ResearchPad - prostate-cancer https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Analytical performance of thrombospondin-1 and cathepsin D immunoassays part of a novel CE-IVD marked test as an aid in the diagnosis of prostate cancer]]> https://www.researchpad.co/article/elastic_article_15745 The Prostate Specific Antigen (PSA) test suffers from low specificity for the diagnosis of Prostate Cancer (PCa). We originally discovered two cancer-related proteins thrombospondin-1 (THBS1) and cathepsin D (CTSD) using a mass-spectrometry-based proteomics approach. The two serum proteins were shown to improve the diagnosis of high-grade PCa. Thus, we developed quantitative ELISAs for the determination of their concentration in human serum. Here we report their analytical performance in terms of limit of detection, specificity, precision, linearity and interferences, which were determined based on CLSI guidelines. Further, we investigated the influence of pre-analytical factors on concentration measurements. For this, blood from 4–6 donors was collected in different tubes and stored at room temperature for different times prior to centrifugation at different centrifugal forces and temperatures. Stability of THBS1 and CTSD under different storage temperatures was also evaluated. Our results show that the assays are specific, linear and sensitive enough to allow measurement of clinical samples. Precision in terms of repeatability and total within-laboratory coefficient of variation (CV) are 5.5% and 8.1% for THBS1 and 4.3% and 7.2% for CTSD, respectively. Relative laboratory-to-laboratory differences were -6.3% for THBS1 and -3% for CTSD. Both THBS1 and CTSD were stable in serum samples, with 80–120% recoveries of concentrations across donors, sample preparation and storage. In conclusion, the ELISAs as part of the novel commercial in vitro diagnostic test Proclarix are suitable for the use in clinical practice. THBS1 and CTSD can be accurately measured for their intended use independent of the lot and laboratory when conditions consistent with routine practice for PSA sampling and storage are used.

]]>
<![CDATA[SULF1 suppresses Wnt3A-driven growth of bone metastatic prostate cancer in perlecan-modified 3D cancer-stroma-macrophage triculture models]]> https://www.researchpad.co/article/elastic_article_14741 Bone marrow stroma influences metastatic prostate cancer (PCa) progression, latency, and recurrence. At sites of PCa bone metastasis, cancer-associated fibroblasts and tumor-associated macrophages interact to establish a perlecan-rich desmoplastic stroma. As a heparan sulfate proteoglycan, perlecan (HSPG2) stores and stabilizes growth factors, including heparin-binding Wnt3A, a positive regulator of PCa cell growth. Because PCa cells alone do not induce CAF production of perlecan in the desmoplastic stroma, we sought to discover the sources of perlecan and its growth factor-releasing modifiers SULF1, SULF2, and heparanase in PCa cells and xenografts, bone marrow fibroblasts, and macrophages. SULF1, produced primarily by bone marrow fibroblasts, was the main glycosaminoglycanase present, a finding validated with primary tissue specimens of PCa metastases with desmoplastic bone stroma. Expression of both HSPG2 and SULF1 was concentrated in αSMA-rich stroma near PCa tumor nests, where infiltrating pro-tumor TAMs also were present. To decipher SULF1’s role in the reactive bone stroma, we created a bone marrow biomimetic hydrogel incorporating perlecan, PCa cells, macrophages, and fibroblastic bone marrow stromal cells. Finding that M2-like macrophages increased levels of SULF1 and HSPG2 produced by fibroblasts, we examined SULF1 function in Wnt3A-mediated PCa tumoroid growth in tricultures. Comparing control or SULF1 knockout fibroblastic cells, we showed that SULF1 reduces Wnt3A-driven growth, cellularity, and cluster number of PCa cells in our 3D model. We conclude that SULF1 can suppress Wnt3A-driven growth signals in the desmoplastic stroma of PCa bone metastases, and SULF1 loss favors PCa progression, even in the presence of pro-tumorigenic TAMs.

