scholarly journals Immune checkpoint-related serum proteins and genetic variants predict outcomes of localized prostate cancer, a cohort study

2020 ◽  
Author(s):  
Qinchuan Wang ◽  
Yuanqing Ye ◽  
Hao Yu ◽  
Shu-Hong Lin ◽  
Huakang Tu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Mrna Expression ◽  
Immune Checkpoint ◽  
Serum Proteins ◽  
Meta Analysis ◽  
Genetic Variations ◽  
Localized Prostate Cancer ◽  
Nucleotide Polymorphisms ◽  
Clinical Predictors ◽  
Related Proteins

Abstract Background The clinical predictors and biological mechanisms for localized prostate cancer (PCa) outcomes remain mostly unknown. We aim to evaluate the role of serum immune-checkpoint-related (ICK) proteins and genetic variations in predicting outcomes of localized PCa. Methods We profiled the serum levels of 14 ICK-related proteins (BTLA, GITR, HVEM, IDO, LAG-3, PD-1, PD-L1, PD-L2, Tim-3, CD28, CD80, 4-1BB, CD27, and CTLA-4) in 190 patients with localized PCa. The genotypes of 97 single nucleotide polymorphisms (SNPs) from 19 ICK-related genes were analyzed in an extended population (N = 1762). Meta-data from ArrayExpress and TCGA was employed to validate and to probe functional data. Patients were enrolled and tumor aggressiveness, biochemical recurrence (BCR), and progression information were obtained. Statistical analyses were performed analyzing associations between serum biomarkers, genotypes, mRNA and outcomes. Results We showed that serum (s)BTLA and sTIM3 levels were associated with PCa aggressiveness (P < 0.05). sCD28, sCD80, sCTLA4, sGITR, sHVEM and sIDO correlated with both BCR and progression risks (all P < 0.05). We further identified ICK variants were significantly associated with aggressiveness, BCR and progression. Among them, 4 SNPs located in CD80 (rs7628626, rs12695388, rs491407, rs6804441) were not only associated with BCR and progression risk, but also correlated with sCD80 level (P < 0.01). rs491407 was further validated in an independent cohort. The CD80 mRNA expression was associated with BCR (HR, 1.85, 95% CI 1.06–3.22, P = 0.03) in meta-analysis of validation cohorts. Conclusion We highlight the prognostic value of serum ICK-related proteins for predicting aggressiveness, BCR and progression of PCa. The genetic variations and mRNA expression in CD80 could be predictors and potential targets of localized PCa.

scholarly journals Addition of Androgen-Deprivation Therapy or Brachytherapy Boost to External Beam Radiotherapy for Localized Prostate Cancer: A Network Meta-Analysis of Randomized Trials

2020 ◽  
Vol 38 (26) ◽  
pp. 3024-3031 ◽  
Author(s):  
William C. Jackson ◽  
Holly E. Hartman ◽  
Robert T. Dess ◽  
Sam R. Birer ◽  
Payal D. Soni ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Randomized Trials ◽  
Practice Patterns ◽  
Meta Analysis ◽  
External Beam Radiotherapy ◽  
Localized Prostate Cancer ◽  
External Beam ◽  
Brachytherapy Boost ◽  
Meta Analyses

PURPOSE In men with localized prostate cancer, the addition of androgen-deprivation therapy (ADT) or a brachytherapy boost (BT) to external beam radiotherapy (EBRT) have been shown to improve various oncologic end points. Practice patterns indicate that those who receive BT are significantly less likely to receive ADT, and thus we sought to perform a network meta-analysis to compare the predicted outcomes of a randomized trial of EBRT plus ADT versus EBRT plus BT. MATERIALS AND METHODS A systematic review identified published randomized trials comparing EBRT with or without ADT, or EBRT (with or without ADT) with or without BT, that reported on overall survival (OS). Standard fixed-effects meta-analyses were performed for each comparison, and a meta-regression was conducted to adjust for use and duration of ADT. Network meta-analyses were performed to compare EBRT plus ADT versus EBRT plus BT. Bayesian analyses were also performed, and a rank was assigned to each treatment after Markov Chain Monte Carlo analyses to create a surface under the cumulative ranking curve. RESULTS Six trials compared EBRT with or without ADT (n = 4,663), and 3 compared EBRT with or without BT (n = 718). The addition of ADT to EBRT improved OS (hazard ratio [HR], 0.71 [95% CI, 0.62 to 0.81]), whereas the addition of BT did not significantly improve OS (HR, 1.03 [95% CI, 0.78 to 1.36]). In a network meta-analysis, EBRT plus ADT had improved OS compared with EBRT plus BT (HR, 0.68 [95% CI, 0.52 to 0.89]). Bayesian modeling demonstrated an 88% probability that EBRT plus ADT resulted in superior OS compared with EBRT plus BT. CONCLUSION Our findings suggest that current practice patterns of omitting ADT with EBRT plus BT may result in inferior OS compared with EBRT plus ADT in men with intermediate- and high-risk prostate cancer. ADT for these men should remain a critical component of treatment regardless of radiotherapy delivery method until randomized evidence demonstrates otherwise.

scholarly journals Hypofractionated radiotherapy versus conventional radiotherapy in patients with intermediate- to high-risk localized prostate cancer: a meta-analysis of randomized controlled trials

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Wei Guo ◽  
Yun-Chuan Sun ◽  
Jian-Qiang Bi ◽  
Xin-Ying He ◽  
Li Xiao
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Adverse Events ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Localized Prostate Cancer ◽  
Hypofractionated Radiotherapy ◽  
Cancer Specific Survival ◽  
Conventional Radiotherapy ◽  
Results Of Treatment

Abstract Background Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer. Methods Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. Results The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93–1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42–3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76–1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12–2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61–0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89–1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86–1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups. Conclusion Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.

Religion and spirituality among patients with localized prostate cancer

2006 ◽  
Vol 4 (4) ◽  
pp. 345-355 ◽  
Author(s):  
NATALIE HAMRICK ◽  
MICHAEL A. DIEFENBACH
Keyword(s):  
Prostate Cancer ◽  
Religious Coping ◽  
Cancer Patients ◽  
General Social Survey ◽  
Cancer Recurrence ◽  
Localized Prostate Cancer ◽  
Religion And Spirituality ◽  
Spiritual Experiences ◽  
Clinical Predictors ◽  
Religiosity And Spirituality

Objective: To examine: (1) daily religious and spiritual experiences among localized prostate cancer patients as compared to a national age and race-matched male sample; (2) cognitive-affective and clinical predictors of prostate cancer diagnosis-related increases in religiosity and spirituality; (3) short-term impact of daily religious and spiritual experiences on cancer recurrence worry.Methods: Analyses of data from a longitudinal questionnaire study among patients (N = 254) diagnosed with localized prostate cancer and data from a random sample (N = 238) of respondents to the national General Social Survey.Results: Compared to the national sample, prostate cancer patients reported higher levels of daily spiritual experiences. Patients with higher worry about prostate cancer and elevated levels of prostate-related symptoms around diagnosis were more likely to report a diagnosis-related increase in religiosity and spirituality. Positive benefits (reduced recurrence worry) of religious coping/practices were restricted to those patients with higher versus lower level of postdiagnosis increase in religiosity; patients not reporting postdiagnosis increases in religion who are not engaging in religious coping/practice adjusted equally well. Results suggest that the development of religious/spiritual interventions is premature.Significance of results: This is the first prospective study to report on the prevalence and influence of daily spiritual and religious experiences among prostate cancer patients.

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