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PurposeThe RAZOR (Randomized Open versus Robotic Cystectomy) trial revealed noninferior 2-year progression-free survival for robotic radical cystectomy. This update was performed with extended followup for 3 years to determine potential differences between the approaches. We also report 3-year overall survival and sought to identify factors predicting recurrence, and progression-free and overall survival.Materials and methodsWe analyzed the per protocol population of 302 patients from the RAZOR study. Cumulative recurrence was estimated using nonbladder cancer death as the competing risk event and the Gray test was applied to assess significance in differences. Progression-free survival and overall survival were estimated by the Kaplan-Meier method and compared with the log rank test. Predictors of outcomes were determined by Cox proportional hazard analysis.ResultsEstimated progression-free survival at 36 months was 68.4% (95% CI 60.1-75.3) and 65.4% (95% CI 56.8-72.7) in the robotic and open groups, respectively (p=0.600). At 36 months overall survival was 73.9% (95% CI 65.5-80.5) and 68.5% (95% CI 59.8-75.7) in the robotic and open groups, respectively (p=0.334). There was no significant difference in the cumulative incidence rates of recurrence (p=0.802). Patient age greater than 70 years, poor performance status and major complications were significant predictors of 36-month progression-free survival. Stage and positive margins were significant predictors of recurrence, and progression-free and overall survival. Surgical approach was not a significant predictor of any outcome.ConclusionsThis analysis showed no difference in recurrence, 3-year progression-free survival or 3-year overall survival for robotic vs open radical cystectomy. It provides important prospective data on the oncologic efficacy of robotic radical cystectomy and high level data for patient counseling.

In meta-analysis based on continuous outcome, estimated means and corresponding standard deviations from the selected studies are key inputs to obtain a pooled estimate of the mean and its confidence interval. We often encounter the situation that these quantities are not directly reported in the literatures. Instead, other summary statistics are reported such as median, minimum, maximum, quartiles, and study sample size. Based on available summary statistics, we need to estimate estimates of mean and standard deviation for meta-analysis. We developed an R Shiny code based on approximate Bayesian computation (ABC), ABCMETA, to deal with this situation. In this article, we present an interactive and user-friendly R Shiny application for implementing the proposed method (named ABCMETAapp). In ABCMETAapp, users can choose an underlying outcome distribution other than the normal distribution when the distribution of the outcome variable is skewed or heavy tailed. We show how to run ABCMETAapp with examples. ABCMETAapp provides an R Shiny implementation. This method is more flexible than the existing analytical methods since estimation can be based on five different distributions (Normal, Lognormal, Exponential, Weibull, and Beta) for the outcome variable.

Myeloid Derived suppressor cells (MDSCs) play a key role in the progression and recurrence of human malignancies and in restraining the efficacy of adjuvant therapies. We have previously shown that Tadalafil lowers MDSCs and regulatory T cells (Treg) in the blood and in the tumor, primes a tumor specific immune response, and increases the number of activated intratumoral CD8+T cells in patients with primary Head and Neck Squamous Cell Carcinoma (HNSCC). However, despite these important immune modulatory actions, to date no clinically significant effects have been reported following PDE5 inhibition. Here we report for the first time interim results of our ongoing phase I clinical trial (NCT02544880) in patients with recurrent HNSCC to evaluate the safety of and immunological effects of combining Tadalafil with the antitumor vaccine composed of Mucin1 (MUC1) and polyICLC. The combined treatment of Tadalafil and MUC1/polyICLC vaccine was well-tolerated with no serious adverse events or treatment limiting toxicities. Immunologically, this trial also confirms the positive immunomodulation of Tadalafil in patients with recurrent HNSCC and suggests an adjuvant effect of the anti-tumor vaccine MUC1/polyICLC. Additionally, image cytometry analysis of scanned tumors indicates that the PDE5 inhibitor Tadalafil in conjunction with the MUC1/polyICLC vaccine effectively reduces the number of PDL1+macrophages present at the tumor edge, and increases the number of activated tumor infiltrating T cells, suggesting reversion of immune exclusion. However, this analysis shows also that CD163 negative cells within the tumor upregulate PDL1 after treatment, suggesting the instauration of additional mechanisms of immune evasion. In summary, our data confirm the safety and immunologic potential of PDE5 inhibition in HNSCC but also point to PDL1 as additional mechanism of tumor evasion. This supports the rationale for combining checkpoint and PDE5 inhibitors for the treatment of human malignancies.

