providers caring for patients with brain metastases from endometrial cancer to appropriately counsel their patients., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Nonsquamous penile cancers comprise 5% of penile malignancies, though their clinicopathologic features and prognostic significance remain unknown. We used a national cancer registry to detail clinical characteristics and compare cancer-specific mortality (CSM) of nonsquamous cancers with squamous cell carcinoma (SCC)., Methods: The Surveillance, Epidemiology, and End Results (SEER) database (1975-2016) was queried to identify adults with nonsquamous penile cancer and penile SCC. Multivariable Fine and Gray competing-risks regression, propensity score matching, and cumulative incidence plots were used., Results: 666 men with nonsquamous penile cancer and 5,894 men with penile SCC were identified. The most commonly represented nonsquamous histological subtypes were Kaposi sarcoma (n = 183, 27.5%), melanoma (n = 74, 11.1%), basal cell carcinoma (n = 65, 9.8%), and extramammary Paget disease (n = 42, 6.3%). Cumulative incidence plots revealed a 10-year CSM rate of 32.6% in the nonsquamous penile cancer group and 25.6% in the matched penile SCC group (P < 0.0001). Among Kaposi sarcoma patients and matched SCC patients, we found a 10-year CSM rate of 29.6% in the Kaposi sarcoma group and 15.3% in the penile SCC group (P = 0.002). Similarly, a comparison of penile melanoma patients with matched SCC patients revealed a 10-year CSM rate of 38.4% in the melanoma group and 16.6% in the SCC group (P = 0.002). There was no difference in CSM between patients with basal cell carcinoma and SCC. In a sensitivity analysis limiting year of diagnosis to 2000 and onward, we found no difference in CSM between the general nonsquamous cohort or the Kaposi sarcoma cohort and matched SCC patients, but contemporary melanoma patients maintained worse CSM with a 10-year rate of 38.4% vs. 15.8% in matched SCC patients (P = 0.045)., Conclusions: The most common nonsquamous penile cancers are Kaposi sarcoma, melanoma, and basal cell carcinoma. Overall, CSM is higher in nonsquamous penile cancers as compared to stage-matched SCC. Outcomes are similar in modern patients, likely due to improved control of systemic HIV in patients with Kaposi sarcoma. However, men with penile melanoma continue to experience a higher rate of CSM., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objective: Immunotherapy for patients with melanoma with brain metastasis has significantly improved outcomes; however, it has also been characterized by potentially dangerous immune-related adverse events (IRAEs). Several reports have suggested that these reactions can precede improved treatment responses. For intracranial disease control, we sought to identify if such an association exists., Methods: We conducted a retrospective chart review of patients with melanoma who underwent immunotherapy treatment after diagnosis of brain metastasis. The study cohort was then stratified into 2 groups based on their history of developing an IRAE that prompted discontinuation of that regimen. The primary outcome variable included intracranial progression-free survival (PFS). Kaplan-Meier and Cox proportional hazard analyses were used to evaluate survival and predictors of outcomes., Results: Fifty-two patients met the inclusion criteria, 17 of whom experienced severe IRAEs that led to discontinuation of immunotherapy. Median intracranial PFS was 19.9 versus 10.5 months (P = 0.053) in patients who did and did not experience severe IRAEs prompting discontinuation, respectively. No additional outcome benefits were identified for systemic PFS or overall survival (mean, 33.1 months and 27.6 months, respectively). Multivariable analysis identified BRAF mutation status as a negative prognosticator of brain progression (P = 0.013; hazard ratio, 3.90). Initial treatment with BRAF inhibitor was also a negative predictor of all-cause mortality (P = 0.015; hazard ratio, 10.73)., Conclusions: Immune-related adverse events may signify an underlying immunogenic response that has intracranial disease control benefits. Despite their associated side effects, immunotherapies continue to show promising outcomes as a first-line agent for melanoma with brain metastasis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brain metastases (BMs) from hepatocellular carcinoma (HCC) are rare, with a paucity of reported cases. In the present retrospective cohort report, we assessed the proportion of BMs arising from HCC and characterized the related details, including patient demographics, clinical characteristics, treatment modalities, and survival outcomes., Methods: We retrospectively identified and reviewed the medical records of 14 patients with BMs