]]>
<![CDATA[Estrogen receptor β exerts tumor suppressive effects in prostate cancer through repression of androgen receptor activity]]> https://www.researchpad.co/article/elastic_article_14708 Estrogen receptor β (ERβ) was first identified in the rodent prostate and is abundantly expressed in human and rodent prostate epithelium, stroma, immune cells and endothelium of the blood vessels. In the prostates of mice with inactivated ERβ, mutant phenotypes include epithelial hyperplasia and increased expression of androgen receptor (AR)-regulated genes, most of which are also upregulated in prostate cancer (PCa). ERβ is expressed in both basal and luminal cells in the prostate while AR is expressed in luminal but not in the basal cell layer which harbors the prostate stem cells. To investigate the mechanisms of action of ERβ and its potential cross-talk with AR, we used RNA-seq to study the effects of estradiol or the synthetic ligand, LY3201, in AR-positive LNCaP PCa cells which had been engineered to express ERβ. Transcriptomic analysis indicated relatively few changes in gene expression with ERβ overexpression, but robust responses following ligand treatments. There is significant overlap of responsive genes between the two ligands, estradiol and LY3201 as well as ligand-specific alterations. Gene set analysis of down-regulated genes identified an enrichment of androgen-responsive genes, such as FKBP5, CAMKK2, and TBC1D4. Consistently, AR transcript, protein levels, and transcriptional activity were down-regulated following ERβ activation. In agreement with this, we find that the phosphorylation of the CAMKK2 target, AMPK, was repressed by ligand-activated ERβ. These findings suggest that ERβ-mediated signaling pathways are involved in the negative regulation of AR expression and activity, thus supporting a tumor suppressive role for ERβ in PCa.

]]>
<![CDATA[Editorial Comment: A 16-yr Follow-up of the European Randomized study of Screening for Prostate Cancer]]> https://www.researchpad.co/article/N80581996-6648-456c-8c8e-ec5e72989dc3 ]]> <![CDATA[Real-time adaptive planning method for radiotherapy treatment delivery for prostate cancer patients, based on a library of plans accounting for possible anatomy configuration changes]]> https://www.researchpad.co/article/5c818e8ad5eed0c484cc24c8

Background and purpose

In prostate cancer treatment with external beam radiation therapy (EBRT), prostate motion and internal changes in tissue distribution can lead to a decrease in plan quality. In most currently used planning methods, the uncertainties due to prostate motion are compensated by irradiating a larger treatment volume. However, this could cause underdosage of the treatment volume and overdosage of the organs at risk (OARs). To reduce this problem, in this proof of principle study we developed and evaluated a novel adaptive planning method. The strategy proposed corrects the dose delivered by each beam according to the actual position of the target in order to produce a final dose distribution dosimetrically as similar as possible to the prescribed one.

Material and methods

Our adaptive planning method was tested on a phantom case and on a clinical case. For the first, a pilot study was performed on an in-silico pelvic phantom. A “library” of intensity modulated RT (IMRT) plans corresponding to possible positions of the prostate during a treatment fraction was generated at planning stage. Then a 3D random walk model was used to simulate possible displacements of the prostate during the treatment fraction. At treatment stage, at the end of each beam, based on the current position of the target, the beam from the library of plans, which could reproduce the best approximation of the prescribed dose distribution, was selected and delivered. In the clinical case, the same approach was used on two prostate cancer patients: for the first a tissue deformation was simulated in-silico and for the second a cone beam CT (CBCT) taken during the treatment was used to simulate an intra-fraction change. Then, dosimetric comparisons with the standard treatment plan and, for the second patient, also with an isocenter shift correction, were performed.

Results

For the phantom case, the plan generated using the adaptive planning method was able to meet all the dosimetric requirements and to correct for a misdosage of 13% of the dose prescription on the prostate. For the first clinical case, the standard planning method caused underdosage of the seminal vesicles, respectively by 5% and 4% of the prescribed dose, when the position changes for the target were correctly taken into account. The proposed adaptive planning method corrected any possible missed target coverage, reducing at the same time the dose on the OARs. For the second clinical case, both with the standard planning strategy and with the isocenter shift correction target coverage was significantly worsened (in particular uniformity) and some organs exceeded some toxicity objectives. While with our approach, the most uniform coverage for the target was produced and systematically the lowest toxicity values for the organs at risk were achieved.

Conclusions

In our proof of principle study, the adaptive planning method performed better than the standard planning and the isocenter shift methods for prostate EBRT. It improved the coverage of the treatment volumes and lowered the dose to the OARs. This planning method is particularly promising for hypofractionated IMRT treatments in which a higher precision and control on dose deposition are needed. Further studies will be performed to test more extensively the proposed adaptive planning method and to evaluate it at a full clinical level.

