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- 2019
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Tidskriftsartikel (refereegranskat)
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- Arndt, D. S., et al.
(författare)
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STATE OF THE CLIMATE IN 2017
- 2018
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Ingår i: Bulletin of The American Meteorological Society - (BAMS). - : American Meteorological Society. - 0003-0007 .- 1520-0477. ; 99:8, s. S1-S310
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Forskningsöversikt (refereegranskat)
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- Chesnut, G. T., et al.
(författare)
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Estimating patient health in prostate cancer treatment counseling
- 2023
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Ingår i: Prostate Cancer and Prostatic Diseases. - : Springer Science and Business Media LLC. - 1365-7852 .- 1476-5608. ; 26, s. 271-275
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Tidskriftsartikel (refereegranskat)abstract
- Background We assessed the concordance among urologists' judgment of health quartiles for patients with localized prostate cancer, and compared the life expectancy (LE) and ensuing treatment recommendations when following National Comprehensive Cancer Network (NCCN) guidelines based on actuarial life tables versus the Kent model, a validated LE prediction model. Methods NCCN suggests using actuarial life tables and relying on surgeon assessment of patient health to increase (for the best quartile) or decrease (for the worst quartile) LE by 50%. Eleven urologic surgeons allocated quartile of health and recommended treatments for ten patient vignettes. The 10-year survival probability was calculated using the Kent model and compared to the life-table estimate based on health quartile by surgeon consensus. Results Surgeon assessment agreed with the presumed true quartile of health based on a validated model in 41% of cases. For no case did three-quarters of surgeons assign health quartile correctly; in half of cases, <50% of surgeons assigned the correct quartile. The NCCN comorbidity-adjusted LE estimates underestimated risk of death in the best health quartile and overestimated risk of death in the worst health quartile, compared to the Kent model. Patients with LE > 10 years on NCCN estimation were recommended more frequently for surgery (81%) and those with <= 10 years estimated LE were more commonly recommended for radiation (57%) or observation (29%). Conclusions A method based on physician-assessed health quartiles for LE estimation, as suggested by the NCCN guidelines, appears too crude to be used in the treatment counseling of men with localized prostate cancer, as compared to a validated prediction model, such as the Kent model.
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- Cheung, K. H., et al.
(författare)
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Extending gene ontology in the context of extracellular RNA and vesicle communication
- 2016
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Ingår i: Journal of Biomedical Semantics. - : Springer Science and Business Media LLC. - 2041-1480. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- Background: To address the lack of standard terminology to describe extracellular RNA (exRNA) data/metadata, we have launched an inter-community effort to extend the Gene Ontology (GO) with subcellular structure concepts relevant to the exRNA domain. By extending GO in this manner, the exRNA data/metadata will be more easily annotated and queried because it will be based on a shared set of terms and relationships relevant to extracellular research. Methods: By following a consensus-building process, we have worked with several academic societies/consortia, including ERCC, ISEV, and ASEMV, to identify and approve a set of exRNA and extracellular vesicle-related terms and relationships that have been incorporated into GO. In addition, we have initiated an ongoing process of extractions of gene product annotations associated with these terms from Vesiclepedia and ExoCarta, conversion of the extracted annotations to Gene Association File (GAF) format for batch submission to GO, and curation of the submitted annotations by the GO Consortium. As a use case, we have incorporated some of the GO terms into annotations of samples from the exRNA Atlas and implemented a faceted search interface based on such annotations. Results: We have added 7 new terms and modified 9 existing terms (along with their synonyms and relationships) to GO. Additionally, 18,695 unique coding gene products (mRNAs and proteins) and 963 unique non-coding gene products (ncRNAs) which are associated with the terms: "extracellular vesicle", "extracellular exosome", "apoptotic body", and "microvesicle" were extracted from ExoCarta and Vesiclepedia. These annotations are currently being processed for submission to GO. Conclusions: As an inter-community effort, we have made a substantial update to GO in the exRNA context. We have also demonstrated the utility of some of the new GO terms for sample annotation and metadata search.
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- Heijnsdijk, E. A. M., et al.