Purpose: To evaluate patient satisfaction and symptom control in hypogonadal men transitioning from other testosterone therapies to oral testosterone undecanoate (TU). Materials and Methods: In this open-label clinical trial, men aged 18 to 75 years with hypogonadism were switched to oral TU after a sufficient washout of previous testosterone therapies. Treatment satisfaction and symptom control were primarily measured using the 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) and quantitative androgen deficiency in aging males (qADAM) questionnaires, respectively. Secondary outcomes included changes in serum testosterone (T), estradiol (E2), hematocrit (HCT), and prostate-specific antigen (PSA) levels. Results: Forty-one men participated, with significant improvements in all TSQM-9 scores observed over 6 months. Symptom control as measured by qADAM remained consistent. There was a significant increase in serum T and E2 levels, but HCT and PSA levels remained stable. Conclusions: Switching to oral TU from other testosterone therapies is associated with increased patient satisfaction and stable hypogonadal symptom control. [ABSTRACT FROM AUTHOR]

Adult T-cell leukemia/lymphoma (ATLL) is a fatal disease caused by human T-cell leukemia virus type 1 (HTLV-1). We retrospectively analyzed 195 patients with ATLL (lymphomatous n = 96, acute n = 80, unfavorable chronic n = 7, chronic n = 5, smoldering n = 3, and unclassified n = 4) diagnosed between 1987 and 2016 (median age 52 years, 77% Afro-Caribbean). Hypercalcemia was associated with acute ATLL (65%, vs 23% lymphomatous) (P = .012). The median survival for patients treated with modern therapies between 2000 and 2016 was 4.1 months for acute, 10.2 months for lymphomatous, 72 months for chronic/smoldering, and not reached for unfavorable chronic type, with 4-year survival rates of 10%, 4%, 60%, and 83%, respectively. The overall response rate (ORR) after first-line multiagent chemotherapy was 78% (complete response [CR] 39%) for acute vs 67% (CR 33%) for lymphomatous ATLL. First-line zidovudine interferon-α (AZT-IFN) resulted in ORR of 56% (CR 23%) for acute (n = 43), 33% (CR 16.5%) for lymphomatous (n = 6), and 86% (CR 29%) for unfavorable chronic ATLL. The median progression-free survival (PFS) in patients with aggressive ATLL who achieved CR after AZT-IFN was 48 months vs 11 months after chemotherapy (P = .003). Allogeneic hematopoietic stem cell transplant (allo-HSCT) resulted in a PFS of 24 and 28 months in 2 patients with lymphomatous ATLL. Our results suggest high-dose AZT-IFN is a reasonable up-front option for patients with aggressive leukemic ATLL followed by chemotherapy switch in nonresponders, whereas chemotherapy should be used in lymphomatous type followed by allo-HSCT when feasible.

Background: There are 54,000 new cases of oral cavity and oropharyngeal cancer in the United States and more than 476,000 worldwide each year. Oral cavity and oropharyngeal squamous cell carcinoma make up most tumors with five-year survival rates of 50% due to prevalence of late-stage diagnoses. Improved methods of early detection in high-risk individuals are urgently needed. We aimed to assess the tumorigenic biomarkers soluble CD44 (solCD44) and total protein (TP) measured using oral rinses as affordable convenient screening tools for cancer detection. Methods: In this prospective cohort study, we recruited 150 healthy current or former smokers through a community screening program. Baseline and four annual visits were conducted from March 2011-January 2016 with records followed until August 2020. Participants provided oral rinses, received head and neck exams, and completed questionnaires. SolCD44 and TP levels were measured and compared across groups and time. Participants were placed in the cancer group if malignancy developed in the study period, the suspicious group if physical exams were concerning for premalignant disease or cancer in the head and neck, and the healthy group if there were no suspicious findings. This analysis used two-sample t-test for comparison of means and two-sample Wilcoxon Test for comparison of medians. For subjects with follow-ups, estimated means of biomarkers were obtained from a fitted Repeated Measures Analysis of Variance (RANOVA) model including group, visit, and their interaction. Pairwise comparisons of mean solCD44 were made, including intergroup and intragroup comparison of values at different years. Results: Most participants were males (58.7%), < 60 years of age. (90.7%), and Black (100%). Baseline mean solCD44 was elevated (2.781 ng/ml) in the cancer group compared to the suspicious group (1.849 ng/ml) and healthy group (1.779 ng/ml). Conclusion: This study supports the feasibility of a CD44-based oral rinse test as an affordable and convenient adjunctive tool for early detection of aerodigestive tract and other cancers in high-risk populations. [ABSTRACT FROM AUTHOR]