]]>
<![CDATA[A natural history model for planning prostate cancer testing: Calibration and validation using Swedish registry data]]> https://www.researchpad.co/article/5c6f1520d5eed0c48467ae2e

Recent prostate cancer screening trials have given conflicting results and it is unclear how to reduce prostate cancer mortality while minimising overdiagnosis and overtreatment. Prostate cancer testing is a partially observable process, and planning for testing requires either extrapolation from randomised controlled trials or, more flexibly, modelling of the cancer natural history. An existing US prostate cancer natural history model (Gulati et al, Biostatistics 2010;11:707-719) did not model for differences in survival between Gleason 6 and 7 cancers and predicted too few Gleason 7 cancers for contemporary Sweden. We re-implemented and re-calibrated the US model to Sweden. We extended the model to more finely describe the disease states, their time to biopsy-detectable cancer and prostate cancer survival. We first calibrated the model to the incidence rate ratio observed in the European Randomised Study of Screening for Prostate Cancer (ERSPC) together with age-specific cancer staging observed in the Stockholm PSA (prostate-specific antigen) and Biopsy Register; we then calibrated age-specific survival by disease states under contemporary testing and treatment using the Swedish National Prostate Cancer Register. After calibration, we were able to closely match observed prostate cancer incidence trends in Sweden. Assuming that patients detected at an earlier stage by screening receive a commensurate survival improvement, we find that the calibrated model replicates the observed mortality reduction in a simulation of ERSPC. Using the resulting model, we predicted incidence and mortality following the introduction of regular testing. Compared with a model of the current testing pattern, organised 8 yearly testing for men aged 55–69 years was predicted to reduce prostate cancer incidence by 14% and increase prostate cancer mortality by 2%. The model is open source and suitable for planning for effective prostate cancer screening into the future.

]]>
<![CDATA[Structured reporting of prostate magnetic resonance imaging has the potential to improve interdisciplinary communication]]> https://www.researchpad.co/article/5c75abfdd5eed0c484d07f7d

Background

Effective interdisciplinary communication of imaging findings is vital for patient care, as referring physicians depend on the contained information for the decision-making and subsequent treatment. Traditional radiology reports contain non-structured free text and potentially tangled information in narrative language, which can hamper the information transfer and diminish the clarity of the report. Therefore, this study investigates whether newly developed structured reports (SRs) of prostate magnetic resonance imaging (MRI) can improve interdisciplinary communication, as compared to non-structured reports (NSRs).

Methods

50 NSRs and 50 SRs describing a single prostatic lesion were presented to four urologists with expert level experience in prostate cancer surgery or targeted MRI TRUS fusion biopsy. They were subsequently asked to plot the tumor location in a 2-dimensional prostate diagram and to answer a questionnaire focusing on information on clinically relevant key features as well as the perceived structure of the report. A validated scoring system that distinguishes between “major” and “minor” mistakes was used to evaluate the accuracy of the plotting of the tumor position in the prostate diagram.

Results

The mean total score for accuracy for SRs was significantly higher than for NSRs (28.46 [range 13.33–30.0] vs. 21.75 [range 0.0–30.0], p < 0.01). The overall rates of major mistakes (54% vs. 10%) and minor mistakes (74% vs. 22%) were significantly higher (p < 0.01) for NSRs than for SRs. The rate of radiologist re-consultations was significantly lower (p < 0.01) for SRs than for NSRs (19% vs. 85%). Furthermore, SRs were rated as significantly superior to NSRs in regard to determining the clinical tumor stage (p < 0.01), the quality of the summary (4.4 vs. 2.5; p < 0.01), and overall satisfaction with the report (4.5 vs. 2.3; p < 0.01), and as more valuable for further clinical decision-making and surgical planning (p < 0.01).

Conclusions

Structured reporting of prostate MRI has the potential to improve interdisciplinary communication. Through SRs, expert urologists were able to more accurately assess the exact location of single prostate cancer lesions, which can facilitate surgical planning. Furthermore, structured reporting of prostate MRI leads to a higher satisfaction level of the referring physician.

]]>
<![CDATA[Histogram analysis of prostate cancer on dynamic contrast-enhanced magnetic resonance imaging: A preliminary study emphasizing on zonal difference]]> https://www.researchpad.co/article/5c6c75d9d5eed0c4843d02ed

Background

This study evaluated the performance of histogram analysis in the time course of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for differentiating cancerous tissues from benign tissues in the prostate.