(författare)
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Lifetime Benefits and Harms of Prostate-Specific Antigen-Based Risk-Stratified Screening for Prostate Cancer
- 2020
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Ingår i: Jnci-Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 112:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Studies conducted in Swedish populations have shown that men with lowest prostate-specific antigen (PSA) levels at ages 44-50 years and 60 years have very low risk of future distant metastasis or death from prostate cancer. This study investigates benefits and harms of screening strategies stratified by PSA levels. Methods: PSA levels and diagnosis patterns from two microsimulation models of prostate cancer progression, detection, and mortality were compared against results of the Malmo Preventive Project, which stored serum and tracked subsequent prostate cancer diagnoses for 25 years. The models predicted the harms (tests and overdiagnoses) and benefits (lives saved and life-years gained) of PSA-stratified screening strategies compared with biennial screening from age 45 years to age 69 years. Results: Compared with biennial screening for ages 45-69 years, lengthening screening intervals for men with PSA less than 1.0 ng/mL at age 45 years led to 46.8-47.0% fewer tests (range between models), 0.9-2.1% fewer overdiagnoses, and 3.1-3.8% fewer lives saved. Stopping screening when PSA was less than 1.0 ng/mL at age 60 years and older led to 12.8-16.0% fewer tests, 5.0-24.0% fewer overdiagnoses, and 5.0-13.1% fewer lives saved. Differences in model results can be partially explained by differences in assumptions about the link between PSA growth and the risk of disease progression. Conclusion: Relative to a biennial screening strategy, PSA-stratified screening strategies investigated in this study substantially reduced the testing burden and modestly reduced overdiagnosis while preserving most lives saved. Further research is needed to clarify the link between PSA growth and disease progression.
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- Perera, M., et al.
(författare)
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Outcomes of Grade Group 2 and 3 Prostate Cancer on Initial Versus Confirmatory Biopsy: Implications for Active Surveillance
- 2023
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Ingår i: European Urology Focus. - : Elsevier BV. - 2405-4569. ; 9:4, s. 662-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Active surveillance (AS) is recommended as the preferred treatment for men with low-risk disease. In order to optimize risk stratification and exclude undiagnosed higher-grade disease, most AS protocols recommend a confirmatory biopsy.Objective: We aimed to compare outcomes among men with grade group (GG) 2/3 prostate cancer on initial biopsy with those among men whose disease was initially GG1 but was upgraded to GG2/3 on confirmatory biopsy.Design, setting, and participants: We reviewed patients undergoing radical prostatectomy (RP) in two cohorts: "immediate RP group,"with GG2/3 cancer on diagnostic biopsy, and "AS group,"with GG1 cancer on initial biopsy that was upgraded to GG2/3 on confirmatory biopsy.Outcome measurements and statistical analysis: Probabilities of biochemical recurrence (BCR) and salvage therapy were determined using multivariable Cox regression models with risk adjustment. Risks of adverse pathology at RP were also compared using logistic regression.Results and limitations: The immediate RP group comprised 4009 patients and the AS group comprised 321 patients. The AS group had lower adjusted rates of adverse pathology (27% vs 35%, p = 0.003). BCR rates were lower in the AS group, although this did not reach conventional significance (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.50-1.06, p = 0.10) compared with the immediate RP group. Risk-adjusted 1- and 5yr BCR rates were 4.6% (95% CI 3.0-6.5%) and 10.4% (95% CI 6.9-14%), respectively, for the AS group compared with 6.3% (95% CI 5.6-7.0%) and 20% (95% CI 19-22%), respectively, in the immediate RP group. A nonsignificant association was observed for salvage treatment-free survival favoring the AS group (HR 0.67, 95% CI 0.42, 1.06, p = 0.087).Conclusions: We found that men with GG1 cancer who were upgraded on confirmatory biopsy tend to have less aggressive disease than men with the same grade found at initial biopsy. These results must be confirmed in larger series before recommendations can
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- Vertosick, Emily A., et al.