Background: Early adverse skin reactions (EASRs) are common side effects of radiotherapy (RT) that impact the quality of life of breast cancer patients. This study used global metabolomics profiles of breast cancer populations to identify metabolic pathways and biomarkers significantly associated with RT-induced EASRs to identify potential targets for precision interventions. Methods: We used a frequency-matched study design to identify pre-RT urine samples from 60 female breast cancer patients (30 with high and 30 with low EASRs) for metabolomic analysis by Metabolon Inc. using UPLC-MS/MS and GC-MS. Using MetaboAnalyst, we performed metabolomic data analysis and visualization on 84 candidate metabolites from 478 total compounds. We used the Oncology Nursing Society (ONS) Skin Toxicity Criteria (0– 6) for EASRs assessment. Results: Seven metabolic pathways were significantly associated with RT-induced EASRs, including alanine, aspartate, and glutamate metabolism (p = 0.0028), caffeine metabolism (p = 0.0360), pentose and glucuronate interconversions (p = 0.0028), glycine, serine, and threonine metabolism (p = 0.0360), beta-alanine metabolism (p = 0.0210), pantothenate and CoA biosynthesis (p = 0.0028), and glutathione metabolism (p = 0.0490). The alanine, aspartate, and glutamate metabolic pathway had the lowest false discovery rate (FDR)-adjusted p-value and the highest impact value of 0.60. Thirteen metabolite biomarkers were significantly associated with RT-induced EASRs. Conclusion: Our data show that the alanine, aspartate, and glutamate metabolism pathways had the highest impact value on RT-induced EASRs. Future larger studies are warranted to validate our findings and facilitate targeted interventions for preventing or mitigating RT-induced EASRs, offering a promising direction for further research and clinical applications. [ABSTRACT FROM AUTHOR]

Purpose: To identify factors associated with urinary incontinence (UI) in women of various Hispanic/Latina backgrounds. Materials and Methods: We analyzed data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), a multicenter, community‐based cohort study which includes a health‐related questionnaire assessing presence and type of UI. Complex survey logistic regression analysis was used to assess the cross‐sectional association of Hispanic/Latina backgrounds and other factors of UI. All estimates accounted for HCHS/SOL survey design. Results: Of 5027 women, 33.4% answered "yes" to UI. Rates of any UI ranged from approximately 21.9% to 40.3% in women of Dominican and Puerto‐Rican background, respectively. Any UI and UI subtypes were associated with age older than 65 years, increasing body mass index, smoking status, any alcohol use, parity ≥3, and postmenopausal status. After controlling for covariates and when compared with women of Mexican background, women of Dominican background were less likely to have any UI (OR = 0.42, 95% CI 0.30–0.57), as were women of Cuban (OR = 0.48, 95% CI 0.37–0.62), Puerto‐Rican (OR = 0.79, 95% CI 0.62–1.0), and mixed (OR = 0.62, 95% CI 0.39–0.99) background; and women of every other background except for South American were less likely to have stress UI. In addition, women of Cuban (OR = 0.53, 95% CI 0.32–0.86) and mixed (OR = 0.38, 95% CI 0.16–0.87) background were less likely to have urge UI than women of Mexican background. Conclusions: Our study demonstrates differences in UI by Hispanic/Latina background, suggesting collective designation of Hispanics/Latinas as a single ethnic group does not adequately describe UI among this diverse group. [ABSTRACT FROM AUTHOR]