Methods

We retrospectively analyzed the histograms of DCE-MRI of 30 patients. Histograms within regions of interest(ROI) in the peripheral zone (PZ) and transitional zone (TZ) were separately analyzed. The maximum difference wash-in slope (MWS) and delay phase slope (DPS) were defined for each voxel. Differences in histogram parameters, namely the mean, standard deviation (SD), the coefficient of variation (CV), kurtosis, skewness, interquartile range (IQR), percentile (P10, P25, P75, P90, and P90P10), Range, and modified full width at half-maximum (mFWHM) between cancerous and benign tissues were assessed.

Results

In the TZ, CV for ROIs of 7.5 and 10mm was the only significantly different parameter of the MWS (P = 0.034 and P = 0.004, respectively), whereas many parameters of the DPS (mean, skewness, P10, P25, P50, P75 and P90) differed significantly (P = <0.001–0.016 and area under the curve [AUC] = 0.73–0.822). In the PZ, all parameters of the MWS exhibited significant differences, except kurtosis and skewness in the ROI of 7.5mm(P = <0.001–0.017 and AUC = 0.865–0.898). SD, IQR, mFWHM, P90P10 and Range were also significant differences in the DPS (P = 0.001–0.035).

Conclusion

The histogram analysis of DCE-MRI is a potentially useful approach for differentiating prostate cancer from normal tissues. Different histogram parameters of the MWS and DPS should be applied in the TZ and PZ.

]]>
<![CDATA[Assessment of patient information needs: A systematic review of measures]]> https://www.researchpad.co/article/5c5ca313d5eed0c48441f0cf

Background

Providing patient information is a central aspect of patient-centered care. Fulfilling personal information needs has positive effects on several health-related outcomes. Measurement instruments help to identify individual information needs in an effective way. The present study gives an overview of existing information needs measures and further evaluates the quality of their psychometric properties and their psychometric studies.

Methods

We conducted a systematic search on psychometric studies of measures that assess information needs in PubMed and Embase. Furthermore, we carried out a secondary search with reference and citation tracking of the included articles. Title, abstracts and full texts were screened by two independent reviewers for eligibility. We extracted data on content of the measures, validation samples and psychometric properties. In addition we rated the methodological quality with the COSMIN checklist and the quality of psychometric properties with the criteria of Terwee and colleagues.

Results

24 studies on 21 measures were included. Most instruments assessed information needs of patients with cancer or cardiac diseases. The majority of the instruments were in English language and from western countries. Most studies included information on internal consistency and content validity. The ratings showed mixed results with clear deficiencies in the methodological quality of most studies.

Discussion

This is the first systematic review that summarized the existing evidence on measures on patient information needs using two instruments for a systematic quality assessment. The results show a need for more psychometric studies on existing measures. In addition, reporting on psychometric studies needs to be improved to be able to evaluate the reliability of the psychometric properties. Furthermore, we were not able to identify any measures on information needs for some frequent chronic diseases. Other methods to elicit information needs (e.g. open-ended interviews, question prompt sheets) could be considered as alternatives if sound measures are missing.

]]>
<![CDATA[Intensity-modulated radiotherapy for prostate cancer with seminal vesicle involvement (T3b): A multicentric retrospective analysis]]> https://www.researchpad.co/article/5c79b004d5eed0c4841e3c37

Objectives

No study has reported clinical results of external-beam radiotherapy specifically for T3b prostate cancer. The possibility of escalating the dose to the involved seminal vesicles (ISV) while respecting the dose constraints in the organs at risk is thus so far not clearly demonstrated. The objective of the study was to analyze the dose distribution and the clinical outcome in a large series of patients who received IMRT for T3b prostate cancer.

Materials and methods

This retrospective analysis included all patients who received IMRT and androgen deprivation therapy for T3b prostate cancer, between 2008 and 2017, in six French institutions, with available MRI images and dosimetric data.

Results

A total of 276 T3b patients were included. The median follow-up was 26 months. The median (range) prescribed doses (Gy) to the prostate and to the ISV were 77 (70–80) and 76 (46–80), respectively. The dose constraint recommendations were exceeded in less than 12% of patients for the rectum and the bladder. The 5-year risks of biochemical and clinical recurrences and cancer-specific death were 24.8%, 21.7%, and 10.3%, respectively. The 5-year risks of local, pelvic lymph node, and metastatic recurrences were 6.4%, 11.3%, and 15%, respectively. The number of involved lymph nodes (≤ 2 or ≥ 3) on MRI was the only significant prognostic factor in clinical recurrence (HR 9.86) and death (HR 2.78). Grade ≥ 2 acute and 5-year late toxicity rates were 13.2% and 12% for digestive toxicity, and 34% and 31.5% for urinary toxicity, respectively. The dose to the pelvic lymph node and the age were predictive of late digestive toxicity.