(författare)
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Individual Patient Data Meta-analysis of Discrimination of the Four Kallikrein Panel Associated With the Inclusion of Prostate Volume
- 2021
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Ingår i: Urology. - : Elsevier BV. - 0090-4295. ; 157, s. 102-106
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Tidskriftsartikel (refereegranskat)abstract
- Objective: To assess whether adding prostate volume to the kallikrein panel improves discrimination for ISUP Grade Group 2 or higher (GG2+) disease, as some men may have volume measurements available at the time of blood draw. While prostate volume predicts biopsy outcome, it requires an imaging procedure for measurement. The four kallikrein panel - commercially available as the 4Kscore - predicts risk of GG2+ disease and requires only a blood draw. Materials and Methods: A total of 9131 patients with available prostate volume and total PSA ≤25 ng/ml from 5 historical (sextant biopsy, pre-ISUP 2005 grading) and 4 contemporary cohorts (10+ cores, ISUP 2005 grading). Previously published kallikrein panel models were used to predict risk of GG2+. Volume was added to the model in each cohort and change in discrimination was meta-analyzed. Results: Increased prostate volume was associated with decreased risk of GG2+ disease after controlling for the kallikrein panel in 7/9 cohorts. However, kallikrein panel discrimination (0.817, 95% CI 0.802, 0.831) was not improved after including volume (AUC difference 0.002, 95% CI -0.003, 0.006). Heterogeneity (P <.0001) was driven by an AUC increase in 1 cohort of academic cancer centers (0.044, 95% CI 0.025, 0.064), with no evidence of heterogeneity after excluding this cohort (P = .15). Conclusion: The kallikrein panel provides a non-invasive approach to assess the risk of high-grade prostate cancer. Our results do not justify the inclusion of prostate volume in the four kallikrein panel. There is some evidence that the predictive value of prostate volume is provider dependent: further research is needed to address this question. © 2021 Elsevier Inc.
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- Friberg, A. S., et al.
(författare)
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Impact of previous depression on the risk of suicide among prostate cancer patients
- 2023
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Ingår i: Acta Oncologica. - : Informa UK Limited. - 0284-186X .- 1651-226X. ; 62:1, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPrior studies of suicide risk among prostate cancer patients are conflicting. We compared the risk of suicide in prostate cancer patients to cancer-free men including adjustment for clinical stage, socioeconomic position, somatic comorbidity, and previous depression.Materials and methodsA cohort of 37,527 men diagnosed with prostate cancer in Denmark during 1998-2011 was identified in the Danish Prostate Cancer Registry (DaPCaR) and compared with 357,384 cancer-free men matched by age at the time of diagnosis. The primary outcome was death from suicide. Data were analyzed using cumulative incidence functions and multivariable Cox regression models.ResultsAmong prostate cancer patients, 3813 had a previous depression, defined as filed antidepressant prescription within three years before diagnosis. In the study period, 108 prostate cancer patients were registered with suicide as the cause of death, hereof 26 with previous depression. There was no difference in the cumulative incidence of suicide between prostate cancer patients and cancer-free men. There was no effect modification of previous depression on the risk of suicide (p = .12). The hazard ratio (HR) for suicide varied with time since diagnosis. A sensitivity analysis showed that the risk of suicide was highest within the first year of diagnosis where prostate cancer patients had a 1.70-fold increased hazard compared with cancer-free men (95% CI, 1.11-2.59). Men with prostate cancer and previous depression had a three-fold increased hazard for suicide compared with prostate cancer patients without a history of depression (HR 2.84, 95% CI, 1.82-4.45).ConclusionThe absolute risk of suicide is low following a prostate cancer diagnosis. Time since diagnosis and a history of depression was associated with the highest risk of suicide. Healthcare professionals should be aware of an increased risk of suicide among men with previous depression, especially in the immediate aftermath of the diagnosis.
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- Haese, A., et al.
(författare)
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A pre-specified model based on four kallikrein markers in blood improves predictions of adverse pathology and biochemical recurrence after radical prostatectomy
- 2020
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 123:4, s. 604-609
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Tidskriftsartikel (refereegranskat)abstract
- Background A pre-specified model based on four kallikrein markers in blood, commercially available as 4Kscore, predicts Gleason Grade (GG) 3 + 4 or higher prostate cancer on biopsy. However, sampling error and variation in pathology reporting may miss aggressive disease. Methods The 4Kscore was measured in cryopreserved blood from 2330 men obtained before prostatectomy at a single institution between 2002 and 2010. Adverse surgical pathology and biochemical recurrence (BCR) were pre-specified to be assessed in all men, biopsy GG 3 + 3, and 3 + 4. Results Adjusted for established clinical predictors, the 4Kscore was significantly associated with adverse pathology (OR 1.49; 95% CI 1.32, 1.67;p < 0.0001). Adding 4Kscore increased discrimination from (AUC) 0.672 to 0.718 and 0.644 to 0.659 within biopsy GG 3 + 3 and 3 + 4, respectively. Higher 4Kscore was associated with higher risk of BCR (HR 1.16, 95% CI 1.06, 1.26;p = 0.001). Adding 4Kscore improved the prediction of BCR (C-index 0.630-0.660) within GG 3 + 3, but not GG 3 + 4. Conclusions The 4Kscore can help guide the clinical decision whether additional risk assessment-such as confirmatory biopsy-is needed to decide between active surveillance versus curative therapy. Evidence that the panel could influence management in biopsy GG 3 + 4 is less strong and requires further investigation.