from HCC seen at our institution from 2008 to 2018., Results: Among all patients with BMs, the proportion originating from primary liver cancer was 0.39%. In every case (n = 14), the liver cancer was HCC. The median age at the BM diagnosis was 64 years (range, 37-82 years). The median alpha-fetoprotein level at the diagnosis of BM was 540 ng/mL (range, 3-10,000 ng/mL). The median interval from the HCC diagnosis to the development of BMs was 31.1 months (range, 3.17-107 months). Of the 14 patients, 8 (57%) had had metastases to the brain parenchyma and 6 had had skull or dural metastases. For patients with brain parenchymal metastases, the median number of metastases was 1 (range, 1-5). Of the 14 patients, 13 have died, with a median overall survival after the BM diagnosis of 2.83 months (range, 0.430-24.0 months). At the latest follow-up examination, the survival for the 14th patient was 142 months after the BM diagnosis. Resection of BMs with radiosurgery was associated with increased survival compared with radiosurgery alone (10.9 months vs. 2.8 months; P = 0.04)., Conclusions: HCC BMs are rare and constitute a small fraction of the total incidence of BMs. The prognostic data we have provided can aid medical providers in caring for patients with HCC BMs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Brain metastases from prostate cancer are rare and poorly described. We sought to assess the proportion of brain metastases arising from prostate cancer and to detail clinical characteristics, treatment modalities, and survival outcomes., Methods: We retrospectively identified and reviewed the charts of 31 patients with intraparenchymal brain metastases from prostate adenocarcinoma seen at our institution from 2008 to 2018., Results: Among all patients with brain metastases, the proportion originating from prostate adenocarcinoma was 0.86%. The median age at the time of brain metastasis diagnosis was 69 (range, 57-90). The median original Gleason score was 8 (range, 6-10), and the median prostate-specific antigen at the time of brain metastasis was 60 ng/mL (range, 0.34-4600). The median months from initial cancer diagnosis to brain metastasis was 81 (range, 3-195). The median number of brain metastases was 2 (range, 1-5). Patients had concurrent metastases to bone (100%), lung (48%), and liver (35%). Median overall survival was 3 months (range, 0.4-25.0). Treatment of the brain metastases was correlated with an increase in median survival from 1.2 months to 4.6 months with radiosurgery (hazard ratio = 0.11, P = 0.001) and surgical resection plus radiotherapy to 13 months (hazard ratio = 0.05, P < 0.001). All patients died of advanced, systemic disease and not of their intracranial disease., Conclusions: Brain metastasis from prostate cancer constitutes a small fraction of total brain metastases, but is associated with poor prognosis and is seen in the setting of advanced, castrate resistant disease. These data enable treating physicians to appropriately counsel their patients with prostate adenocarcinoma brain metastasis., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess the effectiveness of a clinical decision support tool consisting of an electronic medical record best practice alert (BPA) on the frequency of lumbar imaging in patients with acute low back pain in the ambulatory care setting, and to explore why providers order imaging outside of clinical guidelines., Methods: On March 23, 2016, we implemented a BPA pop-up alert that informed the ordering physician of the Choosing Wisely recommendation to not order imaging within the first 6 weeks of low back pain in the absence of red flags. We calculated imaging rates 1 year before and after implementation of the BPA. To override the BPA, providers could ignore the alert or explain their rationale for ordering imaging using either preset options or a free-text submission. We tracked preset options and manually reviewed 125 free-text submissions., Results: Significant decreases in both total imaging rate (9.6% decrease; P = 0.02) and magnetic resonance imaging rate (14.9% decrease; P < 0.01) were observed after implementation of the BPA. No change was found in the rates of X-ray or computed tomography scan orders. Almost two-thirds (64%) of the providers used preset options in overriding the BPA, and 36% of the providers entered a free-text submission. Among those providers using a free-text submission, 56% entered a non-guideline-supported rationale., Conclusions: The present study demonstrates the effectiveness of a simple, low-cost clinical decision support tool in reducing imaging rates for patients with acute low back pain. We also identify reasons why providers order imaging outside of clinical guidelines., (Copyright © 2019 Elsevier Inc. All rights reserved.)