Conclusion

IMRT for T3b prostate cancer allows delivery of a curative dose in the ISV, with a moderate digestive toxicity but a higher urinary toxicity. Lymph node involvement increases the risk of recurrence and death.

]]>
<![CDATA[Recent incidence and surgery trends for prostate cancer: Towards an attenuation of overdiagnosis and overtreatment?]]> https://www.researchpad.co/article/5c61e937d5eed0c48496f9f2

Background

Screening for prostate cancer is frequent in high-income countries, including Switzerland. Notably due to overdiagnosis and overtreatment, various organisations have recently recommended against routine screening, potentially having an impact on incidence, mortality, and surgery rates. Our aim was therefore to examine whether secular trends in the incidence and mortality of prostate cancer, and in prostatectomy rates, have recently changed in Switzerland.

Methods

We conducted a population-based trend study in Switzerland from 1998 to 2012. Cases of invasive prostate cancer, deaths from prostate cancer, and prostatectomies were analysed. We calculated changes in age-standardised prostate cancer incidence rates, stratified by tumor stage (early, advanced), prostate cancer-specific mortality, and prostatectomy rates.

Results

The age-standardised incidence rate of prostate cancer increased greatly in men aged 50–69 years (absolute mean annual change +4.6/100,000, 95% CI: +2.9 to +6.2) between 1998 and 2002, and stabilised afterwards. In men aged ≥ 70 years, the incidence decreased slightly between 1998 and 2002, and more substantially since 2003. The incidence of early tumor stages increased between 1998 and 2002 only in men aged 50–69 years, and then stabilised, while the incidence of advanced stages remained stable across both age strata. The rate of prostatectomy increased markedly until 2002, more so in the 50 to 69 age range than among men aged ≥ 70 years; it leveled off after 2002 in both age strata. Trends in surgery were driven by radical prostatectomy. Since 1998, the annual age-standardised mortality rate of prostate cancer slightly declined in men aged 50–69 years (absolute mean annual change -0.1/100,000, 95% CI: -0.2 to -0.1) and ≥ 70 years (absolute mean annual change -0.5/100,000, 95% CI: -0.7 to -0.3).

Conclusions

The increases in the incidence of early stage prostate cancer and prostatectomy observed in Switzerland among men younger than 70 years have concomitantly leveled off around 2002/2003. Given the decreasing mortality, these trends may reflect recent changes in screening and clinical workup practices, with a possible attenuation of overdiagnosis and overtreatment.

]]>
<![CDATA[Deletion of the p16INK4a tumor suppressor and expression of the androgen receptor induce sarcomatoid carcinomas with signet ring cells in the mouse prostate]]> https://www.researchpad.co/article/5c536a9fd5eed0c484a476f6

The tumor suppressor p16Ink4a, encoded by the INK4a gene, is an inhibitor of cyclin D-dependent kinases 4 and 6, CDK4 and CDK6. This inhibition prevents the phosphorylation of the retinoblastoma protein (pRb), resulting in cellular senescence through inhibition of E2F-mediated transcription of S phase genes required for cell proliferation. The p16Ink4a plays an important role in tumor suppression, whereby its deletion, mutation, or epigenetic silencing is a frequently observed genetic alteration in prostate cancer. To assess its roles and related molecular mechanisms in prostate cancer initiation and progression, we generated a mouse model with conditional deletion of p16Ink4a in prostatic luminal epithelium. The mice underwent oncogenic transformation and developed prostatic intraepithelial neoplasia (PIN) from eight months of age, but failed to develop prostatic tumors. Given the prevalence of aberrant androgen signaling pathways in prostate cancer initiation and progression, we then generated R26hARL/wt:p16L/L: PB-Cre4 compound mice, in which conditional expression of the human AR transgene and deletion of p16Ink4a co-occur in prostatic luminal epithelial cells. While R26hARL/wt:PB-Cre4 mice showed no visible pathological changes, R26hARL/wt:p16L/L: PB-Cre4 compound mice displayed an early onset of high-grade PIN (HGPIN), prostatic carcinoma, and metastatic lesions. Strikingly, we observed tumors resembling human sarcomatoid carcinoma with intermixed focal regions of signet ring cell carcinoma (SRCC) in the prostates of the compound mice. Further characterization of these tumors showed they were of luminal epithelial cell origin, and featured characteristics of epithelial to mesenchymal transition (EMT) with enhanced proliferative and invasive capabilities. Our results not only implicate a biological role for AR expression and p16Ink4a deletion in the pathogenesis of prostatic SRCC, but also provide a new and unique genetically engineered mouse (GEM) model for investigating the molecular mechanisms for SRCC development.