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- Kear, Benjamin P., et al.
(författare)
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First Dinosaurs from Saudi Arabia
- 2013
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:12, s. e84041-
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Tidskriftsartikel (refereegranskat)abstract
- Dinosaur remains from the Arabian subcontinent are exceedingly rare, and those that have been documented manifest indeterminate affinities. Consequently the discovery of a small, but diagnostic, accumulation of elements from Campanian-Maastrichtian (similar to 75 Ma) deposits in northwestern Saudi Arabia is significant because it constitutes the first taxonomically identifiable dinosaur material described from the Arabian Peninsula. The fossils include a series of possible lithostrotian titanosaur caudal vertebrae, and some isolated theropod marginal teeth that share unique character states and metric parameters (analyzed using multivariate statistical methods) with derived abelisaurids - this is the first justifiable example of a non-avian carnivorous dinosaur clade from Arabia. The recognition of titanosaurians and abelisaurids from Saudi Arabia extends the palaeogeographical range of these groups along the entire northern Gondwanan margin during the latest Cretaceous. Moreover, given the extreme paucity of coeval occurrences elsewhere, the Saudi Arabian fossils provide a tantalizing glimpse into dinosaurian assemblage diversity within the region.
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- Perera, M., et al.
(författare)
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Oncologic Outcomes of Total Length Gleason Pattern 4 on Biopsy in Men with Grade Group 2 Prostate Cancer
- 2022
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 208:2, s. 309-316
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Gleason Score 7 prostate cancer comprises a wide spectrum of disease risk, and precise substratification is paramount. Our group previously demonstrated that the total length of Gleason pattern (GP) 4 is a better predictor than %GP4 for adverse pathological outcomes at radical prostatectomy. We aimed to determine the association of GP4 length on prostate biopsy with post-prostatectomy oncologic outcomes. Materials and Methods: We compared 4 GP4 quantification methods-including maximum %GP4 in any single core, overall %GP4, total length GP4 (mm) across all cores and length GP4 (mm) in the highest volume core-for prediction of biochemical recurrence-free survival after radical prostatectomy using multivariable Cox proportional hazards regression. Results: A total of 457 men with grade group 2 prostate cancer on biopsy subsequently underwent radical prostatectomy. The 3-year biochemical recurrence-free survival probability was 85% (95% CI 81-88). On multivariable analysis, all 4 GP4 quantification methods were associated with biochemical recurrence-maximum % GP4 (HR=1.30; 95% CI 1.07-1.59; p=0.009), overall %GP4 (HR=1.61; 95% CI 1.21-2.15; p=0.001), total length GP4 (HR=2.48; 95% CI 1.36-4.52; p=0.003) and length GP4 in highest core (HR=1.32; 95% CI 1.11-1.57; p=0.001). However, we were unable to identify differences between methods of quantification with a relatively low event rate. Conclusions: These findings support further studies on GP4 quantification in addition to the ratio of GP3 and GP4 to classify prostate cancer risk. Research should also be conducted on whether GP4 quantification could provide a surrogate endpoint for disease progression for trials in active surveillance.
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- Austria, M., et al.
(författare)
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Patient Perceptions of a Decision Support Tool for Men with Localized Prostate Cancer
- 2023
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Ingår i: Medical Decision Making Policy & Practice. - : SAGE Publications. - 2381-4683. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Purpose. To evaluate patient perceptions of a Web-based decision aid for the treatment of localized prostate cancer. Methods. We assessed patient perceptions of a multicomponent, Web-based decision aid with a preference elicitation/values clarification exercise using adaptive conjoint analysis, the generation of a summary report, and provision of information about localized prostate cancer treatment options. Using a think-aloud approach, we conducted 21 cognitive interviews with prostate cancer patients presented with the decision aid prior to seeing their urologist. Thematic content analysis was used to examine patient perceptions of the tool's components and content prior to engaging in shared decision making with their clinician. Results. Five themes were identified: 1) patients had some negative emotional reactions to the tool, pointing out what they perceived to be unnecessarily negative framing and language used; 2) patients were forced to stop and think about preferences while going through the tool and found this deliberation to be useful; 3) patients were confused by the tool; 4) patients tried to discern the intent of the conjoint analysis questions; and 5) there was a disconnect between patients' negative reactions while using the tool and a contrasting general satisfaction with the final "values profile" created by the tool. Conclusions. Studies are needed to explore the disconnect between patients' expressing negative reactions while going through some components of decision aids but satisfaction with the final output. In particular, we hypothesize that this effect might be explained by cognitive biases such as choice-supportive bias, hindsight bias, and the "IKEA effect." This is one of the first projects to elicit patient reactions while they were completing a decision aid, and we recommend further similar, qualitative postprocess evaluation studies.
