Dataset Information

Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer.

ABSTRACT: Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics methodology while exemplifying each step on the application of prostate cancer recurrence prediction. In particular, we automatically identified tissue-based biomarkers having significant prognostic value for low- and intermediate-risk prostate cancer patients (Gleason scores 6-7b) after radical prostatectomy. We found that promising phenes were related to CD8(+) and CD68(+) cells in the microenvironment of cancerous glands in combination with the local micro-vascularization. Recurrence prediction based on the selected phenes yielded accuracies up to 83% thereby clearly outperforming prediction based on the Gleason score. Moreover, we compared different machine learning algorithms to combine the most relevant phenes resulting in increased accuracies of 88% for tumor progression prediction. These findings will be of potential use for future prognostic tests for prostate cancer patients and provide a proof-of-principle of the Tissue Phenomics approach.

SUBMITTER: Harder N

PROVIDER: S-EPMC5849604 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer.

Harder Nathalie N Athelogou Maria M Hessel Harald H Brieu Nicolas N Yigitsoy Mehmet M Zimmermann Johannes J Baatz Martin M Buchner Alexander A Stief Christian G CG Kirchner Thomas T Binnig Gerd G Schmidt Günter G Huss Ralf R

Scientific reports 20180313 1

Tissue Phenomics is the discipline of mining tissue images to identify patterns that are related to clinical outcome providing potential prognostic and predictive value. This involves the discovery process from assay development, image analysis, and data mining to the final interpretation and validation of the findings. Importantly, this process is not linear but allows backward steps and optimization loops over multiple sub-processes. We provide a detailed description of the Tissue Phenomics me ...[more]

PMID: 29535336

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Project description:ImportanceStereotactic body radiotherapy harnesses improvements in technology to allow the completion of a course of external beam radiotherapy treatment for prostate cancer in the span of 4 to 5 treatment sessions. Although mounting short-term data support this approach, long-term outcomes have been sparsely reported.ObjectiveTo assess long-term outcomes after stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer.Design, setting, and participantsThis cohort study analyzed individual patient data from 2142 men enrolled in 10 single-institution phase 2 trials and 2 multi-institutional phase 2 trials of stereotactic body radiotherapy for low-risk and intermediate-risk prostate cancer between January 1, 2000, and December 31, 2012. Statistical analysis was performed based on follow-up from January 1, 2013, to May 1, 2018.Main outcomes and measuresThe cumulative incidence of biochemical recurrence was estimated using a competing risk framework. Physician-scored genitourinary and gastrointestinal toxic event outcomes were defined per each individual study, generally by Radiation Therapy Oncology Group or Common Terminology Criteria for Adverse Events scoring systems. After central review, cumulative incidences of late grade 3 or higher toxic events were estimated using a Kaplan-Meier method.ResultsA total of 2142 men (mean [SD] age, 67.9 [9.5] years) were eligible for analysis, of whom 1185 (55.3%) had low-risk disease, 692 (32.3%) had favorable intermediate-risk disease, and 265 (12.4%) had unfavorable intermediate-risk disease. The median follow-up period was 6.9 years (interquartile range, 4.9-8.1 years). Seven-year cumulative rates of biochemical recurrence were 4.5% (95% CI, 3.2%-5.8%) for low-risk disease, 8.6% (95% CI, 6.2%-11.0%) for favorable intermediate-risk disease, 14.9% (95% CI, 9.5%-20.2%) for unfavorable intermediate-risk disease, and 10.2% (95% CI, 8.0%-12.5%) for all intermediate-risk disease. The crude incidence of acute grade 3 or higher genitourinary toxic events was 0.60% (n = 13) and of gastrointestinal toxic events was 0.09% (n = 2), and the 7-year cumulative incidence of late grade 3 or higher genitourinary toxic events was 2.4% (95% CI, 1.8%-3.2%) and of late grade 3 or higher gastrointestinal toxic events was 0.4% (95% CI, 0.2%-0.8%).Conclusions and relevanceIn this study, stereotactic body radiotherapy for low-risk and intermediate-risk disease was associated with low rates of severe toxic events and high rates of biochemical control. These data suggest that stereotactic body radiotherapy is an appropriate definitive treatment modality for low-risk and intermediate-risk prostate cancer.

Project description:BackgroundActive surveillance (AS) is recommended by most national medical organizations as the preferred treatment option for men with low-risk prostate cancer (PCa). However, studies report that up to one third of men on AS dropout within 5 years, without evidence of disease progression. Despite high dropout rates, few studies have purposively explored the opinions and experiences of men who discontinued AS. The aim of this study was to gain insight into the reasons why some men on AS for PCa discontinue active treatment without evidence of disease progression.MethodsSemi-structured interviews were undertaken with 14 men from diverse socio-cultural backgrounds who had been on AS for PCa but dropped out of surveillance to undergo active treatment without signs of disease progression. Purposive sampling to reach data saturation was used to select participants based on their experience of AS and willingness to share their experiences. Interviews were transcribed and analysis undertaken in an inductive thematic manner.ResultsThe following themes arose from interviews as factors that potentially influence adherence to AS: men's experience at diagnosis and follow-up consultations, involvement in shared decision-making, the extent of supportive care and information, administrative procedures and support from partner and peers. A poor experience during diagnosis could adversely influence long-term adherence to AS, given the same diagnostic tests are frequently repeated. The provision of consistent information and support while on AS, similar to that offered to men undergoing radical treatment, was also highlighted as being important to increase confidence in the process.ConclusionsEffective communications skills among health professionals, aimed at building trust in patient-clinician relationships, providing opportunities for shared decision-making and developing self-efficacy, along with structured information and support, are key to enhancing long-term adherence to AS.

Dataset Information

Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer.

Publications

Tissue Phenomics for prognostic biomarker discovery in low- and intermediate-risk prostate cancer.

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