]]>
<![CDATA[regQTLs: Single nucleotide polymorphisms that modulate microRNA regulation of gene expression in tumors]]> https://www.researchpad.co/article/5c21518bd5eed0c4843fab22

Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) associated with trait diversity and disease susceptibility, yet their functional properties often remain unclear. It has been hypothesized that SNPs in microRNA binding sites may disrupt gene regulation by microRNAs (miRNAs), short non-coding RNAs that bind to mRNA and downregulate the target gene. While several studies have predicted the location of SNPs in miRNA binding sites, to date there has been no comprehensive analysis of their impact on miRNA regulation. Here we investigate the functional properties of genetic variants and their effects on miRNA regulation of gene expression in cancer. Our analysis is motivated by the hypothesis that distinct alleles may cause differential binding (from miRNAs to mRNAs or from transcription factors to DNA) and change the expression of genes. We previously identified pathways—systems of genes conferring specific cell functions—that are dysregulated by miRNAs in cancer, by comparing miRNA–pathway associations between healthy and tumor tissue. We draw on these results as a starting point to assess whether SNPs on dysregulated pathways are responsible for miRNA dysregulation of individual genes in tumors. Using an integrative regression analysis that incorporates miRNA expression, mRNA expression, and SNP genotype data, we identify functional SNPs that we term “regulatory QTLs (regQTLs)”: loci whose alleles impact the regulation of genes by miRNAs. We apply the method to breast, liver, lung, and prostate cancer data from The Cancer Genome Atlas, and provide a tool to explore the findings.

]]>
<![CDATA[Wagging the long tail of drivers of prostate cancer]]> https://www.researchpad.co/article/5c61b7c9d5eed0c484937fa7 ]]> <![CDATA[Clinical utility of MRI in the decision-making process before radical prostatectomy: Systematic review and meta-analysis]]> https://www.researchpad.co/article/5c3d0118d5eed0c484038457

Context

Magnetic resonance imaging (MRI) is currently the most accurate imaging modality to assess local prostate cancer stage. Despite a growing body of evidence, incorporation of MRI images into decision-making process concerning surgical template of radical prostatectomy, is complex and still poorly understood.

Objective

We sought to determine the value of MRI in preoperative planning before radical prostatectomy.

Materials and methods

Systematic search through electronic PubMed, EMBASE, and Cochrane databases from 2000 up to April 2018 was performed. Only studies that used preoperative MRI in decision-making process regarding extension of resection in patients with prostate cancer, in whom radical prostatectomy was an initial form of treatment were included into analysis. Their quality was scored by Risk Of Bias In Non-Randomized Studies of Interventions system. Meta-analysis was performed to calculate the weighted summary proportion under the fixed or random effects model as appropriate and pooled effects were depicted on forest plots.

Results

The results showed that the preoperative MRI led to the modification of initial surgical template in one third of cases (35%). This occurred increasingly with the rising prostate cancer-risk category: 28%, 33%, 52% in low-, intermediate- and high-risk group, respectively. Modification of neurovascular bundle-sparing surgery based on MRI appeared to have no impact on the positive surgical margin rate. The decision based on MRI was correct on average in 77% of cases and differed across prostate cancer-risk categories: 63%, 75% and 91% in low-, intermediate- and high-risk group, accordingly.

Conclusions

In summary, MRI has a considerable impact on the decision-making process regarding the extent of resection during radical prostatectomy. Adaptation of MRI images by operating surgeons has at worst no significant impact on surgical margin status, however its ability to decrease the positive surgical margin rates remains unconfirmed.

]]>
<![CDATA[Cost-effectiveness analyses and cost analyses in castration-resistant prostate cancer: A systematic review]]> https://www.researchpad.co/article/5c117bd5d5eed0c48469a9cf

Background

Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer became available with promising survival advantages. However, cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances. The aim of this study was to systematically review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer (CRPC) and metastasizing castration-resistant prostate cancer (mCRPC) on their methodological quality and the risk of bias.