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- Carlsson, Sigrid, 1982, et al.
(författare)
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Long-Term Outcomes of Active Surveillance for Prostate Cancer: The Memorial Sloan Kettering Cancer Center Experience
- 2020
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 203:6, s. 1122-1127
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We report oncologic outcomes for men with Grade Group 1 prostate cancer managed with active surveillance at a tertiary cancer center. Materials and Methods: A total of 2,907 patients were managed with active surveillance between 2000 and 2017, of whom 2,664 had Grade Group 1 disease. Patients were recommended confirmatory biopsy to verify eligibility and were followed semiannually with prostate specific antigen, digital rectal examination and review of symptoms. Magnetic resonance imaging was increasingly used in recent years. Biopsy was repeated every 2 to 3 years or after a sustained prostate specific antigen increase or changes in magnetic resonance imaging/digital rectal examination. The Kaplan-Meier method was used to estimate probabilities of treatment, progression and development of metastasis. Results: Median patient age at diagnosis was 62 years. For men with Grade Group 1 prostate cancer the treatment-free probability at 5, 10 and 15 years was 76% (95% CI 74-78), 64% (95% CI 61-68) and 58% (95% CI 51-64), respectively. At 5, 10 and 15 years there were 1,146, 220 and 25 men at risk for metastasis, respectively. Median followup for those without metastasis was 4.3 years (95% CI 2.3-6.9). Distant metastasis developed in 5 men. Upon case note review only 2 of these men were deemed to have disease that could have been cured on immediate treatment. The risk of distant metastasis was 0.6% (95% CI 0.2-2.0) at 10 years. Conclusions: Active surveillance is a safe strategy over longer followup for appropriately selected patients with Grade Group 1 disease following a well-defined monitoring plan.
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- Carlsson, Sigrid, 1982, et al.
(författare)
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Risk of Metastasis in Men with Grade Group 2 Prostate Cancer Managed with Active Surveillance at a Tertiary Cancer Center
- 2020
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Ingår i: Journal of Urology. - : Ovid Technologies (Wolters Kluwer Health). - 0022-5347 .- 1527-3792. ; 203:6, s. 1117-1121
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: We studied the risk of metastatic prostate cancer development in men with Grade Group 2 disease managed with active surveillance at Memorial Sloan Kettering Cancer Center. Materials and Methods: A total of 219 men with Grade Group 2 prostate cancer had disease managed with active surveillance between 2000 and 2017. Biopsy was performed every 2 to 3 years, or upon changes in magnetic resonance imaging, prostate specific antigen level or digital rectal examination. The primary outcome was development of distant metastasis. The Kaplan-Meier method was used to estimate treatment-free survival. Results: Median age at diagnosis was 67 years (IQR 61-72), median prostate specific antigen was 5 ng/ml (IQR 4-7) and most patients (69%) had nonpalpable disease. During followup 64 men received treatment, including radical prostatectomy in 36 (56%), radiotherapy in 20 (31%), hormone therapy in 3 (5%) and focal therapy in 5 (8%). Of the 36 patients who underwent radical prostatectomy 32 (89%) had Grade Group 2 disease on pathology and 4 (11%) had Grade Group 3 disease. Treatment-free survival was 61% (95% CI 52-70) at 5 years and 49% (95% CI 37-60) at 10 years. Three men experienced biochemical recurrence, no men had distant metastasis and no men died of prostate cancer during the followup. Median followup was 3.1 years (IQR 1.9-4.9). Conclusions: Active surveillance appears to be a safe initial management strategy in the short term for carefully selected and closely monitored men with Grade Group 2 prostate cancer treated at a tertiary cancer center. Definitive conclusions await further followup.
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