Methods

A systematic literature search was performed in the databases PubMed, CINAHL Complete, the Cochrane Library and Web of Science Core Collection for costs-effectiveness analyses, model-based economic evaluations, cost-of-illness analyses and budget impact analyses. Reported costs were inflated to 2015 US$ purchasing power parities. Quality assessment and risk of bias assessment was performed using the Consolidated Health Economic Evaluation Reporting Standards checklist and the Bias in Economic Evaluations checklist, respectively.

Results

In total, 38 articles were identified by the systematic literature search. The methodological quality of the included studies varied widely, and there was considerable risk of bias. The cost-effectiveness treatments for CRPC and mCRPC was assessed with incremental cost-effectiveness ratios ranging from dominance for mitoxantrone to $562,328 per quality-adjusted life year gained for sipuleucel-T compared with prednisone alone. Annual costs for the treatment of castration-resistant prostate cancer ranged from $3,067 to $77,725.

Conclusion

The cost-effectiveness of treatments of CRPC strongly depended on the willingness to pay per quality-adjusted life year gained/life-year saved throughout all included costs-effectiveness analyses and model-based economic evaluations. High-quality cost-effectiveness analyses based on randomized controlled trials are needed in order to make informed decisions on the management of castration-resistant prostate cancer and the resulting financial impact on the healthcare system.

]]>
<![CDATA[A new plan quality objective function for determining optimal collimator combinations in prostate cancer treatment with stereotactic body radiation therapy using CyberKnife]]> https://www.researchpad.co/article/5c06f034d5eed0c484c6d3a1

Stereotactic body radiation therapy with CyberKnife for prostate cancer has long treatment times compared with conventional radiotherapy. This arises the need for designing treatment plans with short execution times. We propose an objective function for plan quality evaluation, which was used to determine an optimal combination between small and large collimators based on short treatment times and clinically acceptable dose distributions. Data from 11 prostate cancer patients were used. For each patient, 20 plans were created based on all combinations between one small (⌀ 10–25 mm) and one large (⌀ 35–60 mm) Iris collimator size. The objective function was assigned to each combination as a penalty, such that plans with low penalties were considered superior. This function considered the achievement of dosimetric planning goals, tumor control probability, normal tissue complication probability, relative seriality parameter, and treatment time. Two methods were used to determine the optimal combination. First, we constructed heat maps representing the mean penalty values and standard deviations of the plans created for each collimator combination. The combination giving a plan with the smallest mean penalty and standard deviation was considered optimal. Second, we created two groups of superior plans: group A plans were selected by histogram analysis and group B plans were selected by choosing the plan with the lowest penalty from each patient. In both groups, the most used small and large collimators were assumed to represent the optimal combination. The optimal combinations obtained from the heat maps included the 25 mm as a small collimator, giving small/large collimator sizes of 25/35, 25/40, 25/50, and 25/60 mm. The superior-group analysis indicated that 25/50 mm was the optimal combination. The optimal Iris combination for prostate cancer treatment using CyberKnife was determined to be a collimator size between 25 mm (small) and 50 mm (large).

]]>
<![CDATA[Machine learning to support social media empowered patients in cancer care and cancer treatment decisions]]> https://www.researchpad.co/article/5bd2324640307c60de5e9970

Background

A primary variant of social media, online support groups (OSG) extend beyond the standard definition to incorporate a dimension of advice, support and guidance for patients. OSG are complementary, yet significant adjunct to patient journeys. Machine learning and natural language processing techniques can be applied to these large volumes of unstructured text discussions accumulated in OSG for intelligent extraction of patient-reported demographics, behaviours, decisions, treatment, side effects and expressions of emotions. New insights from the fusion and synthesis of such diverse patient-reported information, as expressed throughout the patient journey from diagnosis to treatment and recovery, can contribute towards informed decision-making on personalized healthcare delivery and the development of healthcare policy guidelines.

Methods and findings

We have designed and developed an artificial intelligence based analytics framework using machine learning and natural language processing techniques for intelligent analysis and automated aggregation of patient information and interaction trajectories in online support groups. Alongside the social interactions aspect, patient behaviours, decisions, demographics, clinical factors, emotions, as subsequently expressed over time, are extracted and analysed. More specifically, we utilised this platform to investigate the impact of online social influences on the intimate decision scenario of selecting a treatment type, recovery after treatment, side effects and emotions expressed over time, using prostate cancer as a model. Results manifest the three major decision-making behaviours among patients, Paternalistic group, Autonomous group and Shared group. Furthermore, each group demonstrated diverse behaviours in post-decision discussions on clinical outcomes, advice and expressions of emotion during the twelve months following treatment. Over time, the transition of patients from information and emotional support seeking behaviours to providers of information and emotional support to other patients was also observed.

Conclusions

Findings from this study are a rigorous indication of the expectations of social media empowered patients, their potential for individualised decision-making, clinical and emotional needs. The increasing popularity of OSG further confirms that it is timely for clinicians to consider patient voices as expressed in OSG. We have successfully demonstrated that the proposed platform can be utilised to investigate, analyse and derive actionable insights from patient-reported information on prostate cancer, in support of patient focused healthcare delivery. The platform can be extended and applied just as effectively to any other medical condition.

]]>
<![CDATA[Mind the gap: Physicians’ assessment of patients’ importance weights in localized prostate cancer]]> https://www.researchpad.co/article/5b69466b463d7e3867f4ad0d

Background

The management of localized prostate cancer is challenging because of the many therapeutic options available, none of which is generally acknowledged as superior to the others in every respect. The selection of the most appropriate treatment should therefore reflect patients’ preferences.

Objective

The purpose of the following study was to pilot a new approach for investigating whether urologists who had previously provided patients with therapeutic advice actually knew their patients’ importance weights concerning the relevant aspects of the treatments at issue.

Method

Participants were patients recently diagnosed with localized prostate cancer (n = 20), urologists (n = 10), and non-medical professionals (architects, n = 10). These last served as a control group for the urologists and were matched to them for age and gender. Patients’ importance weights were elicited by two standard methods (Direct Rating and Value Hierarchy). Each urologist was asked to estimate (with Direct Rating) his/her patient’s importance weights. The same task was performed by a corresponding architect, who never met the patient and knew only the patient’s age. Univariate and bivariate statistical analyses were performed to investigate the association between importance weights as elicited from patients and as estimated by urologists and architects, as well as to assess whether such agreement was attribute-dependent.

Results

Participants found both elicitation methods easy to use. The correlation between patients’ actual importance weights and urologists’ estimates was poor and comparable to that obtained between patients and architects. This result did not depend on the attribute considered, with the sole exception of the attribute “Effectiveness in curing the cancer”, which was evaluated as the most important attribute by the majority of participants.

Conclusion

These findings demonstrate the feasibility of the employed methodology and highlight the need to support preference-sensitive decisions in clinical practice by facilitating the elicitation of patients’ importance weights, as well as their communication to physicians.

]]>
<![CDATA[Development of a prediction model for late urinary incontinence, hematuria, pain and voiding frequency among irradiated prostate cancer patients]]> https://www.researchpad.co/article/5b600f86463d7e3af00e5a8b

Background and purpose

Incontinence, hematuria, voiding frequency and pain during voiding are possible side effects of radiotherapy among patients treated for prostate cancer. The objective of this study was to develop multivariable NTCP models for these side effects.

Material and methods

This prospective cohort study was composed of 243 patients with localized or locally advanced prostate cancer (stage T1-3). Genito-urinary (GU) toxicity was assessed using a standardized follow-up program. The GU toxicity endpoints were scored using the Common Terminology Criteria for Adverse Events version 3.0 (CTCAE 3.0) scoring system. The full bladder and different anatomical subregions within the bladder were delineated. A least absolute shrinkage and selection operator (LASSO) logistic regression analysis was used to analyze dose volume effects on the four individual endpoints.

Results

In the univariable analysis, urinary incontinence was significantly associated with dose distributions in the trigone (V55-V75, mean). Hematuria was significantly associated with the bladder wall dose (V40-V75, mean), bladder dose (V70-V75), cardiovascular disease and anticoagulants use. Pain during urinating was associated with the dose to the trigone (V50-V75, mean) and with trans transurethral resection of the prostate (TURP). In the final multivariable model urinary incontinence was associated with the mean dose of the trigone. Hematuria was associated with bladder wall dose (V75) and cardiovascular disease, while pain during urinating was associated with trigone dose (V75) and TURP. No significant associations were found for increase in voiding frequency.

Conclusions

Radiation-induced urinary side effects are associated with dose distributions to different organs as risk. Given the dose effect relationships found, decreasing the dose to the trigone and bladder wall may reduce the incidence of incontinence, pain during voiding and hematuria, respectively.

]]>